B2B Nutramedic&Cosmetics No.3

Nutramedic B2B &Cosmetics No.3 / MARCH 2023

Help for a calmer and deeper sleep / Bone health Probiotics in Europe / Bakopa and cognitive functions Urea / Collagen / Skin application of niacin

Nutramedic &Cosmetics

Editor's word Dear business partners and colleagues, We are presenting the third issue of the B2B Nutramedic&Cosmetics di­ gi­tal magazine.

In this issue, we focused specifi­ cally on sleep difficulties and sleep quality, as this continues to be the fastest growing cate­ gory in the field of nutritional supplements.

Another important topic that we paid attention to is the maintenance of bone health by means of supplementa­ tion with ingredients that can help preserve their health and thus ease the problems caused by the loss of bone mass.

We bring you more about the plant Bacopa monnieri, which has been at the center of research due to its bene­ ficial effect on cognitive functions.

As far as cosmetic topics are concerned, we bring a text about the effectiveness of urea for skin hydration, about collagen, niacin in transdermal application and the new pro­tein peptide.

Hoping you will find interesting and useful information for your business, Until the new edition, Daria Šurić, M.pharm.

B2B

Nutramedic &Cosmetics

Ingredients and raw materials / Contract manufacturing Equipment & Packaging / Services / Industry events www.nmc-magazine.com info@nmc-magazine.com Publisher: Darmell d.o.o.

Cvjetna cesta 11, 10000 Zagreb, Hrvatska Mob: + 385 91 68 12 444 darmell@protonmail.com www.dar-mell.com www.inpharma.hr

The publisher does not assume responsibility for the opinions and data that the authors present in the magazine, as well as for the data and materials provided by companies for publication in texts and adver­tisements. It is not allowed to reuse any part of the content with­ out the prior consent of the publisher.

2

4

What can help for a calmer and deeper sleep?

10

DailyZz™: Something to dream about

13

The importance of bones in preserving the integrity of the body’s function and ingredients that help preserve bone mass

20

Functional ingredients for healthy aging and bone support

Bimonthly digital magazine for industry professionals in health, nutrition and cosmetics sector

Supported by

Contents

22

Osteoporosis and vitamin K2

23

Darmell: Expert in the nutritional supplements field

24

Fine Foods and continuous innovation: competitive advantage and shared value

s

Nutramedic &Cosmetics

26

43

29

46

30

48

34

50

Probiotics in Europe: consumer survey in 8 EU countries

IPA expands its scope of work

Bacopa (Bacopa monnieri) and its effect on cognitive functions

An inspiring success story: Adena Natura

35

B2B events calendar

36

NADES solvents – a green revolution

38

Experience the world’s nutraceutical event: Vitafoods Europe 2023

40

Elasderma® advanced skin molecule technology

Urea - an effective molecule for dry skin symptoms

The role of collagen in the skin health

Niacin skin application

Global Omega-3 Day™

51

NutraFood Poland: B2B event dedicated to food supplements and functional food

52

Medicinal plants photo herbarium: yarrow

53

Pomegranate fruit extract linked to improved skin health

54

Bioline – a solution for your needs 3

Nutramedic &Cosmetics

What can help for a calmer and deeper sleep?

Almost one-third of the general population has symptoms of insomnia (defined as difficulty falling asleep and/or staying asleep). The use of drugs for insomnia is limited by their tolerability and the increased risk of addiction, morbidity and mortality with long-term use. The search for safe and effective compounds without harmful effects is crucial in this context.

AUTHOR:

Daria Šurić, M.pharm.

4

F

or a long time, it was believed that sleep is a sta­ te of the organism in which most of its func­ tions cease, and the body is completely at rest.

Today we know that this is not entirely true, because even though when we close our eyes and fall asleep some processes in the body slow down, others re­ main surprisingly active. Sleep begins with the acti­ vation of an area of the brain called the hypothala­ mus, where cascading changes occur that induce changes in the body that result in sleep. Nerve cells in the brain reduce alertness and promote sle­epi­ ness, while electrical activity in the brain begins to

slow. These and other changes that occur as sleep continues to affect nearly every cell in your body.1 In modern society, there is increasing concern about the risks associated with insomnia and lack of sleep.

Recent epidemiological data support the opinion that many segments of the adult population are chroni­ cally sleep deprived. On the other hand, there are experts who claim that our basic required amount of sleep is about 6 hours during one night, and that we can easily forget more sleep, because it is com­ pletely unnecessary. However, experimental data on the effects of both acute and cumulative partial sle­ep

Nutramedic &Cosmetics deprivation (PSD) consistently point out that sleep restriction has significant negative effects on sleepi­ ness, motor and cognitive performance and mood as well as on some metabolic, hormonal and immuno­ logical variables.

Given that chronic partial sleep deprivation can ha­ ve serious, long-term adverse health effects, it should be avoided in the general population. In the short term, the effects of sleep restriction appear to accumulate linearly, while the effects of long-term PSD should be further investigated, as the few ava­ ­i­lable studies are flawed by methodological weak­ nesses. On the other hand, there is evidence that ex­ tending sleep by 2-3 hours beyond the norm brings only marginal benefits to the average individual. Fi­ nally, it is underlined that, as large individual differ­ ences do exist in the need for sleep, the search for the sleep need may be vain. A somnotypology, taking into account age, gender and the position in both the sleep-alert and the morningness-eveningness continuum, should help in the search for the actual individual sleep need. 2 Insomnia and sleep disorders are considered a major problem worldwide, especially in Western so­ cieties. Over a year, the prevalence of general sleep disturbance is estimated at around 85%, and a diag­ nosis of primary insomnia is estimated to be approxi­ mately 10%.9 Insomnia is associated with reduced hippocampal volume, daytime cortical gamma-aminobutyric acid (GABA) levels and activation of the caudate nucleus.

In several parts of the brain, such as the hippocam­ pus or the prefrontal cortex, inhibition of the usual decline in activity that occurs during the transition from waking to sleep has been observed. Thus, gene­ ral overactivity of the arousal, emotion regulation, and cognitive systems probably leads to the patho­ physiology of insomnia. For the treatment of this di­ sease, there are effective drugs such as benzodiaze­ pines or benzodiazepine receptor agonists. However, the use of these sleep medications is limited by their tolerance and the increased risk of addiction, morbi­ dity and mortality with long-term use.10 In this con­ text, the search for safe and effective compounds without adverse effects is essential.

The extent to which sleep is causally related to mental health is unclear.

The aim of the 2006 study was to to trace the con­ sequences of insufficient sleep in terms of chronic sleep reduction, rather than acute sleep deprivation on fatigue, mood, cognitive performance self-estima­ tion, and daytime sleepiness in different age-social groups. The age group of the subjects reflected their social situation and the organization of working hours: adolescents followed strict school schedules with starting times often before 8:00 h; university stu­ dents had more flexible timetables; young employe­es were engaged in regular morning schedules or irre­ gular daytime hours or day or night shifts. 3 The most frequent complaints of adolescents in­ cluded tiredness on awakening (46%), nervousness and general weakness. University students reported excessive sleepiness (50%), tension and nervousness.

Employees suffered the most from negative moods, such as tension (49%), nervousness and irritability.

The findings of the study show that chronic sleep loss seems to affect women more than men. The correla­ tion of fatigue and mood with the need for sleep and the sleep index was more pronounced in younger sub­ jects. Surprisingly, symptoms of fatigue in school children and students were just as common as in hard-working adults. Since the problem of insuffici­ ent amount of sleep is already present among young people, it is necessary to pay more attention to the organization of their working time. 3 One way to test the causal link of sleep quality to mental health is to evaluate the extent to which in­ terventions that improve sleep quality also improve mental health. A meta-analysis of randomized con­ trolled trials was conducted, which reported the ef­ fects of an intervention that improved sleep on complex mental health and on seven specific mental health problems. 65 trials with 72 interventions and 8,608 participants were included in the meta-analy­ sis. Sleep improvement led to a moderately signifi­ cant effect on overall mental health, depression, anxiety, and rumination, followed by a small-to-mode­ rately significant effect on stress, and finally a small-significant effect on positive symptoms in psychosis. A cause-and-effect relationship was also clarified, in the sense that greater improvements in sleep quality led to greater improvements in mental health. These findings suggest that sleep quality is causally related to psychological difficulties. Future research might consider how methods that improve sleep quality could be incorporated into services to improve mental health. We should also study the mechanisms that affect mental health by influenc­ ing the quality of sleep.4 Problems with sleep are common. A review of seve­ ral hundred epidemiological studies concluded that nearly one-third of the general population has symp­ toms of insomnia (defined as difficulty falling asleep and/or staying asleep), between 4% and 26% experi­ ence excessive sleepiness, and between 2% and 4% TABLE 1 Staying awake for 24 hours may cause

symptoms like: drowsiness irritability anger

increased risk of stress decreased alertness impaired concentration brain fog fatigue tremors reduced coordination increased risk of mistakes or accidents food cravings puffy eyes dark undereye circles

5

Nutramedic &Cosmetics of people experience obstructive sleep apnea.5 Ad­ ditionally, a recent study with more than 2,000 par­ ticipants reported that the prevalence of “general sleep disturbances” was 32%. It was previo­usly assu­ med that mental health difficulties lead to sleep prob­ lems, however the reverse may also be true, such that poor sleep contributes to the onset, recurrence, and maintenance of mental health difficulties.

Sleep disorders and stress have been in the top 3 consumer health concerns in recent years.12 Accord­ ing to the Centers for Disease Control and Preventi­on (CDC), 24 hours of sleep deprivation is equivalent to a blood alcohol concentration of 0.10%. Such a 24-hour lack of sleep can cause numerous symptoms (Table 1).

Taking into account everything that has been stated so far, there is a clear need to find other ways to contribute to the quality and duration of sleep, in addition to classical drug therapy, which has longterm unwanted effects. In addition to adjusting the diet and introducing bedtime routines, dietary sup­ plements play a key role. We will discuss several in­ gredients below, as they have shown a positive ef­ fect on sleep in studies and in practice.

Melatonin

Melatonin is a neurohormone secreted by the pi­ neal gland in the brain, and is well known for causing and regulating sleep. Light suppresses melatonin synthesis. The primary use of melatonin as a dietary supplement is to normalize abnormal sleep patterns.

Melatonin may also have general neuroprotective effects related to its antioxidant effects.

TABLE 2 Health claims for melatonin (EFSA)

3-1 ID

Wording

Conditions of use

1953

Melatonin contributes to the alleviation of subjective feelings of jet lag.

Conditions of use: the claim may be used only for food which contains at least 0,5 mg of melatonin per quantified portion. Information to the consumer: the beneficial effect is obtained with a minimum intake of 0,5 mg to be taken close to bedtime on the first day of travel and on the following few days after arrival at the destination.

1698/1780/4080 Melatonin contributes to the reduction of time taken to fall asleep.

6

Conditions of use: the claim may be used only for food which contains 1 mg of melatonin per quantified portion. Information to the consumer: the beneficial effect is obtained by consuming 1 mg of melatonin close to bedtime.

There are some demographic groups that tend to have irregular melatonin production in their body.

Smokers tend to be less responsive to supplementa­ tion, and older people tend to not produce as much during night time. Depression has also been associ­ ated with lower melatonin levels.

Very rarely, serious adverse effects resulting from melatonin supplementation (often in very high dos­ es) have been reported. Taking melatonin is not as­ sociated with negative feedback (when taking a sup­ plement causes your body to produce less of the hor­ mone). It is also not addictive. Melatonin’s primary mechanism is by helping decrease the time it takes to fall asleep (as a hormone, that's its primary job).

Doses between 500 mcg (0.5 mg) and 5 mg of mela­ tonin appear to be effective in regulating the sleep cycle. It is recommended to start with 500 mcg, then increase the dose to 1 mg if necessary. Higher doses belong to the drug category and should be taken un­ der the supervision of a doctor. The benefits of mela­ tonin are not dose-dependent, as taking more will not help to fall asleep faster.

For help to fall asleep, it is recommended to take melatonin approximately 30 minutes before bedtime.

As part of the study to determine the optimal do­ se of melatonin, research was conducted on children.

It showed that their treatment compared to the gen­ eral Dutch population14 can be sustained over a long period of time without significant deviation in deve­ lopment, regarding sleep quality, puberty deve­lop­ ment and mental health scores.

In a multicenter, randomized, placebo-controlled study of 170 ambulatory patients aged 55 years or ol­der, who suffered from primary insomnia, the ef­ fects of 2 mg prolonged-release melatonin (PR-mela­ tonin) for 3 weeks were evaluated compared to pla­ cebo treatment. It was the first drug shown to sig­ nificantly improve sleep quality and morning alert­ ness in these patients, suggesting restorative sleep.

Also, the patients did not have withdrawal symptoms after discontinuation.15 We emphasize the fact that melatonin in that study belonged to the category of drugs due to the high dose contained.

Here is another study that was conducted to sys­ tematically review the effect of melatonin on sleep quality. Evidence from randomized clinical trials (RCTs) investigating the effects of melatonin on sleep qua­ lity as assessed by the Pittsburgh Sleep Quality Index (PSQI) in adults with various diseases is summarized.

According to this index, it was determined that treat­ ment with exogenous melatonin has positive ef­ fects on the quality of sleep in adults.7 In order to overcome the short-term effect of melatonin on easier falling asleep and to prevent la­ te night awakenings, some manufacturers have de­ veloped a unique form of micronized melatonin that enables both immediate and prolonged release, thus comprehensively improving the quality of sleep.

In most European countries where melatonin is al­ lowed as an ingredient in food supplements (includ­ ing Croatia), the maximum dose is 1 mg per day (Table 2). It is different in Turkey, where the content of mela­ tonin is allowed up to 3 mg for adults, but with a mandatory warning on the declaration:"It should not be used by pregnant or breastfeeding women and persons under 18 years of age", "Do not drive, oper­ ate machinery or consume alcohol while using this

Nutramedic &Cosmetics product", "It should not be used for more than two months". Germany, Ireland, Iceland and Slovenia do not allow melatonin in food supplements, but classi­ fy it as a drug, regardless of dosage.

sures, and volunteers with varying demographic and psychographic characteristics are required to re­ plicate and extend these findings.16 In conclusion, the above studies provide evidence that saffron extract could be an interesting natural and safe strategy to improve sleep duration and quality of sleep on population presented mild to mo­ derate chronic primary sleep disorder.

Biopeptides from milk

Saffron, Crocus sativus L.

The saffron extract used in food supplements is among the most expensive extracts, just as the spice used in food preparation is among the most expen­ sive spices. But there is a valid reason for that.

Saffron belongs to the iris family. Its threads loca­ ted in the center of the purple flower are stigmas (Fi­ gure 1). There are only three orange-yellow stigmas in each flower, which means that it takes many flow­ ers to produce a small amount of extract or spice. Each kilogram of saffron contains between 15 and 20 tho­ u­sand stigmas. If you were to grow saffron yourself, you would need 75 thousand flowers to get half a ki­ logram.

But that is not the only reason why saffron is so expensive. Saffron flowers are very delicate, and the only way to properly remove the threads is to tear them off by hand. The flower is so delicate that if the saffron threads are not harvested soon after the flo­wers bloom, they will wilt and become unusable. It ta­kes about 370 to 470 hours of work to harvest one kilogram of saffron. However, if we consider that sleep and the quality of sleep are of inestimable impor­ tance for human health, then the price of saffron ex­ tract is a justified investment.

The dried stigmas of the saffron plant (Figure 2) used in traditional medicine, and the compounds it contains - safranal, crocin and crocetin - have been largely studied for their effects on depression and anxiety in humans.5 Additionally, saffron appears to have beneficial effects on sleep duration and quali­ ty, as evidenced by previous reports using different approaches and protocols. Some studies used a who­ le saffron extract, while others examined the effects of its active compound crocetin.

It is undeniable that saffron extract is effective in the context of depression and anxiety, but its effect on sleep quality has not been investigated by objec­ tive approaches until recently. For this purpose, a randomized, double-blind, placebo controlled study was conducted in subjects presenting mild to mode­ rate sleep disorder associated with anxiety. Sixty-six subjects were randomized and supplemented with a placebo (maltodextrin) or a saffron extract (15.5 mg per day) for 6 weeks.8 Saffron extract intake was associated with impro­ vements in sleep quality in adults with self-reported sleep complaints. Further studies using larger sam­ ples sizes, treatment periods, objective outcome me­a­

Developed in France, Lactium is the generic name of bioactive milk-derived peptides. They are amino acid chains concentrated from casein, derived from cow milk, that act on GABA receptors.

However, its discovery was ultimately thanks to ba­ ­bies. The enzymes present in babies’ digestive sys­ tems are responsible for the release of this bioac­ tive peptide resulting in a state of bliss. The diges­ tive enzyme system of adults is no longer capable of releasing this bioactive milk peptide. After many ye­ ars of work, researchers have developed an innova­ tive process to reproduce a baby's digestive system.

They used the well-known digestive enzyme trypsin to isolate a milk protein hydrolyzate containing the bioactive peptide alpha-casozepine from casein.

Lactium® improves sleep, reduces stress and cor­ tisol levels while inducing relaxation and improving mental function. (Clare & Swaisgood, 2000; Delini-Stu­ la & Holsboer-Trachsler, 2009; de Saint-Hilaire, Mes­ saoudi, Desor, & Kobayashi, 2009). It is an effective alternative to medication for anxiety and insomnia.

The study evaluated the effects of alpha-s1 casein hydrolyzate (ACH) on the subjective and objective sleep profiles in subjects with poor sleep quality. A double-blind, randomized, cross-over trial was con­ ducted with 48 participants (49.0 ± 1.7 years, 65% fe­ male) who exhibited a mild to moderate degree of sleep disturbance. During the first four weeks, they received either ACH or placebo, and the counterpart was administered in precisely the same way after a four-week washout period. Findings suggest that refined ACH is well tolerated and may improve sleep quality, with possible cumulative beneficial effects with long-term administration.17 Lactium® can be used as an ingredient in a wide range of products, in capsules, tablets, powders, che­ ­wing gums, drinks, as an stand alone active substan­ ce or in combination with other ingredients.

Magnesium

Magnesium is found in many food supplements as an independent ingredient, or in combination with other active ingredients for numerous purposes. It

7

Nutramedic &Cosmetics

is often found in food supplements that are intend­ ed to promote healthy sleep. The reason for this is justified. Namely, magnesium plays a role in support­ ing deep, restorative sleep by maintaining healthy levels of GABA, the neurotransmitter that promotes sleep. Research shows that supplemental magne­ sium intake can improve sleep quality, especially in people with poor sleep.

There are many other ingredients that offer pro­ mising results in improving sleep quality. One of them is DailyZz by Kemin, a clinically tested combination of ingredients for natural sleep support. Cli­ni­­cal da­ ta supported by rigorous testing of 100 heal­thy par­ ticipants with occasional sleep problems sho­wed that the ingredient can help improve sleep quality, support healthy sleep and improve an individual's functioning during the following day.

One of the interesting new findings is that sleep fragmentation and short sleep duration are associ­ ated with intestinal dysbiosis, a fact that will surely gain importance in the future. It was also found that the addition of probiotics improves the subjective quality of sleep. The quality and duration of sleep can be an important goal for maintaining a healthy gut microbiota composition, but the cyclical nature of this relationship should not be overlooked.18

References:

8

7

Fatemeh G, Sajjad M, Niloufar R, Neda S, Leila S, Khadijeh M. Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials. J Neurol. 2022 Jan;269(1):205-216. doi: 10.1007/s00415-020-10381-w.

Epub 2021 Jan 8. PMID: 33417003.

8

Pachikian BD, Copine S, Suchareau M, Deldicque L. Effects of Saffron Extract on Sleep Quality: A Randomized Double-Blind Controlled Clinical Trial. Nutrients. 2021 Apr 27;13(5):1473. doi: 10.3390/nu13051473. PMID: 33925432; PMCID: PMC8145009.

9

Sarris J., Panossian A., Schweitzer I., Stough C., Scholey A. Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence. Eur. Neuropsycho­ pharmacol. 2011;21:841–860. doi: 10.1016/j.euroneuro.2011.04.002.

10

Riemann D., Nissen C., Palagini L., Otte A., Perlis M.L., Spiegelhalder K. The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol. 2015;14:547–558. doi: 10.1016/ S1474-4422(15)00021-6.

11

Hausenblas H.A., Saha D., Dubyak P.J., Anton S.D. Saffron (Crocus sativus L.) and major depressive disorder: A meta-analysis of randomized clinical trials. J. Integr. Med. 2013;11:377–383. doi: 10.3736/jintegrmed2013056.

12

Euromonitor survey, 2021

13

Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomo­ tor performance in elderly patients with insomnia. Int Clin Psychopharmacol. 2009 Sep;24(5):239-49. doi: 10.1097/ YIC.0b013e32832e9b08. PMID: 19584739.

14

Van Geijlswijk IM, Mol RH, Egberts TC, Smits MG. Evaluation of sleep, puberty and mental health in children with long-term melatonin treatment for chronic idiopathic childhood sleep onset insomnia. Psychopharmacology (Berl). 2011 Jul;216(1):111-20. doi: 10.1007/s00213-011-2202-y. Epub 2011 Feb 22. PMID: 21340475; PMCID: PMC3111733.

15

Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007 Dec;16(4):372-80. doi: 10.1111/ j.1365-2869.2007. 00613.x. PMID: 18036082.

1

https://thesleepdoctor.com/how-sleep-works/what-is-sleep/

2

Ferrara M, De Gennaro L. How much sleep do we need? Sleep Med Rev. 2001 Apr;5(2):155-179. doi: 10.1053/smrv.2000.0138. PMID: 12531052.

3

Oginska H, Pokorski J. Fatigue and mood correlates of sleep length in three age-social groups: School children, students, and employees. Chronobiol Int. 2006;23(6):1317-28. doi: 10.1080/07420520601089349. PMID: 17190716.

16

Lopresti AL, Smith SJ, Metse AP, Drummond PD. Effects of saffron on sleep quality in healthy adults with self-reported poor sleep: a randomized, double-blind, placebo-controlled trial. J Clin Sleep Med. 2020;16(6):937–947.

4

Scott AJ, Webb TL, Martyn-St James M, Rowse G, Weich S. Improv­ ing sleep quality leads to better mental health: A meta-analysis of randomised controlled trials. Sleep Med Rev. 2021 Dec;60:101556. doi: 10.1016/j.smrv.2021.101556. Epub 2021 Sep 23. PMID: 34607184; PMCID: PMC8651630.

17

Kim HJ, Kim J, Lee S, Kim B, Kwon E, Lee JE, Chun MY, Lee CY, Boulier A, Oh S, Lee HW. A Double-Blind, Randomized, Placebo-Controlled Crossover Clinical Study of the Effects of Alpha-s1 Casein Hydro­ lysate on Sleep Disturbance. Nutrients. 2019 Jun 27;11(7):1466. doi: 10.3390/nu11071466. PMID: 31252661; PMCID: PMC6682925.

5

Ohayon M.M. Epidemiological overview of sleep disorders in the general population. Sleep Med Res. 2011;2(1):1–9.

18

6

Kerkhof G.A. Epidemiology of sleep and sleep disorders in The Netherlands. Sleep Med. 2017;30:229–239.

Matenchuk, Brittany & Mandhane, Piush & Kozyrskyj, Anita. (2020).

Sleep, Circadian Rhythm, and Gut Microbiota. Sleep Medicine Re­ views. 53. 101340. 10.1016/j.smrv.2020.101340.

International Nutraceuticals & Functional Food Exhibition

Gateway to Polish Nutraceuticals & Functional Food industry Join us and create the future together 18 - 20 April 2023 | EXPO XXI Warsaw www.nutrafood.pl

info@nutrafood.pl

9

Nutramedic &Cosmetics

DailyZz : ™

Something to dream about­ DailyZz™ supplementation in healthy people who have occasional sleep problems supports healthy and quality sleep and improves performance the next day. It is a new, dual action of one botanical ingredient and an important point of differentiation that opens up space for innovation in the formulation of sleep products.

AUTHOR:

Samanta Maci, Kemin Human Nutrition and Health

Background

Consumers are increasingly recognizing that poor sleeping patterns can have a greater impact on he­ alth beyond simply feeling fatigue or short temper after a single poor night’s sleep. Getting enough quality sleep can help protect cognitive and physical health, quality of life, and get the best out of your day1.

Research from 2022 shows that 46% of global con­ sumers state their sleeping habits have worse­n­ed ei­ther slightly or a lot in the last two years. 33% of

Eu­ropean consumers are dissatisfied with the quali­ ty of overall life as a result of sleeping habits and 30% do not feel refreshed after sleeping which impacts daytime function and overall health2.

In fact, consumer needs translate to a sleep aids global market size of 4.8 billion USD with Eastern Eu­ rope reaching proximately 280 million USD and ex­ pected to surpass 300 million USD by 2024. Natural, chemical free and additive free are within the top bu­­ying characteristics that consumers look for in their supplements and Eastern Europe is no excep­

FIGURE 1 Benefits of DailyZz™ supplementation in support of sleep quality and next day performance.

Findings for DailyZz™ compared to placebo (p<0.05 for all). ISI-Insomnia Severity Index; BART-Baloon Analog Risk Task; PVT-Psychomotor Vigilance Test16

10

Nutramedic &Cosmetics tion with over 70% of botanicals market share3. This creates the perfect momentum for natural and sci­ ence-based ingredients to breakthrough in this plat­ ­form.

Kemin Human Nutrition and Health blended scien­ ce and nature together to create a powerful botani­ cal blend rich in naturally occurring polyphenols pro­ viding much-needed sleep quality and the strength of next day performance – meet DailyZz™.

Features

DailyZz™ is a proprietary blend of gentle water ex­ traction of a certified sustainably grown spearmint (Mentha spicata L.) and green tea (Camellia sinensis) developed for use as a dietary ingredient in supple­ ments and food and beverages applications. Rich in polyphenols, DailyZz™ is standardized to rosmarinic acid (RA) and epigallocatechin gallate (EGCG) com­ bined and over 25% of total polyphenolic complex.

DailyZz™ meets the condition of use for Camellia sinensis related to the EU on-hold botanical claims ”Supports natural sleep / relaxing / promotes con­ centration” (ID 1222 - EFSA on hold botanical claims list)*.

Powered by science

Sleep and wakefulness are tightly controlled pro­ cesses. Many distinct systems with their neuroche­ micals contribute to specific aspects of the sleep-

wake cycle. Excitatory neurotransmitters such as acetylcholine (Ach), glutamate, and different mono­ amines promote wakefulness while gamma amino­ butyric acid (GABA) together with neuropeptides, pro­ mote sleep4. Interestingly, Ach plays a dual role as a sleep and wake neurochemical5.

On top of the well-known antioxidant and neuro­ protective properties6,7, Mentha spicata and Camel­ lia sinensis have been associated with sleep, relax­ ation and brain function possibly through the ability of RA, a major polyphenol amongst more than 50 other polyphenols from the spearmint plants, to mo­ dulate Ach and of RA and EGCG from the green tea to interact with GABA receptors8-15.

In addition to the scientific rational for the poten­ tial beneficial role of the polyphenols present in the proprietary blend, supportive evidence from an in­ novative dual night and day activity was obtained in a randomized, double blind, placebo-controlled, para­l­l­ el design, clinical trial conducted by leading sleep expert Dr. Michael Grandner in hundred and five healthy men and women with occasional mild sleep complaints16.

The study showed that, when taken daily for 30 days before bedtime at 485mg dose, DailyZz™ sup­ ports healthy and quality sleep and improves next day (following day) performance parameters such as concentration, judgement, reaction time and execu­ tive function when compared to placebo (Figure 1).

Remarkably, these are cognitive areas impacted by a

11

Nutramedic &Cosmetics References:

bad night of sleep. Furthermore, benefits from Dai­ lyZz™ started to be observed as early as 7 days17.

One ingredient – countless applications

DailyZz™ is a versatile water-soluble tan-dry pow­­ der that can be included in different galenic dry for­ mulations such as hard and softgels capsules, tab­ lets, gummies, and water-based applications such as spray, sticks and drops to dissolve in water. The in­ gredient has a 3-years shelf life, is stable across a range of temperatures and pH values and in formu­ lation with melatonin, vitamins and other botanical ingredients. The suggested dosage is 485 mg/day, 30 minutes before bedtime.

Final remarks

In Eastern Europe the use of botanical sleep aid ingredients is very well established. DailyZz™ supple­ mentation in healthy men and women with occa­ sional sleep complaints supports healthy and quali­ ty sleep and improves next day performance. This is a novel finding for a botanical ingredient and an im­ portant point of differentiation that unlocks inno­ vation in sleep formulations. * Consolidated list of Article 13 Health Claims ID1222; Condition of use: Not less than 10 mg of Camellia sinensis leaf extract 5:1 a day.

The determination of the acceptability of a botanical health claim rests fully with the food business operator placing the finished food product on the market.

1

U.S. Department of Health & Human Services Sleep Deprivation and Deficiency. https://www.nhlbi.nih.gov/health-topics/ sleep-deprivation-and-deficiency.

2

FMCG Gurus Sleep and Stress Management in 2022 - Global Report; 2022;

3

Euromonitor Sleep Aids Eastern Europe 2020 - 2025; 2022;

4

España, R.A.; Scammell, T.E. Sleep Neurobiology from a Clinical Perspective. Sleep 2011, 34, 845–858, doi:10.5665/SLEEP.1112.

5

Carley, D.W.; Farabi, S.S. Physiology of Sleep. Diabetes Spectr. 2016, 29, 5–9, doi:10.2337/diaspect.29.1.5.

6

Fonseca, B.A. Key Polyphenols in Neumentix Phenolic Complex K110-42 Can Act in Multiple Ways to Support Cognitive Performance. Kemin Document KHTL-01-134;

7

Cabrera, C.; Artcho, R.; Giménez, R. Beneficial Effects of Green Tea: A Literature Review. J. Am. Coll. Nutr. 2006, 25, 79–99, doi:10.1186/1749-8546-5-13.

8

Falé, P.L.V.; Madeira, P.J.A.; Florêncio, M.H.; Ascensão, L.; Serralheiro, M.L.M. Function of Plectranthus Barbatus Herbal Tea as Neuronal Acetylcholinesterase Inhibitor. Food Funct. 2011, 2, 130–136, doi:10.1039/c0fo00070a.

9

Awad, R.; Muhammad, A.; Durst, T.; Trudeau, V.L.; Arnason, T. Bioassay-Guided Fractionation of Lemon Balm (Melissa Officinalis L.) Using an In Vitro Measure of GABA Transaminase Activity. Phyther. Res. 2009, 23, 1075–1081, doi:10.1002/ptr.

10

Kwon, Y.O.; Hong, J.T.; Oh, K.W. Rosmarinic Acid Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep through the Activation of GABAa-Ergic Systems. Biomol. Ther. 2017, 25, 105–111, doi:10.4062/biomol­ ther.2016.035.

11

Adachi, N.; Tomonaga, S.; Tachibana, T.; Denbow, D.M.; Furuse, M. (-)-Epigallocatechin Gallate Attenuates Acute Stress Responses through GABAergic System in the Brain. Eur. J. Pharmacol. 2006, 531, 171–175, doi:10.1016/j.ejphar.2005.12.024.

12

Vignes, M.; Maurice, T.; Lanté, F.; Nedjar, M.; Thethi, K.; Guiramand, J.; Récasens, M. Anxiolytic Properties of Green Tea Polyphenol (-)-Epigallocatechin Gallate (EGCG). Brain Res. 2006, 1110, 102–115, doi:10.1016/j.brainres.2006.06.062.

13

Park, K.S.; Oh, J.H.; Yoo, H.S.; Lee, Y.M.; Lee, M.K.; Hong, J.T.; Oh, K.W. (-)-Epigallocatechin-3-O-Gallate (EGCG) Reverses Caffeine-In­ duced Anxiogenic-like Effects. Neurosci. Lett. 2010, 481, 131–134, doi:10.1016/j.neulet.2010.06.072.

14

Caro, D.C.; Rivera, D.E.; Ocampo, Y.; Franco, L.A.; Salas, R.D. Pharmacological Evaluation of Mentha Spicata L. and Plantago Major L., Medicinal Plants Used to Treat Anxiety and Insomnia in Colombian Caribbean Coast. Evidence-based Complement.

Altern. Med. 2018, 2018, doi:10.1155/2018/5921514.

15

Campbell, E.L.; Chebib, M.; Johnston, G.A.R. The Dietary Flavonoids Apigenin and (-)-Epigallocatechin Gallate Enhance the Positive Modulation by Diazepam of the Activation by GABA of Recombinant GABA A Receptors. Biochem. Pharmacol. 2004, 68, 1631–1638, doi:10.1016/j.bcp.2004.07.022.

16

Tubbs, A.S.; Kennedy, K.E.R.; Alfonso-Miller, P.; Wills, C.C.A.; Grandner, M.A. A Randomized, Double-Blind, Placebo-Controlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning. Int. J. Environ. Res. Public Health 2021, 18, 1–11, doi:10.3390/ijerph18063044.

17

Sadewasser Chris DailyZz Shown to Improve Sleep Quality Is Less than 2 Weeks. Tech. Lit. 2020.

Kemin Human Nutrition and Health samanta.maci@kemin.com www.kemin.com/health

12

Nutramedic &Cosmetics

The importance of bones in preserving the integrity of the body's function and ingredients that help preserve bone mass Nutrition, exercise and appropriate supplementation can help maintain better mobility and an active lifestyle in later years. In addition to calcium, vitamins D and K, there are many other ingredients that can help maintain bone health.

B

ones and joints play a key role in the muscu­ loskeletal system, a network that includes mus­ ­­cles, ligaments, tendons, and other connecti­ ve tissue. It is well known that as a result of normal aging, changes occur in the musculoskeletal system that can lead to reduced mobility and pain, and thus to a reduced quality of life.

Bones not only give shape to the body and protect organs, but also produce red and white blood cells, act as a storehouse of minerals such as calcium and phosphorus, and help regulate acidity, i.e. the acid­base balance of the blood. Joints, simply put, are pla­ ces where bones come together. Some allow mo­ve­ ment, such as the knee joints, and others do not, such

as the joints between the bones of the skull.

Bone health is determined by genetics and envi­ ronmental factors. Throughout life, both intrinsic factors (eg, genetics and hormonal status) and ext­ rin­sic factors (eg, exercise and diet) continually in­ fluence bone modeling and remodeling. Remodeling occurs through a complex and carefully orchestrat­ ed interaction between bone resorption (bone break­ ­down) and bone deposition (bone formation). Bone mass, i.e. the amount of minerals in the bone, reflects the result of the interaction between these two pro­ cesses.

Most bone mass is accrued early in life, reaching its peak at the age of 30. In later life, bone remodel­

AUTHOR:

Valerija Pandža, M.pharm.

13

Nutramedic &Cosmetics ing continues, but more bone mass is generally lost than gained. However, this does not mean that bone health cannot be improved at any age. In fact, it is es­ timated that most of an adult's skeleton is replaced every ten years, and lifestyle choices can change the strength and health of these "new" bones.

Bone health refers to their strength and structural quality. Their health is assessed by a doctor through a detailed medical history and physical examination that includes proven tools to identify risk factors.

The findings of this assessment determine whether and how bone health will be measured. Bone miner­ al density (BMD) is the most common way of measu­ ring bone health.

Bone health is influenced by nutrient intake, hor­ monal regulation, exercise and age, among other fac­ tors (Table 1).

Age-related bone loss

Decreased bone density, changes in cartilage and connective tissue, and altered muscle function can TABLE 1 Factors affecting bone health

The amount of calcium in the diet: a diet low in calcium contributes to diminished bone density, early bone loss and an increased risk of fractures.

Physical activity: people who are physically inactive have a higher risk of osteoporosis than do their more-active counterparts.

Tobacco and alcohol use: research suggests that tobacco use contributes to weak bones. Similarly, regularly having more than one alcoholic drink a day for women or two alcoholic drinks a day for men may increase the risk of osteoporosis.

Sex: women are at greater risk of osteoporosis, because women have less bone tissue than do men.

Body constitution: persons who are extremely thin are at risk (with a body mass index of 19 or less) or have a small body frame because you might have less bone mass to draw from as they age.

Age: bones become thinner and weaker as people age.

Race and family history: persons of white or of Asian descendant have greatest risk of osteoporosis. In addition, having a parent or sibling who has osteoporosis puts you at greater risk — especially if you also have a family history of fractures.

Hormone levels: too much thyroid hormone can cause bone loss. In women, bone loss increases dramatically at menopause due to dropping estrogen levels. Prolonged absence of menstruation (amenorrhea) before menopause also increases the risk of osteoporosis. In men, low testosterone levels can cause a loss of bone mass.

Eating disorders and other conditions: severely restricting food intake and being underweight weakens bone in both men and women. In addition, weight-loss surgery and conditions such as celiac disease can affect your body's ability to absorb calcium.

Certain medications: long-term use of corticosteroid medications, such as prednisone, cortisone, prednisolone and dexamethasone, is damaging to bone.

Other drugs that might increase the risk of osteoporosis include aromatase inhibitors to treat breast cancer, selective serotonin reuptake inhibitors, methotrexate, some anti-seizure medications, such as phenytoin and phenobarbital, and proton pump inhibitors.

Taken from: https://www.mayoclinic.org/healthy-lifestyle/adult-health/in-depth/bone-health/ art-20045060

14

occur as part of the normal aging process. Changes in muscle function are also seen as part of normal aging. Fortunately, a healthy diet, exercise and prop­ er supplementation can help maintain better mobil­ ity and an active lifestyle well into later years.

Age-related bone loss is often considered a pre­ dominantly female problem. However, it is important to emphasize that although osteoporosis rates are low in men, the prevalence of osteopenia (low bone density) in the femoral neck or lumbar spine in men also increases with age.

A study by Center et al. of 852 women and 635 men (60 years and older) without fractures, reported an age-related decrease in volumetric bone mineral den­ sity (vBMD) at the hip (Center et al. 2004).

As a result of the aging process, the bone deterio­ rates in composition, structure and function, which predisposes to osteoporosis. Osteoporosis is defi­ned as a decrease in bone mass and bone micro-archi­ tecture, with an increased risk of fragility fractures.

Because of the close relationship between the aging process of bone and the pathogenesis of osteopo­ rosis, research on the mechanisms of age-related bo­ ne loss has increased significantly in recent years, in­ cluding a combination of basic, clinical, observati­o­ nal, and translational studies.

Age-related bone loss is a complex and heteroge­ neous disease. A combination of genetic, hormonal, biochemical, and environmental factors underlie its pathophysiology. The result is a decline in bone qua­n­ ­tity and quality that increases fracture risk in a pro­ gressive manner. The two most common forms of primary osteoporosis in the elderly are postmeno­ pausal osteoporosis (type 1) and senile osteoporosis (type 2). The strong ability of estrogen to suppress the activity of osteoclasts in the resorption phase and to increase their apoptosis is lost with the reduc­ tion of estrogen in menopause. Older postmenopau­ sal women probably have both etiologies.

Despite greater understanding of the mechanis­ms of these contributing factors through clinical and animal studies, more research is needed to determi­ ne the relative contributions of each of these factors in order to improve preventative and therapeutic op­tions.1

Food supplements for preserving bone health

As we age, the health of our bones and joints be­ comes more and more important. In addition, after an injury, healing should be supported, and it is also necessary to act preventively against osteoporosis and arthritis, and to look for ways to stay healthy. Vi­ tamins, minerals and other ingredients can play an important role in maintaining bone and joint health.

A recent study conducted by strategic consulting and market research firm, Blue Weave Consulting, re­ ­vealed that the global bone and joint nutritional supplements market was worth USD 10.31 billion in 2021. The market is projected to grow at a CAGR of 9.2%, earning around USD 18.83 billion by the end of 2028. The key growth driver of the global bone and joint health supplements market is the increasing trend of dietary supplements among the elderly po­ pu­lation. It is estimated that the bone and joint health nutritional supplements market will experience sig­

Nutramedic &Cosmetics nificant revenue growth during the forecast period due to the aging of the baby boom population and the increase in harmful lifestyle habits. Moreover, the growing interest of consumers in an active life, the rise in disposable income and the spread of awareness about health are further significant driv­ ers of the sector. However, high R&D investments and the high cost of clinical trials hinder market growth. 2

Ingredients in food supplements with proven effects on maintaining bone health

Many articles have been written and research do­ ne on the topic of the need for supplementation with calcium, vitamin D, vitamin K and other micro­ nutrients to maintain bone health. However, there are many more ingredients that can help preserve bone health, and they deserve additional attention, which we will devote to them in the following text.

In addition to supplementation with useful ingre­ dients, changes in some lifestyle habits that can be undertaken are also important. A balanced diet is certainly the basis of good health, including the maintenance of healthy bones. The best diet plan depends on the possible health problems that the person has. For example, a gluten-free diet can im­ prove bone mass in people with celiac disease. 3 Exercise and movement in nature are essential in the context of maintaining bone health. Regular bo­ ne density screenings according to recommended guidelines and doctor's instructions are also import­ ant.

Vitamin C

Supplementation with vitamin C can help prevent osteoporosis by reducing oxidative stress and con­ sequent bone resorption. Vitamin C is also an essential factor for the formation of collagen (an important component of the bone matrix). In addition, it po­ tentiates the activity of vitamin E in cells, by suppor­ ting the regeneration of α-tocopherol from its oxi­ dized form. Studies have proven the association of higher levels of vitamin C with higher bone density.

A double-blind study of 90 participants showed that supplementation with 1,000 mg of vitamin C and 400 IU of vitamin E was associated with higher bone mineral density after 12 months.4

Phytoestrogens

Phytoestrogens such as soy isoflavones, or res­ veratrol, have a structural similarity to estrogen and can bind to estrogen receptors and thus achieve a multitude of benefits that estrogen is otherwise res­ ponsible for. They have attracted interest as poten­ tial therapies for the bone health of postmenopau­ sal women who lack estrogen.

fun­ction, bone health, cardiometabolic markers, and general well-being in women in postmenopause.

After 12 months of resveratrol supplementation, compared to placebo, positive effects on bone den­ sity in the lumbar spine (+0.016 ± 0.003 g/cm2) and femoral neck (+0.005 ± 0.002 g/cm2) were recorded, which, also compared to placebo, were accompanied by a 7.24% decrease in the level of collagen C-termi­ nal telopeptide type 1, a marker of bone resorption.

An increase in mineral density in the femoral neck resulted in an improvement in T-score (+0.070 ± 0.018) and a decrease in the 10-year probability of a higher risk of hip fracture. The extent of improvement was greater in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T-score as a result of taking resveratrol correlated with the improvement in perfusion. A subanalysis found that the bone-protective benefit of resvera­ trol was greater in participants who took both vita­ min D and calcium. In conclusion, regular supplemen­ tation with 75 mg of resveratrol twice a day has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmeno­ pausal women without significant osteoporosis.5 It is important to note that the dose of 75 mg, who­ se effectiveness for bone health benefits was de­ termined by this study, is as much as 80 times higher than the average daily intake of resveratrol through food and drink.

Genistein Another phytoestrogen, the soy isoflavone ge­ni­s­ tein, has also been proven to benefit bone health in postmenopausal women.

A clinical trial of 389 women with postmenopaus­ al osteopenia evaluated the effects of genistein at a

Resveratrol Resveratrol, a natural polyphenol found in red gra­ pes and berries, can act as a phytoestrogen. A 2-year randomized, double-blind, placebo-control­led cros­ sover trial called RESHAW (resveratrol for healthy aging in women) evaluated the effect of resveratrol (75 mg twice daily) on cognition, cerebrovascular

15

Nutramedic &Cosmetics dose of 56 mg per day (plus 400 IJ of vitamin D). A significant increase in BMD, compared to placebo, was found in the femoral neck (+0.023 g/cm2) and lumbar spine (+0.055 g/cm2) after 12 months of sup­ plementation. BMD continued to increase in the se­ cond year of supplementation.

Participants took 2 tablets with a total of 54 mg genistein or placebo daily for 24 months. The tablets also contained vitamin D3 and calcium, also neces­ sary for healthy bones, and the placebo contained no other active ingredients.

After 24 months, bone density was measured and several blood tests were performed to see if bone breakdown or formation had occurred. Since estro­ gens can make the lining of the uterus thicker and can lead to cancer, ultrasound tests were also used to measure the thickness of the lining of the uterus to see if genistein causes this side effect as well.

After 24 months, women who took genistein had a greater increase in bone mineral density than wom­ en taking a placebo. In addition, bone markers were more favorable in women taking genistein than in women taking placebo. Gastrointestinal side effects were more common in women taking genistein than in women taking placebo. The thickness of the uter­ ine lining did not change in either group, suggesting that genistein may be safe to use in terms of uterine health.

The phytoestrogen genistein, when taken with vi­ tamin D3 and calcium, was proven to have beneficial effects on bone health compared to vitamin D3 and calcium alone.6

Olive leaf extract - bone support from the Mediterranean

In addition to the Mediterranean diet, which has various positive effects on bone health, olive extract also has proven effects. Bonolive® is an olive leaf ex­ tract standardized to a high content of oleuropein, a powerful phytonutrient unique to the olive tree. In various studies, it has shown beneficial properties, especially in reducing the risks associated with me­ nopause.

Bonolive® is a patent-protected innovation that can be seamlessly integrated into nutritional sup­ plements, medical nutrition and functional beverag­ es, with the aim of supporting the health of women during menopause. The health benefits of this ex­ tract have been evaluated in several clinical studies that have shown its positive effect on the health of bones, joints, the cardiovascular system as well as its strong antioxidant properties. Clinically proven to improve bone health. A randomized, double-blind, pla­cebo-controlled study demonstrated that it has significant effects on bone-building cells (osteo­ blasts) and bone mineral density in postmenopausal women.7 Preclinical research has shown that compounds from olive (Olea europaea) can protect against bone loss by increasing the activity of osteoblasts at the expense of adipocyte formation. The aim of this ex­ ploratory study was to get the first insight into the effect of taking olive extract on bone remodeling in postmenopausal women with osteopenia (reduced bone mass).

FIGURE 1 The gut-bone axis

The gut-bone axis: pathways and factors starting from gut dysbiosis that determine bone metabo­ lism alterations favoring osteoclasts. Abbreviations — SCFAs: short-chain fatty acids; PAMPs: pathogen-associated molecular patterns; D Cell: somatostatin-producing cells; T Cell: type of leukocyte that is an essential part of the immune system; OB: osteoblast; OC: osteoclast; RNK-L: receptor activator of nuclear factor-κB ligand; OPG: osteoprotegerin; VDR: vitamin D receptor; IGF-1: insulin-like growth factor one.

Taken from: de Sire A, de Sire R, Curci C, Castiglione F, Wahli W. Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis. Cells. 2022 Feb 21;11(4):743. doi: 10.3390/cells11040743. PMID: 35203401; PMCID: PMC8870226.

16

Nutramedic &Cosmetics A double-blind, placebo-controlled study was con­ ducted in which participants with osteopenia were randomly assigned to treatment or placebo groups.

The study included 64 of them, with a T-score of mean bone mineral density (BMD) in the lumbar spi­ ne (L2-L4) between -1.5 and -2.5. During 12 months, they took 250 mg of olive extract and 1,000 mg of calcium (treatment) or 1,000 mg of calcium alone (pla­ cebo) daily. Primary endpoints consisted of assess­ ment of bone remodeling markers. Secondary end­ points included BMD measurements and blood lipid profiles. After 12 months, levels of the pro-osteo­ blastic marker osteocalcin were found to be signifi­ cantly increased in the treatment group compared to placebo. At the same time, BMD decreased in the placebo group, while it remained stable in the treat­ ment group. In addition, improved lipid profiles were observed in the therapeutic group, with a significant reduction in total and LDL-cholesterol.7 This research study supports preclinical observa­ tions and warrants further research, as it shows that this specific olive polyphenol extract affects serum osteocalcin levels and can stabilize lumbar spine BMD. Moreover, improved blood lipid profiles suggest ad­ ditional health benefits.

The link between gut health and bone health

The relationship between gut health and bone health - known as the gut-bone axis - is an emerging area of scientific research8 (Figure 1).

Today, altered intestinal homeostasis is being in­

vestigated as a potential additional risk factor for reduced bone health, and therefore as a new poten­ tial therapeutic target. Intestinal microflora affects osteoclast activity, regulating serum IGF-1 levels, and at the same time affects intestinal calcium ab­ sorption. It is therefore not surprising that gut dys­ biosis affects bone health. In this context, it has been hypothesized that dietary supplements, prebi­ otics and probiotics contribute to the intestinal mi­ croecological balance, which is important for bone health.

There are a number of possible ways in which this can be connected. First, intestinal dysbiosis makes it difficult to absorb calcium in the intestines. In addi­ tion, several metabolites produced in the gut exert control over the cells responsible for bone repair. Fi­ nally, dysbiosis-induced intestinal permeability cau­ ses the release of inflammatory cytokines into the bloodstream, which can negatively affect BMD and other factors related to bone health.

Prebiotics and probiotics have been investigated for their ability to improve bone health through ef­ fects on the gut microbiome. Although more re­ search is needed, some evidence suggests that pro­ biotics may protect against BMD loss and may im­ prove markers of bone turnover in postmenopausal women.

Modulation of gut microbiota by other means such as diet, synbiotics, postbiotics, antibiotics, and fecal microbiota transplantation is another way to influ­ ence the gut-bone axis and improve bone health.

The Mediterranean diet can have a beneficial ef­

FIGURE 2 Gut microbiota modulators

Lifestyle intervention and supplementation that might reduce bone loss; these modulators might exert their therapeutic effects through different known biological pathways, such as OPG, RANK, and TRAF. Abbreviations — OPG: osteoprotegerin; RANK-L: receptor activator of nuclear factor-κB ligand; RANK: receptor activator of nuclear factor κB; TRAF: tumor necrosis factor receptor-associated factor.

Taken from: de Sire A, de Sire R, Curci C, Castiglione F, Wahli W. Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis. Cells. 2022 Feb 21;11(4):743. doi: 10.3390/cells11040743. PMID: 35203401; PMCID: PMC8870226.

17

Nutramedic &Cosmetics

fect on reducing the risk of bone fractures due to the high content of fiber, fermented milk products and polyphenols that favorably change the compo­ sition of the intestinal microbiome (Figure 2).

Prebiotics share the ability to be converted to shortchain fatty acids (SCFAs)—including acetate, propio­ nate, and butyrate—by the microbiota, incre­a­sing their levels in the gut and serum, thereby lowering gut pH. In an acidic environment, most minerals such as magnesium and calcium become more soluble, so their absorption is increased. Butyrate also acts as a growth factor for enterocytes and colonocytes.

In addition, SCFAs produced from prebiotics regu­ late the number and function of regulatory T cells in the colon, thereby controlling inflammation and mo­ dulating the synthesis of IGF-1 involved in bone re­ modeling. Therefore, fructooligosaccharide supple­ mentation may have beneficial effects on bone me­ tabolism, although further research is needed to con­firm these findings.

Probiotics and their use have a special place in re­ search related to the maintenance of bone health. A new term ‘osteomicrobiology’ was introduced recen­t­ ­ly for the rapidly emerging research field of the ro­le of the microbiota in bone health and disease. This research field is aimed to bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology. There has been a rapid translation from experimental animal studies to ongoing clinical trials of the effect of certain probiotic treatments on bo­ ne health in postmenopausal women and the results from these studies will be informative to determine if the GM might be a novel therapeutic target for os­ teoporosis.9 The combination of three Lactobacilli under the commercial name Probi®osteo - is a probiotic con­ cept for bone health. It is based on the combination of Lactiplantibacillus plantarum HEAL9 (HEAL9™), Lactiplantibacillus plantarum HEAL19 and Lactica­ seibacillus paracasei 8700: 2. This combination is clinically documented in supporting bone health, helps maintain their density and mineral content, maintain a balance in the natural bone remodel, and can lead to stronger bones. It is ideal for capsules and packs in the stick, and for functional foods such as drinks and powder products.12 Its efficiency was proven in a study conducted in

18

Sweden, aiming to determine if supplementation with a combination of three bacterial strains protect from the rapid loss of bone mass of the spine in healthy women in early postmenopause. This randomized, double-blind, placebo-controlled, multicenter trial, conducted on 249 women randomly arranged in a 1: 1 ratio in a placebo or control group. The control group took probiotic treatment of the said probiotic pro­ duct consisting of three Lactobacillus strains (Lacto­ bacillus paracasei DSM 13434, Lactobacillus planta­ rum DSM 15312 and Lactobacillus plantarum DSM 15313; 1x1010).

The primary outcome was the percentage of a chan­ ge in lumbar spine bone mineral density (LS-BMD) after 12 months, compared to the initial value. The primary analysis was done in all participants both at baseline and at 12 months. In conclusion, the treat­ ment of Lactobacillus reduced LS-BMD loss com­pa­ red to placebo. Losing LS-BMD was significant in the placebo group, while the loss of bone mass was not observed in a group treated with Lactobacillus.11

References: 1

Demontiero O, Vidal C, Duque G. Aging and bone loss: new insights for the clinician. Ther Adv Musculoskelet Dis. 2012 Apr;4(2):61-76. doi: 10.1177/1759720X11430858. PMID: 22870496; PMCID: PMC3383520.

2

Bone And Joint Health Supplements Market Size, Share & Trends Analysis Report By Product, By Formulation, By Consumer Group,

By Sales Channel, By Region, And Segment Forecasts, 2022 - 2030

3

Mosca C, Thorsteinsdottir F, Abrahamsen B, Rumessen JJ, Händel MN. Newly Diagnosed Celiac Disease and Bone Health in Young Adults: A Systematic Literature Review. Calcif Tissue Int. 2022 Jun;110(6):641-648. doi: 10.1007/s00223-021-00938-w. Epub 2022 Jan 3. PMID: 34978602; PMCID: PMC8721639.

4

Ruiz-Ramos M, Vargas LA, Fortoul Van der Goes TI, Cervant­ es-Sandoval A, Mendoza-Nunez VM. Supplementation of ascorbic acid and alpha-tocopherol is useful to preventing bone loss linked to oxidative stress in elderly. J Nutr Health Aging. 2010 Jun;14(6):467-72. doi: 10.1007/s12603-010-0099-5. PMID: 20617290.

5

Wong RH, Thaung Zaw JJ, Xian CJ, Howe PR. Regular Supplemen­ tation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial. J Bone Miner Res. 2020 Nov;35(11):2121-2131. doi: 10.1002/ jbmr.4115. Epub 2020 Jul 14. PMID: 32564438; PMCID: PMC7689937.

6

Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D'Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47. doi: 10.7326/0003-4819-146-12-200706190-00005. PMID: 17577003.

7

https://www.bonolive.com

8

Filip R, Possemiers S, Heyerick A, Pinheiro I, Raszewski G, Davicco MJ, Coxam V. Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia. J Nutr Health Aging. 2015 Jan;19(1):77-86. doi: 10.1007/s12603-0140480-x. PMID: 25560820.

9

Ohlsson C, Sjögren K. Osteomicrobiology: A New Cross-Disci­ plinary Research Field. Calcif Tissue Int. 2018 Apr;102(4):426-432. doi: 10.1007/s00223-017-0336-6. Epub 2017 Oct 27. PMID: 29079994; PMCID: PMC5851705.

10

de Sire A, de Sire R, Curci C, Castiglione F, Wahli W. Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis. Cells. 2022 Feb 21;11(4):743. doi: 10.3390/cells11040743. PMID: 35203401; PMCID: PMC8870226.

11

Per-Anders Jansson, Dan Curiac, Irini Lazou Ahrén, Fredrik Hansson, Titti Martinsson Niskanen, Klara Sjögren, Claes Ohlsson, Probiotic treatment using a mix of three Lactobacillus strains for lumbar spine bone loss in postmenopausal women: a ran­ domised, double-blind, placebo-controlled, multicentre trial, The Lancet Rheumatology, Volume 1, Issue 3, 2019, e154 - e162

12

https://www.probi.com/solutions/probiotic-portfolio/probi-osteo/

Nutramedic &Cosmetics

curcuminoids.com Available Grades: Powder, DC (Directly Compressible), Granules, HBD (High Bulk Density), GP (Granulated Process), Dispersible, and Soluble

THE MOST CLINICALLY STUDIED CURCUMIN BRAND THE ORIGINAL 95% PATENTED EXTRACT

4

AWARDS

165

PUBLICATIONS

85

CLINICAL

NATURAL

STUDIES

NO QUESTIONS LETTER FROM US FDA ON GRAS STATUS www.sabinsa.com info@sabinsa.com.pl +48 61 415 66 25

100%

14

C VERIFIED

The name C3 Complex was chosen to represent the ingredient’s three main chemical compounds: Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin, collectively known as Curcuminoids. Curcumin C3 Complex is a specific mixture of Curcuminoids, making it a unique form of Curcumin quite different from generic Curcumin extracts. It has been used in more clinical studies than any other Curcumin ingredient in the world. Carbon based testing done on every batch to ensure natural status. Low in oxalates, and marketed for over 25 years.

* These statements have not been evaluated by the EFSA. This product is not intended to diagnose, treat, cure, mitigate or prevent any disease.

19

Nutramedic &Cosmetics

Functional ingredients for healthy ageing and bone support

Chicory root fibres Orafti® Inulin and Oligofructose are proven prebiotics and as such support the gut microbiome by promoting the growth of beneficial gut bacteria. They promote digestive health and strengthen the immune system, reduce blood glucose response, help in weight management, and promote calcium absorption for bone health.

Bone and joint disorders

Osteoporosis is a disorder best prevented rather than treated. The best it can be done with diet and exercise is to stop the progress. While at least 15 nu­ trients are needed for strong, healthy bones, two stars in the nutrient universe are calcium and vitamin D. Men and women over the age of 50 should aim for 1200 milligrams (or 1.2 grams) of calcium in their dai­ ly diets.1 Calcium rich foods include dairy foods, such as milk, cheese, yogurt, and kefir. It is also found in fortified plant based milk substitutes, canned fish, tofu, dark leafy greens, almonds, and fortified foods, such as breakfast cereals, juices, and energy bars.

Vitamin D plays many roles in the human body, but regarding bone health the main role is helping the body absorb dietary calcium. Without sufficient Vi­ tamin D, calcium absorption is decreased, contribut­ ing to loss of bone mass. 2 Fatty fish provides some vitamin D in the diet, but fortified foods provide the bulk of vitamin D in your diet. Many foods that are calcium-rich are fortified with vitamin D, such as dairy milk, as are most plant-based milk beverages, but other dairy foods, such as cheese or yogurt, may not contain vitamin D. Bone building occurs with growth and development and peak bone density happens in early adulthood.

Therefore, enhancing calcium absorption can have a positive impact on bone health.

Prebiotic fibres not only feed the gut microbiome, but also enhance calcium absorption during adoles­ cence (the best time to build bone) and also later in life (e.g. postmenopausal women). 3,4 That is one more good reason to ensure that prebiotic fibres are part of everyone’s daily diet.

Importance of prebiotics in health

Prebiotic fibres not only feed the gut microbiome, but also enhance calcium absorption during adoles­ cence (the best time to build bone) and also later in life (e.g. postmenopausal women). 3,4 Chicory root fibres Orafti® Inulin and Oligofructo­se are proven prebiotics and as such support the gut mi­ crobiome by promoting the growth of beneficial gut

20

bacteria, they promote digestive health and stren­gt­h­ en the immune system, reduce blood glucose res­pon­ se, help in weight management, and promote calci­ um absorption for bone health.

The human gastrointestinal tract is host to one of the most complex ecosystems on the planet-gut mi­ crobiota. Fibre-rich foods are good for the gut micro­ biota, but a specific type of fibre-rich carbohydrate, called prebiotics, can positively influence the mi­ crobes in the gut.5 Almost all prebiotics are dietary fibres but not all dietary fibres are prebiotics. Bacte­ ria that reside in the gut, specifically Lactobacilli and Bifidobacteria, are the usual targets for prebiotics, helping these good bacteria grow and multiply.6,7 The term prebiotics is relatively new, but it is well estab­ lished that they can improve digestive health and research shows that they can positively influence immune system, improve calcium absorption, and keep blood sugar in check. Five grams of prebiotics eaten each day, from whole foods or as an ingredient in functional foods is recommended for well-being.8,9,10 Whole foods like fruits, vegetables, and whole grains contain prebiotics but are present in low levels which is why prebiotics are being added to foods like bars, drinks, yogurts, cereals, and even chocolate. You would have to eat 10 bananas to get 5 grams of the recom­ mended prebiotic fibre.

One of the most well studied prebiotics is called inulin. Inulin is found in the root of the chicory plant (Cichcorium intybus L.). Extracting the inulin from chi­ cory root is a soft process and such concentrated in­ ulin can be added to foods to boost prebiotic inta­ ke.11 The ISAPP (International Scientific Association for Probiotics and Prebiotics) published a consensus definition for Prebiotics in 2017. This current consen­ sus definition is: “a substrate that is selectively uti­ lized by host microorganisms conferring a health be­ nefit”. Inulin and FOS are 2 of the 3 recognized prov­ en prebiotics by ISAPP. The Chinese Nutrition Socie­ ty (CNS), China’s largest professional nutrition body, has concluded that inulin and oligofructose are among the first accepted prebiotics. The recognition inclu­ des BENEO’s functional fibres derived from chicory root and is a result of the premier prebiotic scienti­

Nutramedic &Cosmetics fic consensus statement in China announced in 2021.

The statement defines prebiotics and its criteria for ingredient classification.12

Chicory root fibres increase calcium absorption

Calcium is considered a nutrient of public health concern for Americans.13 With a sufficient calcium intake as well as efficient absorption and retention for increased bone mineral density in early adult­ hood, the risk for osteoporosis and related fractures can be reduced. Since its bioavailability is very low in humans and calcium absorption is limited, intake recommendations for calcium intake are high. Chic­ ory root fibre helps to increase prebiotic fibre intake and at the same time serves as a dietary approach to increase calcium absorption in the large intestine for maintaining healthy bones.14 In summary, chicory root fibres have been shown to increase calcium absorption through several me­ chanisms tracing back to their intestinal fermenta­ tion pattern and production of organic acids. The fa­ vourable effects of chicory root fibres on calcium absorption are attributed to their fermentation in the colon, which increases production of short-chain fatty acids and subsequently decreases pH. Dietary calcium is mostly present as insoluble complexes making it unavailable for absorption. The reduction of pH in the colon brings some of this calcium into solution and, thus, makes it available for absorption.15,16 In addition, several postulated mechanisms may also contribute to the effects of chicory root fibre on intestinal calcium absorption. Fermentation pro­ ducts (short-chain fatty acid butyrate) increase the absorptive area for calcium due to mucosa growth.

Also, more calcium is absorbed with chicory root fi­ bre intake as the permeability of the intestinal wall is enhanced and as more calcium from the colon lu­ men is exchanged for hydrogen from the cells.16-18 A one year intervention study, conducted at the USDA Children’s Nutrition Research Center at the Bay­ ­lor College of Medicine in Houston, TX, supplied 8 g of Orafti® Synergy1 per day to 100 adolescents to exa­ mine long-term effects of chicory root fibre on cal­ c­i­um absorption and bone health. After one year, the Orafti® Synergy1 group had significantly higher cal­ cium absorption and greater bone mineral density (BMD) compared to the control group, i.e. it was de­ monstrated that the additional calcium absorbed in­ deed reached the bones. This study is one of a kind in demonstrating long-term benefits of Orafti® Syn­ ergy1 (oligofructose-enriched inulin) for bone he­alth.19 The same results were also found in a group of post­ menopausal women where 6 weeks of Orafti® Syner­gy1 (oligofructose-enriched inulin) supplementation im­ proved mineral absorption and impac­ted markers of bone turnover. 20

References: 1

U.S. Department of Agriculture and U.S. Department of Health and Human Services Dietary Guidelines for Americans, 2020-2025: 9thEdition. December 2020. https://www.dietaryguidelines.gov/

2

National Institutes of Health. Office of Dietary Supplements. Vitamin D. https://ods.od.nih.gov/factsheets/vitamind-healthprofessional/

3

Abrams SA, Griffin IJ, Hawthorne KM et al. (2005) A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adoles­

cents. Am J Clin Nutr 82(2): 471–476. https://academic.oup.com/ ajcn/article-pdf/82/2/471/23960080/znu00805000471.pdf 4 Holloway L, Moynihan S, Abrams SA et al. (2007) Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women. Br J Nutr 97(2): 365–372. http://www.ncbi.nlm.nih.gov/ pubmed/17298707 5 Holscher HD (2020) Diet Affects the Gastrointestinal Microbiota and Health. J Acad.Nutr Diet. 120(4): 495–499. https://pubmed.ncbi. nlm.nih.gov/32199522/ 6 Lordan C, Thapa D, Ross RP et al. (2020) Potential for enriching next-generation health-promoting gut bacteria through prebio­ tics and other dietary components. Gut Microbes 11(1): 1–20. https:// www.tandfonline.com/doi/full/10.1080/19490976.2019.1613124 7 International Scientific Association for Probiotics and Prebiotics. https://isappscience.org/ 8 Holscher HD (2017) Dietary fiber and prebiotics and the gastroin­ testinal microbiota. Gut Microbes 8(2): 172–184. https://www.tand­ fon line.com/doi/full/10.1080/19490976.2017.1290756 9 International Scientific Association for Probiotics and Prebiotics. https://isappscience.org/ 10 Slavin J (2013) Fiber and prebiotics: mechanisms and health bene­ fits. Nutrients 5(4): 1417–1435. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3705355/pdf. Accessed 20 Nov 2017 11 https://dietaryfiber.org/ 12 Health and Fitness Journal PH. Inulin and Oligofructose Among the First Accepted Prebiotics by the Chinese Nutrition Society.

13 U.S. Department of Agriculture and U.S. Department of Health and Human Services Dietary Guidelines for Americans, 2020-2025: 9th Edition. December 2020. https://www.dietaryguidelines.gov/ 14 WHO (2003) Prevention and management of osteoporosis: Report of a WHO Scientific Group. WHO Technical Report Series 921. https://apps.who.int/iris/handle/10665/42841 15 Scholz-Ahrens KE, Acil Y, Schrezenmeir J (2002) Effect of oligofructose or dietary calcium on repeated calcium and phosphorus bal ances, bone mineralization and trabecular structure in ovariectomized rats. Br J Nutr 88(4): 365–377. https:// www.ncbi.nlm.nih.gov/pubmed/12323086 16 Raschka L, Daniel H (2005) Mechanisms underlying the effects of inulin-type fructans on calcium absorption in the large intestine of rats. Bone 37(5): 728–735. https://www.ncbi.nlm.nih.gov/ pubmed/16126464 17 Cashman KD (2006) A prebiotic substance persistently enhances intestinal calcium absorption and increases bone mineralization in young adolescents. Nutr Rev 64(4): 189–196. https://www.ncbi. nlm.nih.gov/pubmed/16673754 18 Roberfroid MB, Cumps J, Devogelaer JP (2002) Dietary chicory inulin increases whole-body bone mineral density in growing male rats. J Nutr 132(12): 3599–3602. https://www.ncbi.nlm.nih.gov/ pubmed/12468594 19 Abrams SA, Griffin IJ, Hawthorne KM et al. (2005) A combination of prebiotic short- and long-chain inulin-type fructans enhances 20 Holloway L, Moynihan S, Abrams SA et al. (2007) Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magne sium and bone turnover markers in postmenopausal women. Br J Nutr 97(2): 365–372. http://www.ncbi.nlm.nih.gov/ pubmed/17298707

The company Beneo produces natural prebiotics from chicory and other plant functional ingredients (proteins, starch and flour from rice and beans, isomalt, isomaltulose) for the food and pharmaceutical industry. These in­ gredients help to improve the nutritional and technical properties of a wide range of products, while retain and/or improve flavor and texture. State-ofthe-art production facilities around the world ensure high-quality pro­ ducts, and thanks to its expertise, Beneo offers customers a foundation for new ideas and new product launches.

Distributor: Alimentum Natura Ltd. Gračanska cesta 91, Zagreb, Croatia T. +385 1 38 73 021 GSM. +385 98 224 393

21

Nutramedic &Cosmetics

Osteoporosis and vitamin K2

Without vitamin K2, calcium and vitamin D3 cannot be optimally and safely used for bone health, and daily supplementation of vitamin K2 is a proven way to solve this deficiency.

AUTHOR:

Zagorka Blaževska, M.pharm., MBA, Vitanova

O

ur bones play many roles in our bodies – providing structure, protecting organs, an­ choring muscles and storing calcium. It is important to build strong and healthy bones during childhood and adolescence which is the most inten­ sive bone – building period. You can also take steps during adulthood to improve and protect your bone health.

What are healthy bones?

Healthy bones are bones that are dense and strong.

Your bones are a living part of your body and despite their strength, they are flexible. They can heal them­ selves when broken, and are constantly being rene­ wed by your body. Your bone health is important as your bones support your body, help you move around and protect sensitive organs like your heart and lungs.

What are the symptoms of poor bone health?

Signs of poor bone health include stooped pos­ ture and loss of height, and a common symptom is unexplained back pain or general pain in bones and joints.

Broken bones caused by a minor fall or small inju­ ry are also a sign of poor bone health.

If your bones are extremely weak, you may experi­ ence damaged or fractured bones caused by eve­ryday movement and pressure on your bones.

22

What affects bone health?

A number of factors can affect bone health. For example: • the amount of calcium in your diet • physical activity • tobacco and alcohol use • sex - you're at greater risk of osteoporosis if you're a woman, because women have less bone tissue than do men.

• body constitution - you're at risk if you are extre­m­ ely thin (with a body mass index of 19 or less) or have a small body frame because you might ha­ve less bone mass to draw from as you age.

• age • race • family history • hormone levels • eating disorders and other conditions • certain medications.

What is osteoporosis?

Osteoporosis is defined as a metabolic illness of bones, which characterizes with low bone mass and decrease of the bone mass and thickness.

It is a condition where bones become thin and lose their strength, as they become less dense and their quality is reduced. This can lead to broken bones, which cause pain, disability, and make everyday acti­ vities extremely difficult. Around the world, one in three women and one in five men over the age of fif­ ty will suffer a broken bone due to osteoporosis.

Everyone is at risk for developing osteoporosis and having fractures as a result. Although the main fac­ tors for increasing the risk are age and sex. However, women over the age of 50 or postmenopausal wom­ en have the highest risk of developing osteoporosis.

Age and osteoporosis affect men also. You might be surprised to know that men over the age of 50 are more likely to have an osteoporosis-induced bo­ ne break than to get prostate cancer. About 80,000 men per year worldwide are expected to break a hip, and that number is constantly increasing.

Some common symptoms of osteoporosis are: • loss of height • change in posture (stooping or bending forward) • shortness of breath (smaller lung capacity due to smaller disks) • bone fractures • pain in the lower back.

Nutramedic &Cosmetics Calcium, magnesium, vitamins K2 and D3

Calcium is the building-block of strong bones. Vi­ tamin D3 is an essential helper to calcium because it transports calcium through the intestine wall and in­ to the bloodstream where it can be put to work. Vita­ min K2 activates osteo-calcin proteins which incor­ porate calcium into the bone matrix. Without K2, cal­ cium and D3 are unable to optimally and safely sup­ port bone health.

Daily supplementation of vitamin K2 is a proven way to address deficiency. A study with healthy volunte­ers demonstrated that prior to K2 supplementation lev­ els of inactive osteocalcin (uOC) were high, whe­reas following supplementation uOC levels were lo­wer and most osteocalcin was activated. Studies indicate that a daily dosage of 90 μg to 120 μg of vitamin K2 is required to achieve adequate osteocalcin activation.

Darmell

Expert in the nutritional supplements field

Vitamin K2 regulates bone remodeling

An important review article published in 2017 (V.D. Myneni and E. Messy) summarizes how vitamin K2 re­ ­gulates bone remodeling, a continuous process that helps maintain bone structure, bone mass, and calci­ um homeostasis. The skeleton is a living organ com­ prised of two types of tissues that consist of blood vessels and living cells that need amino acids, fatty acids, carbohydrates, minerals and vitamins to func­ tion properly. The cortical bone is the hard, outer layer which provides body support and protection of the organs. The porous and metabolically active inner layer, the trabecular bone, is where minerals are stored. Osteoblasts, osteocytes, and osteoclasts cells are responsible for bone remodeling. Main Evaluati­ on: old and micro-damaged bone are conti­nuously replaced through the bone remodeling cycle, which consists of five distinct and overlapping phases.

Results: vitamin K2 regulates the bone remo­ deling cycle at several levels: 1. Osteoclasts - vitamin K2 inhibits osteoclast diffe­ rentiation.

2. Osteoblasts - vitamin K2 stimulates osteoblast de­ velopment and protects them from cell death lea­ ding to increased osteoblast , lining cells and oste­ o­cytes.

3. Osteocalcin - vitamin K2 activates or carboxylates osteocalcin that allows binding the calcium and hy­ droxyapatite crystals.

KAPPA BIOSCIENCE is a pioneer in the develop­ ment of biologically active vitamin K2 MK-7 under the name K2VITAL. The innovation of the synthe­ sis of MK-7, combined with other KAPPA inno­ vations, like the patented process of microen­ capsulation K2VITAL DELTA which ensures the sta­bility of K2 in mineral formulations, are the confirmation of the innovation and quality of the K2VITAL brand.

Official representative: Vita Nova www.vitanova.com.mk/ www.linkedin.com/company/2966991/

A

holistic approach to health has always been our first choice when it co­ mes to ways to support it. Nutritional supplements are an extremely important factor that can contribute to maintaining optimal health and are a good ally in the fight against various health disorders.

That is why professional path of Darmell is focused on developing new nutri­ tional supplements and informing interested industry workers about ingredien­ts, evidence of effectiveness, news, regulation and other relevant information in the field.

By combining many years of business experience, continuous acquisition of know­ledge and cultivating business acquaintances, we are able to provide a vari­ ety of services.

Services we offer: • Consulting in the elaboration of ideas and concepts for the development of new products - from the selection of ingredients to the launch of the finished product, with the help of finding the appropriate manufacturer of medicinal forms.

• Consulting related to the registration of dietary supplements.

• Writing content for various purposes, in the field of dietary supplements and functional foods, related to individual ingredients and finished products.

• Help in finding a suitable distributor for finished products.

We also actively deal with: • Representing renowned companies producing branded ingredients/raw mate­ rials for nutritional supplements.

• Publishing professional publications in the field of nutritional supplements, fun­ctional food and cosmetics.

Darmell d.o.o.

20+ years of experience in developing new concepts for food supplements Mob: + 385 91 68 12 444 darmell@protonmail.com www.linkedin.com/company/darmell/ www.dar-mell.com

23

Nutramedic &Cosmetics

Fine Foods and continuous innovation: competitive advantage and shared value Trusting partner, which, in cooperation with customers, analyzes the needs and identifies the best solutions to their extent, solution that will provide them with a competitive advantage.

F

ine Foods & Pharmaceuticals N.T.M. S.p.A. - an Ita­lian independent Contract Development & Ma­nufacturing Organisation (CDMO) that de­ velops and manufactures contract products for the pharmaceutical, nutraceutical, cosmetics, biocides and medical devices industries, has been pursuing go­als of excellence since its foundation.

With €193 million revenue in 2021 and more than 260 customers, Fine Foods - listed on Euronext STAR Milan of Borsa Italiana (Ticker: FF) - is a growing com­ pany geared to meet future challenges.

Fine Foods sees innovation as the driving force be­ hind its growth, and a distinctive feature among CDMO market players. It has established a cross-­ functional team that meets periodically to address integrated product development. A relentless search for customer satisfaction drives the company's focus on continuous innovation, research and development, quality and sustainability.

Continuous Improvement projects involve every department and are an essential part of Fine Foods' competitive strategy and a shared value. This imple­

24

mentation involves assigning each initiative to a con­ tact person, project sponsor, project leader and ste­ ering committee that meets regularly to monitor pro­gress. Project focus meetings are organised for the benefit of all employees.

This is flexible and proactive organisation that transversally involves every company division with defined and shared roles and responsibilities. It sup­ ports a dynamic approach to innovation, and creates a fertile environment to develop the problem solv­ ing and Lean Thinking skills of those involved. This fosters the acquisition of new specific and soft skills.

The in-house R&D division studies and formulates new nutraceutical and cosmetic products. The cata­ logue with more than 100 ready-to-market nutrace­ utical formulas in 17 health categories enables cus­ tomers to grasp market trends quickly. In addition, the division assesses the feasibility of transferring the production processes of already existing phar­ maceutical, nutraceutical and cosmetic products (tec­h­ nology transfer) to its plants.

With trained and experienced staff, selected raw

Nutramedic &Cosmetics materials and up-to-date technology, the R&D divi­ sion develops result-oriented innovation. Fine Foods is a trusted partner, working alongside customers by analysing needs, based on market trends, identify­ ing the best tailor-made solution which provides a competitive advantage.

The R&D team works closely with customers in fi­ nalising the most ambitious projects with ready-tomarket products or by devising out-of-the box solu­ tions presented at meetings where the latest inno­ vations are introduced to customers.

The process for nutraceuticals and cosmetics con­ sists of five key steps: • research into formulation ideas: a synergistic partnership with the best raw material suppliers and constant market data analysis allow to gather insights and ideas on trends and offer the best formulations supported by scientific evidence; • feasibility check: using small-scale plants repre­ sentative of the leading production technologies present in the various plants, Fine Foods can carry out technological feasibility studies and finely-­tu­ ned sensory testing.

• product development: working with Quality Con­ trol, new products are fine-tuned, enhancing the key aspects of market interest and making the products usable for the consumer, with a focus on sustainability; • stability studies: the small-scale plants allow the production of samples that are more representa­

tive of industrial production than small laboratory samples. This allows stability studies to be carried out that represent future products to be placed on the market; • pilot-scale batch production: before proceeding with industrial production, pilot-scale batches are carefully monitored by the industrialisation tech­ nicians. This makes it possible to spot any issues not highlighted in small-scale R&D tests.

Fine Foods allocates approximately 120 people (16 percent) of its workforce to scientific, technical, re­ search and development, quality and control activi­ ties.

Through synergies and affiliations with Italian (Fe­ dersalus, Union Food) and European (FSE) trade as­ sociations, Fine Foods supports customers in the re­ gulatory framework, updating them on new develop­ ments.

Fine Foods & Pharmaceuticals N.T.M. S.p.A Via Berlino, 39 24040 Zingonia/Verdellino Bergamo, Italy T. +39 035 482 13 82 www.finefoods.it info@finefoods.it

25

Nutramedic &Cosmetics

Probiotics in Europe: consumer survey in 8 EU countries

The European branch of the International Association for Probiotics (IPA Europe) conducted a survey on a sample of 8,000 consumers. The aim of the research was to obtain information on how familiar consumers are with currently available probiotic products, how much use these products are in individual markets, and what are consumers' wishes in relation to additional information about this type of product.

T

o monitor the evolution of European consum­ ers' opinions, trends and behaviours regarding probiotic foods and supplements, the International Probiotics Association - Europe1 commissio­ ned the market research company 3Gem to carry out a survey with a representative sample. The online sur­ vey was carried out in 8 European countries (Italy, Denmark, the Netherlands, Spain, Poland, Belgium, Germany and Sweden) on a total of 8000 consum­ ers2 to assess people's understanding of the probi­ otic offer currently on the market, and their use of probiotic foods and supplements in daily life.

The evolution of European consumers’ opinions, trends and behaviours regarding probiotic foods and supplements shows a strong interest in overall health and well-being. It also highlights the fact that con­ sumers would like to be more informed on the label­ ling and in communications about probiotic food and

26

food supplements, and about probiotic microorga­ nisms in food and food supplements.

The overall results indicate that probiotics are popular, even people who do not use or buy probiotics know the term.

It appears that for the majority of consumers the answer to “Do you know what probiotics and probi­ otic foods are?” is “yes” (63%). Women and men seem to consume probiotics almost equally. On average the peak consumption is in the 25-44 age group. There is quite a substantial set of people who know the word ‘probiotic’, even though they say that they do not con­ sume them. This is probably due to the large amount of information available on probiotics in online search engines on the web, mainly from commercial sourc­ es and news outlets. However, these sites often fail

Nutramedic &Cosmetics to paint a complete picture, so consumers may miss relevant information.

ucate consumers about the beneficial role that pro­ biotics can play in diet and well-being.

Consumers do not feel well informed about a product containing probiotics.

Finally, the survey participants were asked what they think probiotics are useful for, and specifically “for what reasons do they consume probiotics”, if they had previously indicated that they consume them.

The survey results show that consumers across Europe are familiar with the word ‘probiotic’, but that they would like to know more.

In fact, the most relevant information is that in 7 out of 8 countries, consumers feel they are not in­ formed about probiotics contained in products they find in shops. Poland is the only market with a bigger group of people feeling they are well informed (55% vs 45%), but even here, 45% of consumers would like to know more.

Probiotics are part of lactic bacteria or live bacteria, but not all live bacteria are probiotics.

Other terms such as ‘live bacteria’ or ‘live cultures’ are more known than the term ‘probiotic’. This is pro­ bably due to the fact that the term ‘probiotic’ was not allowed in Europe since 20073.

The traditional use of the term is also a factor that may influence the knowledge of probiotic-related terms in some countries. This is the case for Italy for example, where a very large part of Italian consum­ ers are familiar with ‘live cultures’ (89%) associated with probiotic products.

When food and supplements with probiotics mi­ croorganisms are available in shops, 79% of all test­ ed consumers indicate that they would like to see the term ‘probiotic’ on the packaging: e.g. the ingre­ dients list or somewhere else on the packaging of food and food supplements, with Italy and Spain be­ ing the countries where the interviewed people feel the strongest about the indication on the labels (90%).

There is an opportunity to inform and further ed­

The result was that consumers are more informed about probiotics in countries that have allowed the use of the term for a longer period of time. Consum­ ers mainly refer to probiotics mentioning their bene­ ficial effect on bacterial flora, the stomach and di­ gestion. Consumers who know what probiotic foods and food supplements are, and who also consume them, mention that their main driver is their overall health and well-being. Very often the guidance for using probiotics comes from healthcare profession­ als, which also explains why so many people are fa­ miliar with this category. However, they find no cor­ respondence when looking at product labels on the market.

Spain Results for Spain show that almost half of the population panel consumes probiotics food and/or food supplements (44%), but even peo­ ple that do not consume them know the word. In fact, two third of the population (67%) know what probio­ tics food and food supplements are. Concerning the use of other terms, 72% of people are familiar with ‘live bacteria’, whereas ‘live cultures’ is known by 59%.

The markets that would like to see more information on the packaging are Spain and Italy (90%). In Spain, like in Italy, there are national guidelines indicating that the use of the term on labels and in com­mu­ni­ cation is allowed, under certain conditions, for domes­ tic and imported foods and food supplements con­ taining probiotics

▷ Do you know what probiotics food and food supplements are? (n = 1.000 by country) I know about probiotics

78% 67%

62% 50%

61% 50%

50%

32%

27

Nutramedic &Cosmetics Poland Almost two third of the population panel in Poland consume probiotics food and/or food supplements (59%). Out of the 8 countries, the Pol­ ish people are the most aware of what probiotics are.

In fact, most of the interviewees (78%) indicated that they know about probiotics food and food sup­ plements. As previously mentioned, Poland is also the only market with a majority of consumers feel­ ing informed that a product contains probiotics (55% vs 45%). Even here, there is still a high propor­ tion of consumers (45%) that would like to have more information. Concerning the use of other probiotic-­ related terms, almost 9 out of 10 people are familiar with ‘live bacteria’ (87%), whereas ‘live cultures ‘ is known by only 58%. When asked if they would like to see the word probiotic on the packaging, 79% of the Polish panel answered ‘yes’.

Italy Italy, together with the Spanish and Polish consumers, show a high percentage of pro­ biotic consumption (41%). This percentage increased to 62% when the panel was asked if they knew what probiotics food and/ or food supplements are. A very large portion of the Italian population is also familiar with ‘live cultures’ (89%). This is also due to the tradi­ tional use of this term associated with the probiotic category of products and ingredients. The ‘term live bacteria’ is less used, only 55% of the consumer pan­ el knows it As mentioned in the focus on Spain, Italy is also in favour (90%) of having more information on probiotics on the packaging and in communication.

Since 2013 Italy enforced national guidance on the use of the term probiotic.

Denmark Denmark stands out as only one-third of the Danish population knows what probi­ otics food and food supplements are, and 19% of the panel of consumers use probiotics food and/or food supplements. Denmark also has the lowest percent­ age of the population that feels informed about pro­ biotics in products (31%). People in Denmark are mo­

re familiar with the terms ‘live bacteria’ (68%) and ‘li­ ve cultures’ (59%). This is also due to the national de­ finition used in this country. Concerning the appear­ ance of the term probiotics on the packaging, 56% declared they would like to know more. This is a sig­ nificant percentage if we consider the fact that until 2021 the term probiotic was banned, and Denmark was following the interpretation of the European Commission indicating that ‘probiotic’ could be used as a health claim only. Since 2021, Denmark recognis­ es the use of the term referring to a category of in­ gredients in food supplements, and the authorities are in favour of a better European approach, a legal certainty and a harmonised way forward at the EU level.

Sweden Half of the population of Sweden knows what probiotics food and food supplements are, but 76% of the Swedish panel are in favour of the information about the presence of probiotics on the packaging. Approximately one-quarter of the Swe­ ­dish population consumes probiotics food and/or food supplements (27%).

Concerning the familiarity with terms, 3 out of 4 people are familiar with both ‘live bacteria’ (77%) and ‘live cultures’ (76%). Sweden joined Denmark in June 2022 and the group of countries asking for a better approach for probiotics food and food supplements in the EU. Germany Probiotics are popular in Germany, despite the fact that this country was following the interpretation of the European Commission of the use of the term probiotic as a health claim only. In Ger­ many, more than 60% of the German panel indicates that they know what probiotics food and food sup­ plements are, and 38% answered that they consume probiotics food and/or food supplements. Con­su­mers are also familiar with the terms ‘live bacteria (66%) and ‘live cultures’ (74%). When asked if they would like to have the indication of probiotics on the packaging, 82% of the population panel responded favourably.

▷ Do you consume probiotics food and/or food supplements? (n = 4.491 subset of total population, only those who know what probiotics are, but don't consume probiotics) I know but do not consume them 36% 22%

28

25%

22%

25% 14%

26%

29%

Nutramedic &Cosmetics The Netherlands Half of the population panel declares that they know what probiotics food and food supplements are. About 27% of the Dutch popula­ tion consumes probiotics food and/or food supple­ ments. In the Netherlands, other terms are also well known: 76% are familiar with ‘live bacteria’, whereas ‘live cultures’ is only known by 59%. When asked if they would like to have the term ‘probiotic’ listed on the packaging, 76% of the panel consumers respon­ ded favourably. The Netherlands has a pragmatic approach, the term ‘probiotic’ is used as the name of the category on the label of probiotic food and food supplements.

Belgium Half of the population panel declares that they know what probiotics food and food supplements are, and 29% of the Belgian panel stat­ ed that they consume probiotics food and/or food supplements. The low results are probably due to the strict approach of the authorities regarding the use of the term, which is currently allowed only for pro­ biotic yoghurt. Belgian people are familiar with ‘live bacteria’ (76%), whereas ‘live cultures’ is less common (52%).

A high percentage of consumers (83%) declared that they would be in favour of the appearance of the term ‘probiotic’ on the packaging.

Conclusion

The panel (8.000 consumers in 8 European coun­ tries) would like to be more informed about probio­ tics food. Also, consumers declare that they are bet­ ter informed in countries where the term ‘probiotics’ is (partially) allowed by National guidance/standard: this is the case, for example, in Italy, Spain, and Po­ land. Very often, the guidance for using probiotics comes from health professionals, which also explains why so many people are aware of this category but find no match when looking at product labels. The regulatory situation is influencing the European mar­ ket. It is evident that the need for a coherent EU regu­ latory approach for probiotics goes hand in hand with the opportunity to further educate consumers on the correct use of these micro-organisms. The high level of uncertainty for most probiotic health claims found online hinders the rational use of pro­ biotics, leaving the field open to unsubstantiated al­ legations and misuse.

1

IPA Europe is the European chapter of IPA, the International Probiotics Association; it was established in Brussels in 2015. The members of IPA Europe are Companies directly engaged in Europe in the manufacture of probiotic cultures or probiotic foods, supplements, and nutritional or therapeutic products. The IPA Europe mission is to gain acceptance of the term “probiotic” throughout Europe as a defined category and to create a favourable environment for probiotics in Europe.

2

3Gem conducted this online survey in 8 European countries on a total of 8000 consumers. Per country: n= 1000 respondents/18+ years old/nat.rep. by age, gender, and region. In Italy, Denmark, the Netherlands and Spain the term ‘probiotic’ is (partially) allowed by National guidance/standards; Poland, Germany, Belgium and Sweden do not have national standards and follow the interpretation of the European Commission indicating the term probiotic as an example of health claim only.

3

European Commission’s guidance of 2007 on the implementation of regulation 1924/2006 https://www.fsai.ie/uploadedFiles/ EU_guidance_ClaimsRegulation.pdf

IPA expands its scope of work The International Probiotics Association (IPA) announces a major expansion of its scope to include the “biotics” categories of prebiotics, postbiotics, and synbiotics within the human, infant, and companion animal segments of food and dietary supplements.

T

he IPA Board of Directors voted to expand the association’s scope to complement its histori­ cal focus on probiotics. The expansion is part of the organization’s strategy to help the ’biotics’ in­ dustry grow in response to market demands and strengthen its ownership within the ‘biotics’ catego­ ries.

The move will not impede IPA’s focused efforts re­ garding the probiotics category but, rather, it will on­ly strengthen the organization’s efforts. “We are better together” said Amy Smith, the newly appointed IPA President.

IPA will work on building the required frameworks and organizational structure to ensure a successful future for the probiotics, prebiotics, postbiotics and synbiotics industry.

“It is a natural progression for the evolution of IPA, and we are delighted to announce this expansion in strategic focus”, said George Paraskevakos, Executi­ ve Director, IPA. “We will continue our solid path of driving and advancing the probiotic category as we replicate our past achievements in these additional ‘biotic’ categories”.

The International Probiotics Association is a global non-profit organization that brings together, through its membership, participants in the probiotic sector including academia, scientists, healthcare professio­ nals, consumers, industry and legislators. The mission of the International Probiotics Association is to pro­ mote the safe and effective use of probiotics world­ wide. Having pre-Codex Alimentarius non-governmen­ tal organization status and ISO observer status, IPA is also recognized as the unique "global voice of pro­ biotics" worldwide. www.internationalprobiotics.org

29

Nutramedic &Cosmetics

Bacopa (Bacopa monnieri) and its effect on cognitive functions Bacopa has been at the center of research because of its effect on cognitive functions such as memory, focus and concentration. Numerous researches in the last thirty years have enabled a better understanding of the effects of this plant and the popularization of its application in the cognitive health segment.

AUTHOR:

Ana Gjergja Sekulić, M.pharm., univ.mag. phytotherapy and dietotherapy

30

B

acopa monnieri (Scrophulariaceae) is a small creeping plant that grows naturally in India and tropical areas. (Figure 1) It likes moist and wet soil, shallow water and swamps, and is easy to grow if it has a sufficient amount of water available.

It is traditionally used in Ayurvedic medicine for the treatment of various disorders of the nervous system such as epilepsy and anxiety, and as a learning sup­ port for the development of memory and concentra­ tion. It is also used for digestive problems, skin dis­ eases, and as an antipyretic and analgesic.1,2 Bacopa has been at the center of research precisely beca­u­ se of its effect on cognitive functions such as memo­ ry, focus and concentration. Numerous researches in the last thirty years have enabled a better under­ standing of the effects of this plant and the popula­ rization of its application in the cognitive health seg­ment.

The pharmacological action of bacopa is attribut­ ed to alkaloids, saponins and sterols. The main sapo­ nins are identified as bacoside A and bacoside B, al­ kaloids brahmin and herpestin, and sterols stigma­ sterol and beta-sitosterol.

Nu­merous other ingredients

have also been identified, including betulinic acid and numerous bacosaponins. 3-7 As already mentioned, the focus of research is the effect of bacopa on brain functions. Some of the mo­ re interesting ones are highlighted below. (Table 1)

Anxiolytic and antidepressant effect

Research conducted on rats showed that bacopa extract containing 25% bacoside A showed anxioly­ tic activity comparable to lorazepam. An additional po­ ­sitive effect is manifested in the fact that the baco­ pa extract did not cause amnesia like lorazepam, but, on the contrary, showed an effect on improving me­ mory.8 The antidepressant potential of bacopa extract tes­ ted in an animal study showed that a dose range of 20-40 mg/kg once a day for 5 days has an effect com­ parable to the standard antidepressant drug imipra­ mine.

Nutramedic &Cosmetics The same study suggested that the antidepres­ sant and anxiolytic effects are mediated by the ac­ tion on the mechanism of serotonin and gamma-­ aminobutyric acid.9 Although animal studies have shown promising re­sults, clinical studies of the anxiolytic and antide­ pressant effects of bacopa on humans are currently still scarce. A review by Brimson et al. from 2021, de­ scribed four randomized, placebo-controlled, dou­ b­le-­blind studies that used bacopa as monotherapy and two studies that used a multi-herb intervention, and analyzed levels of depression or anxiety. It is im­ portant to note that not all patients were diagnosed with clinical depression. The authors emphasize that it is very difficult to draw any general conclusion, gi­ ven that the studies used different assessment and analysis methods, and some showed statistically sig­ nificant results, while some did not. What is interest­ ing to point out is the study that showed that the use of bacopa for a period of 12 weeks can reduce geri­ atric depression in Alzheimer's patients to the level of healthy people.10 The potential for use in the field of anxiety and depression certainly exists, but furth­ er research will certainly give more precise data on the profile of patients who could benefit from baco­ pa therapy.

Memory improvement

Various animal studies have shown that bacopa improves motor learning and the acquisition and re­ tention of newly learned behavior.11 It also has a be­ n­eficial effect on improved memory acquisition and retention in pre-existing benzodiazepine and pheny­ toin therapy, where it reverses drug-induced amne­ sia and cognitive impairment.12,13

A clinical trial on people older than 55 years was conducted with a 12-week application of bacopa at a dose of 300 mg/day. It has been recorded that baco­ pa significantly improves the acquisition and reten­ tion of memory in the elderly.14 The test was also con­ ducted on younger people, and the results showed that the application of 300 mg of bacopa extract con­ taining 55% of combined bacosides for a period of 12 weeks significantly improves verbal learning, me­ mory, consolidation and speed of early information processing. These effects were not recorded at the beginning, nor after five weeks of application of the preparation.15 A randomized, double-blind, placebo-controlled stu­­­dy including sixty older adults examined the ef­ fects of bacopa on attention, cognitive processing, working memory, and cholinergic and monoaminer­ gic fun­ctions. The group treated with bacopa showed improved working memory, attention and cognitive processing. The study was conducted for 12 weeks, and the first changes were noticed after 4 weeks of application.16 Another study, randomized, double-blind and pla­ cebo-controlled, included 60 medical students. Ba­ copa extract (Bacognize), administered 2 x 150 mg twice a day, for 6 weeks, has been shown to signifi­ cantly improve cognitive abilities and performance in various neuropsychological tests (logical memory test, digit span, memory task, etc.). That study show­ ed that bacopa helps with better focus and concen­ tration.17 One study was also conducted on children aged 6 to 14 years. The study was randomized, double-blind, placebo-controlled, and examined the effectiveness of bacopa on cognitive performance. Bacopa is do­

TABLE 1 Summary of various clinical studies

No.

Study design

Dosage of BM extract

Intervention Clinical outcomes

1.

46 healthy participants (11 males, 35 females), aged between 18-60 years

300 mg/day

12 weeks

Significant improvement in speed of visual informa­ tion processing and learning rate. Concentrations were noticed with a reduction in state anxiety.

2.

107 healthy volunteers, aged between 18-60 years

300 mg/day

90 days

Increases accuracy and memory consolidation.

3.

76 participants, aged between 40-65 years

300 mg for persons under 90 kg, and 450 mg for persons over 90 kg

90 days

Significant reduction in the rate at which freshly acquired information is forgotten.

4.

98 healthy adults

300 mg/day

12 weeks

Improvement in memory performance and retention.

5.

60 healthy elderlies (23 males, 37 females)

300 mg/day

12 weeks

Improvement in the working memory, attention and cognitive processing.

6.

17 healthy volunteers

320 mg and 640 mg

-

Reduced stress and improved mood.

7.

100 volunteers (boys and adolescents)

160 mg/day 320 mg/day

16 weeks

Increased cognitive function.

8.

60 medical students

150 mg 2xdaily

6 weeks

Cognitive enhancement.

9.

12 patients, aged 18 and more

250 mg 2xdaily

3 months

Effective for treatment of dementia.

10.

19 patients

300 mg 2xdaily

4 weeks

Effective for managing anhedonia.

Taken from: Fatima U, Roy S, Ahmad S, Ali S, Elkady WM, Khan I, Alsaffar RM, Adnan M, Islam A, Hassan MI. Pharmacological attributes of Bacopa monnieri extract: Current updates and clinical manifestation. Front Nutr. 2022 Aug 18;9:972379. doi: 10.3389/fnut.2022.972379. PMID: 36061899; PMCID: PMC9436272.

31

Nutramedic &Cosmetics sed 1 x 160 mg for body weight 20-35 kg, and 2 x 160 mg for body weight over 35 kg. The study was con­ ducted for 16 weeks and showed a significant bene­ ficial effect on symptoms of hyperactivity or atten­ tion deficit hyperactivity disorder (ADHD) and on cog­ nitive improvement.18 (Table 2)

Effect in Parkinson's disease

The effect of bacopa extract was tested on diffe­ rent animal models. An alcoholic extract in which the main active ingredients were bacosides was investi­ gated on the nematode model Caenorhabditis ele­ gans. Application of the extract has been shown to reduce the aggregation of α-synuclein, a key protein that leads to the degeneration of nerve cells. This prevents dopaminergic neurodegeneration and en­ ables the restoration of nematode lipids.19 A study on mice showed that bacopa extract of­ fers a dopaminergic neuroprotective effect by mo­ dulating oxidative stress and apoptotic mechanisms.20 Another study was conducted by treating mice suffering from Parkinson's disease with bacopa ex­ tract or mucuna extract. The one-month treatment significantly reduced the elevated levels of oxidati­

ve stress. In behavioral tests, a comparative analysis of bacopa extract and mucuna extract showed a sig­ nificant increase in spontaneous locomotor activity and the grip strength test. It was found that the use of bacopa extract significantly improved the activity of tyrosine hydroxylase, caspase-3 and the expres­ sion of a neurogenic gene in the brain area - sub­ stantia nigra. 21 All these results are certainly in favor of bacopa as a potentially beneficial plant for treat­ ing and alleviating the symptoms of Parkinson's dis­ ease.

Effect in Alzheimer's disease

The effect of bacopa extract in patients with Alz­ heimer's disease was tested using different models.

An in silico study examined the effects of two baco­ pa saponins, bacosaponin G and bacosaponin N2, in comparison to donepezil, a drug commonly used in the treatment of Alzheimer's disease. The study show­ ­ed that bacosaponins have a more favorable binding affinity for therapeutic targets in Alzheimer's dise­a­ se, specifically for caspase-3 and tau protein kinase I receptors. 22 The results of that research point to the excellent potential of bacopa.

TABLE 2 Summary of clinical studies of Bacopa extract on cognitive functions

Participants/study design

Intervention

Clinical outcome

Healthy children, 6-8 years old from rural India. Double-blind randomized placebo controlled study.

One teaspoonful of Bacopa syrup 3 times daily for 3 months.

Each teaspoonful was equiva­ lent to 350 mg of crude Brahmi.

Strengthened exploratory drive (as measured by maze learning), improved perceptual images of patterns, and increased perceptual organization and reasoning ability (as measured by reaction time).

Healthy adults (average age 73.5 years). A double-blind randomized placebo-con­ trolled clinical trial conducted at the University of Catania, Italy. Trial with the introduction of a placebo for 6 weeks.

Bacopa extract, 300 mg daily, for Improved delayed memory AVLT scores word recall 12 weeks. compared to placebo, significantly improvement in Stroop test results (P<0.05) and decreased CESD-10 depression score during time as well as anxiety scores.

Children in need of individual educational Bacopa extract, 225 mg daily, for support, 10.5 years at the Center for 16 weeks.

Research on Mental Retardation (CREMERE), Mumbai, India. The research was conducted on an outpatient basis, a procedure in hospital conditions, with close monitoring.

Significant change in the baseline value of working memory and short-term verbal memory from 5.21 ± 0.32 to 6.38 ± 0.25 (P ≤ .05) and 5.33 ± 0.44 to 6.54 ± 0.35 (P ≤ .05). Significant improvement (P ≤ .05) was also seen in logical memory, memory related to personal life and also in visual as well as auditory memory.

Seventeen healthy volunteers (13 women and 4 men) with an average age of 25.23±5.97. A double-blind placebo-con­ trolled crossover study conducted in Melbourne, Australia.

Bacopa extract, 320 mg or 640 mg daily, 1 hour and 2 hour after application.

Positive cognitive effects confirmed in the first and second hours after application. The effects were confirmed by the results of the Stroop test and the letter search test. Some nootropic and adaptogenic effects have been observed. The positive effects of the modification and the reduction of cortisol levels (a physiological response to stress) were associated by the participants with the consumption of bacopa.

Thirty elderly subjects with an average age of 66±3 years. Double-blind cross­ over placebo-controlled group study, conducted in Bologna, Italy.

Combined nutraceuticals containing Bacopa dry extract (320 mg), L-theanine (100 mg), Crocus sativus (30 mg), copper (2 mg), folate (400 µg), B complex (450 µg-9 mg) and vitamin D (25 µg).

After 2 months of therapy, the results of the mental state mini-test and stress perception questionnaire significantly improved compared to the initial results examinations.

Taken from: Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, Wong EH, Rizwan F, Bindal U, Koshy S. Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies. Drug Target Insights. 2019 Jul 31;13:1177392819866412. doi: 10.1177/1177392819866412. PMID: 31391778; PMCID: PMC6669844.

32

Nutramedic &Cosmetics A study was also conducted that compared the ef­ fects of herbal therapy (a combination of Bacopa mon­ ­­nieri, Hippophae rhamnoides and Dioscorea bulbi­ fera) in patients suffering from Alzheimer's disease compared to donepezil therapy. Two groups of sub­ jects were included in the study, which lasted 12 months: a group of patients (aged 60 to 75) and a group of healthy subjects. The study, comparing her­ bal therapy and placebo, observed a significant im­ provement in the results of neuropsychological tests such as the mini mental state test, digital symbol substitution, results of delayed word recall, attenti­ on span, frequently asked questions and depression scores in healthy patients.

In patients with Alzheimer's disease, improvement was comparable to that achieved with donepezil in the Mini Mental State Test, Dementia Screening Sca­ le, Immediate Word Recall, Delayed Word Recall, At­ tention Span, Frequently Asked Questions, and De­ pression Score. 23 Another study on patients with Alzheimer's dis­ ease examined the effect of bacopa in a daily dose of 600 mg for 6 months. The study revealed a statis­ tically significant increase in performance in various aspects of mental state tests, and concluded that B. monnieri is beneficial in patients with Alzheimer's disease. 24

Regulation and labeling

In Croatia, the plant species Bacopa monnieri is on the list of permitted plant species that can be used in formulating food supplements. When labeling the product, it is necessary to state that people who ta­ ke medication should consult a doctor before taking a product containing bacopa, and that the use is not recommended for thyroid diseases, asthma, emphy­ sema, disorders of the digestive and urinary systems, heart disorders, pregnant women, nursing mothers and to children.

In other countries of the European Union, such as Italy, France, Belgium and the Czech Republic, baco­ pa is also on the list of permitted plant species, but no special notes are required when labeling.

Conclusion

All available studies are certainly in favor of the use of bacopa in individuals with difficulties and ill­ nesses, but also in healthy patients who are in states of mental effort. Of particular interest is the wide range of possible patient ages, from the pediatric to the geriatric population. Although bacopa is still a lesser-known plant species in our area, considering the specific effects it shows in the field of cognitive health and functioning, we can conclude that it will surely become recognized in professional circles and among patients.

References: 1

Bammidi SR, Volluri SS, Chippada SC, Avanigadda S and Vangalapa­ ti M. A review on pharmacological studies of Bacopa monniera. J Chem Bio PhySci 2011;1(2), Sec B: 250-259.

2

Mukherjee DG, Dey CD. Clinical trial on Brahmi. I. J Exper Med Sci 1966;10:5-11

3

Kapoor LD. CRC Handbook of Ayurvedic Medicinal Plants. Boca Ra­ ton, FL: CRC Press Inc;1990;61.

4

Chakravarty AK, Garai S, Masuda K, et al. Bacopa sides III-V: three new triterpenoid glyco sides from Bacopa monniera. Chem Pharm Bull (Tokyo) 2003;51:215-217.

5

Hou CC, Lin SJ, Cheng JT, Hsu FL. Bacopa side III, bacopa saponin G, and bacopa sides A, B, and C from Bacopa monniera. J Nat Prod 2002;65:1759-1763.

6

Mahato SB, Garai S, Chakravarty AK. Bacopa saponins E and F: two jujubogenin bisdesmosides from Bacopa monniera. Phytochemis­ try 2000;53:711-714.

7

Chakravarty AK, Sarkar T, Masuda K, et al. Bacopa side I and II: two pseudo jujubogenin glycosides from Bacopa monniera.

Phytochemistry 2001;58:553-556

8

Bhattacharya SK, Ghosal S. Anxiolytic activity of a standardized extract of Bacopa monniera: An experimental study. Phytomedi­ cine 1998;5(2):77-82

9

Shader RI, Greenblatt DJ. Pharmacotherapy of acute anxiety. In: Bloom FE, Kupfer DJ, editors. Psycopharmacology: Fourth Generation of Progress. New York: Raven Press; 1995. p. 1341-8.

10

Brimson JM, Brimson S, Prasanth MI, Thitilertdecha P, Malar DS,Tencomnao T. The effectiveness of Bacopa monnieri (Linn.)

Wettst. as a nootropic, neuroprotective, or antidepressant supplement: analysis of the available clinical data. ScientificRe­ ports | (2021) 11:596. https://doi.org/10.1038/s41598-020-80045-2

11

Singh HK and Dharwan BN. Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn (Brahmi).

Indian Journal of Pharmacology 1997; 29:S359-S365.

12

Saraf MK, Prabhakar S, Pandhi P and Anand A. Bacopa monniera ameliorates amnesic effects of diazepam qualifying behavioral molecula partitioning. Neuroscience 2008; 155(2): 476-484.

13

Vohora D, Pal SN and Pillai KK. Protection from phenytoin-in­ duced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant. J Ethnopharmacol 2000;71:383-390

14

Morgan A, and Stevens J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo controlled, double-blind trial. The Journal of Alternative and Complementary Medicine 2010; 16(7):753–759

15

Stough C, Lloyd J, Clarke J, et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology 2001;156:481-484

16

Peth-Nui T, Wattanathorn J, Muchimapura S, Tong-Un T, Piyavhatkul N, Rangseekajee P, et al. Effects of 12-week Bacopa monnieri consumption on attention, cognitive processing, working memory, and functions of both cholinergic and monoaminergic systems in healthy elderly volunteers.

EvidBasedComplemAltern Med. (2012) 2012:606424. doi: 10.1155/2012/606424

17

Kumar N, Abichandani L, Thawani V, Gharpure K, Naidu M, Venkat Ramana G. Efficacy of standardized extract of Bacopa monnieri (Bacognize R ) on cognitive functions of medical students: a six-week, randomized placebo-controlled trial. EvidBasedCom­ plemAltern Med. (2016)2016:4103423. doi: 10.1155/2016/4103423

18

Kean JD, Kaufman J, Lomas J, Goh A, White D, Simpson D, et al. A randomized controlled trial investigating the effect of a special extract of Bacopa monnieri (CDRI 08) on hyperactivity and in attention in male children and adolescents: BACHI study protocol (ANZCTRN12612000827831). Nutrients. (2015) 7:9931–45. doi: 10.3390/nu7125507

19

Jadiya P, Khan A, Sammi SR, Kaur S, Mir SS, Nazir A. Anti-Parkinso­ nian effects of Bacopa monnieri: insights from transgenic and pharmacological Caenorhabditis elegans models of Parkinson’s disease. BiochemBiophysResCommun. (2011) 413:605–10. doi: 10.1016/j.bbrc.2011.09.010

20

Singh B, Pandey S, Yadav SK, Verma R, Singh SP, Mahdi AA. Role of ethanolic extract of Bacopa monnieri against 1-methyl-4-phe­ nyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice model via inhibition of apoptotic path ways of dopaminergic neurons.

BrainResBull. (2017) 135:120-8. doi: 10.1016/j.brainres­ bull.2017.10.007

21

Singh B, Pandey S, Verma R, Ansari JA, Mahdi AA. Comparative evaluation of extract of Bacopa monnieri and Mucuna pruriens as neuroprotectant in MPTP model of Parkinson’s disease. Indian J ExpBiol. 2016 Nov;54(11):758-66. PMID: 30179419.

22

Roy S, Chakravarty S, Talukdar P, Talapatra SN. Identification of bioactive compounds present in Bacopa monnieri Linn. against caspase-3 and Tau Protein Kinase I to prevent alzheimer’s disease: an insilico study. Pharma Innov. J. (2019)8:855–61.

23

Sadhu, A. et al. Management of cognitive determinants in senile dementia of Alzheimer’s type: Therapeutic potential of a novel polyherbal drug product. Clin. Drug Investig. 34, 857–869. https:// doi.org/10.1007/s40261-014-0235-9 (2014).

24

Goswami, S. etal. Effect of Bacopa monnieri on cognitive functions in Alzheimer’s disease patients. Int. J. Collab. Res. Internal Med. Public Health 3, 285–293 (2011).

33

Nutramedic &Cosmetics

Inspirational success story: Adena Natura

We are introducing the Croatian company Adena Natura d.o.o. which produces and sells herbal food supplements to help with stress, restlessness, anxiety, insomnia, chronic fatigue, problems with concentration and memory...

We present an interview with Ana Gjergja Sekulić, M.pharm. and Adrijana Tomičić, B.Sc., founders of the company.

NMC: How did it all start?

We are both big lovers of nature and plants, so we have always loved helping our bodies with herbal pre­ parations. We came up with and tried various combi­ nations for personal needs, but also for the needs of our loved ones. In one period of our lives, we were both exposed to an extremely high level of stress, and it was with the help of plants that we mitigated its consequences. Given that the designed formula­ tions gave excellent results, we decided to raise ev­ erything to a professional level and turn our experi­ ence and knowledge into a business in order to help as many people as possible to improve their health.

We received financial support from the city of Zagreb for self-employment and started full of energy... How­ ever, just at the moment of launching the products on the market, we were caught by the corona crisis.

Like for others, it wasn't easy for us, but we didn't gi­

34

ve up. We continue to strive, work and believe in our products.

NMC: What was the initial idea and what inspired you?

We know from our own experience how today's busy lifestyle can negatively affect health. People are often not aware of where stress can take them, nor that they can prevent it. And when they find them­ selves in that negative vortex, they don't know how to get out of it. Stress is an inevitable part of our lives, but the problem arises when it is frequent and intense and when we do not get enough rest and re­ covery from it.

Restlessness, anxiety, insomnia, chronic fatigue, problems with concentration and memory, workload and difficulty keeping up with obligations - these are common problems of modern society.

Aware of this, we designed four products that natu­ rally bring the body back into balance and ease the discomfort we feel when we are exposed to shortterm or long-term stress. We designed them so that

Nutramedic &Cosmetics they can be used individually, but also combined with each other for the best effect.

The product Calma offers instant calm, without the effect of falling asleep during the day; Sleepy allows you to fall asleep faster and easier; Cogny can provi­ de support in a state of great mental effort when better concentration and memory are needed, it can alleviate the decline of cognitive functions as a result of illness or old age, and it can help with exposure to high long-term stress and with feelings of chronic mental and physical fatigue. The Adapto product can help restore the necessary strength and energy.

We are very happy and fulfilled by the fact that we can help people feel good and raise their quality of life, because this way coexistence will be better and of higher quality for everyone.

NMC: What did it take for the idea to come true?

Product development itself lasted a little over two years. Formulations, dosages, raw materials, manufa­c­ ­turing, testing, packaging, design, regulations... that's a lot of things that had to be thought about and har­ monized. The process of starting production and in­ troducing the product to the market was challeng­ ing, but everything is solvable. As exciting as it is, it is also stressful, but when you come up with prepara­ tions for stress, it is certainly easier to deal with it.

NMC: Are you satisfied with your achievements?

We encountered a lot of obstacles during the pro­ cess and it took us longer to put the product on the market, however, plan and life are not always the sa­ me. We entered the entrepreneurial waters with en­ thusiasm and a desire to pass on our knowledge and help people feel good. The most important thing for us is that today our users are satisfied with the pro­ ducts and we are happy with every positive feedback we receive. We do what we love, and we do it for the benefit of people. We are building trust in the Adena Natura brand following carefully planned step, which is shown by the recommendations that people give to each other, and this gives us the motivation to con­ tinue and to develop new products for which there is a demand.

NMC: What are you most proud of?

We are proud of everything we have achieved from the very beginning until today, of perseverance de­ spite all the challenges we are facing. And most of all, of our products, in which all our knowledge and ex­ perience are woven, behind which we stand proudly, because we know that they can help everyone, in wha­tever stressful life situation they find themsel­ ves. These are products that will allow them to get out of the negative vicious circle they entered, help them feel good and with which they can realize the full potential of their mental and physical health.

Adena Natura Ltd. Huga Ehrlicha 3, Zagreb, Croatia T. +385 91 8813 016 www.adenanatura.hr info@adenanatura.hr

B2B events calendar An overview of the B2B live events during 2023 7-11 March 2023, Anaheim, USA https://www.expowest.com/ 16-18 March 2023, Bologna, Italy https://www.cosmoprof.com/en/ 28-30 March 2023, Barcelona, Spain https://www.in-cosmetics.com/global 31 March – 2 April 2023, Düsseldorf, Germany https://www.beauty-duesseldorf.com 16-17 April 2023, London, Great Britain https://www.naturalproducts.co.uk/ 18-19 April 2023, New Jersey, USA https://east.supplysideshow.com 18-20 April 2023, Warsaw, Poland https://nutrafood.pl 6-7 May 2023, Hannover, Germany https://www.cosmetica.eu/cosmetica-hannover/ 9-11 May 2023, Geneva, Switzerland https://www.vitafoods.eu.com/ 7-10 September 2023, Bologna, Italy https://www.sana.it 22-24 October 2023, Paris, France https://natexpo.com 24-26 October 2023, Barcelona, Spain https://www.cphi.com/europe/ 28-30 November 2023, Frankfurt, Germany https://www.figlobal.com

35

Nutramedic &Cosmetics

NADES solvents – a green revolution Environmentally acceptable, natural low-temperature eutectic solvents (NAtural Deep Eutectic Solvents) have a low melting point, low volatility, non-flammability, low vapor pressure, chemical and thermal stability, their price is low and they are easy to prepare on an industrial scale.

Therefore, they are good candidates for carrying out plant extraction in industry.

AUTHOR:

Ph.D. Manuela Panić, Nades Design

36

N

owadays, plant extracts have drawn attention for their positive effects on human health. Plant extracts are rich in various biologically active compounds such as antioxidants, essential oils, aro­ mas, vitamins, colors and pigments, organic acids, pectins and others, which possess antioxidant, anti­ bacterial, antiviral, anti-inflammatory, antitumor and/ or antimutagenic and other positive activities1. The­ refore, plant extracts have found wide use in the phar­ maceutical industry, in the food and beverage indus­ try, and in the cosmetic industry.

Consequently, the extraction and identification of biologically active compounds from different plants have become a very important area of scientific re­ search. The market value of plant extracts in 2022 is estimated at 34.4 billion USD, and the market is still growing. The current technology on the market of plant extracts is not in accordance with innovations and ecological trends, and it is necessary to find a sol­ vent that would dissolve both hydrophilic and lipo­

philic phytochemicals from plants, because biolo­gi­ cally active compounds from plants are a chemically diverse group of compounds. Some of them are sol­ uble in water as a solvent, while most dissolve in pe­ troleum-based solvents. Petroleum-based solvents used in extract preparation are toxic, flammable, vo­ latile and explosive, resulting in air pollution. The­se solvents cause 60% of all industrial emissions and 30% of emissions of volatile organic compounds. Although is the fact that in the 21st century according to the directive 2009/32/EC (Food) it is still allo­w­ed to con­ sume 2.9 mg/kg of hexane or 6 mg/kg of dichlorome­ t­hane per day, the goal of the green deal is to replace such solvents with ecological acceptable alternati­ves.

Natural deep eutectic solvents (NADES), which can extract both polar and non-polar biologically active compounds, showed great potential for application in extraction of biologicaly active compounds. NA­ DES are mixtures obtained by the complexation be­ tween a hydrogen acceptor such as non-toxic qua­

Nutramedic &Cosmetics

FIGURE 2 Plant

FIGURE 1

Natural deep eutectic solvents ternary ammonium salt (e.g. cholinium chloride) and a naturally-derived uncharged hydrogen-bond do­ nor (e.g. amines, sugars, alcohols and carboxylic ac­ ids) in a certain molar ratio, bonded with hydrogen bonds between NADES components2,3 (Figure 1).

Structurally, NADES consists of at least two inex­ pensive, non-toxic and easily available components which are able to self-associate at a certain molar ratio to form a new eutectic phase characterized by a melting point below 100°C. Beside their green cha­ racter, one of the prominent characteristics of these solvents is the possibility of designing their struc­ ture, and thus changing their physical and chemical properties, which consequently affects the possibil­ ity and effectiveness of their application in the se­ lective isolation of biologically active molecules. Sin­ c­e the number of possible chemical structures of the­ ­se solvents is tremendeous, as many as 106 different solvents, there is the possibility of designing them for specific purposes4.

NADES fully represent the green chemistry princi­ ples owning to their specific properties: (i) the cost of NADES is comparable or even lower than conven­ tional solvent; (ii) sustainable production with 100% atom economy production, (iii) chemical and thermal stability, (iv) non-volatility and non-flammability, (v) low toxicity and biodegradability. Since NADES build­ ing components can be considered safe for human consumption NADES extracts could be used as rea­ dy-to-use in food and pharmaceutical industry with­ out demanding and expensive downstream purifica­ tion steps5,6.

Another positive aspect of the use of these sol­ vents in extraction processes is related to the effi­ ciency of NADES extraction compared to conventi­ onal solvents. The true benefit of each plant is deliv­ ering at least 100 times higher concentrations of bi­ ologically active molecules compared with conven­ tional solvents used now in the industry. Comparing the activity of NADES-based extracts with the ex­ tracts on the market, NADES extracts possess supe­ rior activity. Furthermore, NADES solvents also af­ fect the stability of biologically active compounds.

Therefore, by applying the extracts prepared in this way, the added value of the final product is achieved, which can have an improved composition and better, longer stability. NADES extracts are characterized by antioxidant properties, increase product longevi­ ty and bioavailability7,8. Such extracts have shown good compatibility with skin cells, and their biologi­ cal effectiveness such as hydration, anti-aging and UV protection has been proven9.

material used for extract preparation

A team of scientists from the Faculty of Food and Biotechnology decided to enter the market with NA­ DES solvents and products based on them. Female scientists are trying to bridge the gap between aca­ demia and industry and bring sustainable green pro­ ducts to market. Their story with NADES solvents be­gan in 2013 in the academic community, and since then they have been working and creating innovati­ ons in the field of green chemistry. They believe that now is the right time and that the industry is ready to implement green solvents in their products.

As entrepreneurs, they started a journey in SPOCK start up incubator. They received the first grant from the ACT group to start their business and develop the products. They are also the winners of Green Hackaton competition in 2022, which was organised in cooperation with the British Embassy and Algebra LAB at the Greencajt festival. They received support from EIT Food through the EWA program implemen­ ted by Lean Start Up Croatia, where they won first pri­ze. Recently, they won 3rd place at the LAQOTHON competition for the best green idea.

References: 1

F. Chemat, M. A. Vian and G. Cravotto, Int. J. Mol. Sci., 2012, 13, 8615–8627.

2

M. Ruesgas-Ramon, M. C. Figueroa-Espinoza and E. Durand, J. Agric.

Food Chem., 2017, 65, 3591–3601.

3

M. A. R. Martins, S. P. Pinho and J. A. P. Coutinho, J. Solution Chem., 2019, 48, 962–982.

4

A. Paiva, A. A. Matias and A. R. C. Duarte, Curr. Opin. Green Sustain.

Chem., 2018, 11, 81–85.

5

K. Radošević, N. Ćurko, V. Gaurina Srček, M. Cvjetko Bubalo, M. Tomašević, K. Kovačević Ganić and I. Radojčić Redovniković, LWT Food Sci. Technol., 2016, 73, 45–51.

6

E. Wang, Y. Yin, C. Xu and J. Liu, J. Chromatogr. A, 2014, 1327, 39–48.

7

J. M. Silva, E. Silva, R. L. Reis and A. R. C. Duarte, Sustain. Chem.

Pharm., 2019, 14, 100192.

8

Y. Dai, E. Rozema, R. Verpoorte and Y. H. Choi, J. Chromatogr. A, 2016, 1434, 50–56.

9

P. Manuela, S. Drakula, G. Cravotto, R. Verpoorte and M. Hruškar, In­ nov. Food Sci. Emerg. Technol., 2020, 66, 102514.

For more information about the products and the NADES team, visit their website www.nades-design.hr or social media : www.linkedin.com/in/nades-design-a2aab0221/ www.twitter.com/NADES_Design?s=20&t=t6cJ8_Gp9_xW0GQ-Q3WHsA)

37

Nutramedic &Cosmetics

Experience the world's nutraceutical event:

Vitafoods Europe 2023 The much-loved nutraceutical event returns both in person and online this May with an expanded offering including new, premium content.

R

egistrations are now open for Vitafoods Eu­ rope 2023, the leading global platform for nu­ traceutical, functional food and beverage, and dietary supplement professionals. The organizers of the event, whose main sponsor is KSM-66 Ashwa­ gandha, expect over 15,000 attendees to the Palex­ po Convention Centre in Geneva (9-11 May) and on­ line (1-12 May). Visitors can experience exclusive ex­ pert-led content on consumer trends, market oppor­ tu­nities and scientific innovations, as well as connect with like-minded peers and suppliers to inspire new collaborations and finished products.

In addition to returning favourites, this year’s event will offer brand new show features – such as the new Sustainability Resource Centre and the Startup In­ novation Challenge, plus the Future of Nutrition Sum­ mit and the Vitafoods Europe Conference.

Presenting Vitafoods Europe 2023 Andy Mather, Brand Director of Vitafoods Europe at Informa Mar­ kets, said “Vitafoods Europe 2023 aims to create a uni­ que experience that visitors will not just find valu­ able, but that they will also really enjoy. This year, we are introducing a host of new content, designed to inspire, engage and provide the spark to propel the industry forward.

The new Sustainability Resource Centre will featu­ re innovations and insights from passionate experts dedicated to driving sustainable change in the nutri­ tion industry. Meanwhile, the Startup Innovation Chal­ lenge provides an opportunity for upcoming nutra­ ceutical stars to make their mark on the industry and develop their innovative projects through a special­ ised support programme. We welcome everyone in the Vitafoods community back for 2023 both in Ge­ neva and online – including those joining us for the first time – to experience the creativity and collabo­ rations on offer.”

Show highlights

• NEW: Future of Nutrition Summit (8 May, Marri­ ott Hotel, Geneva) – join a diverse range of C-suite industry leaders and futurist thinkers for an exclu­ sive, paid-for one-day summit discussing the trends and technologies that will shape the nutrition in­ dustry in 5+ years’ time.

• NEW: Vitafoods Europe Conference (9-10 May) – this premium, two-day conference returns in a new format, focused on current challenges and oppor­ tunities in sports and active nutrition; cognitive and emotional health; metabolic and immune health;

38

life stages and healthy ageing. Now located in a purpose-built theatre on the Vitafoods Europe show floor, visitors can easily combine attending the conference alongside their regular show floor and expo experience.

• The Vitafoods Insights Theatre – returning for 2023, the Vitafoods Insights Theatre offers freeto-attend expert sessions diving into current glo­ bal consumer trends, updates on regulatory and supply chain issues, as well as insights into delive­ ry formats and packaging.

• NEW: Startup Innovation Challenge – discover cutting-edge innovations from the most exciting health and nutraceutical startups as they pitch their ideas live. Together with the popular Startup Pa­ vilion, this challenge provides a unique opportuni­ ty for companies to find innovative ingredients, technologies, services, and finished products to help their businesses grow.

• NEW: Sustainability Resource Centre – dedicated to driving sustainable change in the nutrition in­ dustry, this resource centre offers expert presen­ tations and insights into the full spectrum of sus­ tainability issues, including supply chain traceability, regulatory compliance, certifications, carbon off­ setting, alignment with the UN Sustainable Deve­ lopment Goals, and gender and LGBTQ+ inclusivity.

Experience innovations and ideas

“Standing still simply isn’t an option in this industry; people return to Vitafoods Europe year-after-year to drive their businesses forward and be inspired.” says Mather. “This year, we are offering another lively agen­ da, packed full of exciting opportunities to connect and gather knowledge. This includes both new and reimagined premium, paid-for events that will dive deeper into current trends and future industry pre­ dictions; the Vitafoods Europe Conference and the Future of Nutrition Summit. The latter joins the Vita­ foods Europe 2023 family after being a huge success at previous Food Ingredients Europe events. We truly believe that Vitafoods Europe 2023 has something for everyone, and that this year's attendees will ex­ perience the very best in industry innovations and insights to keep their businesses at the leading-edge of nutrition.”

To register and to learn more about the new pre­ mium content offerings, visit: www.vitafoods.eu.com/

Vitafoods Europe is

Every year, thousands of nutraceutical experts look forward to joining friends, colleagues and suppliers at Vitafoods Europe. They love tasting new products, listening to world-class speakers, discovering new ingredients and connecting with fantastic people from across our industry.

Experience it for yourself 9-11 May Geneva 1-12 May Online Register now at vitafoods.eu.com 39

Nutramedic &Cosmetics

Elasderma

®

Advanced Skin © Molecule Technology Elasderma® is a protein peptide that helps maintain skin elasticity, healthy arteries and the heart, and strengthens bone structure by improving joint health. Also, Elasderma® has proven to be a powerful antioxidant with a unique anti-aging effects. When taken continuously, it promotes cell growth. The restoring effect of Elasderma® makes the skin younger, smoother and fresher.

E

lasderma® is a US Patented Elastin ingredient.

This amazing molecule is the most stable pro­ tein of the extracellular matrix (ECM) which is composed of collagen, glycoproteins, glycosamino­ glycans and proteoglycans. Elastin has been widely used as a skin booster by helping the skin maintain its elasticity and young age, though, this is not the only benefit of this powerful protein.1-3 Along with collagen, elastin is a vital component of the blood vessels and plays a significant role in the remodeling and elasticity of conduit arteries like the carotid and femoral. In terms of cardiovascular health, elastin protein is believed to provide a protective ef­ fect against cardiac rupture, to decrease the area of infarction and help lower the risk of cardiovascular disease by suppressing the formation of harmful blood clots. 2-3 Elastin peptides have also shown protective effect as antioxidative having the advantage of being ef­

40

fective at low concentrations and safe. The ability of elastin peptides as radical scavenger may be due to their ability to chelate metal ions and their good af­ finity for oils, as well as the presence of hydrophobic amino acids.4 Among other benefits, soluble elastin shows anti­ oxidative properties, and the presence or hydropho­ bic aminoacids (Val and Pro) could potentially contri­ bute to the high antioxidant activity.4-5 In recent studies, it has been shown that consum­ ing elastin or tropoelastin may positively impact the bone regenerative capacity by enhancing and accele­ rating osteogeonesis (the process by which new bo­ ne is made by the cells). 29 Elasderma® is considered a skin conditioner, which is purported to help skin maintain its elasticity and young age. This protein has also been used as a skin booster. When taken regularly, it stimulates elastin bio­synthesis. Elastin’s renewing effect makes skin

Nutramedic &Cosmetics look younger, smoother and refreshed.

Elasderma® is obtained from Atlantic Cod Fish through a process involving several steps to refine elastin: from washing and defatting previously in­ spected and cleaned Atlantic Cod Skin to enzymatic hydrolysis using different proteases to remove non-­ elastin proteins, followed by various purification steps to deliver a fully water soluble, additive and high pu­ rity product.

Elastin is a critical skin protein which combines with microfibrils to form elastic fibers that provide stretch and recoil to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins (ECM) are integral to maintaining healthy skin structure, function, and youthful appearance.1 Also, elastin is present in several connective tissues and confers a unique physiological elasticity.7-12 Elastogenesis, the process of elastin formation, mainly occurs during the fetal and early neonatal de­ velopment of organs such as blood vessels, lungs, and skin, principally in elastogenic cell types, such as fibroblasts,11-12 and containing high amounts of elas­ tin to assure their correct function.13 Elastin and elastic fibers are unique in that there is very low and slow turnover. In fact, in skin, the overall half-life of elastin is similar to the human lifespan.14 The benefits of elastin hydrolysate have been cli­ nically proven. Among them are a better condition and greater elasticity of the skin.15-17 Elastin hydroly­ sate activates human skin fibroblasts and has bene­ ficial effects on skin conditions.18 In a Japanese clini­ cal study, ingestion of elastin hydrolysate enhanced the proliferation of fibroblasts and elastin synthe­ sis, improving skin elasticity and blood flow and de­ creasing the number of wrinkles.19 Studies suggest that elastin increases the expres­ sion of long-chain base 1, dihydroceramide desatu­ rase 1, elastin, hyaluronan synthase 2, and ceramide synthase 4 mRNA or protein as well as hyaluronic acid and sphingomyelin levels in UVB-irradiated Ha­ CaT cells. Moreover, elastin regulated factors related to collagen production, wrinkles, and melanin pro­ duction in UVB-irradiated HS27 cells and IBMX-sti­mu­ lated B16F10 cells. 28 Elastin shows protective effects against UVA irra­ diation induced skin damage. 20-21 Other clinical stud­ ies on Elastin showed an improvement in blood flow providing a significant improvement in vascular health after 4 and 8 weeks. 22-23 Also, elastin showed a signifi­ cant improvement in knee joint pain after 12 weeks. 24 After a injury, elastin mechanical properties are adap­ ted to allow for proper work at higher pressures. 25 The formation of Desmosine and Isodesmosine cross-links via allysine-allysine or allysine-lysine re­ actions also contribute to the biomechanical prop­ erties of elastic fibers, as these cross-links can re­ sist elastolysis. 26-27 Elasderma® is the only known elastin with a scien­ tifically validated method to test, verify and quanti­ fy the presence of Desmosine (DES) and Isodesmo­ sine (IDES), two amino acid isoforms uniquely found in elastin.

To measure the quantity of these biomarkers in products containing elastin, Nutraceuticals Group, in collaboration with Dr. Illya Gertsman, Ph.D (Univer­ sity of California-San Diego) and Vertex Analytical

FIGURE 1 Stock standards solution chromatogram. Peak assignments and approximate retention times for IDES (13.27 min), and DES (13.50 min).

Labs an FDA registered and ISO 17025:2017 Accredit­ ed Laboratory, developed and validated a simple, ac­ curate and precise HPLC-UV method to analyze elas­tin hydrolysates. The test method allows to de­ tect each amino acid individually.

Lipids and small peptides are removed from elas­ tin with ice cold ethanol. After that elastin is centri­ fuged and elastin hydrolysates was prepared by acid hydrolysis in 6 M HCl for 24 h at 110 °C under vacuum.

The hydrolyzed elastin was neutralized with NH4OH, evaporated and dried at 60 °C under stream nitro­ gen. The sample was resuspended in 10% MeOH and tested by ion-paring RP-HPLC. HPLC analyses were carried out on a Shimadzu Prominence Series system (LC-20AT Pumps, SIL-20A Autosampler, CTO-20AC Column Oven, SPD-20A UVVis Detector). Data and chromatograms were pro­ cessed with Shimadzu Lab Solutions HPLC Software.

Samples (50 µL) were injected into a C18 HPLC Col­ umn (Nucleosil C18, 5µm, 150 mm x 4.6 mm, Sigma-Al­ drich, cat# Z226173; St. Louis, MO) at 30 °C. The separation mode of each amino acid was the ionpaired chromatographic technique because both DES and IDES amino acids contain pyridinium nucle­ us in their chemical structure. Ion pairs consisted of amino groups (positively [+] charged) and/or pyridi­ nium nitrogen (positively [+] charged for DES and FIGURE 2 Hydrolyzed ELASDERMA® sample chromatogram.

Peak assignments and approximate retention times for IDES (13.18 min), and DES (13.53 min).

41

Nutramedic &Cosmetics IDES), and the alkylsulfonate group (negatively [-] charged) as the other member of the ion pair. The car­boxyl residues were suppressed by 0.1 M MSA (pH 2.0) containing 1.2 mM HSA like mobile phase A, and mobile phase B was used acetonitrile/0.2% FA with a flow rate to 1mL/min and 25°C column temperature.

The optical density was monitored at 275 nm for the determination of DES and IDES amino acids.

Standard solution, a mix of IDES/DES (Sigma-Al­ drich), was used to identify retention time and peak chromatographic parameters. A commercial sample (Elasderma®, Nutraceuticals Group USA; Lot. NIGELAS-­ 2008V478067 and NIGELAS-2012V964125) were ana­ lyzed. The retention time of IDES/DES standard so­lu­ tion (Sigma-Aldrich) were identified at 13.2 and 13.5 respectively (Figure 1).

The presence of IDES/DES on elastin hydrolysate can be observed in Figure 2, with a similar retention time (RT ± 2.0%) compared with stock standards so­ lutions.

Finally, Desmosine and Isodesmosine peaks were identified and integrated using Shimadzu LabSoluti­ ons and the amount of each amino acid in Elasder­ ma® is calculated as µg/g using calibration curves pre­ pared from DES/ISO reference materials (standards).

Reerences:

42

1

Aumailley, M., & Gayraud, B. (1998). Structure and biological activity of the extracellular matrix. Journal of molecular medicine (Berlin, Germany), 76(3-4), 253– 265. https://doi. org/10.1007/s001090050215

2

Basu, P., Sen, U., Tyagi, N., & Tyagi, S. C. (2010). Blood flow interplays with elastin: collagen and MMP: TIMP ratios to maintain healthy vascular structure and function. Vascular health and risk management, 6, 215–228. https://doi.org/10.2147/vhrm.s9472

3

Protti, A., Lavin, B., Dong, X., Lorrio, S., Robinson, S., Onthank, D., ... & Botnar, R. M. (2015). Assessment of myocardial remodeling using an elastin/tropoelastin specific agent with high field magnetic resonance imaging (MRI). Journal of the American Heart Association, 4(8), e001851.

4

Hattori, M., Yamaji-Tsukamoto, K., Kumagai, H., Feng, Y., & Takahashi, K. (1998). Antioxidative Activity of Soluble Elastin Peptides. J. Agric.

Food Chem., 46, 6, 2167– 2170.

5

Nadalian, M., Kamaruzaman, N., Yusop, M. S. M., Babji, A. S, and Yusop, S.M. (2019) Isolation, Purification and Characterization of Antioxi­ dative Bioactive Elastin Peptides from Poultry Skin. Food Sci Anim Resour. 2019, 39(6), 966-979. doi: 10.5851/kosfa.2019.e90

6

Shiratsuchi, E., Nakaba, M., Shigemura, Y., Yamada, M., & Sato, K. (2013). Fish-elastin Hydrolysate: Development and Impact on the Skin and Blood Vessels. In: Kim, S. E. (Ed.). Marine Proteins and Peptides: Biological Activities and Applications. Wiley. https://doi. org/10.1002/9781118375082.ch23 7 Skjøt-Arkil, H., Clausen, R.E., Nguyen, Q.H. et al. (2012).

7

Skjøt-Arkil, H., Clausen, R.E., Nguyen, Q.H. et al. (2012). Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique infor­ mation on lung tissue degradation. BMC Pulm. Med., 20, 12–34.

8

Calleja-Agius, J., Brincat, M. & Borg, M. (2013). Skin connective tissue and aging. Best. Pract. Res. Clin. Obstet. Gynaecol., 27, 727–740.

9

Momot, K.I., Powell, S.K., Mithieux, S.M. & Weiss, A.S. (2013). Biome­ chanics of synthetic elastin: insights from magnetic resonance microimaging. Adv. Mat. Res., 699, 257–463.

10

Halper, J. & Kjaer, M. (2014). Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.

Adv. Exp. Med. Biol., 802, 31–47.

11

Kristensen, J.H., & Karsdal, M.A. (2016). Elastin. Biochemistry of Col­ lagens, Laminins and Elastin. London: Academic Press.

12

Chiquet, M., Renedo, A.S., Huber, F., & Flück, M. (2003). How do fibro­ blasts translate mechanical signals into changes in extracellular matrix production? Matrix Biol., 22,73-80.

13

Le Page, A., Khalil, A., Vermette, P., Frost, E. H., Larbi, A., Witkowski, J. M., & Fulop, T. (2019). The role of elastin derived peptides in human physiology and diseases. Matrix Biol., 84, 81-96. https://doi. org/10.1016/j.matbio.2019.07.004

14

Shapiro, S.D., Endicott, S.K., Province, M.A., Pierce, J.A., & Campbell, E.J. (1991). Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. J Clin Invest., 87(5),1828-1834. https://doi.org/10.1172/JCI115204

15

Shiratsuchi, E., Nakaba, M., Shigemura, Y., Yamada, M., & Sato, K. (2013). Fish-elastin Hydrolysate: Development and Impact on the Skin and Blood Vessels. In: Kim, S. E. (Ed.). Marine Proteins and Peptides: Biological Activities and Applications. Wiley. https://doi. org/10.1002/9781118375082.ch23

16

Pezzoli, D., Di Paolo, J., Kumra, H., Fois, G., Candiani, G., Reinhardt, D.P., & Mantovani, D. (2018). Fibronectin promotes elastin deposition, elasticity and mechanical strength in cellularised collagen-based scaffolds. Biomaterials, 180,130-142. https://doi. org/10.1016/j.biomaterials.2018.07.013

17

Wang, R., Yu, X., & Zhang, Y. (2021). Mechanical and structural con­ tributions of elastin and collagen fibers to interlamellar bonding in the arterial wall. Biomech Model Mechanobiol. 20(1),93-106. https://doi.org/10.1007/s10237-020-01370-z

18

Robert, L., Jacob, M.P., Frances, C., Godeau, G., & Hornebeck, W. (1984). Interaction between elastin and elastases and its role in the aging of the arterial wall, skin and other connective tissues. A review. Mech Ageing Dev., 28(2-3), 155-66. https://doi.org/10.1016/ 0047- 6374(84)90015-0

19

Shiratsuchi, E., Nakaba, M., & Yamada, M. (2016). Elastin hydrolysate derived from fish enhances proliferation of human skin fibro­ blasts and elastin synthesis in human skin fibroblasts and im­ proves the skin conditions. Journal Science, Food and Agriculture, 96, 1672–1677. https://doi.org/10.1002/jsfa.7270

20

Amakye, W. K., Yang, L., Yao, M., Yuan, E., Ren, R., & Ren, J. (2021). Skipjack (Katsuwonus pelamis) elastin hydrolysate-derived peptides atte­ nuate UVA irradiation-induced cell damage in human HaCaT kerati­ nocytes. Food Frontiers, 2(2), 184-191. https://doi.org/10.1002/fft2.74

21

Liu, Y., Su, G., Zhou, F., Zhang, J., Zheng, L., & Zhao, M. (2018).

Protective Effect of Bovine Elastin Peptides against Photoaging in Mice and Identification of Novel Antiphotoaging Peptides. J Agric Food Chem., 66(41),10760-10768. https://doi.org/10.1021/acs. jafc.8b04676

22

Takemori, K., Yamamoto, E., Ito, H., & Kometani, T. (2015).

Prophylactic effects of elastin peptide derived from the bulbus arteriosus of fish on vascular dysfunction in spontaneously hypertensive rats. Life Sciences, 120, 48-53. https://doi. org/10.1016/j.lfs.2014.10.011

23

Takemori, K., Akahoshi, Y., & Kometani, T. (2018). Hypertensive vascular changes were suppressed by elastin peptide obtained from fish bulbus arteriosus. Pathophysiology, 25(3), 183-184. https://doi.org/10.1016/j.pathophys.2018.07.055

24

Schauss, A. G., Stenehjem, J., Park, J., Endres, J. R., & Clewell, A. (2012). Effect of the Novel Low Molecular Weight Hydrolyzed Chicken Sternal Cartilage Extract, BioCell Collagen, on Improving Osteoarthritis-Related Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Agricultural and Food Chemistry, 60, 4096-4101. https://doi.org/10.1021/jf205295u

25

Faury, G. (2001). Function-structure relationship of elastic arteries in evolution: from microfibrils to elastin and elastic fibres. Pathol Biol, 49(4), 310-25. https://doi.org/10.1016/s0369-8114(01)00147-x

26

Akagawa, M., & Suyama, K. (2000). Mechanism of Formation of Elastin Crosslinks. Connective Tissue Research, 41(2), 131-141. https://doi.org/10.3109/03008200009067665

27

Lamberg, S.I., Poppke, D.C., & Williams, B.R. (1980). Isolation of elastic tissue microfibrils derived from cultured cells of calf ligamentum nuchae. Connect Tissue Res., 8(1), 1-8. https://doi. org/10.3109/03008208009152115

28

Park, S. J., Kim, D., Lee, M., Jung, J., Eun, S., & Kim, O. K. (2022). Effects of Bonito Elastin HC on Skin Dryness, Wrinkles, and Pigmentation In Vitro and In Vivo. Journal of Medicinal Food, 25(1), 48-60.

29

de Moraes, R., de Guzzi Plepis, A. M., da Conceição, A. M. V, Duarte, M. A. H., Alcalde, M. P., Buchaim, R.L., Pomini, K.T., Machado, E. G., de Aze­ vedo, E., Sousa Munhoz, M., Cunha, F. B., Calegari, A. R. A., Iatecola, A., Silva, S. K., da Cunha, M. R. (2019). Suitability of the use of an elastin matrix combined with bone morphogenetic protein for the repair of cranial defects. Am J Transl Res, 11(8):5261-5271

Nutraceuticals Group USA(a) Vertex Analytical Labs(b) (a) 50 Sindle Avenue, Little Falls, NY 07424 (b) 7098 Miratech Dr Ste 120, San Diego, CA 92121 customersupport@vertexanalytical.com www.elasderma.com

Nutramedic &Cosmetics

UREA - an effective molecule for dry skin symptoms Urea is molecule naturally present in epidermis, as a component of natural moisturizing factor (NMF) and is fundamental for the optimal skin water capacity and proper skin barrier function.

Applied topically, urea helps improve symptoms of dry skin by providing hydration and by reducing dead skin cells. Urea is also used in dermatology for treatment of skin disorders.

AUTHOR:

Lana Brkić, M.Eng.

Function of skin

The main role of the skin is to protect the body form the environmental harmful factor, such as dirt, air pollutants, irritants, harmful microorganism. Mi­ crobiota supports skins defense role. Also, it regula­ tes the body temperature.

The stratum corneum is the outermost layer of the skin, the outer sublayer of epidermis. Although it is 0,015 mm thick, it plays an important role as a barrier, protecting the inner layers of skin. Most body parts contains about 20 layers of cells, while the eye area has fewer layers and parts of hands and heels have thicker layers.

The stratum corneum is often described as a brick wall or “brick and mortal wall”. “The brick” is formed of dead cells, called corneocytes, which are mainly fi­l­­l­ ed with fibrous proteins – keratin and filaggrin. “The

brick” gives mechanical strength. Corneocytes are sur­rounded by lipids and fats – ceramides, fatty ac­ ids, cholesterol) and they are organized into lamellar membranes. “The mortal” fills the area around cor­ neocytes and stops water from moving across the stratum corneum. Brick and mortal wall is strong and impermeable, it keeps water in the skin and microor­ ganisms out. If the wall is damaged by environmen­ tal conditions, chemicals, change of temperature or by intrinsic factors, the skin barrier function is weak­ ened. It leads to disturbance of filaggrin expression or reduction of lipids. The result is increased water loss. The proper skin function is disturbed. The skin barrier is now favoring the penetration of irritants and allergens, triggering inflammation and skin be­ comes prone to infections.

The hydroscopic substances, with properties of ab­ sorption and retaining water molecules are natural­

43

Nutramedic &Cosmetics ly present in stratum corneum, within corneocy­tes.

They are known as natural moisturizing factor (NMF).

Among these ingredients are: urea, free amino acids, lactic acid and pyrrolidone carboxylic acid. The NMF components act as humectant by keeping the moist and maintaining hydrated skin barrier. The skin stays smooth and maintains a healthy appearance.

Water capacity of the stratum corneum is influen­ ced by two factors. First is the presence of hydrosco­ pic substances within corneocytes, natural moistur­ izing factors (NMF) and second factor is undisturbed lipid intracellular structure.

Dry skin

Dry skin is also known as xserosis.

The causes of dry skin are different, from environ­ mental causes to health conditions. Environmental factors depend on the way of living and everyday ha­ bits. Certain diseases tend to cause dry skin.

It is considered that stratum corneum contains about 10-20% water and that if the water content is reduced to below 10%, visible symptoms of dry skin occur.

First symptoms of dry skin that appear are rough­ ness and tightness. Without treating the symptoms and with further water loss, the skin will become itchy, start to crack and scaling will occur. Severe symptoms may include flaky skin with rough peeling surface, deep painful cracks, skin that burns. In cases of more serious dry skin symptoms medical treat­ ment is needed.

Different types of eczema and dermatitis are skin conditions that cause itchy and inflamed dry skin.

The NMF production can decrease in the skin and is influenced by: • ageing and hormonal changes, genetic predispo­ sition, • environmental factors: climate, dry air, UV radia­

tion, smoking, exposure to chemicals, • skin conditions: irritant contact dermatitis, atopic dermatitis, xserosis, ichthyosis.

Lack of natural moisturizing factors (NMF) leads to a reduction of hygroscopic capacity of skin, resu­l­ting in increased transepidermal water loss (TEWL). Wa­ ter loss disrupts the proper functioning of the skin resulting in xserosis. Reduction of water in the epi­ dermis influence the proper function of the skin bar­rier, allowing the penetration of irritants or be­ coming the predisposing factor to skin infections.

Application of topical preparations containing urea, a hygroscopic molecule, will support the water-binding capacity of NMF and enable hydration of the stra­ tum corneum and contribute to its barrier function.

Urea

Urea is today the most common ingredient, which is added to preparations for topical application to help eliminate the problems of dry skin. Urea is a wellknown ingredient in dermatology for the skin disor­ ders such as atopic eczema, ichthyosis, psoriasis and contact dermatitis. Urea is recognized to have posi­ tive effects in skin function. It is a fundamental mole­ cule for adequate hydration, which the skin needs to function properly.

Urea is the major constituent of NMF, the hygro­ scopic substance, and is present up to 7%. As a high­ ly reactive molecule, urea is capable of drawing wa­ ter from the dermis into the epidermis and attract­ ing water from the external environment. Higher hu­ midity favors better water absorption. In addition, urea retains water within skin cells.

The following effects of xserosis skin are attribut­ ed to the action of urea: hydration, exfoliation, rege­ neration, irritation calming. Also, further effects on the skin are antimicrobial action and increase of drug

FIGURE 1 The process of natural moisturizing factor (NMF) production.

The precursor protein, profilaggrin, is present in the keratinocyte in the granular layer. As the cells transi­ tion into corneocytes, proteases cleave the precursor into filaggrin where it aggregates keratin filaments into macrofibrils. In the upper layers of the stratum corneum, the filaggrin is proteolyzed to form the NMF, where they absorb and bind water from the atmosphere. Adapted with permission from O’Regan, et al.

Taken from: Understanding the Role of Natural Moisturizing Factor in Skin Hydration, Joseph Fowler, Practical Dermatology, July 2012

44

Nutramedic &Cosmetics penetration. Urea has antifungal and antimicrobial efficacy. It can improve skin penetration of other sub­ stances or drugs.

Urea – moisturization effect

Urea is providing moisturization by drawing water from deeper layers and from the air and by locking the water in the stratum corneum. In addition, urea has an emollient function, meaning it soften and smoothes the skin. By reduction of water loss, it keeps the outer layers of the skin moisturized. Urea im­ proves the water binding capacity, keeps the stratum corneum well hydrated.

Urea – exfoliation effect

Urea is a keratolytic agent. It breaks down the hy­ drogen bond in protein keratin, the outer layer of skin.

It softens the horny layer and enables the easier re­ moval of rough skin. Thus, it eliminates skin flakes and scales. This improves the appearance of treated skin and relieve symptoms. Dead skin cells are remo­ ved from the surface. Breakage through the surface layer allows better hydration of the new skin cells.

Skincare products with urea

As urea is a highly water-soluble molecule, it can be easily incorporated into skin care products for to­ pical applications. Many dermatological preparati­ons contain urea for treatment of different skin disorders.

The skincare market offers a variety of different products that include urea in combination with oth­ er active ingredients and with various urea concen­ trations.

Most of the topically applied products are intend­ ed to moisturize the skin and help exfoliation, but al­ so to improve conditions of scaly and dry skin.

Urea concentration ranges vary between 5-40%, in­ tended for the treatment of different skin conditions: • 5 - 10% urea concentration – skin moisturization, as a humectant or an emollient • 10 – 30% urea concentration – reduce itching, im­ prove scaly skin conditions • 40% urea concentration – proteolytic effect.

The moisturization can be achieved with products containing up to 10% of urea, it enables the binding of water to the protein chain in the stratum corne­ um. As a moisturizer, urea acts as a humectant – with a function to attract and hold moisture, and as an emollient – with a function to soften and smooth the skin. Products with lower urea concentration can al­ so be used for prophylactic use in preventing more difficult skin disorders. Such moisturizers are suitable for the long-term care of large skin areas.

Topical products with urea concentration of 10% and higher are considered to have keratolytic effect.

They can reduce itching and improve conditions of scaly skin and are appropriate for the treatment of xerotic skin conditions such as eczema, dermatitis, or psoriasis. Such products reduce the feeling of tight­ ness and provide skin comfort.

Products containing 40% of urea have proteolytic effect, helping to break down molecules of proteins.

They are suitable for skin areas with thicken dead cells patches, found on hands, feet, and elbows. Their me­ chanism is exfoliation, and they purify the skin. These

products can be used for the treatment of dystro­ phic nails, nails that are thickened or deformed.

Most of the marketed products are face creams and body lotions for the care of dry and rough skin, providing intensive skin moisturization. They provi­ de a quick relief effect and reduce tightness. Body washes effectively clean the skin and do not leave a feeling of dryness.

Urea is the most common ingredient included in feet care creams due its intensive moisturizing property and exfoliating effect. Feet care cream is also recom­ mended for treatment of corns and calluses. It can also help treating the nail condition like fungal infections.

Hair shampoos are mainly intended for dry and itchy scalp, providing relieve of itching and irritation.

They relieve dryness by moisturization and exfolia­ tion of scalp. Scalp is becoming hydrated and contri­ bute to healthier hair and stimulates hair grow. As urea has the antifungal effect, urea-containing shampoo is beneficial against dandruff. With so ma­ ny beneficial effects, shampoo with urea is conside­ red as a complete scalp treatment.

In dermatology urea is used for topical application of skin disorders, like atopic dermatitis, ichthyosis, seborrheic dermatitis, and psoriasis. The increase of water content in the stratum corneum and improve­ ment of the skin barrier function are considered as fundamental for the treatment of skin disorders.

Therefore, urea with its mechanism of action is of­ ten used in dermatological preparations.

From the safety point of view, urea is considered safe and well tolerated. Studies have shown not sig­ nificant side effects. Known side effects are sting­ ing, redness or irritation. But, these side effects are rare and temporary.

Urea is a well-known humectant and emollient used in skincare products to help moisturize and exfoliate the skin. Urea is effective in reducing water loss and thus improves skin barrier function. Dermatological urea-containing products treat conditions of skin dis­orders. Application of urea products will improve dry skin condition: itchy skin, scaly skin, flaky skin, rough texture, cracks in the skin. Skin discomfort like stings, redness, irritation, tightness will be relieved.

Urea will support healthier skin appearance.

References:

Berardesca E, Cameli N. Non-invasive assessment of urea efficacy: A review. Int J Clin Pract. 2020 Dec;74 Suppl 187:e13603. doi: 10.1111/ ijcp.13603. PMID: 32639641.

Dirschka T. Mode of action of urea. Int J Clin Pract. 2020 Dec;74 Sup­ pl 187:e13569. doi: 10.1111/ijcp.13569. PMID: 33249710.

Celleno L. Topical urea in skincare: A review. Dermatol Ther. 2018 Nov;31(6):e12690. doi: 10.1111/dth.12690. Epub 2018 Oct 30. PMID: 30378232.

Verdier-Sévrain S, Bonté F. Skin hydration: a review on its molecular mechanisms. J Cosmet Dermatol. 2007 Jun;6(2):75-82. doi: 10.1111/j.

1473-2165.2007.00300.x. PMID: 17524122.

Voegeli, David. (2012). Urea creams in skin conditions: composition and outcomes. Dermatology in Practice. 18. 13-15.

Piquero-Casals, J., Morgado-Carrasco, D., Granger, C., Trullàs, C., Je­ sús-Silva, A., & Krutmann, J. (2021). Urea in Dermatology: A Review of its Emollient, Moisturizing, Keratolytic, Skin Barrier Enhancing and Antimicrobial Properties. In Dermatology and Therapy (Vol. 11, Issue 6, pp. 1905–1915). Adis. https://doi.org/10.1007/s13555-021-00611-y Pan, M., Heinecke, G., Bernardo, S., Tsui, C., & Levitt, J. (2013). Urea: a comprehensive review of the clinical literature. Dermatology Online Journal, 19(11). https://doi.org/10.5070/D31911020392 Fowler, J. (2012.). Understanding the Role of Natural Moisturizing Factor in Skin Hydration. Practical dermatology, July 2012., 36-40.

45

Nutramedic &Cosmetics

The role of collagen in the skin health and beauty In recent years, the food supplement market has become increasingly rich in collagen-containing products. The reason for this lies in numerous confirmations of its effectiveness in preserving and improving the youthful appearance and overall condition of the skin, as well as in preserving the health of the musculoskeletal system.

AUTHOR:

Vesna Marijanović Jukić, M.pharm., univ.spec.oec., Pharmatop

46

C

ollagen is a strong and flexible fibrous prote­in that is produced daily in the body, and is the main component of connective tissue, mus­ cles and skin. It makes up 25-35% of the protein con­ tent in the human body, which makes it one of the most abundant proteins. The word collagen itself co­ mes from the Greek word "kolla" which translates as "glue" (collagen type I and type III join in the dermis li­ ke connective pads).

In addition to being necessary for the health and appearance of the skin, this protein is also necessary for reducing the typical signs of aging, which begin to appear as early as the twenties. It is a true ally in preserving flawless skin, tissues and healthy joints, so it must be taken into the body regularly.

Collagen also has numerous benefits for the health of joints, tendons and bones - it improves joint mo­ bility, reduces bone pain and helps regenerate the cartilage that protects the joints. As its amount in the body decreases with age, the risk of osteoarthri­ tis and other painful conditions in the joints increas­ es. It also helps to preserve the strength of bones, as it is an integral part of them, which has been confir­m­ ed by studies.

However, as we age, collagen production in the bo­ dy decreases more and more. Already after the age of 21, the production process slows down significan­t­ ly, by about 1.5% every year. This means that the number and activity of cells that produce collagen (fibroblasts) decrease with aging. As the number of new fibers noticeably decreases from year to year, signs of aging gradually begin to appear.

The amount of collagen in the body begins to de­ crease even more significantly after the age of 40.

This process is influenced by internal factors such as genetic inheritance and hormonal changes, but it can also be accelerated by external influences such as al­cohol consumption, smoking, photoaging, diet, stress and air pollution. Free radicals and glycation (the bi­ ological process by which sugar molecules attach to collagen) can provoke existing collagen fibers to har­ den and join together. Ultraviolet rays stimulate en­ zymes that break down collagen (matrixins).

Food supplements containing collagen

Due to all the previously mentioned knowledge about the importance of collagen in preserving youth, vitality and improving the overall condition of the skin and in preserving the health of the musculoske­ letal system, the over-the-counter products market has in recent years increasingly turned to the pro­ duction of food supplements based on collagen for oral use, in the form of capsules and /or in liquid form.

Considering the popularity that liquid form pro­ ducts currently enjoy, various types are available on the market, the most common being collagen of ani­ mal origin - bovine collagen, and marine collagen from fish. Marine collagen has long been used in the production of cosmetics and contains predominant­ ly type I collagen. On the other hand, bovine collagen contains type I and III collagen, which, in addition to the health of the skin, are also important for the health of the intestines, bones, joints and connecti­ ve tissue.

Type I and type III collagens are secreted by fibro­ blasts, cells in the dermis, the deeper layer of the skin, which are also responsible for the formation of elastin. Together with elastin and other proteins call­ ed glycoproteins, collagen forms the extracellular matrix. It is the network that makes up the skin and, like muscle, provides it with physical properties such as tone, resilience and firmness. Although it seems that bovine collagen is better, because in addition to

Nutramedic &Cosmetics helping maintain the health of the skin, it is also im­ portant for the health of the whole body, marine col­ lagen contains smaller peptide molecules, so it is easier to digest than animal collagen, and because of this, it is absorbed faster in the body.

No matter which origin of collagen you choose, you can't go wrong because each one provides health be­ nefits.

The role of collagen in the skin health and beauty

We can thank collagen for the youthful, fresh and radiant appearance of the skin and hair. When we are young, our body continuously produces collagen. Its most important role is to maintain the structure and resistance of the skin. In the middle layer of the skin - the dermis - it contributes to the creation of a fi­ brous network that strengthens the layers of the skin, enabling the growth of new cells.

Smooth, firm and youthful skin requires an opti­ mal level of well-organized collagen fibers that will ensure that the skin maintains its elasticity, firmness and ability to bind moisture. Research has shown that exogenous collagen can stimulate the synthe­ sis of new collagen fibers by stimulating fibroblasts.

Collagen loss occurs throughout the whole body.

The first signs of collagen loss are the appearance of fine lines and wrinkles, dry and sagging face and neck skin, thinner and more brittle hair and weaker nails. This should not be surprising, given that 75% of the skin's composition is made up of collagen and that with aging the production of collagen decreas­ es. It happens because the number and activity of the cells that produce collagen decrease, so the skin becomes thin and dehydrated.

In addition, the thickness of the skin is constantly decreasing - on average by 7% every 10 years. After menopause, the situation worsens drastically – in the first five years of menopause, as much as a third of collagen is lost from the skin. This is exactly why sup­ plementation is necessary to maintain the elasticity and health of the skin. After menopause, skin thick­ ness decreases by 1.13% per year, and skin elasticity by 0.55% per year. A decrease in skin collagen is also associated with a decrease in bone mineral density.

Use of collagen in cosmetic preparations

There is no outfit luxurious enough, nor a piece of jewelry extravagant enough to distract attention from the face. Well-nourished, healthy and glowing skin is still the best "decoration" that can be worn. We often hear from dermatologists, cosmetic surgeons and ot­ her beauty professionals that it is crucial to create a good "base" for a smooth, youthful and flawless com­ plexion and skin appearance. Experts believe that to create such a "base" it is necessary to use treatments for deep hydration of the skin, have a balanced diet and compensate for the necessary collagen3. Derma­ to­logists advise that after the age of 35, products containing collagen, i.e. products that stimulate its pro­duction, should be included in the beauty routi­ne.

When it comes to the application of collagen in cos­ ­metic preparations, we can find it in various cre­ams, serums and ampoules for application on the face.

Collagen is a very powerful ally in the fight against skin aging. It is also called "natural botox", because it

increases the elasticity of the skin and slows down its aging. In addition, it actively works to alleviate ex­ isting wrinkles and slows down the formation of new ones. Collagen creams usually contain a high concen­ tration of natural, active collagen of marine origin.

Today, there is more and more evidence that colla­ gen can be "returned" to the skin, or that its disap­ pearance and destruction can at least be slowed down, with a healthy diet (especially by consuming less sugar) and avoiding excessive exposure to the sun light. Skin care that protects collagen has a double effect: it protects the existing collagen in the skin and at the same time stimulates the production of additional collagen. Skin care creams fill the skin with peptides and can target certain signs of skin aging that are the result of collagen loss: wrinkles, skin la­ xity, loss of firmness and tone.

Although it is a powerful anti-aging ingredient, its local application can be difficult to transfer to the skin. Therefore, in addition to local therapy, it is ideal to use mesotherapy and microneedling to enable safe application in the right skin layer, where it will have maximum effectiveness. In order to be able to penetrate the skin, the collagen molecule must be extremely small, which is very difficult to achieve in preparations that are applied locally. However, the popularity of these products lies in the fact that the collagen and other proteins leave a film on the skin that fills in irregularities on the surface. When the product dries, the protein film tightens, causing a subtle tightening of wrinkles.

With regular use of face creams containing colla­ gen, the skin looks younger and fresher, and the depth and length of wrinkles are reduced. Thanks to their natural composition, such face creams are sui­ ta­ble for all skin types. They are especially recom­ mended for the care of dry and photodamaged skin.

If the cream with collagen additionally contains al­ mond oil, it will also additionally hydrate, care for and nourish the skin, making it soft and silky. The combi­ nation of collagen and almond oil is an excellent for­ mulation for skin care, as both ingredients im­prove its elasticity.

In addition to the previously described benefits of collagen in reducing wrinkles and skin dryness, it can also help with other skin problems. When the amount of collagen in the skin is sufficient, it is more resis­ tant to the influence of external factors. It also pro­ vides the skin with better regeneration and faster recovery after injuries.

In case the skin is damaged by acne, collagen is used for wound healing. It plays a key role in scarring, as the immune system uses it to close the wound and create "new" skin in that area.

Genetics is something that cannot be fought and it is largely responsible for whether someone is pro­ ne to cellulite. But collagen can help fight against its appearance on the skin. Namely, one of the conse­ quences of a decrease in collagen levels is thinning of the skin, and it is precisely this thinning that caus­ es cellulite and stretch marks to become more visi­ ble. By maintaining a high level of collagen (which gi­ ves the skin firmness and elasticity), the appearance or appearance of cellulite is less likely. Studies have shown that regular intake of dietary supplements with collagen improved the appearance of the skin of women with moderate cellulite.

47

Nutramedic &Cosmetics

Skin application of niacin and its action in skin detoxification Menthyl nicotinate is a lipophilic derivative of niacin, capable of significantly activating the microcirculation of the skin, without causing irritation or a sudden rush of heat known as “niacin flush”. It is also characterized by the delivery of high doses of niacin to the epidermis, very fast absorption and enabling prolonged release in the skin.

Tea Višek, Director, Cos Chem, Fraktal Beauty

A

s we age, our skin's natural barrier often times becomes damaged due to intrinsic and ext­ rinsic factors and does not provide the need­ ed protection to our skin. This is specialy true if we look at the skin of perimenopausal and menopausal women. Due to lower levels of estrogen in the body, intrinsic factors include loss of collagen production, thinner skin, dryness and dehydration, skin sensiti­ vity and in some cases even atopic skin and acne. Ad­ ditionaly, there are different extrinsic factors that influence the skin today – exposure to UV light, in­ door and outdoor air pollution. If we consider all these factors together, the amount of possible dam­ age to the skin, especially for that specific age group of women, is notable and cannot be underestimated.

Having in mind these influences, we have embar­ ked on the project to create the skin care product that will address some of these factors and try to re­ generate skin at the cellular level, so that the skin would get new life from within. This concept was ve­ ry important to us and after an extensive research into possible active ingredients and formulation fra­ meworks that could give that result, we have chosen menthyl nicotinate as the main active ingredient to deliver this task.

Menthyl nicotinate as an active ingredient in cosmetics

Findings of different studies on mechanisms of the skin responsible for defense against intrinsic and extrinsic damage were underlined by few stud­ ies (Ref. 1-3). Mentioned studies have evidenced the importance of niacin (nicotinic acid or vitamin B3), a precursor of the coenzyme NAD+ (nicotinamide ade­ nine dinucleotide). NAD+ plays a very important ro­le in skin's ability to respond to stressors and start re­ pairing DNA damage that UV light and air pollutants cause in the skin. Consequently, the deficiency of NAD+ can cause the inability of skin cells to regene­ rate from extrinsic factors and lead to oxidative stress, premature skin ageing, lipid peroxidation, skin irritation and with time to more serious skin cel­ lular damage.

48

Menthyl nicotinate is a lipophilic derivative of ni­ acin, capable of significantly activating the skin mi­ crocirculation, without causing an irritation or sud­ den flushes known as „niacin flush“.

Other interesting characteristics of menthyl nico­ tinate are that it is able to deliver high doses of nia­ cin in epidermis and that it absorbs rapidly into the skin, with prolonged release of niacin.

In-vitro absorption study of menthyl nicotinate

3000 μg of menthyl nicotinate was applied to a sample of RHE (in vitro reconstructed human epi­ dermis). In 30 minutes 53,8% menthyl nicotinate was absorbed into the stratum corneum. After 24 h from application nearly the whole dose (87,8%) of menth­ yl nicotinate is absorbed.

SKIN ABSORPTION OF MENTHYL NICOTINATE 3000

Menthyl nicotinate µg

AUTHOR:

2.437

2500 1.993

2000

78.2%

2.482 82.7%

2.558 85.3%

2.633 87.8%

66.4%

1.615 53.8%

1500 1000 0.605 500 0

20.2%

15 min

30 min

1h

2h

4h

8h

24 h

HPLC analysis was conducted subsequently to es­ tablish the release of niacin into the sample of RHE. Results showed that 254 μg of released niacin pene­ trated through the skin barrier (from the initial 1413 μg contained in the 3000 μg applied dose of menth­ yl nicotinate). The result is: menthyl nicotinate pro­ vides niacin absorption rate of approx. 18% of the applied dose in 24 hours.

Compared to the absorption rate of the common­ ly used niacinamide, which is only 2.2% in 24 hours; or to the absorption rate of pure niacin itself, which is less than 0.2% in 24 hours, menthyl nicotinate has shown significantly better results.*

Nutramedic &Cosmetics The GST activity was observed in skin explants when exposed to urban pollutants in repeated conditions.

200 150 150 100 100 50 50 0 0

Finished cosmetic formulation with 5% menthyl nicotinate – efficacy tests

Unexposed UV-A/UV-B Finished formulation chosen for delivery of men­ thyl nicotinate was a light fast absorbing oil, to en­ Unexposed Acute UV-A/UV-B hance the active ingredient delivery into the skin, whi­ le also leaving skin nurtured. Acute INCI of the finished cosmetics formulation that was tested for efficacy is: Caprylic/Capric Triglyceride, Propylheptyl Capry­ late, Undecane, Menthyl Nicotinate, Tridecane, Par­ fum, Tocopherol, Pentaerythrityl Tetra-di-t-butyl Hy­ ­­d­roxyhydrocinnamate, Benzyl Salicylate, Citronel­lol, Eugenol, Geraniol, Hydroxycitronellal, Linalool The dosage of menthyl nicotinate used in tested formulation is 5,0% (purity grade > 99.0 %).

Untreated Repeated Untreated Repeated

A/UV-B

Untreated Repeated

Untreated

Treated

Cigarette Repeated

Cigarette Repeated

Test 1. represents the values obtained for skin explants that were treated with the test item and were either left unexposed or exposed to UV-A/UV-B (Acute). The bar chart represents mean ± SEM. *represents p value <0.05, ** represents p <0.01, and *** represent p<0.001

0.01 0.01 0.00 0.00

Cigarette Repeated

Dust-Repeated

100 100 50 50 0

0.02 0.03

0.01 0.02

0.00 0.01

0.00 Untreated Repeated Untreated Repeated

Cigarette Dust-Repeated Repeated Cigarette Repeated

0.03 0.03

0.02 0.02

0.01 0.01

0.00 0.00

Treated Treated

150 150

** **

Total GST Activity (umol/mL/min) Total GST Activity (umol/mL/min)

200 200

Treated Treated

Concentration Concentration of MDA (ng/ml) of MDA (ng/ml)

250 250

** **

Untreated Untreated

0 Unexposed UV-A/UV-B Unexposed Untreated UV-A/UV-B Repeated Acute Acute

0.02

Dust-Repeated

Test 3. Human malondialdehyde Assay (MDA) 0.03 (Ex-vivo) **

0 Treated

50

0

Treated

100

50

Untreated

150

Test item Test item

0

100 200

Untreated Treated Untreated

0

**

Untreated

1

150 250

Test item Test item

1

of MDA (ng/ml)

2

200

Untreated Untreated

3

2

**

*

Untreated

Test item

UV-A/UV-B

Concentration of MDA (ng/ml) Concentration

Cell viability Cellreadings viability arbitrary units) (Absorbance (Absorbance readings arbitrary units)

Test item

Untreated

*

4 3

*

0.02

Cigarette Repeated

**

Test 1: MTT Cytotoxicity Assay (Ex-vivo) 250

**

0.03

Skin cell damage prevention efficacy of tested formulation, after repeated exposure to cigarette smoke, was tested with following results:

The ability of the skin cells to recover after an acute exposure to the UVA / UVB light was tested, with fol­ lowing results:

4

0.03

Test 2. represents the values obtained for skin explants that were treated with the test item and were exposed to the dif­ ferent environmental stressors (urban pollutants) - (Repeat­ ed). The bar chart represents mean ± SEM. * represents p value <0.05, ** represents p <0.01, and *** represent p<0.001

Efficacy test methods used and test results

*

Treated Treated

Test item Test item

Untreated Untreated

0

Test item Test item

Untreated Untreated

Source: *Cfr.: ABSORPTION OF SOME ORGANIC COMPOUNDS 2 1 THROUGH THE SKIN IN MAN - Robert J. Feldmann, Howard J. Mai­ bach. The Journal of Investigative Dermatology – © 1970 The Wil­ 1 liams & Wilkins Co. 0

Total Total GST Activity GST Activity (umol/mL/min) (umol/mL/min)

24 h

Untreated Untreated

8h

Treated

4h

Untreated Untreated

2h

Treated

1h

**

Treated Treated

330 min 2

250 200

Untreated

15 min

*

66 49

4 3

250

Untreated

20

106

4

**

Treated Treated

0

*

Total GST Activity (umol/mL/min) Untreated Untreated Total GST Activity (umol/mL/min)

50

149

**

Test 2. Glutathione S Transferase (GST) assay (Ex-vivo) Concentration Concentration of MDA of (ng/ml) MDA (ng/ml)

100

Cell viability Cell viability (Absorbance (Absorbance readings readings arbitrary arbitrary units)units)

Niacin µg

150

18% of applied dose

192

200

Untreated Untreated

250

Treated Treated

254

Untreated Untreated

NIACIN DELIVERED TO SKIN BY MENTHYL NICOTINATE 300

Dust-Repeated Dust-Repeated

Dust-Repeated

Test 3. The graphs above showed the concentration of MDA (ng/mL) observed in skin explants that were exposed to ciga­ rette smoke in repeated conditions. The bar chart represents mean ± SEM. * represents p value <0.05, ** represents p <0.01, and *** represent p<0.001

49

Nutramedic &Cosmetics

Global ™ Omega-3 Day Approximately 80% of people worldwide are not getting enough EPA and DHA omega-3s, and GOED would like to see that statistic improve.

Conclusion

Light oil formulation with 5,0% of menthyl nicoti­ nate has proven to have a significant efficacy in: 1. Recovery of skin cells after UVA / UVB damage by 104 %; 2. Recovery of skin cells after repeated exposure to urban pollutants by 61% 3. Prevention of skin cell damage after exposure to cigarette smoke by 39%.

Above mentioned efficacy results prove that this light oil formulation provides unique set of perfor­ mances that will enable, in particular to perimeno­ pausal and menopausal skin, to recover and regene­ rate from extrinsic factors of aging at a deep cellular level, thanks to successfully enhanced skin microcir­ culation and targeted prolonged niacin delive­ry.

References: 1

Benavente CA, Jacobson MK, Jacobson EL (2009) NAD in Skin: Therapeutic Approaches for Niacin. Current Pharmaceutcal Design 15(1):29-38

2

Jacobson EL, Hyuntae K, Moonsun K, Georg T. Wondrak GT, Jacobson MK (2005) Developing Topical Prodrugs for Skin Cancer Preventon Reprint from: Alberts David S, Hess Lisa M (Eds) Fundamentals of Cancer Preventon pp 139-160 © Springer-Verlag Berlin Heidelberg (2005)

3

Jacobson EL, Kim H, Kim M, Williams JD, Coyle DL et al (2007) A topical lipophilic niacin derivatve increases NAD, epidermal differentaton and barrier functon in photodamaged skin.

Experimental Dermatology 16(6):490-499

Cos Chem Ltd. Podgaj 2 10000 Zagreb, Croatia T. +385 1 467 33 47 / 48 / 49 M. +385 98 416 706 www.coschem.hr tea.visek@coschem.hr info@coschem.hr

50

E

very March 3rd, GOED rallies its members, communications partners and the public to shine a spotlight on EPA and DHA omega-3s, under-consumed nutrients that help support a healthy heart, brain, eyes and pregnancy.

The original International Omega-3 Awareness Day was established in 2010 by Dr. Carol Locke, founder of GOED member OmegaBrite, as a non-profit interna­ tional initiative to raise awareness of the science and benefits of omega-3 fatty acids. GOED is proud to continue the Global Omega-3 Day™ tradition with an ex­ panded goal, which is to raise awareness of the importance of omega-3s around the world through outreach to stakeholders including those in the omega-3 in­ dustry, consumers, key influencers and health professionals. With more than 180 GOED members representing companies throughout the EPA and DHA omega-3 supply chain, we now have many avenues to get the word out about the impor­ tance of EPA and DHA omega-3s.

Key Messages

• 80% of people worldwide are not getting enough EPA and DHA omega-3s (and in the US it's higher than 95%).

• When it comes to omega-3s, EPA and DHA are most important, not just for your heart or during pregnancy, but throughout your entire life.

• The best food source of EPA+DHA omega-3s are fatty/oily fish. You can also get these nutrients from an omega-3 supplement.

• Aim for at least 500mg EPA+DHA per day. Get this from eating fatty/oily fish, eating foods fortified with EPA/DHA, and by taking an omega-3 supplement.

• Pregnant and lactating women should get at least 700 mg per day of EPA+DHA, with at least 300 mg of that as DHA. There is no concern about the safety of EPA and DHA omega-3s. Both the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) recognize that long-term intake of 5g/day of EPA+DHA is safe.

“We’ve been working on growing Global Omega-3 Day with new activities each year, and for 2023 we feel we’ve truly gone global,” said Ellen Schutt, managing di­ rector of GOED. “It’s so important to reach consumers about the need to increase EPA and DHA omega-3 levels, and we’re hoping that the broader omega-3 indus­ try will help us spread this important message.”

For this year's Global Omega-3 Day, GOED prepared a toolkit for communica­ tion with consumers, organized retail activities in several grocery chains in the US, and media campaigns in Poland and Turkey aimed at consumers. Also current were special discounts on access to the GOED Clinical Studies Database and on the prices of the Ingredient Market Report and the Finished Product Report. www.goedomega3.com

Nutramedic &Cosmetics

NutraFood Poland:

the only B2B event in Poland dedicated to food supplements and functional food Thousands of visitors, more than a hundred manufacturers and distributors of nutritional supplements, pharmaceutical products and suppliers of raw materials and services, await you in Warsaw from April 18-20, 2023.

NutraFood Poland

NutraFood Poland is the only fair of nutritional supplements and functional food supplements in Poland. Visitors, who last year numbered more than 7,000 from a total of 25 countries, are presented with a large selection of novelties among nutritional sup­ plements, pharmaceutical products, functional food, nutraceuticals, equipment and services for industry as well as active ingredients and raw materials need­ ed in the production process.

NutraFood Poland is the main place for meeting, socializing and negotiating deals in the food supple­ ments industry in this part of Europe, and a platform that offers numerous presentations and content de­ dicated to trends, business and current legislation.

Exhibitors and visitors at NutraFood Poland come from various industry sectors: ingredients and raw materials, functional food and beverages, nutrition­ al supplements, nutraceuticals, equipment and ser­ vices, and contract manufacturing.

Participation in the fair will be especially interest­ ing for companies that want to bring their products from the field of nutritional supplements or func­ tional foods and beverages to the Polish market.

WorldFood Poland

The NutraFood Poland fair is part of WorldFood Poland - the largest B2B food industry fair in Poland.

The WorldFood Poland fair has an international cha­ racter and over the years has become the main event for all participants in the food industry. Today, it is a platform for business development in the food market, which offers the possibility of meeting and talking with existing and potential new partners, participat­ ing in panels and conferences, and a platform for mo­

nitoring new trends and discovering new products.

WorldFood Poland gives exhibitors the opportunity to arrange meetings in advance with key customers and other participants present at the fair, and gi­ves customers the opportunity to - by arranging meet­ ings in advance - they use their time effectively and get to know the offer of the selected exhibitors.

A survey conducted among last year's visitors show­ ed that 38% of them were interested in food sup­ plements and functional foods, and 56% in healthy products and products of organic origin. More than 82% of the respondents from the exhibiting compa­ nies rated the established business contacts as "sig­ nificant" for future business, and 88% of the partici­ pants would recommend participation in the fair to other companies.

Attractive Polish market

• Poland is the largest economy in the middle and east Europe and the 6th strongest market in the European Union.

• The population of Poland exceeds 38 million, mak­ ing it one of the largest Eastern European markets.

• Since joining the European Union in 2004, Poland has adopted many legislative reforms. The ease of doing business has improved significantly, accor­ ding to this criterion ranked 55th in the world. In the last two decade, Poland almost doubled its GDP. • Poland's positive attitude towards foreign direct investment makes the country an attractive busi­ ness environment.

• Poland has a favorable location and provides easy access to Southeastern Europe and the Baltic coun­tries.

More detailed information: www.nutrafood.pl

51

Nutramedic &Cosmetics

medicinal plants photo herbarium

Yarrow

Yarrow (Achillea millefolium L., Asteraceae) is one of the oldest medicinal plants known, and the main areas of its application are dyspeptic complaints and spasms in the stomach and digestive tract. Due to its anti-inflammatory, antimicrobial and antifungal effects, it was also used in folk medicine for wound healing.

Y

arrow (Achillea millefolium L.) is a perennial herb distributed in Europe, Asia and North Ame­­­rica. It was introduced to Australia and New Zealand a long time ago, so today it is conside­ red domesticated and invasive.

Yarrow is a perennial herbaceous plant from the Asteraceae family. The stem is upright, mostly simp­le, covered with woolly hairs, and grows up to 80 cm in height. The rhizome is horizontal, crawling. The lea­ ves are alternate, oblong-lanceolate, double or tri­ple pinnately divided into numerous fine small segments.

The flower heads are 3-5 mm in diameter, gathered in dense, paste-like inflorescences at the top of the stem. They are composed of tubular flowers in the middle and tongue-shaped white or pink flowers on the rim. The fruit is a pod about 2 mm long. 3 It grows wild all over Europe, usually in groups, on dry pastures, fields, meadows and as a weed in gar­ dens. It is propagated by seeds or by dividing the roots in spring or autumn. 3

u­sed for stomach problems, lack of appetite and dys­ pepsia.

The results of a study conducted on mice show the anti-ulcer potential of the aerial parts, which is not accompanied by signs of toxicity even with very long chronic exposure.6 Milefolli aetheroleum essential oil is dark blue in color due to its azulene content. It should not be used orally, because it is neurotoxic due to the thujone content, but it is used in cosmetics. Azulene is a high­ ly valued ingredient in suntan creams and oils. It also works well for inflammation of the mucous mem­ brane and skin.

Use for medicinal purposes

For medicinal purposes, the green parts of the plant Milefolli herba, harvested from VI-X months, or the flowers of the yarrow Milefolli flos are used. The dried flowers contain at least 0.02% of Milefolli aetheroleum essential oil. The stem has no medici­ nal properties, so it is unnecessary ballast.

The drug is obtained by drying the collected parts in a thin layer at a temperature of 35-40°C.

Ingredients

• essential oil in which: pinene, cineole, azulene, thu­ jone, borneol, caryophyllene prevail • formic acid • valeric acid • bitter substances: achillein • aconic acid • sesquiterpene lactones • tannins • flavonoids.

Use for medicinal purpose

Yarrow is used in folk medicine to treat skin in­ flammation, pain, wounds, bleeding and gastrointes­ tinal disturbances.

The bitter substance (achilein) acts as a tonic. It is

52

References: 1

Flora Croatica database, hirc.botanic.hr

2

Josip Gelenčir, Jasenka Gelenčir: Atlas ljekovitog bilja, izdavač: Prosvjeta Zagreb 1991.

3

Source: Stolisnik https://www.plantea.com.hr/stolisnik

4

SCHAFNER, Willi: Ljekovito bilje: kompendij, Izdavač:Leo-com­ merce, 1999.

5

Prof.dr.sc.Zdenka Kalođera, Sveučilište U Zagrebu, Farmaceuts­ ko-biokemijski fakultet, Farmakognozija II, Zagreb, 2006/2007.

6

Cavalcanti AM, Baggio CH, Freitas CS, Rieck L, de Sousa RS, Da Silva-Santos JE, Mesia-Vela S, Marques MC. Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic treatment in Wistar rats. J Ethnopharmacol. 2006 Sep 19;107(2):277-84. doi: 10.1016/j.jep.2006.03.011. Epub 2006 Mar 22.

PMID: 16647233.

TAXONOMY kingdom: Plantae order: Asterales

family: Asteraceae

genus: Achillea

species: Achillea

millefolium

common name

common yarrow, old man's pepper, devil's nettle, sanguinary, milfoil, soldier's woundwort, thousand seal flowering time

VI, VII, VIII, IX month

Nutramedic &Cosmetics

Pomegranate fruit extract linked to improved skin health

Natural ingredient Pomanox® can positively modulate skin health and beauty related parameters

A

ccording to a recent in-vitro study conducted

by EURECAT and published in the Internati­o­ nal Journal of Food Sciences1, Euromed's po­ megranate fruit extract Pomanox® may reduce un­ aesthetic signs of skin ageing such as hyperpigmen­ tation, skin dryness and loss of elasticity, by reduc­ ing melanogenesis and oxidative stress while modu­ lating collagen and hyaluronic acid metabolism. The results from this proof of concept, in-vitro assay with human foreskin fibroblast cells, therefore sug­ gest that Pomanox® is a promising ingredient for nu­ tricosmetic and beauty-from-within applications.

Skin photoageing is primarily caused by ultravio­ let radiation and can lead to the degradation of skin extracellular matrix components, resulting in hyper­ pigmentation and loss of skin elasticity. In this area, polyphenols have become of great interest because of their antioxidant, anti-inflammatory and healthy ageing properties.

Pomanox®P30 is standardised to more than 50% total polyphenols and not less than 30% punica­la­ gins α+β, making it an ideal candidate for skin ageing studies. Multiple assays evaluated the effects of va­ rious concentrations of Pomanox® on human fibro­ blast Hs68 cells under normal and UV-induced pho­ toageing conditions. The inhibitory effects of Poma­ nox® on tyrosinase activity were also investigated.

Analysis showed that under normal conditions, Po­manox® significantly increased the collagen and hyaluronic acid metabolism. In cells exposed to UV, both preventive and regenerative treatments with Pomanox® positively influenced hyaluronic acid me­ tabolism and decreased ROS (Reactive Oxygen Spe­ cies) levels. A significant decrease in levels of MMP1, the main inhibitor of collagen synthesis, was also verified. Finally, Pomanox® showed a significant in­ hibitory effect on tyrosinase activity, thus potential­ ly reducing hyperpigmentation by decreasing mela­ nin synthesis.

In summary, the results highlight strong proper­ ties of Pomanox® in the modulation of several skin health-associated parameters. A clinical study is now being prepared to further investigate and explore these insights.

Pomanox® is a standardised pomegranate fruit ex­ tract obtained from pomegranates cultivated in Me­ diterranean regions of Spain through sustainable far­ming. It is available in organic form and extracted with an eco-friendly, water-only proprietary techno­

logy. Beyond skin health, Pomanox® is also known to provide proven benefits for cardiovascular and meta­ bolic health, sports nutrition, mood and cognitive health.

Reference: 1

Roger Mariné-Casadó et al. (2022); Pomegranate natural extract Pomanox® positively modulates skin health-related parameters in normal and UV-induced photoaging conditions in Hs68 human fi­ broblast cells Foods; https://doi.org/10.1080/09637486.2022.2152189

Founded in 1971 by the German pharmaceutical company Madaus, Euromed S.A. is a vertically integrated leading producer of standardised botanical extracts and natural active substances for the pharmaceutical, nutraceutical, food and cosmetic industries to support health and well-being with plant-based solutions.

All extracts comply with worldwide GMP norms, international pharmaco­ poeias and regulations. EUROMED has a long history of expertise in research and development, laboratory analyses and extraction technolo­ gies, and is committed to the highest quality standards in terms of analytics, chemistry and evidence-based therapeutics. www.euromedgroup.com

53

Nutramedic &Cosmetics

Bioline a solution for your needs

A company committed to customers' needs and timely service

B

ioline is an independent company specializing in providing a variety of pharmaceutical ser­ vices. Through its representative office, it pro­ vides the opportunity to cooperate with a number of selected internationally renowned pharmaceutical companies and manufacturers of medicines, medici­ nal products, food supplements, cosmetics and food.

We have been a reliable partner for your projects for 23 years. We realize finished products professi­o­ nally and on time. Our professionalism has been re­ cog­nized by many clients in the region.

Our advantages: ✓✓Speed of product placement – we have a ready range of products ready for placement; ✓✓Innovation laboratory - "out of the box" ideas; ✓✓Superior taste masking, excellent texture, color, qua­ lity and stability (stability studies by arrangement); ✓✓Development of new product formulations in ac­ cordance with market needs, with "added value" that separates you from the competition; ✓✓Careful approach that adapts to your needs, pro­ fessional and timely service, quick reactions to all your inquiries and short deadlines for implemen­ tation.

We provide various potential projects and various pharmaceutical forms - tablets, capsules, sticks, sticks for dissolving in the mouth (direct), soft gelatin cap­ sules, sachets with powder for dissolving in water.

We cover numerous markets throughout the re­ gion: Slovenia, Croatia, Bosnia and Herzegovina, Ser­ bia, Kosovo, North Macedonia and Montenegro, which we connect with service providers in Portugal, Italy, Poland and Spain, selected with care and emphasis on quality, innovation, flexibility and speed of delive­ ry of desired products.

We give added value to all projects in the form of proposals for new product concepts, thanks to our many years of experience on the international mar­ ket. So far, we have participated in the successful im­ plementation of more than 50 projects, and the ser­ vices we offer our partners provide the opportunity to always find the most suitable solution.

Bioline Prečna Street 6 Ljubljana, Slovenia Cell. +386 41 663 347 e-mail: plus.bioline@siol.net

54

Food supplements: • Products based on granules: effervescent tablets, water-soluble granules, granules directly dissolving in the mouth without water • Tablets, chewable tablets, fast-dissolving tablets, sublingual tablets, effervescent tablets, coated tablets • Hard gelatine\vegetarian capsules • Powders • Sprays • Drops • Twist off soft gelatin capsules • Soft Gelatin Capsules • Packaging: sachets, blisters, glass bottles for tablets, tubes, secondary packaging in boxes.

Medicines: • Capsules • Effervescent granules, granules • Tablets, film-coated tablets • Powder

Medicinal products for oral use: • Soft Gelatin Capsules • Spray • Syrups • Drops

Cosmetics, biocides, medicinal products: • Liquids, gels, creams, ointments, pastes, wipes • Shower gel, baths, srubs, liquid soaps, intimate care soaps • Creams, milks and oils for the body • Creams, serums, lotions, tonics, micellar face water • Toothpastes and tooth gels • Mouthwash • Wipes • Sun protection products • Perfumes, scented waters, aftershave lotions, deodorant sticks, deodorant sprays • Natural and BIO products for disinfection

In Croatian pharmacies since 2009

www.inpharma.hr 55