B2B Nutramedic&Cosmetics No.2

Dear business partners and colleagues, the second edition of the B2B Nutramedic&Cosmetics digital magazine is in front of you. In this issue, we covered several topics related to health problems - thyroid health and urinary tract infections - and made an overview of ingredients that could alleviate them. We also bring a text about ashwagandha - a plant that is conquering the world market. We present the company Fine foods, a contract manufacturer that you will get to know in more detail in the following editions of the magazine. We will introduce you to the peculiarities of hyaluronic acid produced by the ROELMI HPC company, and bring new information about Hytolive olive extract and its impact on long-term COVID syndrome. We also bring a report from the Fi Europe, where we presented our magazine for the first time.

In the new year 2023, we wish you good health and new projects, and we invite you to join our digital magazine - by reading, participating or sharing with those you think will be useful.

Until the new edition, Daria Šurić, M. pharm.

Nutramedic &Cosmetics B2B

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

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

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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 download any part of the content without the prior consent of the publisher.

Rising star: ashwagandha's market potential

Although one of the most famous Ayurvedic plants, ashwagandha has only recently become known on the world stage, primarily due to the increase in the number of tests in the field of its action and pharmacology.

AUTHOR: Kristina Harča, M.pharm.

Ashwagandha (Withaniasomnifera(L.) Dunal) is a small woody shrub of the Solonaceae family, which takes approximately 7 months to reach full harvesting potential. It thrives on dry soil resistant to drought conditions, such as can be found in the plant's native habitat in India. It can also be found in some parts of Asia, Africa and the Mediterranean.

Ashwagandha is a plant that has been used in traditional Indian medicine, Ayurveda, for thousands of years. Although it is one of the most famous Ayurvedic plants, it has only recently become known on the world stage, primarily due to the increase in the number of tests in the field of its action and pharmacology.

Ashwagandha promotes balance in the body, because as an adaptogenic plant it helps it to successfully adapt to stressful environmental influences. It is one

of the few plants that has a significant positive effect on both the psychological and physiological aspects of the human organism. It is known for its beneficial effect on stress and anxiety, and for lowering cortisol levels. A growing number of studies point to the effectiveness of ashwagandha in improving the duration and quality of sleep in people with insomnia, and it is becoming increasingly popular among athletes. Because of ashwagandha's positive effect on immunity, the post-COVID environment has also influenced its increasing use.

There are various forms of preparations on the market that contain ashwagandha. It is primarily used to improve mental health and secondarily for cognitive health. Most of the studies were done on the topic of anxiety and infertility.

The European ashwagandha market

In 2021, the entire food supplement market, including food supplements containing ashwagandha, was on the rise. This especially applies to nutritional supplements in the segment of immunity and quality sleep. Ashwagandha is recognized as a plant that contributes to these and other positive effects on health.

During that year, a large number of products on the market contained ashwagandha in powdered root form. Such a powder form can be mixed with liquids such as water, juice or milk. Ashwagandha powder has excellent solubility in water and other liquids and is very easy to take.

In 2022, the European ashwagandha market is dominated by products containing its root. Thousands of years of traditional practice, bolstered by numerous modern independent clinical trials, confirms only the root of ashwagandha as the optimal choice for adaptogenic and rejuvenation benefits. The Government of India has strictly advised to refrain from using ashwagandha leaves, citing unavailability of substantial safety and efficacy data on the leaves.

Only ashwagandha roots are the standard in global pharmacopeias, including the Indian, British, and United States Pharmacopeias as well as various globally-accredited monographs, including the World Health Organization (WHO) and Health Canada. Also, in modern research the predominant majority (125 of 126) of independent published clinical trials today use only root-based formulations.

As for the withanolide content, there are products on the European market with a withanolide content of 1% to 10%, and most often with 5%, which ensures the effectiveness and optimal medicinal effect of the ashwagandha extract.

In terms of indications, the European ashwagandha market is segmented so that it is mostly consumed for improving libido, immunity, for general health, reduction of anxiety and stress, cognitive health and improvement of sports performance. It is predicted that the reduction of stress impact and anxiety will become the most prevalent indication for the use of ashwagandha.

Regarding product categories, ashwagandha is found in foods and beverages, dietary supplements, and sports supplements. Dietary supplements predominate.1 Talking about pharmaceutical forms, it is most often found in the form of powder, capsules or liquid products.

In terms of the size of the ashwagandha market, Germany dominates in Europe, and the United Kingdom also plays a significant role.

Mode of action

Ashwagandha is a plant that has been traditionally used for an impressive number of health indications, and modern studies attribute an increasing number of proven health effects to it (Figure 1). The reason for this is complex chemistry and a large number of active substances. Ashwagandha contains alkaloids, flavonoids, glucosides, steroids and steroid lactones. Withanolides belong to the steroidal lactones, which are believed to be responsible for most of the positive effects. 2

Most of ashwagandha's beneficial effects come from its powerful antioxidant and anti­inflammatory properties. It can increase the amount of antioxi-

dant enzymes such as glutathione peroxidase and superoxide dismutase, while simultaneously inhibiting lipid peroxidation. The ability of this plant to relieve stress and anxiety is attributed to the fact that it affects the hypothalamus­pituitary­adrenal gland axis, and has been proven to lower cortisol levels. Stress can be described as the sum of "non-specific reactions of the organism to any stimuli". Stress is a process that affects all organs and tissues, and causes highly integrated responses and reactions. However, the first systems that are affected and changed by stress are the neuroendocrine, cardiovascular, gastrointestinal and immune systems. These systems first show functional changes that can lead to better adaptation, or to wrong adaptation, i.e. maladaptation and disease. Numerous neurotransmitters also participate in the complex response of

18:2, 183-226, DOI: 10.1080/ 19390211.2020.1741484

FIGURE 1 Action of ashwagandha (Withania somnifera (L.) Dunal)

Taken from: Deepa S. Mandlik (Ingawale) & Ajay G. Namdeo (2021) Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects, Journal of Dietary Supplements,

the organism to stressors - both in signal transmission in the central and peripheral nervous system and as a link between the nervous and endocrine systems at the level of the hypothalamus, as well as by direct action on executive structures. 3 Furthermore, ashwagandha affects the signal transmission of several neurotransmitters which are dysfunctional in anxiety disorders. Its ability to enhance GABAA receptor signaling is thought to be responsible for its beneficial effects on sleep.

Ashwagandha may improve endurance in athletes by increasing hemoglobin levels,4 but further studies are needed in this area.

Its ability to positively affect reproductive health is attributed to its antioxidant activity and ability to raise testosterone levels.5

The influence of ashwagandha on the thyroid gland

Ashwagandha has a significant effect on the thyroid gland. Studies have shown that it can have an impact on improving the balance of thyroid hormone

secretion. A clinical double-blind, randomized, placebocontrolled trial concluded that subjects with subclinical hypothyroidism who received 600 mg of a 100% aqueous extract (5% withanolide) of ashwagandha root per day for 8 weeks showed a reduction in serum TSH levels compared to placebo, and an increase in serum levels of hormones T3 41% and T4 20%. 50 subjects with elevated thyrotropin (TSH) (4.5-10 μIU/L) between the ages of 18 and 50 took part in the study.6

In another randomized, double-blind, placebo-controlled study, the cognitive abilities of 60 people with bipolar disorder were monitored while taking 500 mg of ashwagandha extract. During the 8-week study, the effect of ashwagandha extract on thyroid hormone levels was also monitored, although this was not the primary aim of the study. Changes in the results of thyroid hormone levels were found in 10 people and are in accordance with the previously mentioned study. In several participants, the level of the hormone TSH decreased at the end of the study, while an increase in the level of the hormone T4 was observed in several participants. These preliminary re-

ID NO. EFSA WORDING CONDITIONS

13-1 ID 3251 Ashwagandha has adaptogenic properties

13-1 ID 4507 Protect tissue from injuries / Protect the general health by antioxidant activity.

13-1 ID 3657 Helps to maintain physical and mental capacities in cases of weakness, exhaustion, tiredness, and loss of concentration / Nerve tonic

13-1 ID 4194 Improves the body's resistance to stress / Helps the body to deal with stress / Helps maintain mental balance / Supports mental function in the elderly / Supports the onset of sleep / Supports learning, memory and recall / Helps you recover from stressful events / Helps maintain emotional stability

13-1 ID 2183 Anti­inflammatory

13-1 ID 2183 Supports in periods of mental and nervous tension and of anxiousness / Contributes to optimal relaxation / Helps to support relaxation, mental and physical wellbeing/contributes to emotional balance and general wellbeing

13-1 ID 2503 Beneficially affects the heart and cardiovascular system

13-1 ID 4197 Has a general rejuvenating effect

13-1 ID 4195 Helps maintain energy levels / Helps you gain weight and muscle mass / Helps build muscle / Energy tonic / Invigoration of the body / Helps to maintain optimal stamina, feelings of energy and vitality, physical and mental well-being / Helps to support the body´s vitality / Contributes to the body's resistance to stress / Helps to make you feel more energetic

13-1 ID 4196 Supports the health of the female reproductive organs / Helps maintain strength in pregnancy / Supports male sexual function / Helps maintain sperm mobility and sperm count.

13-1 ID 4198 Helps maintain the health of the respiratory system

13-1 ID 4199 Helps maintain the health of the skin.

Adults: 300-1000 mg of Ashwagandha root once or twice per day at meal times.

Root/ 3-6 g dry powdered root/day

Root 0.5-3 g/day

Root Powder: 2.0-0.1 g/day; as aqueous extract 1.0-0.05 g/day

Root / 0.5-3 g/day

Root / The equivalent of 3-6 g of powder root per day

Root: 60 mg / Used as part of a multibotanical combination

Root / Powder: 2.0-0.1 g/day; as aqueous extract 1.0-0.05 g/day (Not allowed in Belgium)

Root Powder: 2.0-0.1 g/day; as aqueous extract 1.0-0.05 g/day. Root 0.5-3 g/day

Root / Powder: 2.0-0.1 g/day; as aqueous extract 1.0-0.05 g/day

Root / Powder: 2.0-0.1 g/day; as aqueous extract 1.0-0.05 g/day

Root / Powder: 2.0-0.1 g/day; as aqueous extract 1.0-0.05 g/day

TABLE 1 Decision of the legislative text Health claim which may continue to be used pending a decision by the European Commission

sults point to the need for further tests.7

One of the modes of action in which ashwagandha can increase thyroid hormone levels is through its effect on lowering cortisol levels. As an adaptogenic plant, it stimulates the endocrine system so that the body can better withstand chronic stress, which has a favorable effect on balancing the secretion of thyroid hormones. Through the mentioned mechanisms, it is possible to improve the symptoms that occur with hypothyroidism - depression, fatigue, muscle weakness, memory problems and elevated cholesterol levels. It has been shown to reduce cortisol levels by 14.5-27.9% in healthy people under increased stress conditions, which is a significantly greater effect than has been observed with other dietary supplement ingredients.

Three studies provided significant evidence on the subject. In a randomized, double-blind, placebo-controlled trial, 60 adults with mild anxiety received 240 mg of ashwagandha extract with 35% withanolide glycosides for 60 days. The results, including the reduced cortisol level, indicate that the effect of ashwagandha on reducing the body's harmful response to stress can be achieved through the hypothalamus-pituitary-adrenal gland axis.8 This may be related to the fact that the activity of this axis decreases, i.e. it becomes less reactive to stressors. Additionally, although not considered in that study, another potential mechanism of ashwagandha's anxiolytic action could be its anti­inflammatory and antioxidant effects. Inflammatory processes and oxidative stress are increased during periods of high stress, and higher levels of inflammatory processes and oxidative stress have been observed in adults with depression and anxiety.

It is important to note that additional studies on a larger number of subjects are needed to determine the effectiveness of ashwagandha in the treatment of hypothyroidism.

Recommended dosage

The amount of ashwagandha root extract used in trials ranges from 250-600 mg per day. The most common dosing protocol in studies is 600 mg per day, divided into two doses, morning and evening.

Product formulation

Although ashwagandha is becoming more recognizable and popular in the nutritional supplement market, it is extremely important to choose proven quality and standardized extract and a reliable supplier. The ideal choice is an extract that has proven effectiveness in clinical studies. In addition to the quality of the extract itself, in terms of the content of pesticides, solvent residues and the declared content of the active substance, the content of potentially toxic withanolide A, which is naturally found in the root and needs to be removed, is also important. It is found in small amounts in the roots, but in case of long-term consumption it can be harmful. Therefore, it is safest to remove it from the extract.

Ashwagandha food supplement can be on the market as a monocomponent product that contains only ashwagandha extract or as a product intended for a specific indication that also contains additional active ingredients.

Choosing a reliable ashwagandha manufacturer is of great importance. One of the world's most famo-

us manufacturers is Ixoreal Biomed, which produces the branded KSM­66 ashwagandha root extract. This extract has a high concentration and a full spectrum of active substances. The product has been in development for 14 years, and Ixoreal is the industry leader in clinical studies on ashwagandha. KSM­66 extract has been tested in 24 published clinical studies. Today, KSM­66 ashwagandha can be found in thousands of products in more than 40 countries.

Ixoreal Biomed also made a study in which the safety of consuming ashwagandha root in healthy people is investigated. In this randomized, double-blind, placebo-controlled study, 80 healthy participants received 300 mg of KSM­66 extract or placebo twice daily for 8 weeks. The results of the study showed that taking ashwagandha root extract was safe for both women and men during the 8-week study period. Despite this, the conclusion is that it is necessary to conduct more tests with different daily doses and duration of intake.11

Ashwagandha extract KSM­66 is one of the easier to formulate finished products. According to the experiences of manufacturers of finished products, there are no bitter notes or other organoleptic or stability limitations, and the active amount of the extract is not big. It is particularly easy to formulate in powder and capsules. It is also applicable for tablets and soft gelatin capsules, although it is mostly used as a powder or in hard capsules. Recently, it is increasingly found in functional foods and hot and cold drinks.

Regulatory frameworks in the EU

According to current regulations in the EU, ashwagandha can be registered as a dietary supplement with certain differences in individual member countries, depending on national regulations. In Croatia, for products with ashwagandha that belong to the food category (dietary supplements), it is necessary to submit prescribed documentation to the Ministry of Health, and to obtain a decision related to the individual finished product. This procedure is common for substances/extracts that are not included in Annex II of the Ordinance on substances that can be added to food and used in food production and for substances whose use in food is prohibited or restricted (Official Gazette No. 160/13).

In Serbia, ashwagandha is not on the official list of prohibited substances, which means that with the prescribed documentation, you should be able to get a decision to put it on the market.

In Belgium, for example, ashwagandha is on the positive list, it is necessary to prove that it is safe for use. This procedure is based on the BELFRIT list, a project of the Belgian, French and Italian legislatures that should facilitate legislative harmonization.9

Germany is the leading country in Europe when it comes to plant extracts. Ashwagandha is allowed for use in it, but dietary supplements containing plant extracts are evaluated individually. Ashwagandha is on the list of herbal substances that can be used in food and medicine.

In Lithuania and Turkey, ashwagandha is on the prohibited list for consumption in food.

In Poland, the following conditions have been established for the use of Withania somnifera (L.) Dunal in food supplements (Resolution No. 7/2020):

1. Withania somnifera (L.) Dunal root powder can be used in amounts less than 3 g per day;

2. the highest content of withanolides in the recommended daily intake of the product must not exceed 10 mg;

3. the entity that places a certain food on the market is obliged to attach a quantitative specification confirming the withanolide content per the recommended daily dose of the product.

Also, on the label of food supplements containing ashwagandha, it is recommended to put a warning: "The product must not be consumed simultaneously with sedatives, hypnotics, antiepileptics" and "Do not use in children, pregnant and lactating women".10

Certain on-hold claims can be used on the declaration of food supplements in the EU, if the legislation of a particular member state allows it (Table 1).

Conclusion

Ashwagandha is an interesting herbal ingredient and a "rising star" among dietary supplement ingredients. Since its popularity is growing, it is predicted that an increasing number of finished products on the European market will contain its extract. In order for the use of ashwagandha in the food supplement market to realize its full potential, it is necessary to expand the scope of research and work on professional education about this plant.

References:

1 Europe Ashwagandha Market Report – Industry Trends and Forecast to 2029 | Data Bridge Market Research

2 Paul, Subhabrata et al. “Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects.” Biomedicine & pharmacotherapy = Biomedicine & pharmacotherapie vol. 143 (2021): 112175. doi:10.1016/j.biopha.2021.112175

3 Pivac, N. (2008) Os hipotalamus­hipofiza­nadbubrežna žlijezda i stres. U: Krznarić­Vohalski, G. (ur.) Psihoneuroimunologijapovezanost imunosustava sa živčanim i endokrinim sustavom. Zagreb, Školska knjiga d.d., str. 19-51.

4 Diego A Bonilla, Yurany Moreno, Camila Gho, Jorge L Petro, Adrián Odriozola­Martínez, Richard B Kreider Effects of Ashwagandha (Withania somnifera) on Physical Performance: Systematic Review and Bayesian Meta­AnalysisJ Funct Morphol Kinesiol. (2021 Feb 11)

5 Ramin Nasimi Doost Azgomi, Afshar Zomorrodi, Hossein Nazemyieh, Seyed Mohammad Bagher Fazljou, Homayoun Sadeghi Bazargani, Fatemeh Nejatbakhsh, Arezoo Moini Jazani, Yadollah Ahmadi AsrBadr ­ Effects of Withania somnifera on Reproductive System: A Systematic Review of the Available EvidenceBiomed Res Int.(2018 Jan 24)

6 Sharma AK, Basu I, Singh S. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. J Altern Complement Med. 2018 Mar;24(3):243-248. doi: 10.1089/acm.2017.0183. Epub 2017 Aug 22. PMID: 28829155.

7. Gannon, Jessica M et al. “Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder.” Journal of Ayurveda and integrative medicine vol. 5,4 (2014): 241-5. doi:10.4103/0975-9476.146566

8 Lopresti, Adrian L et al. “An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.” Medicine vol. 98,37 (2019): e17186. doi:10.1097/ MD.0000000000017186

9 https://www.feierboristi.org/fei/wp-content/uploads/DM-27.3.14Allegato-1-bis-Lista-BELFRIT.pdf

10 https://gis.gov.pl/wp-content/uploads/2020/03/Uchwa%c5%82anr-7-2020-Withania-somnifera-L.-Dunal.pdf

11 Verma, Narsing et al. “Safety of Ashwagandha Root Extract: A Randomized, Placebo-Controlled, study in Healthy Volunteers.” Complementary therapies in medicine vol. 57 (2021): 102642. doi: 10.1016/j.ctim.2020.102642

AstaZine® astaxanthin improves visual function

BGG World announces the results of a randomized, double-blind, placebo-controlled parallel study in humans.

BGG World (BGG) announced the publication of a peer­reviewed human clinical trial demonstrating AstaZine® natural astaxanthin’s ability to improve visual function in healthy adults.1

The study enrolled 60 subjects working on visual display terminals (VDT) and ingesting 9 mg per day of AstaZine® natural astaxanthin or placebo over six weeks.

In subjects over 40 years of age, visual acuity of the dominant eye after VDT work demonstrated a stronger protective effect in the astaxanthin group versus the placebo group, suggesting that astaxanthin reduces oxidative stress caused by visual display terminal work.

“This is the second publication for visual health which used AstaZine®, said Yanmei Li, PhD, BGG’s Global Chief Scientific Officer. “As we age, doctors believe that key muscles in our eyes lose strength which, in turn, leads to a reduction in our ability to see detail. This is particularly pronounced in people overusing computers and smartphones. Fortunately, supplementing with AstaZine® is an effective way to combat this condition that affects so many of us in today’s world.”

AstaZine® is natural astaxanthin, a naturally occurring carotenoid extracted from Haematococcus pluvialis . Research has shown ten distinct health benefits in over 100 clinical trials for algae­based astaxanthin. Health benefits include eye & brain health; skin health & “beauty from within;” immune system modulation; cardiovascular support; anti-aging properties; and support for athletes and active people.

References:

1 Sekikawa, T., Kizawa, Y., Li, Y., Miura, N. “Effects of diet containing astaxanthin on visual function in healthy individuals: a randomized, double-blind, placebo-controlled parallel study.” Journal of Clinical Biochemistry and Nutrition; 18 October 2022:1-8.

LC-MS in quality control analysis

AUTHORS:

Dinko Šoić, MPharm

Prof. Olga Gornik

Kljaić, PhD

Department of Biochemistry and Molecular Biology

Faculty of Pharmacy and Biochemistry University of Zagreb

Nowadays, rigorous quality control has become a standard almost in every industry, guaranteeing the legitimacy, safety and quality of the product. In depth characterization of complete composition together with detailed information on every ingredient are required by both consumers and regulatory authorities. With ever-increasing demand for proclaimed health and appearance benefits, it’s no wonder that producers of dietary supplements and cosmetics lead the way, with their quality controls more and more resembling pharmaceutical ones.1,2

To ensure overall quality of the product and consistency between batches, emphasis is progressively placed on available analytical techniques for identification and characterization of chemical compounds. Innovative and validated analytical methods

are needed not only for determination and quantification of active ingredients and excipients and their quality evaluation, but also for adulteration detection. What’s more, both food supplement as well as cosmetic industries are in need for reliable, robust and repeatable analytical methods that would facilitate evaluation of a large number of samples in a quick manner. Regarding all things mentioned, it is hardly surprising that LC-MS technique is becoming more and more widespread in many quality control analyses. 2-6 Workflow of typical LC­MS analysis can be seen in Figure 1.

Liquid chromatography coupled to mass spectrometry (LC-MS) is a powerful analytical technique widely used to identify and quantify the chemical composition of complex mixtures. LC-MS involves the separation of the components of a sample using liq-

FIGURE 1 Typical workflow of LC­MS analysis. Sample preparation and data analysis are also essential steps of the analysis.

uid chromatography, followed by detection of the individual components using mass spectrometry. Liquid chromatography separates different components of a sample using liquid mobile phases by passing it through a column filled with a stationary phase material, commonly modified silica gel. Different components of the sample move through the column at different rates, based on their size, charge and other physio-chemical properties, allowing them to be separated from one another. Once the compounds have been separated, they are ionized and introduced into a mass spectrometer which measures their mass-to-charge ratios. The resulting mass spectra can be used to identify the components of the sample, as well as to determine their relative concentrations which could then be used for their quantification.7-9

LC-MS has several advantages over other analytical techniques, making it well-suited for the analysis of food supplements and cosmetics. Firstly, it offers high sensitivity allowing for detection and quantification even of trace components. This is of utmost importance in quality control analyses, as many of the products contain a wide range of ingredients at varying concentrations, with presence of certain compounds indicative of the quality or purity of the product. LC-MS analysis is also highly selective, meaning that it can differentiate between different compounds even if they have the same chromatographic retention time and are present at similar concentrations. This can be useful in the analysis of complex mixtures containing multiple ingredients or contaminants. In contrast, UV/Vis or fluorescence detectors rely on the retention time of a compound to identify it, which is far less specific. Moreover, LC­MS analysis offers high accuracy and precision. When performed properly, this technique can provide reliable and reproducible results that can be used to make decisions about the quality and safety of the product. 3,7,8,10-12

In the dietary supplement and cosmetics industry, it is essential to ensure that products are free of any contaminants that could potentially cause adverse effects in consumers. LC­MS analysis facilitates accurate measuring of each individual ingredient, ensuring that the product meets label claims and regulatory standards. This technique is particularly useful for detecting impurities or adulterants that may be present in the sample, allowing manufacturers to ensure that their products are free from harmful substances. Namely, mass spectrometer provides detailed information about the molecular weight and structure of a compound, which can be used to identify it with high accuracy. By analyzing fragmentation MS spectra of the unknown compound, experienced analyst can indisputably determine the exact chemical structure in question, ensuring the product safety. Because of superb sensitivity that this type of analysis offers, all this can be done even in trace amounts of contaminants present.7,8,10,13-15

Another important use of LC-MS is to monitor the stability of products over time. Many products are sensitive to environmental factors such as temperature and light, which can cause their degradation. This can not only cause diminished product efficacy but can also possibly threaten its safety. LC-MS enables the manufacturers to track the stability of

their products throughout the manufacturing process and during storage, making this technique an indispensable tool for ensuring the quality and safety of food supplement and cosmetic products.7,8,15,16

Ability to identify and quantify a wide range of compounds, along with its high sensitivity and precision, make LC-MS well-suited for a broad-spectrum of different analysis.8 Nevertheless, huge complexity and the need for specialized equipment make experienced personnel an inevitable key factor for successful interpretation of the obtained results.

Analysts at the Department of Biochemistry and Molecular Biology of the University of Zagreb Faculty of Pharmacy and Biochemistry possess knowledge, skills and equipment to perform demanding LC-MS tasks, and are looking forward to new collaborations.

Practical examples

Several studies have demonstrated the usefulness of LC-MS in the analysis of food supplements and cosmetics.

Vitamins - It is known that UV detection is often not selective enough for simultaneous analysis of different analytes which exhibit weak and non­specific absorbances. That is also the case for certain vitamins, so this kind of complex samples require tedious sample preparation for analysis.17-18 In contrast, LC-MS provides high sensitivity and selectivity which can be utilized for simultaneous determination of vitamins with minimum sample preparation, enhancing the throughput of the analysis.19 One study applied newly developed LC-MS/MS method to identify water-soluble vitamins in commercial beverages and dietary supplements. By comparing results with the label values and traditionally used techniques, the study concluded that the method could successfully be used for quality control and to compose nutrition labels.17

Cannabinoids - In another study, authors developed a novel LC–MS/MS method for the simultaneous determination and quantification of 13 natural and 117 synthetic cannabinoids present in the form of oil in dietary supplements. Despite the large number of analytes, the analysis was carried out in a single 13-

min chromatographic run, showcasing the power and convenience of this type of analysis.16

Mycotoxins - Moreover, LC-MS can also be used for analysis of mycotoxins present in plant extracts, as evidenced in a study that developed and evaluated a method for quantification of 34 mycotoxins in dietary supplements containing green coffee bean extracts. 20

Preservatives - In order to protect cosmetic products that contain water against the microorganism growth, preservatives are often added at relatively low levels. They are not only preventing undesirable chemical changes, but also extending the shelf life of the product. The determination of preservatives is of utmost importance for quality control and prevention of allergic reactions and other health issues. Most methods previously published were able to determine only single class of preservatives in pharmaceutical or personal products. Recently, LC-MS method for simultaneous measurement of multiple preservatives was developed. A short chromatographic run can successfully quantitate preservatives such as different parabens, triclosan, DL­α-tocopherol acetate, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in cosmetics and personal care products. 21

Hormones - LC-MS is also used for quantitative analysis of hormones in cosmetics. 22 A reliable LCMS/MS method for the simultaneous determination of 7 female sex hormones (estriol, estradiol, estrone, ethinyloestradiol, dienestrol, hexestrol, diethylstilbestrol) in essential oil was developed in one study. 23 Another study fruitfully developed simultaneous detection method based on LC-MS/MS for determination of 43 prohibited glucocorticoids (such as beclomethasone, betamethasone, dexamethasone, budesonide, hydrocortisone, prednisolone, etc.) in cosmetic products. 24

References:

1 Durazzo A, Sorkin BC, Lucarini M, Gusev PA, Kuszak AJ, Crawford C, et al. Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives. Front Pharmacol [Internet]. 2022 [cited 2022 Dec 14];12. Available from: https://www.frontiersin.org/articles/10.3389/ fphar.2021.714434

2 Donno D, Mellano MG, Gamba G, Riondato I, Beccaro GL. Analytical Strategies for Fingerprinting of Antioxidants, Nutritional Substances, and Bioactive Compounds in Foodstuffs Based on High Performance Liquid Chromatography–Mass Spectrometry: An Overview. Foods. 2020 Dec;9(12):1734.

3 Breemen RB van. Role of mass spectrometry in establishing safety and efficacy of botanical dietary supplements. Clin Mass Spectrom. 2020 Jan;15:25.

4 Hu L, Jhoo JW, Ang CYW, Dinovi M, Mattia A. Determination of Six Kavalactones in Dietary Supplements and Selected Functional Foods Containing Piper methysticum by Isocratic Liquid Chromatography with Internal Standard. J AOAC Int. 2005 Jan 1;88(1):16–25.

5 Sage A, Taylor P, Stahl-Zeng J. Novel Methods Using Mass Spectrometry for Food Safety—From Contamination to Nutrition. Column. 2018 May 15;14(5):13–9.

6 Motoyama A, Kihara K. Mass Spectrometry in Cosmetic Science: Advanced Ionization Techniques for Detecting Trace Molecules in or on Human Skin. Mass Spectrom. 2017;6(Spec Iss 2):S0071.

7 Pitt JJ. Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry. Clin Biochem Rev. 2009 Feb;30(1):19–34.

8 Hoffmann E de, Stroobant V. Mass spectrometry: principles and applications. 3rd ed. Chichester, West Sussex, England ; Hoboken, NJ: J. Wiley; 2007. 489 p.

9 Zhou B, Xiao JF, Tuli L, Ressom HW. LC-MS-based metabolomics. Mol Biosyst. 2012 Feb;8(2):470–81.

10 Francese G, Corana F, Meneghetti O, Marazza F. LC­MS characterization of trace impurities contained in calcium folinate. J Pharm Biomed Anal. 2005 Sep 15;39(3–4):757–63.

11 de Jager LS, Perfetti GA, Diachenko GW. Analysis of ginkgolides and bilobalide in food products using LC–APCI–MS. J Pharm Biomed Anal. 2006 Aug;41(5):1552–9.

12 Fibigr J, Šatínský D, Solich P. Current trends in the analysis and quality control of food supplements based on plant extracts. Anal Chim Acta. 2018 Dec;1036:1–15.

13 Xu Y, Wang D, Tang L, Wang J. Separation and Characterization of Unknown Impurities and Isomers in Cefminox Sodium and Study of the Forming Mechanisms of Impurities by Liquid Chromatography Coupled with Ion Trap/Time-Of-Flight Mass Spectrometry. J Chromatogr Sci. 2019 Mar 1;57(3):204–12.

14 Karakawa S, Nakayama A, Ohtsuka N, Sato K, Smriga M. Detection of impurities in dietary supplements containing l-tryptophan. Amino Acids. 2022;54(5):835–9.

15 Stępień KA, Giebułtowicz J. Application of Liquid Chromatography Coupled to Mass Spectrometry in Quality Assessment of Dietary Supplements—A Case Study of Tryptophan Supplements: Release Assay, Targeted and Untargeted Studies. Pharmaceuticals. 2022 Apr;15(4):448.

16 Galant N, Czarny J, Powierska­Czarny J, Piotrowska­Cyplik A. Development and Validation of the LC-MS/MS Method for Determination of 130 Natural and Synthetic Cannabinoids in Cannabis Oil. Mol Basel Switz. 2022 Dec 6;27(23):8601.

17 Kakitani A, Inoue T, Matsumoto K, Watanabe J, Nagatomi Y, Mochizuki N. Simultaneous determination of water-soluble vitamins in beverages and dietary supplements by LC-MS/MS. Food Addit Contam Part Chem Anal Control Expo Risk Assess. 2014;31(12):1939–48.

18 Hadjmohammadi MR, Sharifi V. Use of solid phase extraction for sample clean-up and preconcentration of vitamin B12 in multivitamin tablet before HPLC-UV, UV and atomic absorption spectrophotometry. J Food Drug Anal [Internet]. 2020 Jul 14;15(3). Available from: https://www.jfda-online.com/journal/vol15/iss3/7

19 Heudi O, Kilinç T, Fontannaz P. Separation of water­soluble vitamins by reversed-phase high performance liquid chromatography with ultra-violet detection: application to polyvitaminated premixes. J Chromatogr A. 2005 Apr 8;1070(1–2):49–56.

20 Vaclavik L, Vaclavikova M, Begley TH, Krynitsky AJ, Rader JI. Determination of multiple mycotoxins in dietary supplements containing green coffee bean extracts using ultrahigh­performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). J Agric Food Chem. 2013 May 22;61(20):4822–30.

21 Pritchett TH, Myers EA, Brettell TA. Determination of Preservatives in Cosmetics and Personal Care Products by LC–MS–MS. LCGC Suppl [Internet]. 2015 Jun 1 [cited 2022 Dec 19];33(6). Available from: https://www.chromatographyonline.com/view/ determination-preservatives-cosmetics-and-personal-care-products-lc-ms-ms-0

22 Shi CX, Chen ZP, Chen Y, Yu RQ. Quantitative analysis of hormones in cosmetics by LC-MS/MS combined with an advanced calibration model. Anal Methods. 2015;7(16):6804–9.

23 Huang B, Han Z, Xu X, Cai Z, Jiang W, Ren Y. [Simultaneous determination of 7 female sex hormones in essential oil by high performance liquid chromatography-tandem mass spectrometry with isotope dilution]. Se Pu Chin J Chromatogr. 2011 Jan;29(1):20–5.

24 Kim NS, Yoo GJ, Lee JH, Park HJ, Cho S, Shin DW, et al. Determination of 43 prohibited glucocorticoids in cosmetic products using a simultaneous LC-MS/MS method. Anal Methods. 2017;9(13):2104–15.

Department of Biochemistry and Molecular

Faculty of Pharmacy and Biochemistry

University of Zagreb Ante Kovačića 1, 10000 Zagreb

Contact: dsoic@unizg.pharma.hr ogornik@unizg.pharma.hr

Biology

Fine Foods: a partner for excellence

Founded in 1984 as a fluid­bed granulation laboratory for food and pharmaceutical industries, Fine Foods & Pharmaceuticals N.T.M. S.p.A. started producing excipients and semi­finished products across both sectors.

Today, Fine Foods & Pharmaceuticals N.T.M. S.p.A. is an Italian independent Contract Development & Manufacturing Organisation (CDMO), i.e., it develops and manufactures contract products for the pharmaceutical, nutraceutical, cosmetics, biocides and medical devices industries. Fine Foods deliberately holds no proprietary brands, in order to maintain healthy partnerships and an integer image with its clients.

After the acquisitions - Pharmatek-PMC in January 2021 and Euro Cosmetic S.p.A. in October 2021the Group has four production plants and more than 750 employees and is at the forefront in the nutraceuticals, cosmetics, biocides and medical devices sectors.

With € 193 million revenue in 2021, more than 11 per cent CAGR over the last decade, and more than 260 customers, Fine Foods is a growing and futureoriented company. Fine Foods & Pharmaceuticals N.T.M. S.p.A. is listed on Borsa Italiana’s Euronext STAR Milan (Ticker: FF).

A 40-year history

From the beginning, the pursuit of excellence has been Fine Foods’ hallmark. It provides customers the Italian high quality scientific rigour in pharmaceutical contract manufacturing, while focusing on ethics and human capital. Customer loyalty and retention confirms its first­class production which is exported to several countries. Investment in R&D, Quality Control and ESG programmes enabled production capacity to grow over the 40 years of Fine Foods' corporate life, along with its range of technical and scientific solutions.

The business model sustainability, synergy between business units, product quality, production flexibility, product and process innovation capability, holistic ESG approach and customer support in product development are the company's core values.

ESG practices to support customers

ESG practices have been a decisive factor in Fine Food's growth for more than a decade. Through environmental and social certifications and awards, Fine Foods is a strategic and reliable partner based on its financial and environmental, social, and corporate governance criteria.

Having Fine Foods as a strategic partner means having an organisation that enables successful design process to be implemented together with customers on issues concerning product sustainability. The Group consults on the environmental labelling of packaging, supports calculating the environmental footprint of products following an LCA approach (i.e. throughout the product life cycle), commits in

While focusing on ethics and human capital, Fine foods provides customers the high quality scientific rigour in pharmaceutical contract manufacturing. It's core values are the sustainability business model, synergy between business units, product quality, production flexibility, product and process innovation capability, holistic ESG approach and customer support in product development.

the search for new, more environmentally friendly materials by supporting the customers' R&D in designing their products using eco-design principles. The Cosmetics Business Unit has certifications that enable product labelling according to sustainability features (such as the origin of ingredients from organic farming).

Based on this vision, Fine Foods amended its Articles of Association to become a Benefit Corporation in April 2021. This decision is a formal commitment to common benefit purposes and operating responsibly, sustainably and transparently towards people, communities, regions and the environment, cultural and social assets and activities, bodies and associations and other stakeholders. In addition, in November 2021 Fine Foods joined the UN Global Compact. This international organisation invites companies worldwide to respect and promote ten universal principles on human rights, labour standards, environmental protection and the fight against corruption. By embracing the Global Compact principles, Fine Foods commits to the Sustainable Development Goals (SDGs) of the United Nations 2030 Agenda.

During 2022, Fine Foods received the Platinum Rating from EcoVadis with a new score, increased by 12 from 66 to 78 points out of 100 compared to the previous year. This allowed the company to enter the Top one per cent of the best companies in the EcoVadis global ranking (out of more than 90,000 companies), earning the Platinum Medal

Ongoing technological innovation

The company’s name is a statement of innovation: N.T.M is the acronym for New Technology Manufacturing which proves Fine Foods' commitment to the search for innovations that allow it to maintain or increase the technological advantage acquired over the years. Fine Foods factories’ highly specialised technicians’ knowledge combines with the most advanced production technologies of granulation, mixing, compression, capsuling, filming and milling.

1 Updated on 30 June 2022

2 ESG ­ short for Enviromenmental, Social and Governance ­ a set of standards in the company’s operations, measuring its impact on society and the environment and how transparent and responsible its business is.

3 EcoVadis is one of the most crucial international eco-sustainability rating platforms. It quantifies a company's ability to manage environmental, human rights, ethical principles and sustainable procurement within the sector's boundaries.

Fine Foods & Pharmaceuticals N.T.M. S.p.A: HEADQUARTER: Via Berlino 39 24040 Zingonia / Verdellino Bergamo Italia T. +39 035 4821382 www.finefoods.it info@finefoods.it

Nutritional therapy of thyroid disease

AUTHOR: Sandra Krstev Barać, M.Sc.Nutrition, IFMCP, NutriHuB Consult

The thyroid gland plays an invaluable role in the metabolism, growth and development of the human body - its 2 basic hormones: thyroxine (T4) and triiodothyronine (T3) affect every cell and organ in the body.1 Therefore, maintaining optimal thyroid function is essential for overall health, and disruption in its work can affect numerous organ systems and cause a wide range of disorders and symptoms.

It is believed that thyroid diseases affect a significant part of the population, and are considered the most common endocrine disorder. 2 The most common form of thyroid disorder is hypothyroidism. For most patients with thyroid diseases, replacement therapy with thyroid hormones is often necessary for life. However, we have come a long way from treating thyroid problems exclusively with hormone replacement - more and more scientific knowledge supports the supporting role of appropriate nutrition and lifestyle in improving thyroid function and the quality of life of patients. 3

Nutrition is an important feature when we talk about thyroid health, and this is also evidenced by the fact that food (its quality and quantity) is one of the environmental factors that we can influence the most,

and which determines the activity of the hypothalamus-pituitary-thyroid axis.4 Just as an example, energy-restrictive diet reduces thyroid function5, and adequate intake of micronutrients such as iodine and iron is crucial for the synthesis of thyroid hormones themselves, while selenium and zinc are essential in the conversion of T4 into active T3.

Body mass and thyroid diseases

Thyroid hormones play a significant role in energy expenditure through several mechanisms. They affect basal metabolism and adaptive thermogenesis, modulate appetite and food intake, and regulate glucose and lipid metabolism.1 Therefore, it is not surprising that thyroid hormone status actually correlates with body mass.6,7

It is well known that hypothyroidism is often accompanied by weight gain. In addition to the fact that a significant lack of thyroid hormone can slow down the basal metabolism (according to an estimate of 15 to even 40%), hypothyroidism is often accompanied by increased levels of ghrelin and insulin as well as leptin resistance, respectively factors that contribute to weight gain.8 Conversely, hyperthyroidism is a hypermetabolic state characterized by increased energy consumption of basal metabolism as well as increased lipolysis and gluconeogenesis, which usually, although not necessarily, leads to weight loss.

It is a common view that thyroid hormone replacement will also lead to body weight regulation, however, this does not have to be the case.8,9 Since negative changes in nutritional status, especially when we talk about obesity, which has been shown to potentiate the basic symptoms of Hashimoto's thyroiditis (HT) as well as increase the risk of developing metabolic syndrome and diabetes type 210, an important nutritional goal is to adapt the energy value of the diet to the individual needs of the patient and to optimize body mass.8

Basic nutritional modifications in thyroid disease

Despite the undeniable role of diet and nutritional status on thyroid function, there is a lack of offi

cial dietary guidelines for thyroid diseases. However, there are several important nutritional goals in working with patients, one of which is achieving the desired body mass.8

But, body mass is only part of the story - in recent years, our understanding of the role of micronutrients in thyroid function as well as the pathophysiology of autoimmune processes has deepened, which is why individually tailored anti­inflammatory nutrition and micronutrition show potential in the diet therapy of thyroid disease.11

Thus, in the context of nutrition, several dietary patterns have given promising results, primarily the Mediterranean diet, but also the gluten-free diet as well as other forms of food elimination. The Mediterranean diet is certainly the first choice, and in addition to being sustainable in the long term, its beneficial effect is attributed to its anti­inflammatory effect, as well as a beneficial effect on the microbiome, which is an important item when we talk about autoimmune thyroid diseases.11

Apart from the fact that it is important that the diet for thyroid disease is anti­inflammatory ­ in other words, based on foods rich in fiber, lean meat and healthy fats, and devoid of processed and industrial food, alcohol and refined sugar, it is extremely important to maintain stable glycemia in patients. Namely, both deficiency and excess of thyroid hormone can have a negative impact on glucose metabolism and lead to the development of insulin resistance and other disorders of carbohydrate metabolism, which is why some experts advise checking for the possible presence of disorders and individual adaptation of carbohydrate intake.8,12,13

The justification for eliminating certain foods

Eliminating gluten is one of the most common dietary eliminations that patients decide on, but we still don't have the right answer to the question of whether it is really appropriate. The fact is that research has found a link between gluten and autoimmune thyroid diseases ­ HT and Graves' disease. Gliadin, the main component of gluten, appears to structurally resemble thyroid autoantibodies, leading to an exaggerated immune response. Additionally, it has been shown that gluten can lead to increased intestinal permeability, for which we kown, thanks to the work of Dr. Alessio Fasano, is one of the factors underlying the development of autoimmune diseases.14,15

A strict gluten-free diet is absolutely necessary for patients with autoimmune thyroid diseases present in parallel with celiac disease, but gluten elimination is also desirable for patients with non-celiac gluten/ wheat sensitivity (non­celiac gluten, NCGS and nonceliac wheat sensitivity, NCWS).16 Research shows that a gluten-free diet can slow the progression and symptoms of autoimmune thyroid diseases, but not all studies have established the benefit of such elimination. Some authors believe that this is so due to associated conditions, in which case the elimination of gluten is not sufficient for some, and that the elimination of lactose17, FODMAP foods (foods with a high content of fermentable carbohydrates), etc. should also be considered.

However, while we wait for studies to shed light on

this topic, most experts point out that a gluten-free diet is justified in patients with celiac disease, NCGS or NCWS; elimination of lactose when lactose intolerance is present, and low FODMAP diet in cases where thyroid diseases are associated with irritable bowel syndrome or small intestinal bacterial overgrowth (SIBO).

Is the concept of goitrogenic foods outdated?

Thyroid diseases, especially when we are talking about hypothyroidism, are almost routinely accompanied by nutritional advice that it is necessary to eliminate the so­called goitrogenic. These are different biologically active compounds from food such as glucosinolates, which have been shown to interfere with the bioavailability of iodine and thus can lead to thyroid hypertrophy and goiter formation. The most important food sources of goitrogens are cabbage, broccoli, cauliflower and other representatives of the cruciferous family, as well as soybeans due to the content of the isoflavones genistein and daidzein.

The goitrogenic effects of these foods have been observed in research on animal models, but a similar effect has not been confirmed in humans. What is known so far, and what some case reports point to, is that the goitrogenic effect of these compounds has been recorded during the regular consumption of raw foods, and in large quantities.18,19 Thermal processing, freezing or fermentation reduces the proportion of questionable ingredients and thus reduces the potential harmful effect on the thyroid gland.8 Additionally, the adverse impact of goitrogens from food has primarily been recorded in people with an iodine deficiency, which is rare in countries with mandatory iodization of salt.

Therefore, today there is no reason to completely eliminate the questionable foods from the diet. Moreover, it has been shown that the intake of foods from the cruciferous group has a positive effect on the level of glutathione20, an important body antioxidant that plays an invaluable role in protecting the thyroid gland from oxidative stress. With this in mind, moderate consumption of food containing goitrogens, but primarily in thermally processed and fermented form, can be recommended for people who have not had an iodine deficiency.8

Iodine and its role in thyroid disease therapy

Iodine is both a controversial and an extremely important topic when we talk about thyroid diseases. The thyroid diligently concentrates iodine in itself (it contains about 70-80% of the body's reserves), which is logical if we consider that this trace element is necessary for the production of its hormones. Thanks to the indisputable importance of iodine in the proper functioning of the thyroid gland, the practice of additional intake through preparations (sometimes in mega doses!) is often widespread among patients. But routine supplementation, especially in geographic areas with sufficient intake, is not recommended and may even worsen the condition.8,21,22

Neither deficit nor surplus of iodine is good for thyroid health. The fact is that iodine deficiency is the most common cause of hypothyroidism. However, in areas where intake is adequate (for example,

FIGURE 1

where salt is iodized), chronic iodine excess can increase the risk of developing autoimmune thyroid diseases and subclinical hypothyroidism. There are several proposed mechanisms that explain why this is so - in addition to the potential activation of autoimmune processes, the toxic effect of iodine results from its prooxidative action and inhibition of selenoenzymes (including the powerful antioxidant glutathione peroxidase), which can lead to progressive destruction of thyroid tissue and its atrophy. 23

Given the complex relationship between iodine and the thyroid gland, it is recommended that patients check their iodine status, for example through 24-hour urine sample, and adjust their dietary intake and/or resort to supplements in the event of a proven deficiency.

Other micronutrients important for thyroid health

Along with iodine, other micronutrients also play an important role in optimizing thyroid function. In this context, selenium, iron, zinc and vitamin D stand out the most. Nutritional deficits of these nutrients, or in some cases an excess, have an undeniable role in the etiopathogenesis of hypothyroidism and HT.8 That is why their adequate status in patients is an important support part of the therapy itself.

Of all tissues, the thyroid has the highest concentration of selenium, which is primarily stored in thyrocytes as selenoproteins (eg. glutathione peroxidase and deiodinase) necessary for a number of metabolic processes. If dietary intake of selenium is adequate, selenoproteins protect thyrocytes from oxidative stress and are necessary for the conversion of T4 into active T3 in peripheral tissues and target cells. 24,25 However, in case of deficiency, the protective effect is absent and thyroid dysfunction is likely. Therefore, it is not surprising that the lack of this mineral is associated with numerous thyroid diseases, including hypothyroidism, subclinical hypothyroidism, HT, Graves' disease, and even malignant thyro­

id diseases. 26 Selenium deficiency is often present among patients, which is why optimizing selenium status is extremely important in thyroid gland nutritional therapy.

The practice of consuming Brazil nuts to ensure selenium intake is often widespread among patients. Although they are its richest food source, the content itself often varies, which is why it is not recommended to rely on them to meet selenium needs. 26 The most important sources are, in fact, meat and seafood. It can also be useful to take selenium in food supplements, especially in autoimmune thyroid diseases, where it has been shown that selenium can help reduce the level of antibodies, improve the structure and function of the thyroid gland, and have a positive effect on clinical symptoms. 27,28 It is important not to overdo it with intake, since higher doses (more than 400 μg per day) are associated with toxic effects of selenium (alopecia, dermatitis, etc.). 29

Iron and zinc are also essential in thyroid function. Iron, as a component of the enzyme thyroperoxidase (TPO), participates in the production of T4 and T3. Low levels correlate with the appearance of hypothyroidism, but also with increased hair loss, a frequent problem of sufferers. Anemia itself caused by iron deficiency is often present in people with hypothyroidism and HT, most often due to associated comorbidities: celiac disease and autoimmune gastritis.17,26,28 That is why one of the basic steps in working with these patients is regular checking and optimization of iron status through diet and, if necessary, food supplements.

Zinc is important for the synthesis of thyroid hormones and participates in the activation of deiodinase, the enzyme that catalyzes the conversion of T4 to T3. Zinc deficiency is noted in both hypo­ and hyperthyroidism8 and affects thyroid activity through several mechanisms, the most significant of which are a decrease in serum levels of T4 and T3 and a possible increase in the titer of antithyroid antibodies. Interestingly, as in the case of iron deficiency, the clinical picture that often accompanies zinc deficiency is increased hair loss, which is reduced by improving zinc status. Although few, studies show that correction of zinc status can help restore normal thyroid function in HT patients.17,28

Among other things, it is extremely important to pay attention to the status of vitamin D. Its deficiency, namely, is associated with a higher risk of developing autoimmune thyroid diseases ­ HT and Graves' disease. 30 Vitamin D itself has complex effects on the immune system, and is expressed with its ability to inhibit the pro­inflammatory effect of Th1 and Th17 lymphocytes and the activation of the anti-inflammatory effect of Treg lymphocytes, thus contributing to the suppression of the autoimmune response. 31 In light of this, the advice is to regularly check the status and individually correct the deficits with vitamin D preparations (in the form of cholecalciferol).

The thyroid-gut axis: how the microbiota affects the thyroid

Taken from Nutrients. 2020 Jun 12;12(6):1769. doi: 10.3390/nu12061769. PMID: 32545596; PMCID: PMC7353203.

It is well known that thyroid hormones affect gastrointestinal neuromotor function, that is, that fluctuations in thyroid hormones cause various diges-

The influence of the intestines on the thyroid gland

tive disturbances recorded in both hypo- and hyperfunction of the thyroid. 32 However, the connection between the thyroid gland and the intestine is, as expected, bidirectional. Balanced microbiota has a beneficial effect not only on the immune system, but also on thyroid function.

On the other hand, dysbiosis, which is a common clinical finding in HT and Graves' disease, can negatively affect the level of thyroid hormones through several mechanisms ­ indirectly by promoting inflammation and increased intestinal permeability, and directly by a negative effect on the absorption of iodine, selenium, zinc and of iron, which are important for the proper functioning of the thyroid gland (Figure 1). There is more and more evidence that the health of the microbiota is crucial for the health of the thyroid, so an additional goal of nutritional intervention is the prevention or treatment of dysbiosis, primarily with an anti­inflammatory diet rich in dietary fiber, but also probiotics and prebiotics can be helpful. 28

Although it is necessary to conduct more highquality studies on humans, which will focus at the impact of probiotic supplementation (especially the dose and strains) on thyroid health, those conducted so far give reason for optimism. Among them, the work of Telabi et al. should be singled out as it found in 60 subjects with hypothyroidism that supplementation with a mixture of probiotics and fructo-oligosaccharides (500 mg synbiotic for 8 weeks) significantly reduced serum TSH levels and increased fT3. 33

The use of food supplements is extremely interesting for patients, so it is not surprising that it is a topic that is intensively researched. Among the dietary supplements that show the potential to alleviate the dynamics and consequences of thyroid disease through different mechanisms, for now we can single out myo-inositol34, glutathione35 and two interesting plants: ashwagandha (Withania somnifera (L.) Dunal) and black cumin (Nigella sativa L.). It is to be expected that the future will bring a better understanding of the mechanisms of their action and in which patients it makes sense to consider their application.

References:

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2 Strikić Đula I, Pleić N, Babić Leko M, Gunjača I, Torlak V, Brdar D, Punda A, Polašek O, Hayward C, Zemunik T. Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population. Biology (Basel). 2022 Mar 2;11(3):394.

3 Danailova Y, Velikova T, Nikolaev G, Mitova Z, Shinkov A, Gagov H, Konakchieva R. Nutritional Management of Thyroiditis of Hashimoto. Int J Mol Sci. 2022;23(9):5144.

4 Lartey LJ, Werneck­de­Castro JP, O­Sullivan I, Unterman TG, Bianco AC. Coupling between Nutrient Availability and Thyroid Hormone Activation. J Biol Chem. 2015;290(51):30551-61.

5 Pałkowska­Goździk E, Lachowicz K, Rosołowska­Huszcz D. Effects of Dietary Protein on Thyroid Axis Activity. Nutrients. 2017;10(1):5.

6 Fox CS, Pencina MJ, D'Agostino RB, Murabito JM, Seely EW, Pearce EN, Vasan RS. Relations of thyroid function to body weight: cross- sectional and longitudinal observations in a community-based sample. Arch Intern Med. 2008;168(6):587-92.

7 Iwen KA, Schröder E, Brabant G. Thyroid hormones and the metabolic syndrome. Eur Thyroid J. 2013 Jun;2(2):83-92.

8 Anziani N. The Health Professional's Guide to Nutrition Management of Thyroid Disease. 1 izd. Chicago: Academy of Nutrition and Dietetics, 2020.

9 Lee SY, Braverman LE, Pearce EN. Changes in body weight after treatment of primary hypothyroidism with levothyroxine. Endocr Pract. 2014 ;20(11):1122-8.

10 Walczak K, Sieminska L. Obesity and Thyroid Axis. Int J Environ Res Public Health. 2021;18(18):9434.

11 Ruggeri RM, Giovinazzo S, Barbalace MC, Cristani M, Alibrandi A, Vicchio TM, Giuffrida G, Aguennouz MH, Malaguti M, Angeloni C, Trimarchi F, Hrelia S, Campennì A, Cannavò S. Influence of Dietary Habits on Oxidative Stress Markers in Hashimoto's Thyroiditis. Thyroid. 2021; 31(1):96-105.

12 Gierach M, Gierach J, Junik R. Insulin resistance and thyroid disorders. Endokrynol Pol. 2014;65(1):70-6.

13 Brenta G. Why can insulin resistance be a natural consequence of thyroid dysfunction? J Thyroid Res. 2011;2011:152850

14 Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):71-78.

15 Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012;10(10):1096-100.

16 Losurdo G, Principi M, Iannone A, Amoruso A, Ierardi E, Di Leo A, Barone M. Extra-intestinal manifestations of non-celiac gluten sensitivity: An expanding paradigm. World J Gastroenterol. 2018 Apr 14;24(14):1521-1530.

17 Ihnatowicz P, Drywień M, Wątor P, Wojsiat J. The importance of nutritional factors and dietary management of Hashimoto's thyroiditis. Ann Agric Environ Med. 2020 Jun 19;27(2):184-193.

18 Felker P, Bunch R, Leung AM. Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism. Nutr Rev. 2016;74(4):248-258.

19 Babiker A, Alawi A, Al Atawi M, Al Alwan I. The role of micronutrients in thyroid dysfunction. Sudan J Paediatr. 2020;20(1):13-19

20 Minich DM, Brown BI. A Review of Dietary (Phyto)Nutrients for Glutathione Support. Nutrients. 2019 Sep 3;11(9):2073.

21 Dahiya V, Vasudeva N, Sharma S, Kumar A. Role of Dietary Supplements in Thyroid Diseases. Endocr Metab Immune Disord Drug Targets. 2022;22(10):985-996.

22 Garber JR at al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988-1028.

23 Xu J, Liu XL, Yang XF, Guo HL, Zhao LN, Sun XF. Supplemental selenium alleviates the toxic effects of excessive iodine on thyroid. Biol Trace Elem Res. 2011;141(1-3):110-8.

24 Benvenga S, Feldt­Rasmussen U, Bonofiglio D, Asamoah E. Nutraceutical Supplements in the Thyroid Setting: Health Benefits beyond Basic Nutrition. Nutrients. 2019;11(9):2214.

25 Gorini F, Sabatino L, Pingitore A, Vassalle C. Selenium: An Element of Life Essential for Thyroid Function. Molecules. 2021 Nov 23;26 (23):7084.

26 Rayman MP. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease. Proc Nutr Soc. 2019;78(1):34-44.

27 Drutel A, Archambeaud F, Caron P. Selenium and the thyroid gland: more good news for clinicians. Clin Endocrinol (Oxf). 2013; 78(2): 155-64.

28 Knezevic J, Starchl C, Tmava Berisha A, Amrein K. Thyroid­Gut­Axis: How Does the Microbiota Influence Thyroid Function? Nutrients. 2020;12(6):1769.

29 Ventura M, Melo M, Carrilho F. Selenium and Thyroid Disease: From Pathophysiology to Treatment. Int J Endocrinol. 2017;2017:1297658.

30 Kim D. The Role of Vitamin D in Thyroid Diseases. Int J Mol Sci. 2017 Sep 12;18(9):1949.

31 Mele C, Caputo M, Bisceglia A, Samà MT, Zavattaro M, Aimaretti G, Pagano L, Prodam F, Marzullo P. Immunomodulatory Effects of Vitamin D in Thyroid Diseases. Nutrients. 2020 May 16;12(5):1444.

32 Virili C, Fallahi P, Antonelli A, Benvenga S, Centanni M. Gut microbiota and Hashimoto's thyroiditis. Rev Endocr Metab Disord. 2018 Dec;19(4):293-300.

33 Talebi S, Karimifar M, Heidari Z, Mohammadi H, Askari G. The effects of synbiotic supplementation on thyroid function and inflammation in hypothyroid patients: A randomized, double blind, placebo controlled trial. Complement Ther Med. 2020 Jan;48: 102234.

34 Benvenga S, Nordio M, Laganà AS, Unfer V. The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management. Front Endocrinol (Lausanne). 2021 May 10;12:662582.

35 Rostami R, Aghasi MR, Mohammadi A, Nourooz-Zadeh J. Enhanced oxidative stress in Hashimoto's thyroiditis: inter-relationships to biomarkers of thyroid function. Clin Biochem. 2013 Mar;46(4-5): 308-12.

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Well-being in menopause

ons working in synergy, matching biological needs, effectively supporting health, and improving life quality.

HA Tech 2.0® Hyaluronans technology and ExceptionHYAL® product line are designed to fully integrate in tissues physiology.

ExceptionHYAL® Star

Targeting skin beauty and anti-aging from within, its rejuvenating effect is quick and visible in 14 days only, with significantly less marked and deep wrinkles. Further, it effectively improves healthy skin parameters, providing hydration, tone and elasticity. It does not only prevent and support skin ageing, but can also help in case of dryer and sensitive skins due to sun/cold exposure.

zing and recovery effect. It also promotes bone regeneration being a support in osteoporosis preventions.

ExceptionHYAL® Jump

Designed for joint pain reduction and enhanced mobility. Completely changing the approach to Osteoarthritis management with HA, ExceptionHYAL® Jump boosts joint recovery by supporting synovial fluid regeneration and exerting a lenitive effect on local inflammation to induce the reduction of anti­pain drugs use. It acts like a shock absorber, lubricating & plumping tissues, helping cushioning effect and reducing friction caused pain.

ExceptionHYAL® Wink

Developed to support ocular well-being. Thanks to the moisturizing effect on eye mucosa, it helps to keep the correct lubrication levels. It is a valid ally to boost eye health and foster vision performance and longevity, by reducing dry eye symptoms and performing better eye tolerance to blue lights linked to the use of digital devices.

References:

1 Gupta RC, Lall R, Srivastava A, Sinha A. Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory. Front Vet Sci. 2019; 6: 192.

2 Cyphert JM, Trempus CS, Garantziotis S. Size matters: Molecular weight specificity of hyaluronan effects in cell biology. Int J Cell Biol. 2015; 2015: 563818.

3 Girish KS, Kemparaju K. The magic glue hyaluronan and its eraser hyaluronidase: A biological overview. Life Sci. 2007; 80: 1921–1943.

4 Fallacara A, Baldini E, Manfredini S, Vertuani S. Hyaluronic Acid in the Third Millennium. Polymers. 2018; 10(7): 701.

ExceptionHYAL® Relief

Created to effectively alleviate unpleasant digestive issues as heartburn and acid reflux. By mimicking tissue biology together with a moisturizing ability, it effectively helps epithelium integrity, smoothness and regeneration, for an improved barrier effect. It promotes tissue recovery when abraded by acids, by relieving from Gastro Esophageal Reflux Disease (GERD) symptoms.

As

All

Official

ExceptionHYAL® Blossom

Realized to counteract menopause discomforts. It concurs to improve the quality of life in women by alleviating the symptoms of vaginal atrophy (urinary urgency, itching, burning, irritation, dryness involving significant pain during sex) thanks to a moisturi­

MPG LAB d.o.o. Sermin 75 P 6000 Koper, Slovenia info@mpg-lab.com www.mpg-lab.com

ROELMI HPC strongly focuses its activity on researching, designing, and producing high technological ingredients to reach the highest performing results in final formulas by offering the ethical and responsible choice for sustainable innovations.

Hytolive® beneficial effects of use in patients with "long COVID"

After the active phase of the disease of COVID-19, some patients recover very slowly, with a constantly present feeling of persistent fatigue. It is a long-term condition, the so-called long COVID or post-COVID syndrome (Long-COVID syndrome, LCS) which can last for weeks and months.

It is extremely difficult to understand why some people recover quickly after infection with the SARSCoV-2 virus, while others develop a post-COVID syndrome, and the mechanisms by which the virus causes the disease to prolong are still unclear. Most patients with post-COVID syndrome experience fatigue and extreme weakness as a condition that per-

sists even after the active phase of the disease.

Several papers have been published on the mechanisms underlying LCS. Clinically confirmed evidence shows that the use of dietary supplements as adjuvant therapy in the treatment of LCS is rare. (Z. Naureen et al. "Proposal of a food supplement for the management of post-COVID syndrome"; 2021)

The health challenges and implications brought by the long-term condition of COVID have been investigated and defined by experts of the World Health Organization (WHO) (Coronavirus Disease (COVID19): Post COVID-19 Condition. Available online: https:// www.who. int/news-room/questionsand-answers/item/

coronavirus-disease-(COVID-19)-post-COVID-19-condition).

Nitas B. et al . in their paper state lines of evidence suggest that systemic and chronic tissue inflammation, autoimmunity, and persistence of viral proteins/ RNA may contribute to the pathogenesis of long-term COVID. Moreover, it seems that increased oxidative stress plays a crucial pathogenetic role in this scenario.

Hydroxytyrosol is known to exhibit strong antioxidant and anti­inflammatory effects. Doctors from the Regional Universitary Hospital in Malaga (Spain), together with the companies Genosa and Solvitae Medical, conducted an observational clinical study on patients who suffered from post­COVID syndrome, the results of which are awaiting publication. Forty patients with a wide range of symptoms including asthenia, fatigue, forgetfulness, dyspnea, headache, hair loss, dizziness, etc. were included in that study. The subjects were aged between 27 and 80 years. The aim of the study was to evaluate the effects of a dietary supplement called Endothelyx® 45 on perceived fatigue in patients recovering from LCS. Endothelyx® 45 contains natural hydroxytyrosol, with the addition of flavonoids from bitter orange, and vitamins B1, B6 and B12.

After six months, the study concluded that Endothelyx® 45 contributed to improving the subjects' quality of life by reducing fatigue symptoms and, at the same time, affected several markers. Namely, 50% of patients showed significant improvement in symptoms; 78% improved their total cholesterol levels; 73% reduced their glucose levels; 70% improved their D-dimer levels; and 81% reduced ferritin levels without affecting iron levels. In patients whose ferritin values were above the normal range, it decreased to a normal level.

The Endothelyx® 45 formulation was originally designed to contribute to the proper functioning of the endothelial function, which many recent studies confirm is very relevant both in the acute phase of the disease and during the post-COVID syndrome. ("The Role of Endothelium in COVID-19"; Mihaela Ionescu et al.; 2019).

Concept for your new product

The WHO (World Health Organization) recommends a daily intake of 400 g of fruits and vegetables for the prevention of non-communicable diseases and for the prevention and mitigation of deficiencies of several important micronutrients. This means approximately 5 servings a day.

World Health Organization estimates that in more than half of the countries in the European region this amount is less than 400 g per day, and in a third of the countries the average intake is less than 300 g per day. EFSA's analysis based on national nutrition surveys shows that the recommended amount is reached only in 4 EU member states participating in the surveys. Considering that consumption of the recommended amounts of fruits and vegetables helps to preserve health and prevent disease, it is clear that a lower intake has a negative effect on health. That's why we suggest replenishing antioxidants in the form of a food supplement for stronger immunity and skin health.

New product concept

The branded ingredient™ is a complete food concentrate of fruit and vegetable extracts, which provides polyphenols corresponding to the amount of daily consumption of 5 portions of fresh fruit and vegetables. It offers a wide range of 100+ different polyphenols from plant extracts.

• Contains natural antioxidants from fruits and vegetables.

• It has clinically proven 24-hour bioavailability and preventive protection.

• Helps stimulate collagen synthesis and prevents its breakdown.

The branded ingredient™ brings bioavailable natural antioxidants that will stimulate the innate immune response, and thanks to the prebiotic effect, helps promote a healthy inflammatory response and an appropriate response of the immune system in the fight against pathogens.

The branded ingredient™ that we propose as an active substance has a proven effect, i.e. a clinical study.

Dosage and possibilities of communication 450 mg: clinical data (24-hour bioavailability, preventive antioxidant protection, reduction of mean arterial pressure), equivalent to 5 servings of fruit and vegetables, available on-hold health claims;

• 270 mg: clinical data (24-hour bioavailability), equivalent to 3 servings of fruit and vegetables, available on-hold health claims; 90 mg: clinical data (24-hour bioavailability), equivalent to 1 serving of fruit and vegetables.

The branded ingredient™ is suitable for formulation in various pharmaceutical forms: capsules, tablets, bags, sticks.

Genosa was founded in 2001 and it is the worldwide innovator and pioneer company in the production and commercialization of natural hydroxytyrosol derived from the olive fruit. Its technology consists of a process using just physical and mechanical means and has been patented internationally. No solvents are used to extract the hydroxytyrosol.

GENOSA ID SL

Parque Tecnológico de Andalucía

C/ Iván Pavlov, 8, bajo G Bajo G 29590 Campanillas MÁLAGA (Spain)

Phone: +34 952 02 85 80 info@genosa.com www.genosa.com

If you want to know more about the proposed branded ingredient™, the concept of this or other new product proposals, please contact us, we have 20+ years of experience in developing new food supplement concepts.

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

Urinary tract infections

food supplements and their ingredients as a potential for prevention and relief of symptoms

The most commonly used dietary supplements for the prevention and treatment of urinary tract infections contain cranberry, vitamin D, D-mannose, probiotics, bearberry, hibiscus or a combination of several ingredients. For example, combinations of cranberry and lactobacillus or cranberry and propolis have proven to be very effective.

AUTHOR: Daria Šurić, M.pharm.

Urinary tract infections are the most common bacterial infections in women and one of the most common reasons for visits to the family doctor. They occur much more often in women than in men. Although, especially in women, it is mostly a question of harmless infections, sometimes they can be a symptom of more serious diseases, and even lead to various complications.

The causative agents of urinary tract infections are bacteria that create the physiological flora of the intestines. The most common causative agent is the bacteria Escherichia coli , and bacteria of the genus Proteus, Klebsiella, Enterobacter, Pseudomonas and others occur less often. Bacteria enter the urinary bladder through the urethra, after which they can progress further towards the kidneys. They most often affect the bladder and urethra.

Urinary tract infections (UTIs) can be divided into acute inflammation of the urinary bladder (cystitis),

acute inflammation of the kidneys (pyelonephritis), infections without symptoms (asymptomatic bacteriuria), recurrent infections and complicated infections.

Uncomplicated urinary infections are bacterial inflammations of the bladder and associated structures (cystitis). The patients have no tissue changes, nor co-morbidities such as diabetes, immunocompromised conditions or pregnancy. Uncomplicated urinary tract infections cause symptoms such as frequent urination, a sudden urge to urinate, pressure in the lower abdomen, and difficulty urinating.

Urinary tract infections occur during the lifetime in approximately 50% of women and in 10% of pregnant women. Of these, 20–40% of women experience recurrent UTIs. In men, any inflammation of the urinary system is considered complicated infection.

Many cases of uncomplicated urinary tract infection resolve spontaneously, without medication, but patients seek help to relieve symptoms. Treatment is

necessary in cases where it is estimated that the inflammation could spread to the upper urinary tract.1

The prevalence of UTIs in the community (CAUTI) is 0.7%, and the main risk factors are age, history of UTIs, sexual activity and diabetes. The most common pathogen is Escherichia coli, and resistance to common antibiotics is highly geographically dependent. In urology departments, the prevalence of healthcare-associated urinary tract infections is 5.1%. Resistance to almost all antibiotics in healthcare-associated UTIs (HAUTI) is above 20% and there is significant geographic variation. 2

The role of nutritional supplements in the prevention and supportive therapy of urinary tract infections

Studies have been done on several ingredients in nutritional supplements that are used to help prevent and treat urinary tract infections. The most commonly used dietary supplements contain cranberry, vitamin D, D-mannose, probiotics3, bearberry, hibiscus, or a combination of several ingredients. For example, combinations of cranberry and lactobacillus or cranberry and propolis have proven to be very effective.

Vitamin D and recurrent urinary tract infections in menopausal women

Menopausal women are particularly susceptible to recurrent UTIs. Recurrent UTI can be defined as at least 3 episodes of UTI in a period of one year, or 2 episodes in 6 months. A recurrent UTI can be a relapse or re-infection. Recurrence refers to UTIs caused by the same microorganism after appropriate treatment.

Various antibiotics are the main therapy for improving recurrent infections, but even so, they still affect a large number of women. That is why it is necessary to research alternative forms of therapy.

It has been shown that recurrent UTIs in premenopausal women are associated with vitamin D deficiency.4 Namely, urinary tract infections stimulate epithelial cells to produce cathelicidin LL-37, protecting them from bacterial infection. Vitamin D is a potential stimulator of antimicrobial peptides, including cathelicidin LL-37, in innate immunity. Recently, Hertting et al.5 observed a significant increase in cathelicidin in response to vitamin D in the infection process. Previous studies have shown the importance of vitamin D for innate immunity in defense against bacterial infections, mainly by increasing phagocytic function and neutrophil motility. The results showed that vitamin D deficiency can increase the risk of UTI.

More clinical trials and studies are needed to determine the effects of vitamin D supplementation on the prevention of urinary tract infections. According to the findings of a systematic review and meta-analysis of studies on UTIs and vitamin D status in the body6, healthcare providers should encourage the public to follow guidelines for daily vitamin D intake.

Probiotics and UTI

Vaginal lactobacilli have a protective role - they are able to produce antimicrobial compounds such as lactic acid and hydrogen peroxide to produce biosurfactant that inhibits the adhesion of uropathogens to surfaces and to stimulate the non­specific innate

FIGURE 1 Vacciniummacrocarpon , american cranberry

immune system. Restoring the vaginal flora with lactobacilli using probiotics is an effective strategy for reducing the frequency of urinary tract infections.

With frequent use of antibiotics due to frequent UTIs, antimicrobial resistance of uropathogenic E.coli occurs. In addition, antibiotics are associated with intestinal and vaginal dysbiosis, which further favors frequent UTIs.

Studies have shown that women without a history of urinary tract infections had a vaginal microbiota dominated by lactobacilli, and the most common strains were Lactobacillus crispatus, Lactobacillus jensenii and Lactobacillus iners , while the microbiota of patients who suffered from recurrent urinary tract infections was relatively depleted of lactobacilli.7

A randomized, double-blind, placebo-controlled pilot study on a product containing two strains of Lactobacillus and cranberry extract (Figure 1) was conducted on 115 subjects. The subjects received this product or a placebo twice a day for 26 weeks. The primary endpoint was the proportion of subjects with recurrent UTI at the end of the trial. After 26 weeks, significantly fewer women who took the probiotic and cranberry combination experienced recurrent UTIs compared to the placebo group.

The results showed: a greater number of respondents who did not have UTI (90 vs. 67%; P<0.05); longer time to first UTI (174 vs. 90 days; P=0.001); shorter duration of active UTI (5 vs. 12 days; P=0.009); fewer subjects who needed antibiotics (3 vs. 11; P<0.05); and a shorter median duration of antibiotic treatment (4 vs. 7 days; P=0.09). It was concluded that the probiotic with 2 lactobacillus strains and cranberry extract was safe and effective in preventing recurrent UTIs in premenopausal adult women. These findings support the need for further well-designed trials to clarify the benefits that may be achieved.9

D-mannose

D-mannose is a natural sugar that is considered to prevent bacterial colonization of the urinary tract. Studies examining whether this added sugar can reduce the recurrence of urinary tract infections have been promising. In a meta-analysis of clinical trials, taking 2 grams of D-mannose powder daily for up to 6 months reduced the risk of recurrent UTIs compared to placebo.10

D-mannose in a dose of 2 grams or more represents a challenge in product formulation, because it occupies a large volume, so the dosage form is usually a sachet with powder. Recently, products with smaller doses of D-mannose have also appeared, but in

combination with other ingredients, such as cranberry extract.

Bearberry

Arctostaphylosuva-ursi (L.), also known as uva ursi or bearberry (Figure 2), is a plant that grows in cold climates. Its leaves are traditionally brewed as a tea and used to improve urinary health.

extract containing 105 mg of arbutin. It is assumed that arbutin is well absorbed from tea or leaf extract after oral intake, as evidenced by urinary elimination (requires absorption from the gastrointestinal tract) with an approximate bioavailability between 67.370.3% for the main bioactive substance - arbutin. It is assumed to travel to the intestine where it is absorbed intact via the glucose transporter. By evaluating the concentration of arbutin metabolites in urine, it is concluded that it is well absorbed. After absorption, arbutin is metabolized into hydroquinone glucuronide. It is then broken down into hydroquinone by bacteria in the urinary tract, which then accumulate free hydroquinone. Hydroquinone is believed to be responsible for the therapeutic effects of bearberry on urinary tract infections.

Bearberry also contains corilagin, which significantly reduces the minimum inhibitory concentration of some antibiotics.12 It is thought that leaf extracts may have additional antibacterial properties compared to isolated arbutin.

Uva ursi has antibacterial properties because of its main bioactive substance - arbutin. Arbutin creates a metabolite called hydroquinone glucuronide.

Uva ursi tea and capsules are effective medicinal forms for bringing arbutin into the urinary tract. Supplementation with bearberry is usually recommended as a response to a specific disease, not as a preventive measure. Supplementation should not last longer than one to two weeks continuously.

The dose used for the treatment of urinary diseases is determined by the content of arbutin in the product. The recommended daily dose is between 420600 mg, taken in three doses of 140-220 mg during the day (three times per day).

According to Commission E from 1998 (Germany), the recommended dose is 150 ml of tea, brewed from 3 g of leaves, taken four times a day. Since each dose of tea prepared in this way provides 100-210 mg of arbutin, the total daily dose varies between 400-840 mg. The tea should be used immediately after preparation.

The tablets should contain 472.5 mg of dry leaf

A total of 57 women who experienced at least three episodes of cystitis during one year participated in the study. During one month, they were given bearberry in the form of tablets (three tablets per day that also contained dandelion) and were monitored for a year. In the group receiving the placebo, a low recurrence of cystitis was observed (23%), and in the group receiving the therapy there were no recurrences at all.13

In Croatia, the permitted dose of arbutin in a food supplement is 160 mg per day. Products containing more arbutin belong to the category of herbal medicinal products.

Cranberry in combination with propolis

Cranberry and its role in IMS is already well known. Recent studies also support this (Figure 3). Recent evidence suggests that cranberry is effective in preventing urinary tract infections14 mainly due to its anti-bacterial properties. A-type proanthocyanidins

Microarray results. Proportion of genes up­regulated and down­regulated by cranberry (190 μg/mL) and propolis (102.4 μg/mL) alone and combined. Cranberry up­regulates 1,245 genes and down­regulates 2,190 genes. Propolis up­regulates 94 genes and down­regulates 1,384 genes. Cranberry + propolis up-regulate 2,950 genes and down-regulate 2,150 genes.

Taken from Ranfaing, J., Dunyach­Remy, C., Louis, L. et al. Propolis potentiates the effect of cranberry (Vacciniummacrocarpon) against the virulence of uropathogenic Escherichia coli . Sci Rep 8, 10706 (2018). https://doi.org/10.1038/s41598-018-29082-6

FIGURE 3 Propolis enhances the action of cranberry (Vacciniummacrocarpon) against the virulence of uropathogenic Escherichia coli

(PAC-A) in cranberry have been shown to be important inhibitors of the adhesion of E. coli type I fimbriae to uroepithelial cells, by modifying the shape of the bacteria, promoting cell rounding and thus reducing their adhesion surface.

Propolis, a resinous material produced by bees by mixing plant materials with wax and bee enzymes, is traditionally used for its antiseptic and local anesthetic properties. It also shows antimicrobial, anti­inflammatory, antitumor, immunomodulatory and antioxidant activity. A study showed that propolis could enhance the effect of PAC, offering some protection against bacterial proliferation and virulence.15 Moreover, a recent study showed that cranberry and propolis supplementation significantly reduced the incidence of urinary tract infections.16

FIGURE 4 Hibiscus sabdariffa (L.), floral calyxes

lines for antimicrobial treatment and prophylaxis of urinary tract infections - contain products with cranberry for the prophylaxis of recurrent UTIs. That should be just the beginning.

References:

1 Bono, Michael J., et al. “Urinary Tract Infection.” StatPearls, StatPearls Publishing, 28 November 2022.

2 Tandogdu, Zafer, and Florian M E Wagenlehner. “Global epidemiology of urinary tract infections.” Current in infectious diseases vol. 29,1 (2016): 73-9. doi:10.1097/QCO.0000000000000228

3 Gupta, Varsha et al. “Recurrent urinary tract infections in women: How promising is the use of probiotics?.” Indian journal of medical microbiology vol. 35,3 (2017): 347-354. doi:10.4103/ijmm. IJMM_16_292

4 Nseir, William et al. “The association between serum levels of vitamin D and recurrent urinary tract infections in premenopausal women.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases vol. 17,12 (2013): e1121-4. doi:10.1016/j.ijid.2013.06.007

5 Hertting, Olof et al. “Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder.” PloS one vol. 5,12 e15580. 14 Dec. 2010, doi:10.1371/journal.pone.0015580

6 Deng, Qi-Fei et al. “Vitamin D and Urinary Tract Infection: A Systematic Review and Meta-Analysis.” Annals of clinical and laboratory science vol. 49,1 (2019): 134-142.

7 Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol. 2006;24:28–32.

Hibiscus

Hibiscus sabdariffa (L). is a plant probably native to West Africa and Asia. It is grown in tropical areas including the Caribbean, Australia, Brazil, Central America, India, Africa, the USA and the Philippines (Figure 4).

Hibiscus sabdariffa is used in traditional medicine for bladder and kidney health. The dried sepals of that flower are used to produce an infusion popularly known as hibiscus tea, calorie­free and caffeinefree, with acidic and antibacterial properties thought to protect against urinary tract infections. Hibiscus sabdariffa is also known for its antioxidant properties, thanks to its very high content of bioflavonoids and anthocyanins, especially hibiscin, which has also been shown to be useful in the prevention of urinary tract infections.

A University of London (UCL) Faculty of Pharmacy review published in the journal Food Chemistry examined phytochemical and pharmacological research on Hibiscus sabdariffa . Several in vitro and in vivo studies have shown a strong antioxidant effect due to its "powerful reactive oxygen and free radical scavenging effect".18

Conclusion

Due to the resistance of bacteria to antibiotic therapy and the side effects of continuous use of antimicrobial drugs, supplementation plays a significant role in UTI. The full potential of nutritional supplements in UTI has not yet been officially used enough, so continuous work on product development and studies that will prove their effectiveness are needed. This will provide a scientific basis that contributes to the introduction of as many nutritional supplements as possible into the official guidelines for the treatment of UTI around the world. For example Croatian national guidelines ISKRA ­ guide-

8 Parshottam Koradia, Shital Kapadia, Yamini Trivedi, Gajendrasinh Chanchu & Ashton Harper (2019) Probiotic and cranberry supplementation for preventing recurrent uncomplicated urinary tract infections in premenopausal women: a controlled pilot study, Expert Review of Anti-infective Therapy, 17:9, 733-740, DOI: 10.1080/14787210.2019.1664287

9 Parshottam Koradia, Shital Kapadia, Yamini Trivedi, Gajendrasinh Chanchu & Ashton Harper (2019) Probiotic and cranberry supplementation for preventing recurrent uncomplicated urinary tract infections in premenopausal women: a controlled pilot study, Expert Review of Anti-infective Therapy, 17:9, 733-740, DOI: 10.1080/14787210.2019.1664287

10 Lenger, Stacy M et al. “D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis.” American journal of obstetrics and gynecology vol. 223,2 (2020): 265.e1-265.e13. doi:10.1016/j.ajog.2020.05.048

11 Schindler, Gernot et al. “Urinary excretion and metabolism of arbutin after oral administration of Arctostaphylos uvae ursi extract as film­coated tablets and aqueous solution in healthy humans.” Journal of clinical pharmacology vol. 42,8 (2002): 920-7. doi:10.1177/ 009127002401102740

12 Shimizu, M et al. “Marked potentiation of activity of beta-lactams against methicillin-resistant Staphylococcus aureus by corilagin.” Antimicrobial agents and chemotherapy vol. 45,11 (2001): 3198-201. doi:10.1128/AAC.45.11.3198-3201.2001

13 Larsson B, Jonasson A, Fianu S Prophylactic effect of UVA­E in women with recurrent cystitis: A preliminary report Curr Ther Res.(1993 Apr)

14 Howell, Amy B et al. “Dosage effect on uropathogenic Escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study.” BMC infectious diseases vol. 10 94. 14 Apr. 2010, doi:10.1186/1471-2334-10-94

15 Ahuja, S et al. “Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth medium of P­fimbriated Escherichia coli.” The Journal of urology vol. 159,2 (1998): 559-62. doi:10.1016/s0022-5347(01)63983-1

16 Bruyere, F. et al. A multicentre, randomized, double-blind, placebo­controlled study evaluating the efficacy and safety of a combination of propolis and cranberry (Vaccinium macrocarpon) (DUAB®) in preventing recurrence of low urinary tract infections in women. Med Mal Infect 47, S109 (2017).

17 Chou, Shun­Ting et al. “Exploring the effect and mechanism of Hibiscus sabdariffa on urinary tract infection and experimental renal inflammation.” Journal of ethnopharmacology vol. 194 (2016): 617-625. doi:10.1016/j.jep.2016.10.059

18 https://www.sciencedirect.com/science/article/pii/ S030881461400692X

19 ISKRA guidelines on antimicrobial treatment and prophylaxis of urinary tract infections – croatian national guidelines

Bioline a solution for your needs

We are committed to our customers' needs and timely service

Bioline is an independent company specializing in providing a variety of pharmaceutical services. Through its representative office, it provides the opportunity to cooperate with a number of selected internationally renowned pharmaceutical companies and manufacturers of medicines, medicinal products, food supplements, cosmetics and food.

We have been a reliable partner for your projects for 23 years. We realize finished products professionally and on time. Our professionalism has been recognized 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, quality and stability (stability studies by arrangement);

✓ Development of new product formulations in accordance with market needs, with "added value" that separates you from the competition;

✓ Careful approach that adapts to your needs, professional and timely service, quick reactions to all your inquiries and short deadlines for implementation.

We provide various potential projects and various pharmaceutical forms - tablets, capsules, sticks, sticks for dissolving in the mouth (direct), soft gelatin capsules, sachets with powder for dissolving in water. We cover numerous markets throughout the region: Slovenia, Croatia, Bosnia and Herzegovina, Serbia, 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 delivery 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 market. So far, we have participated in the successful implementation of more than 50 projects, and the services we offer our partners provide the opportunity to always find the most suitable solution.

Bioline

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Ljubljana, Slovenia

Cell. +386 41 663 347 e-mail: plus.bioline@siol.net

Medicines:

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• Effervescent granules, granules

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• Powder

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

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• Liquids, gels, creams, ointments, pastes, wipes

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Sun protection products

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• Natural and BIO products for disinfection

Bakuchiol

a promising new functional analog of retinoids in cosmetic products

Numerous scientific studies have shown that topical application of bakuchiol can reduce the signs of aging. The intensity of its effect can be compared to that of retinol, but with fewer side effects such as itching, dryness and redness. In addition, its antioxidant, anti-inflammatory and antimicrobial effectiveness has been confirmed.

AUTHOR: Marija Tomas

Bakuchiol is thought to act as a functional analogue of retinoids on the skin, by inducing similar metabolic pathways. Scientific studies show that this compound, like retinol and its derivatives, can be widely used in dermatology and cosmetology to prevent wrinkles, acne lesions and skin hyperpigmentation. These effects are the reason why bakuchiol is increasingly becoming a component of preparations used not only in cosmetics but also in the treatment of skin diseases.

Characteristics of bakuchiol

The combination of the characteristic structure of meroterpene phenol (Figure 1) called bakuchiol, creates an increasingly successful career, not only in cosmetology but also in the therapy of health skin problems. Bakuchiol was first isolated from the seeds of Cullen corylifolium L. Medik (formerly called Psoraleacorylifolia L.).1 C.corylifolium is currently the only natural, valuable source for obtaining backuhiol. 2 The content of bakuchiol in the fruit of this plant ranges from 1-7 %. 3 It was also isolated from other species that are taxonomically from different families, however, the concentration of bakuchiol in these plants is too low to be considered natural sources for obtaining this compound.

Speaking in chemical terms, bakuchiol is a meroterpene phenol (Figure 1), a chiral compound with one asymmetric center4. Terpene and 4-hydroxystyryl groups are responsible for its biological activity.5 The 4-hydroxystyryl part, characteristic of bakuchiol, is also present in another compound with high biological activity – resveratrol.6

Bakuchiol is approved in European Union countries as a safe component of cosmetic products. The CosIng database7 recommends using it as an ingredient that has antioxidant and antimicrobial effects and as an agent for skin regeneration. Today, it is widely used as a component of cosmetic preparations that has an anti­aging effect on the skin. Newer recommendations related to cosmetics suggest it as a "herbal substitute for retinol", with a much higher level of safety of use.

Cullencorylifolium L. Medik

Cullen corylifolium (Linn.) Medik is the officially accepted Latin name of representatives from the Fabaceae family, which previously appeared under many synonyms: Psoraleacorylifolia,C.corylifolia,C. corylifolius, Lotodes corylifolia, Psoralea patersoniaeandTrifoliumunifolium8 C.corylifolium popular is called babchi in Hindi.

C.corylifolium seed extracts are used as a diaphoretic, stimulant and aphrodisiac. It is also used in the treatment of asthma and chronic cough. In traditional Ayurvedic medicine, extracts of the whole plant are used to relieve skin inflammation that occurs in diseases such as psoriasis, vitiligo and leprosy.

FIGURE 1 Chemical structure of bakuchiol

Today, due to the presence of psoralen in its chemical composition, the most commonly used species is C. corylifolium . Isolated psoralen is used in PUVA therapy. It is a form of photochemotherapy that involves treatment with ultraviolet light (UV-A) combined with oral psoralen to make the skin sensitive to radiation. The therapy is used in the treatment of, among other things, psoriasis, vitiligo, alopecia areata and in the early stage of mycosis (granuloma) fungoides.9 Psoralen, apart from its therapeutic effect, has a very toxic effect, so it cannot be used in the usual cosmetic preparations that are applied on the skin. In chemical terms, psoralen belongs to the group of furanocoumarins, which have a strong phototoxic effect and cause numerous photodermatoses. Under the influence of UV radiation, they cause severe sunburns and blisters, acute dermatitis and lead to cell damage when exposed to the sun.10

The chemical composition of Cullen corylifolium fructus (C. corylifolium fruit) shows that the largest amount of biologically active substances is found in the seeds, which fill a significant part of the fruit. The dominant groups of secondary metabolites found in the composition of the fruit are meroterpenes, furanocoumarins, flavonoids and terpenoid compounds. C. corylifolium is a plant known mainly for its high amount of furanocoumarins (90.4%), with psoralen (39.6 mg/100 g DN) and angelicin (isopsoralen) (50.8 mg/100 g dry water) as quantitatively dominant compounds.11 Interest in this plant is currently growing, especially due to the high content of bakuchiol (1-7%).

Retinoids

Retinoids were first defined as a family of natural compounds consisting of vitamin A (retinol) and its derivatives such as vitamin A aldehyde (retinal) or vitamin A acid (retinoic acid). Retinoic acid is considered to be the active form of the vitamin. Human dermal fibroblasts treated with retinol metabolize retinol to retinoic acid. The bioactivity and bioavailability of retinol in the dermis has been proven in vitro.12

Retinoic acid and its derivatives have been used as therapeutic agents for numerous skin conditions from psoriasis to acne, and have been clinically found to be effective against wrinkles.

Application of retinol is believed to be a more effective method of delivering retinoic acid to skin cells than direct retinoic acid treatment. However, in the use of retinoid therapy, even newer analogs are still limited by many undesirable side effects.

Preparations with retinol and its derivatives, socalled retinoids, applied directly to the skin can cause itching, burning, redness, rash, dryness, increased keratinization of the epidermis and hypersensitivity to solar radiation. When taken orally, they cause excessive sweating, hair loss and dryness of the mucous membranes of the nose and eyes.13 Retinoids have a negative effect on fat metabolism (they generate an increase in triacylglycerol and cholesterol in the blood) and on the osteoarticular system (they cause muscle pain, decalcification of bones and premature closure of joints cartilage).

Nowadays, retinoids are most often used against skin aging, but due to unwanted side effects such as itching, burning, peeling and skin photosensitivity, their use has decreased.

There is a growing interest in innovative, natural products that will be positively evaluated based on health and clinical studies. Bakuchiol is a component of plant origin that has proven to be a very good substitute for retinol, as it regulates the expression of genes and proteins that have an impact on the aging process of the skin and significantly affects the reduction of lines and wrinkles on the skin, affects pigmentation, elasticity, firmness and the reduction of photodamage without the unwanted side effects that occur when using retinol.

Skin aging and bakuchiol

Skin aging is a complex process influenced by genetic, environmental, mechanical and socioeconomic factors. The intrinsic or genetic structural changes of skin aging include increased skin fragility and decreased ability to heal the skin. The most important environmental factor that affects extrinsic skin aging is the sun's ultraviolet radiation (UVR). Longterm exposure of the skin to the sun's ultraviolet radiation leads to premature aging of the skin, which is characterized by deep wrinkles, sagging and a wrinkled appearance. This process is called photoaging of the skin.

FIGURE 2 View of the "laugh lines" or so-called crow's feet.

Taken from https://londonskin.com.au/skin-concern-crowsfeet-wrinkles/

Scientists have clinically evaluated the effectiveness and safety of already developed 3-in-1 night facial serums (Night Facial Serum, NFS) against skin photoaging.14,15 Night oil serums contain three ingredients that actively support biological processes on aged skin under the influence of photoaging, namely: melatonin, bakuchiol and ascrobyl tetraisopalmitate. Research provides insight into the effectiveness and tolerability of the anti-aging night face serum, hydration kinetics, transepidermal water loss, effectiveness in oily skin and comedogenesis. In addition, the clinical and histological effects of the 3in-1 night face serum on signs of skin aging were determined.

Research into the effectiveness and tolerability of the night serum for the face was conducted on 39 healthy women aged 40-65, who had the so-called crow's feet around the eyes (Figure 1) and moderate skin aging. The participants had to have at least one pigment spot on their face, Fitzpatrick's phototype

I-IV, they had to have a daily facial care routine and use serum regularly. Every evening for three months, they applied the night serum as described.

In clinical studies of the nightly application of a 3in-1 serum containing melatonin, bakuchiol and ascorbyl tetraisopalmitate, on a total of 103 women covering all skin types during 28-84 days, clinically and statistically significant effectiveness against signs of skin aging without irritating side effects has been proven.

Acne vulgaris - the effect of bakuchiol on improving the appearance of the skin

So far, there is not a single topical anti-acne drug that has the ability to act on their four main pathophysiological features. That is why it is important to mention the test of a dermocosmetic cream containing a triple complex ­ bakuchiol, Ginko bilobae extract and mannitol (BGM). Researchers16,17 aimed to evaluate the antibacterial, anti­inflammatory and antioxidant potential of the BGM complex and its individual components, as well as its influence on sebum composition.

ces, the active formulation contains enoxelone (18β glycyrrhetinic acid), salicylic acid, esters of alpha hydroxy acids and zinc gluconate. All these components are well-known pharmacologically active agents used in the treatment of acne. Additionally, it was confirmed that the BGM complex increases the established clinical effectiveness of adapalene 0.1% gel used by acne patients.

Clinical in vivo studies have also proven the antiinflammatory effect of bakuchiol in adolescent acne. It is assumed that this is due to the antibacterial properties of bakuchiol against the Propionibacterium acnes strain (Polakov et al. 2015).

Further in vitro research18 confirmed the antibacterial activity against P. acnes strains, by determining the minimum inhibitory concentration (MIC) using a standard method. It was shown that the growth of P. acnes after the application of bakuchiol was only 0.0005%, and there was a reduction in inflammation. The antioxidant effect of bakuchiol has also been confirmed.

Application of bakuchiol in postural hyperpigmentation (PIH)

The BGM complex mimics the effect of vitamin E, enabling protection against the potentially harmful effects of squalene oxidation products such as hyperkeratinization and inflammation. In the triple complex prepared in this way, bakuchiol regulates increased secretion of sebum (seborrhea) and has antibacterial properties. In addition to auxiliary substan-

FIGURE 4 Formation of hyperpigmentation

Postinflammatory hyperpigmentation (PIH) is an acquired hypermelanosis that occurs as a reaction to inflammation (acne, psoriasis, atopic dermatitis) or injury (can be caused by dermabrasion, chemical peeling, or laser therapy). Hyperpigmentation occurs as a result of increased melanin production under the influence of internal or external factors. PIH manifests itself as shallow, dark areas on the skin. The resulting spots can vary from pink to red, brown or black, depending on the color of the skin and the degree of discoloration. All skin types are susceptible to PIH, but it is most prevalent in people with darker complexions. The severity of PIH is determined by the skin phototype according to Fitzpatrick, the degree and depth of inflammation, the degree of disruption of the dermal-epidermal layer and the stability of melanocytes (Figure 5).

Despite the frequent occurrence of PIH in humans, treatment can be quite challenging, and various inflammations and oxidative stress play a significant

Taken from https://www.eucerin.hr/o-kozi/indikacije/hiperpigmentacija-uzrokovana-upalom

Melanocyte

FIGURE 3 Acne

role in the formation of pigment. Scientists at Unigen Inc. developed Bakutrol® which is an extract of Psoralea corylifolia , a tree native to Asia that contains bakuchiol, a compound with antimicrobial, anti­inflammatory and antioxidant properties, which may play a role in reducing acne-induced PIH. In the paper19, the authors aimed to evaluate the effectiveness of topical bakuchiol in reducing PIH associated with acne, and to additionally confirm the model of PIH induced by trichloroacetic acid (TCA) and compare that model by topically applying bakuchiol with PIH which is a consequence of acne.

A 2011 study20 aimed to investigate the safety, tolerability, and efficacy of a cream preparation UP256 containing bakuchiol for the treatment of facial acne and acne-related PIH. The use of bakuchiol has been linked to the treatment of various inflammatory diseases and conditions mediated by cyclooxygenase and lipoxygenase. The potentially beneficial effects of the prepared cream were tested during a 12-week pilot study.

Bakuchiol and allergies in cosmetics

Certain substances found in the composition of herbal components in natural cosmetics can be used for years in usual concentrations without reaction, but sometimes a sudden reaction of the immune system can occur. In order to find out which substances the body reacts to with an allergy, testing for individual natural ingredients plays an important role so that they can be avoided by choosing cosmetic products that do not contain them.

Although there are cases where bakuchiol has caused allergic reactions, these are very rare and this ingredient is considered safe for use on sensitive skin and for use by pregnant and lactating women.

Conclusion

Bakuchiol has become known as a natural alternative to retinol. It is considered gentler on the skin, which is an advantage over retinol. It is necessary to take into account that to date it has been tested less than retinol. It can be used for all skin types, except for those allergic to that ingredient. Additional tests on this new and promising cosmetic ingredient are definitely needed to fully understand its action and reveal its full potential.

References:

1 Uikey SK, Yadav AS, Sharma AK, Rai AK, Raghuwanshi DK, Badkhane Y. 2010. The botany, chemistry,pharmacological and therapeutic application of Psoralea corylifolia L. - a review. Int J Phytomed. 2(2):100–107.

2 Khushboo P, Jadhav V, Kadam V, Sathe NS. 2010. Psoralea corylifolia Linn.­"Kushtanashini".—“. Pharmacogn Rev. 4(7):69–76.

3 Yao S, Yang B, Xu Z. 1995. Determination of bakuchiol in the fruit of Psoralea corylifolia L. China J Chin Materia Medica. 20:601–683.

4 Rao P, Bhalla AS, Nayak V, Dev UR, Meroterpenoids S, Psoralea I, Linn IC. 1973. Absolute configuration of (þ)­bakuchiol. Tetrahedron. 29(8):1127–1130.

5 Cornforth J. 1968. Terpenoid biosynthesis. Chem Br. 4(3):102–106.

6 Pirola L, Fr€ojd€o S. 2008. Resveratrol: one molecule, many targets. IUBMB Life. 60(5):323–332.

7 https://ec.europa.eu/growth/sectors/cosmetics/cosing_en

8 http://www.theplantlist.org/

9 Yalc¸in B, Sahin S, Bukulmez G, Karaduman A, Atakan N, Akan T, Kolemen F. 2001. Experience with calcipotriol as adjunctive treatment for vitiligo in patients who do not respond to PUVA alone: a preliminary study. J Am Acad Dermatol. 44(4):634–637..

10 Bruni R, Barreca D, Protti M, Brighenti V, Righetti L, Anceschi L, Mercolini L, Benvenuti S, Gattuso G, Pellati F. 2019. Botanical sources, chemistry, analysis, and biological activity of furanocoumarins of pharmaceutical interest. Molecules. 24(11):2163–2125..

11 Liu R, Li A, Sun A, Kong L. 2004. Preparative isolation and purification of psoralen and isopsoralen from Psoralea corylifolia by high-speed counter-current chromatography. J Chromatogr A.1057(1–2):225–228.

12 Bailly, J., Crettaz, M., Schifflers, M.H. et al. In vitro metabolism by human skin and fibroblasts of retinol, retinal and retinoic acid. Exp. Dermatol. 7, 27–34 (1998).

13 Brecher AR, Orlow SJ. 2003. Oral retinoid therapy for dermatologic conditions in children and adolescents.J. Am.Acad. Dermatol. . 49(2):171–182.

14 Goldberg, D. J., Robinson, D. M., & Granger, C., Clinical evidence of the efficacy and safety of a new 3‐in‐1 anti‐aging topical night serum‐in‐oil containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate: 103 females treated from 28 to 84 days. Journal of Cosmetic Dermatology, 18(3), 2019.,806–814.

15 Goldberg, D. J., Mraz‐Robinson, D., & Granger, C., Efficacy and safety of a 3‐in‐1 antiaging night facial serum containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate through clinical and histological analysis. Journal of Cosmetic Dermatology. 2020.

16 Jourdan, E., Fauger, A., Sayag, M., & Poláková, K. A dermocosmetic containing bakuchiol, Ginkgo biloba extract and mannitol improves the efficacy of adapalene in patients with acne vulgaris: result from a controlled randomized trial. Clinical, Cosmetic and Investigational Dermatology, 2015., 187.

17 Jourdan, E., Fauger, A., Sayag, M., & Poláková, K. A dermocosmetic containing bakuchiol, Ginkgo biloba extract and mannitol improves the efficacy of adapalene in patients with acne vulgaris: result from a controlled randomized trial. Clinical, Cosmetic and Investigational Dermatology, 2015., 187.

18 Jourdan, E., Trompezinski, S., Weber, S., Cadars, B., Larue, F., Ardiet, N., Sayag, M., Assessment of a new biological complex efficacy on dysseborrhea, inflammation, and Propionibacterium acnes proliferation. Clinical, Cosmetic and Investigational Dermatology, Volume 9, 2016., 233–239.

19 Lyons, A. B., Kohli, I., Nahhas, A. F., Braunberger, T. L., Mohammad, T. F., Nicholson, C. L., Hamzavi, I. H., Trichloroacetic acid model to accurately capture the efficacy of treatments for postinflammatory hyperpigmentation. Archives of Dermatological Research, Germany, 2020.

20 Shalita, A. R., Geen, S. C., Lee, W., Yaping, E., A clinical study evaluating the dermatologic benefits of topical bakuchiol (UP256) cream on facial acne, Journal of the American Academy of Dermatology, 2011., 64(2)

Two new Nutricosmetics products

SternLife

SternLife, one of Germany's leading suppliers of private label solutions for functional foods, is expanding its Nutricosmetics portfolio with two concepts for the mental health megatrend: "Mood" and "Sleep" are water-soluble drink powders in Spicy Vanilla Chai and Cherry flavors. Thanks to this dosage form, the innovative active ingredient complexes are better absorbed by the body. They promote resilience against everyday stresses and strains, and are characterized by proven formulations with highquality, selected ingredients. The composition of both products can also be customized, giving companies the opportunity to tailor trendy finished products to their chosen target groups. In addition, health claims can be used on-pack.

Unhealthy eating habits, hectic lifestyles and excessive workloads are very much part of everyday life for many people. These can result in difficulty sleeping – a problem that is thought to affect 10­40 per cent of adults at some point in their lives. Insufficient regeneration leads to reduced stress resilience, impaired performance and metabolic disorders such as high blood pressure, cardiovascular disease and diabetes mellitus, and can affect mood, mental wellbeing and quality of life. So it’s perhaps not surprising that dietary supplement products for improved sleep quality and reduced nervous stress have been the fastest growing category for several years in a row.

"Sleep" supports the natural sleep cycle and comprises calming natural extracts such as lavender, ashwagandha and pumpkin seed. Studies have proven that pumpkin seed extract has a muscle_relaxing effect and leads to less frequent urination. It also contains amino acids, vitamins and magnesium, which has been shown to reduce cortisol and thus improve slow wave sleep.

"Mood" is based on an anti-stress complex of various nutrients and natural extracts that can help reduce the body's stress molecules cortisol and homocysteine, thereby easing nervous stress. It also contains calcium, biotin, magnesium, panthothenic acid and riboflavin which support normal energy metabolism function. Calcium also aids the normal function of digestive enzymes. "Mood" and "Sleep" complement Sternlife's Nutricosmetics line, which so far in-

cludes the powder supplements "Detox Booster" for self-cleansing, "Skin-Care" for a fresh complexion and "Hair-Care" for healthy hair. The water-soluble applications are easy to store and prepare, and because the active and vital substances are contained in a beverage, they are more quickly absorbed.

Marc van Essen, Sales Manager at SternLife, says: "Our scientifically based Nutricosmetics concepts covering all aspects of beauty, lifestyle and health are ideal for companies looking to expand or build their product portfolio. We use state-of-the-art manufacturing equipment, which guarantees high and consistent quality, and also provide additional advice on individual customization options and marketing strategies."

SternLife GmbH & Co. KG develops and manufactures functional foods and food supplements. The company's portfolio includes various forms of products - from powder preparations, through functional bars and snacks, functional drinks and shots, to capsules and tablets. Brands have at their disposal comprehensive knowledge and experience in the innovative sector of healthy, sports and lifestyle nutrition, as well as an assortment of products adapted to specific target groups.

The

company expands its Nutricosmetics concept with new nutritional supplements in powder, which dissolve quickly in water and provide additional health benefits, and are intended for well-being and improving the quality of sleep.

Cosmetic innovations in hair loss prevention

AUTHOR: Maja

,

Introduction

Hair loss (alopecia) is a progressive condition that has different forms and causes. The most common type of hair loss, known as androgenetic alopecia, is hereditary. If left untreated, hair loss usually progresses over time.

Did you know?

• 80% of all men experience androgenic alopecia during their life.

40% of all women experience androgenic alopecia during their life.

The hair system is fragile and can be easily affected when exposed to internal and external factors such as inadequate care, environmental pollution, and aggressive treatments. It has been reported that when the bulb, scalp and shaft are nourished and protected from external aggression, the treatment of alopecia may have a superior dermatological response.

It has been observed that the treatment and prevention of alopecia can have a superior response if the scalp, hair shaft and hair follicle are nourished and protected from external influences.

Pavlić

Industry Sales Manager, Fagron Croatia

FIGURE 1 Hair follicle

Several products that are currently used in hair formulations, such as alcohol, propylene glycol and some surfactants, can modify the hydrolipidic layer.

Hair growth cycle

The hair growth cycle is directly correlated with the health of the hair follicle and of the scalp. The hair growth cycle has been a matter od debate for many years. Classically, it is divided in phases: the fiber production phase (anagen), the regression phase (telogen). Each of these phases last in average 2 to 6 years, 3 weeks, and 3 to 4 months.

FIGURE 2 Hair growth cycle

A phase known as “exogen phase” has been described as an independent phase in which the fiber is released from the hair follicle without interfering directly in the beginning of the anagen phase. Between the elimination of a hair fiber in exogen phase and the appearance of a replacement hair in anagen phase, a latency period is observed in 805 od hair cycles – the kenogen period (duration of 2 to 5 months, in average).

It is possible to conclude that the hair follicle undergoes steady periods (telogen and anagen phases) that are interrupted by short and intensively active periods of remodeling, regression, and regeneration.

Dermal papilla cells: essential for hair follicle development in the hair growth cycle

DP cells are highly specialized fibroblasts with multiple roles:

• scaffold for hair follicle

• cell signaling activation of stem cells; downward growth of the hair follicle’s epithelial part production of surrounding connective tissue

DP cells in Alopecia Androgenetica:

• decreased formation of connective tissue

• loss of proliferation capacity

FIGURE 3 DP cells in cell culture

In vitro self-aggregating behavior under the influence of Follicusan™ DP. Key to induction of hair follicle development.

Follicusan™ DP - active innovation that prevents accelerated hair loss

Follicusan™ DP stimulates the functionality of the dermal papilla cells at the base of the hair follicles, thus counteracting premature hair loss. It increases the number of anagen hair follicles (growth stage) and decreases that of telogen hair follicles (resting stage). Hair density as well as cumulative hair thickness is increased.

Follicusan™ DP contains biologically active signaling proteins, ethyl panthenol (provitamin B5), inositol as well as acetyl cysteine and acetyl methionine in a water-ethanol medium.

Follicusan™ DP - raw material properties

Appearance, Odor: Off­white opaque, particle­free liquid; characteristic odor. Solubility: If used at the maximum concentration of 5%. Follicusan™ DP dissolves in water and water alcoholic mixtures with a maximum alcohol content of 50 % v/v.

Recommended Use: Aqueous and aqueous-alcoholic hair care preparations (high-grade hair lotions) for application to scalps with functional disorders (prevention of accelerated loss of hair). In addition, Follicusan DP can be applied to scalps with a tendency to greasiness and dandruff.

Characterization: Follicusan™ DP contains biologically active signaling molecules, ethyl panthenol, inositol as well as acetyl cysteine and acetyl methionine, in aqueous-alcoholic medium. Follicusan DP vitalizes the cells of the scalp including the hair follicles, thus counteracting premature, accelerated loss of hair. Origin: Synthetic/animal-derived

Mode of action

Premature, accelerated loss of hair, also known as Alopecia, can be caused by various factors. Frequently, it is due to functional disorders in the hair growth cycle. Follicusan DP stimulates cellular functioning in the scalp and in the hair follicles and thus counteracts premature loss of hair, as could be demonstrated in a study. A gel containing 5 % Follicusan DP, used over a period of three months, was found to normalize hair growth cycles in individuals suffering from Alopecia diffusa and Alopecia androgenetica, which was proven by preparing trichograms: The number of anagen hair follicles (growth stage) was found to have increased and that of telogen hair follicles (resting stage) decreased.

Follicusan DP helps prevent functional disorders of the scalp by vitalizing the cells. Furthermore, due to its active ingredient composition, it can normalize excess sebum secretion, thus counteracting formation of dandruff.

Hair and scalp benefits

• Vitalizes scalp and hair follicles, stimulates dermal papilla cells

Improves hair density and thickness

Reactivates the hair growth cycle

• Effectively counteracts premature accelerated hair loss

Marketing opportunities

Provides new vitality and energy to thinning hair

• Revitalizes the scalp, designed to counteract hair loss

Stimulates and revitalizes the hair roots

• Improves health and structure of hair

• Fights hair follicle aging at its root

Selected efficacy studies

Stimulation of proliferation - Dermal papilla cells are the most important cell type found in the hair root. A strong stimulatory influence of Follicusan™ DP on dermal papilla cells was observed. This feature is essential for the development of new hair to increase the number of anagen hair and effectively fight hair loss (Figure 4).

FIGURE 4 Stimulation of proliferation

FIGURE 6 Effect on the ATP content

Impact on hair density - Density is the number of hairs per cm2 on the scalp. The 24 volunteers, suffering from alopecia androgenetica, showed a reduced hair density of only ~180 /cm2. With the daily use of Follicusan™ DP a positive trend could be noticed after only 3 months, indicating that Follicusan™ DP was able to re-activate the hair growth cycle (Figure 5).

FIGURE 5 Influence on hair density

Influence on the anagen hair rate - Daily use of Follicusan™ DP halted the progression of alopecia androgenetica after only 3 months and increased the number of hair follicles in the anagen growth phase over the subsequent 3 months (Figure 7).

Influence on ATP content - Follicusan™ DP significantly increases the ATP content in dermal papilla cells (Figure 6).

Standard percentage of hair in the anagen phase ~ 85%

Summary

• Follicusan DP prevents functional disorders of scalp and follicle cells through vitalization Stimulates proliferation and ECM (Extracellular Matrix) synthesis of human dermal papilla cells

• Stops the progression of Alopecia androgenetica in women.

FIGURE 7 Effect on anagen hair rate Fagron Hrvatska d.o.o. Donjozelinska 114 10382 Donja Zelina, Hrvatska info@fagron.hr

CLR Chemisches Laboratorium

Delicious new ways to increase fibre content

Omya enriches its European distribution portfolio with a versatile range of natural fibre powders. By increasing the fiber content in the finished product, manufacturers can use nutrition claims such as "source of fiber" or "high in fiber" or health claims related to normal bowel function.

Always focusing on holistic solutions with added value, Omya presents dietary fibres that not only enhance the nutritional profile of a wide range of applications but also positively impact processing procedures for efficient manufacturing. The new range consists of apple fibre, oat fibre and cocoa fibre – all­natural, clean label ingredients without chemical treatment or E numbers. By increasing the healthy fibre content of the formulation, the micronized powders allow a health or nutrition claim to be made for the final product. Moreover, the ingredients contribute to natural binding of water, improved texture and support emulsification, and therefore allow for a smooth production process.

The apple, oat and cocoa fibre are processed by micronization of sterilized dried fruit pomace and peels, grain husks or shell parts into powder with different particle sizes in order to create appropriate powder solutions for specific applications. All powders are 100% natural and insoluble. In terms of the functional properties of water binding and fat mimicking, the fibre solutions enable a reduction of sugar and fat content in a formulation, and thus improve the nutritional quality of a food product. Manufacturers can also use the powders to increase the fibre content of the finished product and therefore make on­pack claims such as “source of fibre” or “high in fibre” if required. In addition to nutritional claims,

the dietary fibre solutions also allow for the promotion of health claims relating to normal bowel function.

Cocoa fibre is ideal for all those applications where the perception of cocoa in combination with improved nutritional value of a food is highly desirable from a consumer perspective. Neutral­tasting oat fibres are a versatile dietary fibre solution designed to bring natural functionality and fibre enrichment not only to a wide range of bakery and snack solutions, but also vegan foods and nutritional beverages. Apple fibre can partially replace pectins, substitute modified starches and is thus an ideal dietary fibre solution for a diverse range of food applications such as bakery products, vegan applications, sauces & dips and fruit preparations.

Stefan Lander, Vice President Consumer Goods, Group Sales & Marketing at Omya, says: “Today, more than ever, consumers place a special emphasis on the highest quality and safety of the food they consume. At the same time, manufacturers are under high pressure to produce efficacious products as efficiently as possible. As Omya has been committed to implementing sustainability at all levels since its foundation, we are delighted to support both sides with added value ingredients that help keep health and environment in balance.”

Inspirational success story

BITE ME products contain dried fruits, nuts, seeds and spices, and do not contain gluten, additives or added sugars. The ingredients have an ecological certificate, and in the bars there is an emphasis on a larger amount of nuts than the competition. We bring you an interview with co-founder Petra Mihalić, a food technologist and nutritionist in charge of creating recipes.

NMC: How did it all start?

BITE ME entered the market in the same year when the whole world stopped or began to face challenges of the COVID-19 pandemic. Regardless what was happening in the world, we decided to jump headfirst. As the name of the brand says, we decided to bite all the challenges and handle all obstacles. It wasn't easy but, from the handmade cookies which we were selling in Vivas bars, we ended up with ten different products that are now sold in several European countries. It was a long and difficult journey, but we don't regret it, in fact, we learned a lot and gained valuable experience. Today, from this per-

spective, we are happy to remember the beginnings.

NMC: What was the idea and what inspired you to do it?

BITE ME was actually created in response to the demands of pro and amateur athletes who wanted to replace usual sports nutrition with 100% natural products. We ourselves went through that path where we got fed up with various sports nutrition products that were not good for our health in the long term. Over time, we realized that this is not only a problem of athletes, but also of people in general who want to live a healthier life and change their bad nutritional habits.

We found inspiration for product development in the historical heritage of the Mediterranean and local ingredients, where we combined characteristic flavors into refreshing and organic energy bars and cookies. We thought about nutritionally rich food which can give you energy and keep you full for a longer period of time. We understood what our ancestors did, especially in Dalmatia. When they had to

work on their land all day, they would put some nuts and dried fruits in their pockets. That is our basis. Sometimes it is necessary to take a few steps back, remember what worked before, take the essence and improve it.

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

To have such delicious and successful products today required a lot of work, effort and failed recipes. Before the energy bars hit the market, we tested the recipes for almost two years. It was a long process, but that's why now we have such tasty and high-quality products. When you look at the ingredients and experience the taste, you will know why it took us so long. It is this recipe that separates us from the competition.

Also, the initial investment we received meant that we were embarking on a serious business venture, and today we have seven employees. Everything is easier with a good team, and luckily we have just that.

NMC: How satisfied are you with what was achieved?

We are very satisfied with where we are today. We are building the business slowly but surely. The sure foundations and experience are here, and now it's time to take everything to an even higher level. Plans for the future are getting bigger, but they no longer seem impossible. When you see your products on the shelves of big retail chains, you know that you are going in the right direction. When those products come for example, on the shelves of Decathlon Hong Kong or when you present them at the largest food & tech exhibition in Paris, then you are sure that everything is as it should be. Feedback from people who try our products for the first time is extremely important to us, and the superlatives we hear push us forward.

Biofach and Vivaness 2023

Organic system paves the path for ecological transformation

to 17 February 2023

Following the one­off summer edition held at the end of July 2022, the organic food and natural and organic cosmetics sectors will revert to February again for their annual gathering. The new Tuesday to Friday schedule from 2022 will be retained. Having been integrated into the Biofach halls just for the summer edition, Vivaness will now be returning to Hall 3C.

“We are already looking forward to gathering the organic food and natural and organic cosmetics communities on site in Nuremberg again and offering them a framework for innovation and transformation, inspiration and networking! In 2023, our international trade visitors can look forward to the comprehensive product displays of around 2,700 exhibitors, 200 of them at Vivaness,” says Danila Brunner, Director Biofach and Vivaness. “Especially in the current times, it is more important than ever to meet and exchange ideas and knowledge in person, and to look to the future to prepare the ground for the issues that will define it. In other words, to pave the path together!”

In addition to classic exhibition content, visitors will be able to attend rich educational programs at the Biofach and Vivaness congresses.

The Biofach Congress will be concentrating on two key questions: How do organic products contribute to food security and sovereignty, and how do “true prices” – prices that include ecological after-costs –pave the path for the necessary transformation of the food and grocery industry?

The thematic content is being organised in conjunction with Biofach's international patron, International Organization of Organic Agriculture Movements (IFOAM) and national organization BundÖkologischeLebensmittelwirtschaft (BÖLW).

The Vivaness Congress, with its comprehensive programme and wide range of sessions, also offers the opportunity for discussion, dialogue and knowledge transfer from the field of natural and organic cosmetics.

BITEME Nutrition Ltd.

www.biteme-nutrition.com bite@biteme-nutrition.com

As was the case during the one­off summer edition in 2022, all participants will have the opportunity to watch parts of the Biofach and Vivaness congresses as a live stream via the digital platform. The sessions will subsequently be available as on-demand videos.

For more information, visit: www.biofach.de and www.vivaness.de

Biofach, world leading trade fair for organic food, will open its doors in Nuremberg from 14

alongside Vivaness, international trade fair for natural and organic personal care.

medicinal plants photo herbarium

Dandelion

AUTHOR: Daria Šurić, M.pharm.

Dandelion is a plant without an aerial stem. Its root is cylindrical and slightly branched, and can be about 20 cm long. Like other parts of the plant, the root contains considerable amounts of white, milky juice.

The leaves are in the shape of a rosette, pinnately cut. The aerial part consists of a rosette of leaves, from the central part of which, at the time of flowering, a naked, tubular flower stalk 15­30 cm high with a flower head on top develops.

The flowers are bisexual, tongue­shaped, golden yellow, collected in heads with a diameter of 3-5 cm. The flowers are open until noon, and when the light disappears and in cloudy weather, they close. After flowering, the flower turns into recognizable white airy balls similar to lanterns, which we all happily blew into in childhood. These are seeds that have a plume

Dandelion, Taraxacum officinale (L.) Weber, is a wild plant with yellow flowers that, after flowering, turn into distinctive airy balls composed of plumed seeds. The root (Taraxaci radix) and the leaf (Taraxaci folium) are medicinal. TAXONOMY

or pappus, that is, small hairs, which serve as a parachute for spreading the seeds with the help of the wind.

Use for medicinal purposes

The root (Taraxaci radix) and leaf (Taraxaci folium) are used for medicinal purposes.

The drug is the dried root of the dandelion, Taraxacum officinale (L.) Weber. In some pharmacopoeias, the official drug is root with the aerial part ­ Taraxaci radix cum herba .

The aerial part of the plant is collected in the spring when the amount of bitter substances is the highest, while the root is collected in the fall, when it contains the highest amount of inulin (40%). Due to its high inulin content, it can, like chicory, be used as a substitute for coffee.

common name

Blowball, cankerwort, doon-head-clock, witch's gowan, milk witch, lion's-tooth, yellow-gowan, Irish daisy, monks-head, priest's-crown, and puff­ball

flowering time IV,V, sometimes repeatedly IX,X month

Dandelion leaves, which are collected young in spring, are used as food in salads.

Ingredients

• bitter substances: sesquiterpene compounds

• triterpenes

• phytosterols

• vitamins A, B, C and D polysaccharides: inulin mineral substances: potassium salts

Leaves contain:

• coumarins carotenoids

• minerals: especially potassium

Roots contain:

• taraxacosides phenolic acids

• minerals: potassium, calcium

Mode of action

Bitter substances (sesquiterpene lactones) stimulate the secretion of saliva and gastric juice (gastric acid, pepsin) and stimulate the appetite. Bitter substances reduce the pH value in the stomach. They also improve the efficiency of proteolytic enzymes in the digestive tract (by stimulating a suitable pH). The bitter substances of dandelion also stimulate the secretion of bile (choleretic effect).

Inulin is a polyfructoside that has a favorable effect on bifido bacteria and, as a vegetable fiber, has a favorable effect on digestion. Due to the content of potassium salts, the drug Taraxaci radix cum herba has a diuretic effect.

Usage

The drug Taraxaci radix cum herba is used for disorders in the secretion of bile, to stimulate the appetite and for dyspeptic problems. Dandelion is also used to stimulate the excretion of urine, i.e. to promote diuresis. In traditional medicine, it is used in the so-called spring cure for "organism cleansing" (improvement of digestion, acceleration of diuresis).

The daily dose of the drug is 3-4 g (2½-3½ teaspoons) per cup, and it is prepared by putting it in cold water and boiling it. It is also available on the market in finished products in the form of tablets or capsules.

Care should be taken when using it in people who have gallstones. Contraindications are biliary obstruction and ileus. When in contact with the fresh plant, allergic reactions are possible due to the content of sesquiterpene lactones.

References:

Flora Croatica database, hirc.botanic.hr

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

Izvor: Maslačak https://www.plantea.com.hr/maslacak

Schafner, Willi: Ljekovito bilje: kompendij, Leo-commerce, 1999.

Prof.dr.sc. Zdenka Kalođera, Sveučilište u Zagrebu, Farmaceutsko-biokemijski fakultet, Farmakognozija II, Zagreb, 2006./2007.

Novelties in the Sunfiber® and Sunphenon® range

Taiyo GmbH, a pioneer in the research and manufacture of functional ingredients for the food and pharmaceutical industries, presents new variants within two wellknown product lines.

Sunfiber® is a soluble prebiotic dietary fiber produced from the guar bean which promotes the acitivity and multiplication of beneficial probiotics in the gastro­intestinal tract. Sunfiber® VB can be utilised in baby food, and Sunfiber® AF in pet food. Because of its slow fermentation, Sunfiber® does not cause uncomfortable bloating, cramps or other digestive discomfort. All variants of Sunfiber® decrease the glycemic index of food products, which helps to stabilize blood sugar levels. Furthermore, the prebiotic dietary fiber supports the health and function of the intestinal tract, and increases overall wellbeing. Sunfiber® VC is characterised by its low viscosity which perfectly suits technological requirements. The functional ingredient makes baked goods crispier and fluffier, and is suitable for use in fruit gummies. Sunfiber® VC also dissolves well in fluids such as milk beverages or supplements in the form of syrups and shots.

Green tea catechins in the Sunphenon® range are innovative ingredients. Their health-promoting properties differ depending on the catechin: Sunphenon XLB can be used in oral hygiene and disinfectant products to make it more difficult for viruses to penetrate. Sunphenon® EC is a myostatin blocker that can positively contribute to muscle growth. In sufficient doses, it can also have beneficial effects against diabetes and obesity. The Sunphenon® EGC variant is an amylase and glucosidase blocker that can also have a healthpromoting effect in type 2 diabetes and obesity.

"Consumers are increasingly questioning a product's ingredients and looking for natural and plant-based alternatives with added health benefits," says Dr. Stefan Siebrecht, managing director of Taiyo's German subsidiary. "Taiyo is therefore presenting innovative solutions and products that enable the industry to meet these demands."

Psychotherapy with movement and dance

people worldwide

today

AUTHOR: Vedrana Kurjan Manestar, prof. of pedagogy, Gestalt psychotherapist, EAGT, ECP, movement and dance psychotherapist (RDMP), Center for therapy through dance and movement "Terpsichore", centar-terpsichore.hr, info@centarterpsichore.hr, Vice President of the Croatian Association for Psychotherapy through movement and dance, HUPPP

Introduction

According to the AmericanDanceTherapistsAssociation (ADTA), movement and dance psychotherapy is the therapeutic application of movement and dance in a creative process aimed at achieving emotional, cognitive, social and physical integration of the individual. Just like body-oriented psychotherapy directions, movement and dance psychotherapy advocates the necessity of including the body in psychotherapy.

In psychotherapy with movement and dance, in addition to focusing on the body and its appearance and position, as well as on the so-called blockages and sensations in the body, importance is also attached to the way the client moves (which includes every type of movement, from the way of breathing, gesturing, facial expressions, muscle tension and more). The basic assumption is that body movements reflect the inner state, and that changes in movement patterns also lead to changes in psychological patterns.

In psychotherapy with movement and dance, psychotherapists start from the so-called Laban's movement analysis, where the movement can be analyzed

through movement factors, i.e. the ways in which a certain movement is performed. If we consider time ­ the movement in its final stages can be fast or slow; in relation to space - movement can be direct or indirect; in relation to the weight of the movement - light or heavy (that is, tense or relaxed); and if we observe the flow ­ the movement can be free or bound. Very simplified, we can connect the four factors of movement ­ time, space, flow and weight (that is, force)to the inner psychological state of a person, by associating space with thinking, time with decision-making, flow with feelings and weight with identity.

Perhaps at first glance it may seem strange to associate the ways of movement with the psychological state of an individual, but if we notice, for example, at the state and movements of our body when we are angry or when we are joyful, we will notice that when we are joyful the movements are more often free (flow) and light (weight, i.e. force), and in anger they are more often bound, restrained (flow) and heavy, i.e. tense (force, weight).

Through movement and dance, psychotherapists work with clients on their movement patterns and thus gradually expand the spectrum of their movement. On the other hand, through the body and movement, they affect the expansion and development of different patterns of behavior, thinking and dealing with emotions. Simply put, in psychotherapy with movement and dance, we believe that if we move the body, we will move emotions and vice versa ­ through emotions, we will affect the body.

Due to the possibility of communicating with clients on a non-verbal level, and due to the release and resolution of certain repressed contents that remained "closed and written in the body" in the form of some illness or tension, dance psychotherapy is used in working with a wide range of clients, with various difficulties. In this article, I will focus on the application of movement and dance psychotherapy to patients suffering from depression and anxiety.

According to data from the World Health Organization, research shows that depression affects 121 million people around the world and today it is one of the leading factors of disability as a cause of loss of productivity (Koch S. et al. , 2007). Within the US public health system, it has been estimated that the cost of treating depression is even higher than the cost of

According to WHO data, depression affects 121 million

and is

one of the leading factors of disability as a cause of loss of productivity. Depression creates extremely high social and financial costs, so discovering financially acceptable, nonaggressive and effective treatment methods is an essential goal of public health.

treating heart disease (Greenberg, Stiglin, Finkelstein & Berndt, 1993). Thus, depression creates extremely high social and financial costs, so discovering financially acceptable, non­aggressive and effective treatment methods is an essential goal of public health.

The results of numerous studies speak of the positive impact of psychotherapy with dance and movement on various symptoms of depression such as apathy, fatigue, lifelessness, meaninglessness, lack of goals and strength to face life (Koch, S. et al. , 2007).

The cause of anxiety disorders is a wide range of factors, from biochemical imbalance to conflict and trauma from early childhood. All these causes can be divided into four categories: psychodynamic, behavioral, cognitive and biochemical. Psychotherapy with movement and dance includes techniques that change all four levels of the cause of the disease. Relaxation techniques, focusing on body sensations, active imagining and dramatization are some of the activities that help with anxiety disorders, and are used in movement and dance psychotherapy.

Anxiety is a disorder manifested by physical symptoms that include rapid pulse, shortness of breath, tremors and irritability. Other diagnoses may also form part of the clinical picture such as phobia, post-traumatic stress disorder and obsessive-compulsive disorder. A panic attack can be part of the picture of anxiety, and can be recognized as a momentary, overwhelming fear that occurs suddenly and has extremely strong physical sensations that occur in situations of perceived danger (palpitations, sweating palms, rapid breathing, tremors, etc.).

The connection between the experience of anxiety and its physical expression

The article by Fiasca, P. (1993) describes the results of a study that examined the relationship between anxiety experiences and descriptions of the physical expression of anxiety at a certain moment. Ten professional dancers and 10 amateurs participated in the research, 5 men and 5 women in each group. They were asked to describe two situations in which they were anxious, and then to physically demonstrate the experience of anxiety.

The research showed that respondents from all categories (female non-dancers, male non-dancers, female dancers, male dancers) expressed anxiety through 4 body areas - chest, neck, abdomen and back ­ which can be a reliable criterion for defining anxiety. This research supports the usefulness of defining anxiety through physical symptoms.

If the anxiety is so present that it can be adequately interpreted during the session, the clinician may consider it to be related to memories stored in some of the areas of the body described above. Based on this information, the therapist can gain a deeper understanding of the client and, based on this, can create a more adequate plan and treatment.

From another perspective, this research says that the therapist can use his own sensations during the session to analyze countertransference, that is, to check his own reaction to the client, examining which part of his body reacts to the client's problem.

However, it should be borne in mind, although the research does not take this into account, that the transfer of knowledge in our culture relies mostly on concepts and language. Articulation and trans-

mission of acquired "knowledge" based on the experience of sensations in our culture is, at best, of second-rate importance, and is often placed last in the process of acquiring knowledge.

On the other hand, the question is whether knowledge about the body can be adequately conveyed through conceptual linguistic meanings? Such questions bring with them complicated philosophical discussions about the possibilities of human coexistence on tactile and incompletely clarified aspects of knowledge about the body, which cannot be articulated through conceptual and linguistic analyses.

If more attention were paid to this aspect of the mind-body connection in clinical work, many psychosomatic diseases could at least be alleviated, if not cured. If we take into account the fact that, unlike animals, humans suffer from existential pain, we could find one of the causes of this human suffering precisely in the great capacity of the mind. Regardless of all its benefits, the problem arises when that magnificent mind, in the midst of certain pains and sufferings (in order to avoid those sufferings), is so far removed from the wisdom of the body that it leads to illness.

S. C. Koch et al. (2007) investigated the specific effects of a dance intervention on reducing depression. Total of 31 patients from the psychiatric hospital in Heidelberg participated in the study (18 women and 13 men). All patients in the study were diagnosed with depression as a main or secondary diagnosis. The examined patients were divided into three groups. One was involved in dance therapy, another in listening to music, and the third was exercising on an exercise bike. In dance therapy, the subjects danced a circular dance together with small vertical jumps (Kestenberg's theory predicts a feeling of joy induced by using bouncy rhythms). In the music group, subjects listened to the same music as the dance group while sitting relaxed with their feet on the floor. The third group of subjects rode an exercise bike to the same level of pulse acceleration as the dance group.

Considering the small sample size, the results of this study are encouraging and very helpful in prioritizing future research in the use of movement and dance psychotherapy with psychiatric patients. Namely, the participants in the dance group showed a significant reduction in depression, while the level of depression did not change in the patients in the other two groups. Furthermore, in patients in the dance group, there was an increase in vitality to a significantly greater extent compared to the other two groups. The biggest changes in the dance group were manifested in motivation, strength, energy and pleasure. Depression, lifelessness, anxiety and fatigue decreased.

This research is one of the first attempts to understand the specific factors that are influenced by dance psychotherapy in working with psychiatric patients diagnosed with depression. Although the authors expected benefits from all three interventions, dance proved to be the only tool that significantly reduced the level of depression.

The progress was more significant in men than in women, and was greatest in patients with the highest degree of depression. The authors concluded that patients with the highest degree of depression

gained the most from psychotherapy with movement and dance.

Also, it is important to emphasize that research has shown that the secondary effects of psychotherapy with movement and dance, unlike pharmacotherapy, are also positive. While drugs can cause fatigue, changes in muscle tone and nervousness, psychotherapy with movement and dance affects the body in a positive and invigorating way and leads to secondary results such as prevention of cardiovascular diseases, reduction of anxiety, etc.

At the end of that research, it was concluded that the intensive intervention of psychotherapy with movement and dance for two to three months, in 45 patients diagnosed with depression in a day psychiatric psychotherapeutic institution, showed positive effects on increasing the range of movement, relation to the body and self-perception, as well as perception of the relationship with to others.

Psychotherapy with movement and dance is often particularly attractive to female patients due to the expectation of improvement in their own body image, improvement of mood and stimulation of libido and general joy and will to live.

The results of some studies suggest that psychotherapy with movement and dance stabilizes the sympathetic nervous system, that it is effective in beneficially modulating serotonin and dopamine and in improving psychological disturbances in adolescents suffering from mild depression. In addition to patients suffering from depression, psychotherapy with movement and dance also enables people with minor difficulties to find more joy in life.

For me, dance is a metaphor for life. When we are born, we are given the opportunity to "dance" our unique dance. Each of us has our own unique movements, our own specific dance. But each of us has the ability to dance in different ways. The more we develop these ways, the easier it will be to "dance" to the different music that life brings us.

"Those who can't dance say the music is bad," says a Jamaican proverb. That is, for most of what life brings them, people blame the outside world or judge themselves too much. Those who know how to dance and dare to dance, dance regardless of the music, they find music in themselves, and with it the joy of life.

Literatura:

1 Sabine C. Koch, PhD, MA, Katharina Morlihghaus, Thomas Fucks, PhD, MD Sveučilište Heiderberg, odjel psihologije, Haupstr. 47­51, 60117 Heidelberg, Germany Psihijatrijska sveučilišna bolnica Heideberg, Njemačka: The joy dance – Specific effects of a single dance intervention on psychiatric patients with depression, The Arts in Psychotherapy 34, 2007, 340 – 349 str.

2 Fiasca, P.: “A research Study on Anxiety and Movement”, American Journal of Dance Therapy, Fall/Winter 1993, Volume 15, izdanje 2, 89-105 str.

3 Web stranica Američkog udruženja plesnih terapeuta ADTA https://adta.memberclicks.net/what-is-dancemovement-therapy

4 R. Martinec, T. Šiškov, R. Pinjatela, D. Stijačić. Primjena psihoterapije pokretom i plesom u osoba s depresijom. Soc. psihijat. Vol. 42 (2014). Br. 3, str. 145-154

B2B events calendar

An overview of on-site B2B events, from January to June 2023

4-6 February 2023, Seville, Spain https://www.expobellezandalucia.com

1-2 February 2023, Paris, France https://www.pharmapackeurope.com

6-8 February 2023, Barcelona, Spain https://probiotaevent.com

14-17 February 2023, Nuremberg, Germany https://www.biofach.de

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/

Successful debut at Paris

Fi Europe 2022: three days of sourcing, exchange and innovation, with more than 900 exhibitors and close to 19,000 attendees on site.

This year’s Fi Europe, the world’s leading food and beverage ingredients trade show, proved once again that it is the trusted meeting place for the global food and beverage ingredients industry. Celebrating its on-site debut at Paris Expo Porte de Versailles and framed by an extensive online event, the show saw attendance figures jump from 13,000 online and in person in 2021 to 21,881 to date – and counting. The top 3 countries in attendance were France, Netherlands and Germany, with Italy, UK, Spain, Belgium, Poland, USA and Denmark completing the top 10 list. Visitors were able to meet with and explore opportunities from 934 exhibitors – almost one third up on 2021.

Julien Bonvallet, Food Group Brand Director at Informa Markets, said: “We’re thrilled with the success of Fi Europe 2022 in Paris and online, with high-quality visitors and exhibitors showcasing pathbreaking solutions and products. It’s extremely heartening to see the entire F&B industry come together, build new business relationships, and share ideas and expert insights.”

Show highlights included live presentations to the winners of the Fi Europe Innovation Awards and the Startup Innovation Challenge; the New Product Zone, showcasing the latest ideas from leading industry players, and the Innovation Hub, where keynote speakers explored challenges and opportunities as well as sustainability and future-proof solutions.

Great to be back: what the exhibitors say

Gelita: “We were so excited to be back in person at FiE this year. Expectations were really high for this “re-start” event… And what can we say? All our expectations have been fulfilled – not only by the numbers of visitors, but also by the high quality of contacts we generated.”

Cargill: “It was great to be back on the FiE floor this year and to participate in such a buzzing event. FiE 2022 was a real reminder of the value of meeting again in person. It was the perfect opportunity for us to catch up with hundreds of our customers and partners from Europe and beyond, and to inspire them with new business opportunities. We continue to see FiE as the premier event for food ingredients supply and partnership – and long may it continue to set the tone.”

Alvinesa: “Exhibiting for the first time at FiE has been a great success. The interest in our upcycled, natural ingredients has exceeded our expectations and we’ve had some very interesting conversations with customers and potential new partners. We look forward to seeing where these new projects go, and have already booked our booth for next years’ show.”

Fi Europe Innovation Awards

During the event, the awarding of the prestigious Fi Europe Innovation Awards was held, the winners of which were awarded for their exceptional contri-

bution to the food industry.

Julien Bonvallet, Informa Markets Group Brand Director, said: “Over the years Fi Europe has provided the industry with a platform to discover new alternatives and find solutions to overcome challenges. Once again, the quality of entries to the Fi Europe Innovation Awards and the Startup Innovation Challenge was exceptionally high. This clearly shows that even – or especially – in challenging times, the ingredients industry continues to be both resilient and innovative, always findings ways to adapt to current market needs and driving initiatives that will shape a more sustainable food industry in the longer term.”

The winners of this year's awards by category are:

Food Training & Education Award: Mane (France) for its Food Development Training with flavourist students at ISIPCA, Paris, and future chefs at the Culinary Arts Academy in Switzerland.

Sustainability Innovation Award: Ofi (Singapore) for Cocoa Compass, a project that provides 100 per cent traceability for cocoa produced across nine countries, and makes sure that farmers earn a living wage, child labour is eliminated and the natural world is protected.

Diversity & Inclusion Innovation Award: Ingredion (USA) for its Women in Ingredion Business Resource Group. Established in December 2020 to empower women for an equal future, the group now has an inclusive network of members across the globe.

Plant-based Innovation Award: Bunge (USA) for its PurePro pea and faba proteins. Delivering 2g protein per serving, PurePro can be used to create superior vegan cheeses with improved sensory and nutritional profiles.

Sensory Innovation Award: Cargill (USA) for Gerkens Sweety Cocoa Powders, two natural cocoa powders that enable 30 per cent sugar reduction in chocolate drinks, without the need for sweeteners or artificial ingredients.

Health Innovation Award: Limagrain (France) for LifyWheat wheat flour, a multipurpose functional ingredient for bread, pasta and biscuits. High in fibre and resistant starch, LifyWheat helps reduce blood sugar levels after a meal and has a prebiotic effect on gut microbiota.

Food Tech Innovation: Sweegen (USA) for its novel bioconversion process for the production of Bestevia Reb M, the first new stevia ingredient produced via a new production technology to be approved for use in the European market by the European Food Safety Authority (EFSA).

In 2023, Fi Europe will return to Messe Frankfurt, Germany, from 28­30 November, and online to audiences around the world from 20-30 November 2023.

ence intake (DRI) has been set so far. Part of the benefits obtained from fruit and vegetable consumption stands in the diversity of polyphenols provided, sustaining the release of a large spectrum of polyphenol in circulation throughout the day and having metabolites released in the bloodstream at different times.

Based on such observations, Fytexia has developed a combination of plant extracts based on the “5a-day” recommendations in terms of phenolic compound intake, as a possible strategy to increase the daily consumption of bioactive compounds in the context of a varied and balanced diet.

Promoted under the brand Oxxynea®, the plantbased ingredient has been developed to answer the proper definition of a dietary supplement: Oxxynea® provides a large spectrum of bioactive polyphenols to equal the quantity and diversity of polyphenols found in 5 servings of fresh fruit and vegetables. Not suggested as an alternative to the consumption of fruit and vegetables, Oxxynea® is a scientifically supported ingredient aiming to complete the diet when polyphenol sources are not being consumed in a sufficient manner.

A recent study sponsored by Fytexia and run in collaboration with the UCAM (Universidad Católica de Murcia) aimed to evaluate the effect of a single intake of 450 mg of a phenolic supplementation developed to enhance the daily consumption of bioactive compounds. The bioavailability following Oxxynea® intake was evaluated through the absorption profiles and the urinary excretion of the supplemented (poly)phenols.

The randomized, double-blind, cross-over clinical trial study demonstrated that the supplementation with Oxxynea® delivers a representative fingerprint of bioactive polyphenols capturing the main sub-families of phenolic compounds (flavan­3­ols, secoiridoids, ellagitannins, and flavanones) and allowing to be perfused with more than 100 bioavailable polyphenols throughout the day providing long exposure to bioactive compounds to protect the metabolism. This study has been published in the peer-review journal Nutrients.6

References:

1 Wang, X.; Ouyang, Y.; Liu, J.; Zhu, M.; Zhao, G.; Bao, W.; Hu, F.B. Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: Systematic review and dose-response meta-analysis of prospective cohort studies. BMJ 2014, 349, g4490. [CrossRef] [PubMed]

2 Aune, D.; Giovannucci, E.; Boffetta, P.; Fadnes, L.T.; Keum, N.N.; Norat, T.; Greenwood, D.C.; Riboli, E.; Vatten, L.J.; Tonstad, S.Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-A systematic review and dose-response meta-analysis of prospective studies. Int. J. Epidemiol. 2017, 46, 1029–1056. [CrossRef] [PubMed]

3 Li, M.; Fan, Y.; Zhang, X.; Hou, W.; Tang, Z. Fruit and vegetable intake and risk of type 2 diabetes mellitus: Meta-analysis of prospective cohort studies. BMJ Open 2014, 4, e005497. [CrossRef]

4 Afshin, A.; Sur, P.J.; Fay, K.A.; Cornaby, L.; Ferrara, G.; Salama, J.S.; Mullany, E.C.; Abate, K.H.; Abbafati, C.; Abebe, Z.; et al. Health effects of dietary risks in 195 countries, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2019, 393, 1958–1972. [CrossRef]

5 Eurostat https://www.farmersfresh.eu/wp-content/uploads/ 2022/03/Fruit-Vegetable-consumption-statistics-in-theEU.pdf

6 Romain, C.; Bresciani L.; Muralidharan J.; Mena P.; Chung L.; Alcaraz P.; Del Rio D.; Cases J. Exposure to (Poly)phenol Metabolites after a Fruit and Vegetable Supplement Intake: A Double-Blind, Cross-Over, Randomized Trial. Nutrients. 2022 14, 4913. [https:// doi.org/10.3390/nu14224913

Vita Nova professional services offering raw materials and application

The beginnings of the company Vita Nova date back to 2006, when the first office and official representation of respectable foreign producers of the highest quality raw materials intended for the pharmaceutical, cosmetic, food and other industries was opened in Skopje. Driven by the desire to offer quality raw materials to producers from the region, Vita Nova expanded its operations in 2008 by opening another office based in Belgrade, enabling companies from the region to deliver raw materials quickly and on time.

We offer: minerals and mineral salts, vitamins and vitamin premixes, emulsifiers, aromas, stabilizers, enzymes, hydrocolloids, lanolin, sweeteners and plant extracts. The Vita Nova team consists of responsible and ambitious food technologists, engineers, nutritionists and pharmacists who, together with colleagues from logistics and finance, provide our clients with top­notch and professional service in the offer and application of raw materials, from the idea to the realization of the final product.

Through successful cooperation with foreign partners, Vita Nova provides its clients with continuous support and additional education through seminars and training. Each client enjoys an individual approach, with the aim of recognizing their specific needs and expectations, so that we implement our knowledge and ideas in the form of a quality final product.

After 16 years of doing business with the countries of the central Balkans, we can be proud of a large number of realized projects in the food, pharmaceutical and cosmetic industries.

We look forward to new challenges and the realization of new ideas from our clients. For all your ideas and projects, contact us via the contact form on our website. Because we would like to grow together with you...

www.vitanova.com.mk/ www.linkedin.com/company/2966991/

Aromatherapy help from nature to achieve psychophysical balance

Aromatherapy is a method of holistic approach to health, which is gaining more and more importance. With the help of aromatherapy, it is possible to contribute to the health of the individual, even to ease the symptoms in people suffering from thyroid disorders.

AUTHOR: Irena Lisjak, aromatherapist, Kyphi aromatherapy

Aromatherapy and essential oils

The use of plants and their preparations is as old as humanity itself. People have used plants for healing and beautification since ancient times. The beginnings of aromatherapy, i.e. the use of essential oils, date back to the Stone Age. The first written data on the use of essential oils can be found in Egypt. The Egyptians used them for embalming, for body care, religious ceremonies and for medicinal purposes. The Greeks took the knowledge of essential oils from the Egyptians, and the Romans from the Greeks. Galen was the first to start working on the so­called galenic preparations, whose methodology is still used today.

Essential oils are a mixture of volatile, biologically active chemical compounds obtained from plants by

distillation or pressing. Most often they are colorless or yellowish, sometimes they can have a pronounced color, such as the essential oil of German chamomile and yarrow. As a rule, plants contain very small amounts of essential oils. On average, it is between 0.021%.

Although the practice of using essential oils goes back thousands of years, the term aromatherapy was created recently. French chemist and professor R. M. Gatefosse published a book in 1937 in which he called his method of therapeutic application of essential oils aromatherapy. The method is based on the pharmacological effects of essential oils. In the book, he described the results of his research, the properties of various essential oils and methods of ap-

plication with examples of their antiseptic, bactericidal, anti­inflammatory and antiviral effects.

Aromatherapy represents the controlled use of essential oils through inhalation or application to the skin for the purpose of improving and/or improving the physical, emotional and mental health of people. So, aromatherapy has a holistic approach, because it looks at the client as a whole through all aspects of his existence and living.

Any physical ailment occurs as a result of an imbalance on an emotional, mental, and even spiritual level. What aromatherapy aims to achieve is to balance the mental-emotional level of the client and strengthen him on the spiritual level, in order to reduce the consequences on the physical level. Aroma massage is the dominant method of applying essential oils in aromatherapy and has an anti-stress effect.

Aromatherapy and thyroid diseases

Emotions associated with the thyroid gland in aromatherapy are self-esteem, expression, guilt, concern, sadness, creativity. They are associated with the questions: What do I really want? Do I want that rhythm that I imposed on myself? Why do I feel guilty? Whose worries and problems am I storing in the thyroid gland? What is it that I do not want to express (my opinion, suppressing creativity, putting myself in the background).

The aromatherapy process begins with determining the client's needs through an informative interview, taking an anamnesis, and examining the body. This is followed by the planning and implementation of aromatherapy - which conditions will be treated, which essential oils will be used and how they will be applied (massage, compresses, for home use of baths, inhalation, relaxing breathing) and then evaluation, determination of what has been achieved.

In thyroid disease, anxiety, depression, fatigue, exhaustion, insomnia, nervousness are most often treated with essential oils. It works to improve the quality of life, raise mood and life energy, reduce feelings of guilt and sadness...

When the aromatherapist determines the conditions (symptoms) to be treated, essential oils are selected. As mentioned earlier, essential oils have a comprehensive effect on the body. How it will work depends not only on its chemical composition, therapeutic effect, but also on the character of the essential oil. Like every living thing, essential oil has its own character.

When preparing a mixture of essential oils for an individual client, the general rule is to not mix more than 5 types of essential oils, because then the synergistic effect is lost.

Some of these essential oils are used for hyperthyroidism: lavender, Lavandula officinalis/syn.angustifolia/vera; myrrh, Commiphora myrrha; immortelle,Helichrysumitalicumssp.serotoninum; frankincense, Boswellia carterii.

Geranium, Pelargoniumgraveolensoils can be used for hypothyroidism and Hashimoto's syndrome; rosemary, chemotype 1,8 cineole; Rosmarinusofficinalis ct. 1,8 cineol; basil, Ocimum basilicum; lemon, Citruslimonum; bergamot, Citrusaurantiumssp.bergamia; clary sage, Salvia sclarea; marjoram, Origanum majorana; myrtle, Myrtuscommunis

Myrrh essential oil

One of my preferred choices when treating the disease of overactive thyroid or hyperthyroidism is myrrh essential oil, Commiphoramyrrha Myrrh essential oil is obtained from the resin collected from thorny, stunted bushes that grow in the Middle East, northern India and northern Africa. The shrub can reach a height of up to 3 meters, and has numerous knotty branches, sparse trifoliate leaves and small white flowers. Through incisions in the bark, the trunk exudes a pale yellow oily resin that solidifies when exposed to air and turns into semitransparent reddish-brown "tears" (Figure 1).

Essential oil is obtained by steam distillation from resin (oleoresin). Its chemical composition contains furanoeuderm-alpha-1,3-diene, lindertren, elemen, copaene, 1-cadinol, germacrene.

Throughout history, due to its antibacterial, antiviral and anti­inflammatory effects, myrrh has found its way into ointments and salves of all kinds, from Greek, Egyptian and Roman times, until today.

More recently, it has been shown to be an oil that has a calming effect on overactive thyroid.

Like frankincense, this essential oil has a beneficial effect on the nervous system and can deeply calm the mind. With its warm, resinous fragrance, basic earthy notes, it is calming, clarifying and grounding for the intellect, and is one of the main oils against excessive thinking, anxiety and mental confusion. It manifests itself in inner silence and peace. It has the ability to ease grief and mourning, and subtly helps heal the wounds of loss, rejection, and guilt. It is often used to induce a meditative state.

Lavender essential oil

For symptoms such as anxiety and insomnia, which accompany thyroid disorders, I also often use lavender essential oil, Lavandulaangustifolia Mill (Figure 2).

Lavender is a plant from the Lamiaceae family. It is one of the widely known plants, whose essence has an even wider application in aromatherapy as an "oil for everything". You can't make a mistake with lavender and it's suitable for all age groups. Due to its extremely wide range of effects, lavender oil fully deserves the honorable first place it holds in aroma-

FIGURE 1 Oleoresin from Commiphoramyrrha

therapy. It has a pronounced effect on the whole organism and stimulates its defense abilities.

Lavender oil is used in cosmetic preparations for allergic conditions and infectious skin inflammations. Massaging lavender on the neck and temples relieves headaches. It is a very good repellent, especially for small babies. It is one of the few oils that babies can use. It is also used for burns, as it can be applied directly to the burn.

Due to its chemical composition, lavender essential oil belongs to ester oils and it is the esters that are responsible for the fine smell of this group of oils. It is obtained by water distillation of flowers. The two most important ingredients in lavender oil are linalyl acetate and linalool, which have shown a significant hypnotic effect (Bikmoradi et al. , 2015; Karadag et al. , 2017; Nikfarjam et al. , 2010).

Lavender essential oil has traditionally been used as an anxiolytic, analgesic, sedative and hypnotic (Bradley et al. , 2007; Coelho et al. , 2018) and is therefore recommended for anxiety, insomnia and depression. Lavender essential oil promotes sleep mainly in the amygdala, acting on the limbic system. Furthermore, it improves the quality of sleep by producing a hypnotic effect and inhibiting the secretion of acetylcholine (Jezdic et al. , 2018; Lillehei et al. , 2015; Najafi et al., 2014; Nikfarjam et al. , 2010).

On the emotional and spiritual level of action, it is recommended to people who have suffered many troubles, whose "soul is wounded", because lavender does not force or force them, but gives them time to recover. It provides support, relieves frustration and irritability, and encourages self-expression. Lavender encourages you to move forward, to look into yourself, not to give up. It brings back negative experiences to the past so that purified and healed you can move forward. No matter how painful the process may be, lavender "doesn't give peace and doesn't let go" as long as the process lasts, but at the same time it supports the healing process as painlessly as possible. In the end, it encourages and leads to a new life...

In addition to the mentioned individual essential oils that we have listed, there is also evidence of the effectiveness of a mixture of several essential oils. A randomized, blinded, placebo-controlled clinical stu-

dy found the effect of an aromatherapy inhalation blend of essential oils on fatigue, one of the neglected symptoms of hypothyroidism. The participants were women aged 18-55 who had a diagnosis of hypothyroidism. At the end of the study, it was determined that the participants who used the aromatherapy blend of essential oils had improved values on a validated scale for measuring fatigue symptoms (Multidimensional Fatigue Symptom Inventory (MFSI)) compared to the group that received a placebo.

Conclusion

Aromatherapy is a holistic method that undeniably positively affects the improvement of people's health. It helps as a complementary therapy in many diseases, including thyroid imbalance.

So, the right direction in the future should be to work to ensure that aromatherapy gets its rightful place - as a complementary treatment to conventional treatment methods.

References:

Morris N.E., Bitrwiatle S., Tomas M., Anxiety reduction by aromatherapy Setzer W. N. Essential oils and anxiolytic aromatherapy Price S., Price L. Aromatherapy for health professionals; Price S. Aromatherapy and your emotions Mojay G. Aromatherapy for healing the spirit Mailhebiau P. Portrets in oil Segal I. The secret language of your body Cooper D.S., Sipos J. Medical management of thyroid disease Poštić Slobodanka A kao aromaterapija: priručnik za primjenu eteričnih ulja, Etera 2005

Lee IS, Lee GJ. [Effects of lavender aromatherapy on insomnia and depression in women college students]. Taehan Kanho Hakhoe Chi. 2006 Feb;36(1):136­43. Korean. doi: 10.4040/jkan.2006.36.1.136. PMID: 16520572.

Hawkins J, Hires CY, Dunne EW, Keenan LA. Aromatherapy reduces fatigue among women with hypothyroidism: A randomized placebo-controlled clinical trial. J Complement Integr Med. 2019 Aug 22;17(1):/j/jcim.2019.17.issue-1/jcim-2018-0229/jcim-2018-0229. xml. doi: 10.1515/jcim-2018-0229. PMID: 31437124. Nasiri Lari Z, Hajimonfarednejad M, Riasatian M, Abolhassanzadeh Z, Iraji A, Vojoud M, Heydari M, Shams M. Efficacy of inhaled Lavandula angustifolia Mill. Essential oil on sleep quality, quality of life and metabolic control in patients with diabetes mellitus type II and insomnia. J Ethnopharmacol. 2020 Apr 6;251:112560. doi: 10.1016/j.jep.2020.112560. Epub 2020 Jan 10. PMID: 31931160.

Vitamin D3V® human intervention bioavailability trial

Vitamin D is essential for maintaining healthy bones, teeth, muscles and for immunity strengthening. Most people are able to produce all the vitamin D their bodies require from sunlight between March to September. However, with less sunlight during the winter, towards the end and start of the year, this can be a struggle for many.

Conventional vitamin D3 is obtained from animal sources. Under the name Vitamin D3V® the company ProTec Nutra offers to the market vitamin D from plant sources, which is chemically identical to vitamin D3 of animal origin.

Vitamin D3V® is cholecalciferol of 100% plant origin, produced from algae. It is suitable for everyone and is produced in various formats and strengths, making it ideal for the food, drinks and nutraceuticals industry. In addition to being natural, it meets all quality and purity requirements, and the production process ensures complete removal of pesticides and other contaminants.

The company ProTec Nutra recently conducted a survey with the aim of confirming Vitamin D3V® as a bioavailable source of vitamin D3. The study was completed in Ireland through Research & Development business AnaBio Technologies Ltd together with University College Dublin.

The main objective of the study involved assessment of the impact of Vitamin D3V® on adults that are “insufficient” in Vitamin D. While there is no universal consensus on Vitamin D levels and status, the following table (Figure 1) provides the commonly accepted ranges as discussed in several publications.1,2,3

The study included healthy, physically active participants who exercised at least 30 minutes a day, five or more days a week. The individual dose was 300 IU of Vitamin D3V®, and the participants received two doses a day, so a total of 600 IU of vitamin D3.

Results:

Assessment was completed upon 10 healthy volunteers.

• Each daily dose comprised 600 IU of Vitamin D3V®

• In all treatment cases the plasma levels of vitamin D increased significantly over baseline.

• The average increases were from 43.43 to 77 nmol/L (33nmol/L). See Figure 2 below. This marks an average increase of approximately 77.3% above baseline for participants.

• The results were statistically significant, with a p-value using a paired t-test of 0.002.

Chart showing the average plasma levels of vitamin D across the subjects, comparing between baseline (initial) and following 7 days supplementation with 600 IU per day of Vitamin D3V®. The average increase was 77.3%.

The study confirmed that Vitamin D3V® is a bioavailable source of Vitamin D3, supporting the existing analytical data.

References:

1 Pearce SH, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ.340:b5664

2 SACN. Update on Vitamin D: Position Statement by the Scientific Advisory Committee on Nutrition. London: TSO; 2007.

3 Bischoff­Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28.

4 https://www.nutritics.com/p/clinical 5 https://myfreestyle.ca/en/products/precision_neo

Source:

https://protecnutra.com/2022/11/16/elementor-2950/

In Croatian pharmacies since 2009