Dear readers,
In the new issue of the digital magazine
B2B Nutramedic&Cosmetics, we paid special attention to the digestive system, because it is already well known that a large number of bodily functions and immunity depend on its health. In connection with this, we touched in more detail on the unique postbiotic BetaVia by Kemin, enzymes in food supplements, and vitamin D as a link that connects gut health and immunity.
An important topic that we also paid attention to are the dosage forms of nutritional supplements, which are also changing with the development of the market, in accordance with the needs and wishes of consumers.
We announce a number of novelties that will be presented at the Vitafoods Europe fair in Geneva, from May 911. May.
We continue the series about the contract manufacturerthe company Fine Foods from Italy and their sustainable development, and we present Silvan, a manufacturer of special soaps with natural ingredients.
We provide texts on ingredients for preparing the skin for the sun through supplementation, cosmetic products for selftanning, and antiaging ingredients in cosmetic products, which slow down the aging of the skin.
We would love to receive feedback, comments, and impressions about the magazine from you readers, and we thank you in advance for that.
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.nmcmagazine.com info@nmcmagazine.com
Publisher: Darmell d.o.o.
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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 reuse any part of the content without the prior consent of the publisher.
4 BetaVia™ A natural, postbiotic for immune & gut health
9 Healthy body, healthy mind
10 Fine foods – sustainability: A seed planted 10 years ago bears fruit
13 Confixx® inspires breakthroughs in fortified gummy production
14 Vitamin D and gut health: the missing link?
16 Enzymes in dietary supplements application and challenges
20 Galenic forms of dietary supplements
from capsules to gummies
Strong and wellfunctioning immune and gastrointestinal (GI) systems are essential for staying healthy. Market studies show that consumers recognize the link between poor digestive health and week immunity. Globally, 40% of consumers suffer from digestive health problems on a regular basis and a survey from 2022 conducted in three Eastern European (Poland, Serbia, Slovenia) countries indicated that 72% of consumers recognize the link between immune and digestive health respectively1,2
The GI and immune system are tightly connected, and their balance is essential for good health. The gut is considered the largest immunological organ in the body, controlling through the intestinal barrier
what needs to “go in” or stays “out” of the body and having a central role in regulating immune homeostasis3. Approximately 70% of the entire immune system is located around the gut4. Responses to pathogens, recognition and tolerance of selfantigens, tolerance to commensal microflora, and sensitization/desensitization to food components, all take place in the gut5
Among the lifestyle triggers that have been associated with negatively altering intestinal permeability are western diets low in fiber and stress6. Interestingly, the disruption of the intestinal barrier integrity is suggested to be the principle behind “leaky gut” a condition gaining more attention and reportedly more prevalent. Leaky gut has been associated
BetaVia™ is a clinically studied, natural, postbiotic offering food and beverage and dietary supplement manufacturers the opportunity to address the emerging consumer demand for immune and gut benefits.
Microbiological Tests
Aerobic Plate Count (CFU/g)
Yeast and Mold (CFU/g)
Coliforms(mpn/g)
E.coli
Salmonella
Staphylococcusaureus
L. monocytogens
with a wide range of conditions from mild occasional GI symptoms such as bloating, gas and cramping, to more severe conditions including disease states including autoimmune and allergic diseases, food allergies and Inflammatory Bowel Syndrome7,8
The integrity and function of the intestinal barrier is influenced by internal and external factors. Bacterial overgrowth and gluten are known to increased intestinal permeability9. Dietary components can also play beneficial roles beyond basic nutrition including the influence of immune and gut health. Betaglucans (BG) are one such food component that can act via immunegut health promoting mechanisms10
Kemin Human Nutrition and Health has recently introduced in the market BetaVia™, a clinically studied, natural, postbiotic offering food and beverage and dietary supplement manufacturers the opportunity to address the emerging consumer demand for immune and gut benefits.
FIGURE 1 Tripleaction mechanism of BetaVia™ demonstrated in preclinical and clinical research
BetaVia™ is naturally sourced, algaebased dietary ingredient that supports both the immune and gastrointestinal systems, providing benefits for digestive and respiratory health.
This natural and clinically studied ingredient is sustainably produced from a proprietary strain of Euglenagracilis algae through a patented fermentation process (US 9,574,217 B2). Euglena gracilis from Kemin, is grown heterotrophically in closed tanks under controlled conditions. The optimization of this vertically integrated process results in the production of paramylon, granules made exclusively of long chains of linear, nondigestible, beta 1,3 glucan.
BetaVia is available in 4 diverse product forms suitable for different applications including water dispersible ones: 2 forms with ≥50% beta 1,3 glucans (on a dry weigh basis) also containing significant quantities of protein (≥15%), and small quantities of fat vitamins, minerals, carotenoids and longchain polyunsaturated fatty acids naturally present in the Euglena gracilis algae, and 2 forms with ≥95% beta glucan content. Fewer
BetaVia has an established regulatory status on a global basis and is Kosher, Halal certified as well as vegetarian, glutenfree, allergenfree and nonGMO. Product characteristics and use is summarized in table 1.
Invitro and invivo research indicates that beta 1,3 glucans from Euglena gracilis can play a beneficial role in both immune and gut health through a
tripleaction protection mechanism 1115 (Figure 1).
Insoluble beta 1,3 glucans are part of a class of molecules known as pathogenassociated molecular patterns (PAMPs) that serve as the critical, “nonself” alert signals recognized by cells of the innate immune system (macrophages, neutrophils, dendritic cells) present in the Peyer’s patches that are the sentinels in body’s natural defense present in the GI. Beta 1,3 glucans from BetaVia™ can reach the small intestine undigested, be phagocyted by the cells of the innate immune systems, prime these cells and recruit them to the GI tract12,16
Studies conducted in farm and companion animals suggest that continuous intake of algaesourced beta 1,3 glucans can promote the host immunegut regulation and health, reducing gut susceptibility to inflammation and shaping gut microbiota1619
From a clinical perspective BetaVia’s efficacy on immune health was explored in a randomized, doubleblind, placebocontrolled, parallel study 90day supplementation with BetaVia (providing at least 187.5mg of beta 1,3 glucans) where healthy participants self-reported significantly fewer symptoms associated with upper respiratory tract infections14 Statistically significant reductions versus placebo at 90 days were found on global severity of symptoms, number of URTI symptoms, number of days with
symptoms, URTI episodes and fewer sick days (Figure 2). Interestingly, BetaVia effect started to be significant as early as 3 days of supplementation (posthoc analysis)20
Recently, to expand the knowledge about the benefits of this ingredient on immune-gut homeostasis, a randomized doubleblind, controlled crossover clinical trial was conducted15. The clinical trial assessed the effect of supplementation of BetaVia™ on GI tolerability, symptoms, and blood markers of GI health in 50 generally healthy subjects with mild GI symptoms. Participants were randomized to receive capsules containing either 375 mg BetaVia (providing 187.5 mg beta 1,3 glucan) or matching capsules containing microcrystalline cellulose (MCC- fiber control) and instructed to consume 1 capsule daily, 30 min before the breakfast meal for 4 weeks. Following 3 weeks wash out period participants initially taking BetaVia received placebo and viceversa for additional 4 weeks.
The study showed that BetaVia™ can promote gut health. Interesting unique intestinal health benefits noted exclusively with 4 weeks of supplementation with BetaVia™ are reported in Figure 3.
Furthermore, intestinal health benefits on additional markers of intestinal integrity, bowel movements and overall GI symptoms were comparable to
the low-dose fiber used as the control.
BetaVia™ has an established regulatory status on a global basis. In Europe BetaVia (≥50% beta 1,3 glucans) is approved as a novel food ingredient for different range of foods and beverages in the general population and food supplement from 1year of age onward21. A second Novel Food evaluation is expected soon making all product forms available for the European market22
BetaVia Complete is the first and only ingredient derived from Euglena gracilis algae to be approved in Europe. Furthermore, the positive NF opinion grants Kemin an exclusivity on sales in Europe.
The daily recommended dose of BetaVia for adults is 375 mg (≥50% beta 1,3 glucans) or 200 mg (≥95% beta glucan) administered 30 minutes before breakfast.
Companies wishing to offer consumers an innovative new generation postbiotic ingredient for yearround immune and gut support can rely of a broad variety of applications to choose from.
BetaVia™ can be incorporated as an ingredient in foods and beverages such as cereal bars, yogurts and yogurt drinks, fruit and vegetable juices and soft drinks. Also, the ingredient can be included in diverse food supplements formulated in solid and liq
uid forms such as capsules, tablets, sticks, softgels and syrups.
The dossier provided to EFSA also contained information on the stability of the ingredient as raw material and when used in food supplement and food and beverages applications. Since the ingredient is sourced from algae, depending on the selected product form it may require some flavor masking, just like most of other nutritionals derived from algae.
The comprehensive preclinical and gold standard clinical research conducted by Kemin on beta 1,3 glucans from its proprietary strain of the alga Euglena gracilis confirms and extends the evidence that algal 1,3-glucans have beneficials effects for both immune and gastrointestinal health14,2328. BetaVia™ could be a useful nutritional intervention for disrupted intestinal permeability (“leaky gut”) or dysbiosis (microbial imbalance), both of which are linked to immune health and with lifestyle habits such as diets low in fiber and stress.
BetaVia™ fits the definition of a postbiotic viz “a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.”29 making it naturallysourced, new generation postbiotic offering the dietary complement consumers are seeking for better immune and gut health.
References:
1 FMCG GURUS Custom Survey Geographical Immunoty Poland, Serbia, Slovenia 2022;
2 Sperber, A.D.; Bangdiwala, S.I.; Drossman, D.A.; Ghoshal, U.C.; Simren, M.; Tack, J.; Whitehead, W.E.; Dumitrascu, D.L.; Fang, X.; Fukudo, S.; et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology 2021, 160, 99114.e3, doi:10.1053/j. gastro.2020.04.014.
3 Takiishi, T.; Fenero, C.I.M.; Câmara, N.O.S. Intestinal Barrier and Gut Microbiota: Shaping Our Immune Responses throughout Life. Tissue Barriers 2017, 5, doi:10.1080/21688370.2017.1373208.
4 Vighi, G.; Marcucci, F.; Sensi, L.; Di Cara, G.; Frati, F. Allergy and the Gastrointestinal System. Clin. Exp. Immunol. 2008, 153, 3–6, doi:10.1111/j.13652249.2008.03713.x.
5 Shi, N.; Li, N.; Duan, X.; Niu, H. Interaction between the Gut Microbiome and Mucosal Immune System. Mil. Med. Res. 2017, 4, 1–7, doi:10.1186/s4077901701229.
6 Madison, A.; GlaserKiecolt, J.K. Stress, Depression, Diet, and the Gut Microbiota: Human–Bacteria Interactions at the Core of Psychoneuroimmunology and Nutrition. Curr Opin Behav Sci 2019, 28, 105–110, doi:10.1016/j.cobeha.2019.01.011.
7 Camilleri, M. The Leaky Gut: Mechanisms, Measurement and Clinical Implications in Humans. 2019, 68, 1516–1526, doi:10.1136/ gutjnl2019318427.The.
8 Niewiem, M.; GrzybowskaChlebowczyk, U. Intestinal Barrier Permeability in Allergic Diseases. Nutrients 2022, 14, doi:10.3390/ nu14091893.
9 Fasano, A. All Disease Begins in the (Leaky) Gut: Role of ZonulinMediated Gut Permeability in the Pathogenesis of Some Chronic Inflammatory Diseases. F1000Research 2020, 9, 1–13, doi:10.12688/f1000research.20510.1.
10 Taylor, H.B.; Gudi, R.; Brown, R.; Vasu, C. Dynamics of Structural and Functional Changes in Gut Microbiota during Treatment with a Microalgal βGlucan, Paramylon and the Impact on Gut Inflammation. Nutrients 2020, 12, 1–17, doi:10.3390/nu12082193.
11 Kemin Technical Literature KHTL017159.
12 Kemin Technical Literature KHTL017150.
13 Kemin Technical Literature KHTL017149.
14 Evans, M.; Falcone, P.H.; Crowley, D.C.; Sulley, A.M.; Campbell, M.; Zakaria, N.; Lasrado, J.A.; Fritz, E.P.; Herrlinger, K.A. Effect of a Euglena Gracilis Fermentate on Immune Function in Healthy, Active Adults: A Randomized, DoubleBlind, PlaceboControlled Trial. Nutrients 2019, 11, 2926.
15 Kemin Source Document Data TD206867
16 Kemin Source document TD1700322
17 Kemin Source Document SD1700243 (TL1700067
18 Kemin Source Document SD1921271
19 Kemin Source Document WP1800135
20 Kemin Source Document. KHTL017164
21 Commission Implementing Regulation (EU) 2020/1820 of 2
December 2020 authorising the placing on the market of dried Euglena gracilis as a novel food under Regulation (EU) 2015/2283 of the European Parliament and of the Council and amending Commission Implementing Regulation (EU) 2017/2470 https:// eurlex.europa.eu/legalcontent/EN/TXT/PDF/?uri=CELEX
:32020R1820&from=EN
22 https://food.ec.europa.eu/system/files/2022-11/novel-food_sum_ ongoing-app_2019-1261.pdf
23 Nakashima, A.; Sasaki, K.; Sasaki, D.; Yasuda, K.; Suzuki, K.; Kondo, A. The Alga Euglena Gracilis Stimulates Faecalibacterium in the Gut and Contributes to Increased Defecation. Sci. Rep. 2021, 11, 1–8, doi:10.1038/s41598020803060.
24 Umei, M.; Akazawa, H.; SagaKamo, A.; Yagi, H.; Liu, Q.; Matsuoka, R.; Kadowaki, H.; Shindo, A.; Nakashima, A.; Yasuda, K.; et al. Oral Administration of Euglena Gracilis Z Alleviates Constipation and Cardiac Dysfunction in a Mouse Model of IsoproterenolInduced Heart Failure. Circ. Reports 2022, 4, 83–91, doi:10.1253/circrep.cr210094.
25 Bhattad, T.; Koradiya, A.; Prakash, G. Prebiotic Activity Of Paramylon Isolated From Heterotrophically Grown Euglena Gracilis. Heliyon 2021, 7, e07884, doi:10.1016/j.heliyon.2021.e07884.
26 Sakanoi, Y.; Shuang, E.; Yamamoto, K.; Ota, T.; Seki, K.; Imai, M.; Ota, R.; Asayama, Y.; Nakashima, A.; Suzuki, K.; et al. Simultaneous Intake of Euglena Gracilis and Vegetables Synergistically Exerts an Anti-Inflammatory Effect and Attenuates Visceral Fat Accumulation by Affecting Gut Microbiota in Mice. Nutrients 2018, 10, 1–15, doi:10.3390/nu10101417.
27 Ishibashi, K.; Nishioka, M.; Onaka, N.; Takahashi, M. Effects of Euglena Gracilis EOD1 Ingestion on Salivary IgA Reactivity and HealthRelated Quality of Life in Humans. Nutrients 2019, 11, 1144.
28 Nakashima, A.; Suzuki, K.; Asayama, Y.; Konno, M.; Saito, K.; Yamazaki, N.; Takimoto, H. Oral Administration of Euglena Gracilis Z and Its Carbohydrate Storage Substance Provides Survival Protection against Influenza Virus Infection in Mice. Biochem. Biophys. Res. Commun. 2017, 494, 379–383, doi:10.1016/j.bbrc.2017.09.167.
29 Salminen, S.; Collado, M.C.; Endo, A.; Hill, C.; Lebeer, S.; Quigley, E.M.M.; Sanders, M.E.; Shamir, R.; Swann, J.R.; Szajewska, H.; et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) Consensus Statement on the Definition and Scope of Postbiotics. Nat. Rev. Gastroenterol. Hepatol. 2021, 18, 649–667, doi:10.1038/s41575021004406.
Kemin Industries is a global ingredient manufacturer that strives to sustainably transform the quality of life every day for 80 percent of the world with its products and services. Kemin is the science inside countless products you interact with every day. Established in 1961, Kemin is a privately held, familyownedandoperated company producing more than 500 specialty ingredients, spanning six continents, employing thousands of team members, and serving more than 120 countries. The company science, spirit of innovation, and servant leadership has driven it to make things better for people, animals, plants, and the planet. The Human Nutrition and Health division grows and extracts functional ingredients from natural sources around the world. These ingredients, clinically shown to support the vision, cognition, immune health and weight management platform, are used in a range of dietary nutrition products, including supplements and snack foods.
Kemin Human Nutrition and Health
Samanta Maci
samanta.maci@kemin.com
Tel. +351 214 157 500 www.kemin.com
Vitafoods Europe 2023, booth C92: Euromed presents its broad range of botanical extracts for improved health and wellbeing.
At Vitafoods Europe, Euromed will showcase its certified organic herbal extracts, as well as a growing portfolio of natural ingredients inspired by the healthpromoting properties of the Mediterranean diet. Two presentations during the show online and inperson will provide nutraceutical professionals with indepth knowledge about the benefits of botanical ingredients for a healthy body and mind.
Mediterranean fruit and vegetable extracts™ from lemon, pomegranate, olive, artichoke, fig and spinach contain valuable nutrients that play a key role in the Mediterranean diet, and have been proven to support cardiovascular, metabolic, digestive, immune and skeletal muscle functions, all of which are vital for healthy ageing. In addition, Wellemon®, Pomanox®, Mediteanox®, Cynamed®, ABAlife® and Spisar® are all gently processed with an ecofriendly, proprietary extraction technology that uses only purified water as a solvent.
Euromed will also showcase its Earth Harmony Organic Extracts®. The 16 available ingredients, from artichoke leaf to valerian root extract, are produced in accordance with sustainable practices and full traceability from seed to the final organic-certified extract.
During a lecture at 3pm on May 10 in the New Ingredients Theatre, attendees will be able to discover the power of botanicals from the Mediterranean diet for mental and physical health. Under the title “Mens Sana in Corpore Sano: Unlocking the Active Nutrition Potential of Mediterranean Extracts for MindBody Health”, Andrea Zangara, Head of Scientific Communications & Marketing at Euromed, will give insights into botanical traceability, sourcing, quality control, research findings and formulations for holistic health products.
Another digital presentation will dive deeper into the topic and provide product developers with insightful information on how best to select appropriate botanical ingredients. Entitled “Beyond the Plant: How Our Bodies Process and Benefit from Botanical Extracts”, the presentation will explore digestion, bioavailability and effectiveness of specific botanical extracts, and will be available ondemand from 1 May at the Vitafoods online platform.
Andrea Zangara explains: “Considering chemical complexity of plants and all the external variables,
it’s increasingly relevant to investigate both efficacy and bioavailability of certain extracts, such as those high in polyphenols like pomegranate and lemon. From mental wellbeing to active ageing, our standardized botanical compounds provide a broad range of clinically validated health benefits which are specific to the extracts tested, and cannot necessarily be applied to other extracts. Our vertically integrated supply chain and strict quality protocols ensure the development of highquality functional foods, supplements and other products for active nutrition and holistic health. At our booth and during our presentations, visitors will learn more about that botanical journey from seed to final extract.”
www.euromedgroup.com
The six pillars of sustainability that underpin the company's sustainability strategy: ethics and governance, people, environment, sustainable products, supply chain, land development.
On 30 March 2023, Fine Foods & Pharmaceuticals N.T.M. S.p.A. an Italian independent Contract Development & Manufacturing Organisation (CDMO) that develops and manufactures contract products for the pharmaceutical, nutraceutical, cosmetics, biocides and medical devices industries, listed on Euronext STAR Milan (ticker: FF), approved the Sustainability Report 2022.
The second Sustainability Report of the Group, which has been a "Benefit Corporation" since 2021, shows the activities launched during 2022, the significant progress made, and several milestones achieved which further improved its ESG performance.
The Fine Foods business model creates value not only for the company, customers and investors, but the environment and people. Fine Foods ESG Manager Marta Pettena confirmed: "We are proud of the activities we carried out during 2022 for our six sustainability pillars underlying our Sustainability strategy: ethics and governance, people, environment, sustainable products, supply chain, land development."
The Group updated and issued Policies incorporating the latest internationally recognised guidelines and drafted and shared its Sustainability strategy.
The actions and initiatives carried out led to prestigious awards such as the EcoVadis rating, which went from "Gold" to "Platinum" in a year and which placed Fine Foods in the top one per cent of companies in the global ranking. Additionally, we obtained the accreditation from the Lombardy region as a "Workplace Health Promotion Lombardy WHP Network" by implementing good practices in cancer prevention, promoting physical activity and healthy diet.
The Group contributed to the fight against climate change by starting two new photovoltaic systems at its plants that increased the power of electrical energy installed by 550 kW which were entirely supplied by renewable sources.
Commitments made to the region were fulfilled by involving more than 230 young students and teachers in actively experiencing working in a company like Fine Foods, addressing issues related to enhancing diversity and how companies are required to integrate sustainability into their business model.
Fine Foods supported customers in calculating the carbon footprint of their products and we lo
ESG ratings from external companies:
EcoVadis: 78 Platinum medal (ESG performance improved by 12 points)
CO2 emission intensity Scope 1-2:
16% Tons CO2/€ million compared to 2021
9% in absolute terms compared to 2021
MWh of energy produced from renewable sources:
371 MWh
+20% compared to 2021
kW Installed capacity from photovoltaic systems
850 kWp
+550 kWp compared to 2021
Value of raw and packaging materials ordered from suppliers assessed according to social and environmental criteria:
79% of orders
+4% compared to 2021
Number of raw and packaging material suppliers assessed:
106
+50% compared to 2021
Number of people involved in sustainability issues:
+234 students
Number of people who have taken part in company health promotion initiatives:
More than 280
More than 40 per cent
Fine Foods contributes to 11 Sustainable development goals defined by the United Nations.
• Installation of new photovoltaic systems
• Training on managing Diversity and Inclusion issues for the HR and ESG departments.
• Valore D association membership Publication of the new Policy for safety, health, wellbeing and inclusion.
• Project for inclusion and experimentation initiated with schools
Study guidance meetings and discussion on sustainability issues
• Testing new packaging materials
• Partnership on product carbon footprint calculation
• Implementing the crossdepartmental ecodesign process
Supplier Code of Conduct publication and dissemination
• Suppliers assessed on ESG criteria
• Skin cancer prevention screening for employees
• Initiatives to adopt healthy lifestyles
• New hires
Each activity that contributes to a Sustainable Development Goal is detailed in the relevant chapters within this document: https://finefoods.it/en/esg-report/
oked for strategies to make them more sustainable. Fine Foods is selecting and testing new materials for the circular economy.
The Group's strategy included the increasingly active and responsible involvement of players along the supply chain. We expanded the number of suppliers engaged in the process of assessing and improving their environmental and social performance, with a focus on respect for human rights.
Fine Foods' commitment to sustainability has deep roots in the organisation's operational functioning. Through environmental and social certifications and awards, Fine Foods has proven to be a strategic and reliable partner based on its financial, environmental, social, and corporate governance criteria. By embracing the Global Compact principles, Fine Foods commits to the Sustainable Development Goals (SDGs) of the United Nations 2030 Agenda.
Fine Foods Group ESG Manager Marta Pettena said: "Despite the geopolitical, economic, environmental and social challenges, Fine Foods is confident and convinced that the new rules, which increasingly in
tegrate environmental and social sustainability into European companies’ business models, are an opportunity to be seized to accelerate the process towards a sustainable future, together with customers, suppliers, employees and stakeholders."
Fine Foods & Pharmaceuticals N.T.M. S.p.A
Via Berlino, 39 24040 Zingonia/Verdellino Bergamo, Italy
T. +39 035 482 13 82 www.finefoods.it
info@finefoods.it
By moving away from starch-based towards starchless manufacturing with Confixx® , manufacturers can make considerable efficiency gains in the field of fortified gummiesboth in terms of cost and active ingredients.
Gelita, the leading manufacturer of collagen peptides and tailored gelatins, has launched a fastsetting gelatin that enables a breakthrough in fortified gummy production. Branded Confixx® , the new gelatin allows for the starchfree production of gummies with a sensorial profile that has previously only been attainable with a starchbased manufacturing process. This opens up opportunities for manufacturers of these ontrend supplements to work with different active ingredients, simplify the production process and make considerable cost savingsall the while confident in the knowledge that there will be no compromise on allimportant texture.
By moving away from starchbased towards starchless manufacturing with Confixx®, manufacturers can make considerable efficiency gains in the field of fortified gummies - both in terms of cost and active ingredients. Eliminating the starch preparation and gummy drying steps reduces production time from two days to just a few hours and reduces the overall footprint of the process; less space is needed and the quicker, more streamlined process is far less energy intensive. Confixx® also enables GMPcompliant production of functional and fortified gummies and rules out the risk of crosscontamination through full separation of batches with different active ingredients.
With Confixx®, manufacturers have greater freedom to innovate too. The simplified process lends itself to production of small batches, with greater flexibility in terms of product changes and tighter control over ingredient dosing. This, coupled with the high tolerance of gelatin to formulation changes and the more gentle treatment of ingredients, makes it easy to accommodate a broader range of active ingredients including difficult to work with and heat-sensitive ingredients. And all this while delivering the chewy, jelly texture that consumers have come to expect from their gummies.
Dr. Johanna Schmidgall, Global Head of Application Development at GELITA, comments: “The market for functional and fortified fruit gummies offers exciting growth prospects. Until now, product developers in this space have had their creativity curbed by practical manufacturing limitations. With the introduction of Confixx® it is possible to produce gelatinbased
gummies with virtually any active ingredient from collagen peptides to melatonin, vitamins and minerals. We can’t wait to see what new innovations this development will inspire.”
The popularity of fortified gummies has exploded in recent years as consumers eschew conventional pill and capsulebased supplement formats in favour of soft and chewy “candyceuticals”. According to data from Innova Market Insights, gummy supplements accounted for 9.4% of global supplement launches in 2021an increase of 70% since 2017, and between 2020 to 2021 alone, the number of gummy supplement launches globally rocketed by 81%. (Innovadatabase: Innova New Products Launches, last accessed: 05.01.2023)
A leader in gelatin and collagen protein innovation, Gelita provides customers worldwide with the highest standard products, comprehensive technical expertise and sophisticated solutions. With 140 years of experience in the field of collagen, proteins are the basis of the company's operations. Gelita offers collagen peptides with proven abilities to stimulate the body, customized gelatins and collagens that are insoluble or partially soluble in the void, and rely on natural, healthy, allergenfree ingredients. Products also possess a number of unique technical and physiological properties that, in addition to their traditional use as natural stabilizers and emulsifiers for numerous products, enable other, increasingly important properties.
Vitamin D deficiency is the most common nutritional deficiency in the world. In addition to affecting the bones, the extraskeletal effects of this vitamin are aimed at the immune system, muscles, heart and blood vessels, nervous system and brain.
The „sunshine vitamin” is attracting great attention of scientific community and lay people for the past three decades, and the interest does not seem to diminish, on the contrary,it seems like new discoveries arise all the time. Vitamin D is a powerful hormone, one of the few molecules we can synthesize in our body with the help of sunrays. It is considered conditionally essential, meaning that we can provide enough vitamin D for the body without ingestion through food. But in some situations the synthesis is insufficient and we require supplementation. The problem is that those situations are in fact very common, considering that almost half of the global population has a deficiency or insufficiency of vitamin D. Nevertheless, vitamin D deficiency is the most common nutritional deficiency in the world. Low levels are noticed especially during the autumn, winter and early spring in individuals who are not taking food supplements or medications containing vitamin D1. Vitamin D receptors (VDR) are found in the tissues of most organs and organ systems. Extraskeletal effects of vitamin D are aimed at the immune system, muscles, heart and blood vessels, nervous system and brain.
The most challenging attribute of vitamin D is immunomodulatory action. After ingestion or skin synthesis, 25OH vitamin D is metabolized to produce the endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2D). This form of vitamin D regulates gene expression in various targeted tissues by interacting with the vitamin D receptor (VDR) a ligandactivated transcription factor2. Interestingly, the most responsive target tissue is the intestine. The well known role of vitamin D in the intestine is control of calcium metabolism by regulating the intestinal calcium absorption. But it is only one part of this interaction. Scientific data show that other functions of the intestine are regulated by the biological actions of 1,25(OH)2D through the VDR. Vitamin D status and VDR activity in the intestine impacts the integrity and function of gut barrier, suppression of colon carcinogenesis, re
gulation of intestinal stem cells, and inhibiting gut inflammation3
Vitamin D and vitamin D receptors (VDRs) play a role in regulating the microbiome of the digestive and respiratory systems in both health and disease. The body of scientific evidence shows that vitamin D is one of the protagonists in the complex interplay between intestinal microbiota and immune system modulation2. Vitamin D status in the gut, and low vitamin D concentrations in the blood are associated with increased intestinal permeability and consequent metabolic endotoxemia associated with lowgrade inflammation. The use of vitamin D can affect the composition of the intestinal microbiota, and the results of in vitro research show that vitamin D enhances the ability of macrophages to suppress Escherichia coli . In animal models of mice deficient in vitamin D or in those with inactive VDR receptors, dysbiosis develops, which favors intestinal and metabolic disorders, and presents a risk for development of various diseases and conditions. The synergy of probiotics and vitamin D in humans is supported by the results of a randomized placebocontrolled study published in 2013. showing that the use of vitamin D in combination with the probiotic strain L.reuteriresulted in a 25% increase in vitamin D levels in the blood4
The first studies that indicated the synergistic effect of the use of probiotics (LactobacillusreuteriDSM 17938) and vitamin D3 were conducted on children with asthma in 20165. More recent interventional clinical studies observe the use of this combination on adult patients in very diverse indications. For example, the combination of vitamin D and probiotics showed a beneficial effect on mental health and hormonal, inflammatory and oxidative stress markers in women with polycystic ovary syndrome (PCOS)6. Furthermore, this combination was investigated in patients with schizophrenia and a favorable clinical and metabolic effect was recorded7. A doubleblind clinical study published in 2018 showed that the combination of vitamin D and probiotics can be effective in patients with type 2 diabetes and coronary heart disease, and the beneficial effects were reflected in mental health, inflammatory parameters, and regulation of glycemia and lipids in the subjects8. Indications in which the use of a combination of vitamin D and probiotics certainly makes sense are inflammatory bowel diseases (especially ulcerative colitis) and nonalcoholic fatty liver disease, as well as in pregnant women with gestational diabetes, children with type 1 diabetes and obesity9,10
Cardiometabolic diseases might be linked to vitamin D deficiency through microbiota. A combination of vitamin D insufficiency or deficiency and dysbiosis may contribute to the progression of cardiometabolic diseases. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of development and progression of metabolic syndrome11.
Multiple investigations indicate that the gut microbiota could play a role in the onset and progression of colorectal cancer (CRC). Furthermore, low levels of vitamin D (vitD) in the bloodstream are linked to an increased risk of CRC as well as poorer prognosis. Nevertheless, the relationship between these two factors remains unclear. One possibility is that vitD supplementation could have an impact on the composition of the gut microbiota, and that the microbiota could play a role in mediating the effects of supplementation12
Vitamin D replacement therapy increases the concentration of 25(OH)D in the blood, and the increase depends on the body weight of the individual and the initial concentration of 25(OH)D.
Control of vitamin D replacement therapy is laboratory monitoring of concentration 25(OH) vitamin D in the blood and achieving a target value of ≥75 nmol/L (30ng/mL) for adults13 and ≥50 nmol/L (20 ng/mL) for children14. Preferred values for various the extraskeletal effects of vitamin D can be significantly higher and range up to 150 nmol/L, and interpretations of other ranges and limit toxic concentrations are presented in Figure 1.
The concentration of 25(OH)D in the range of 75–100 nmol/L is usually achieved by the replacement Therapy with doses in the range od 2.000 to 4.000 IU of vitamin D3 per day. Achieving blood concentration greater than 100 nmol/L requires the use of higher doses.
For the purpose of preventive use, vitamin D is usually dosed in the range of 800 – 2,000 IU per day, and the dose is adjusted depending on age and risk factors. The dose of 400–1000 IJ/day is recommended for infants, 1.000–1.500 IJ/day for children from 1 to 10 years, 1.500–2.000 IJ/day for adolescents and 2.000–4.000 IU/day for adults15. The same range of daily doses is used as maintenance dose in people who have reached the desired vitamin concentration D in blood (75125 nmol/L). If the replacement therapy is applied to people who are obese or have malabsorption, the daily dose should be increased two to three times.
In laboratory-confirmed vitamin D deficiency (concentration in blood < 75 nmol/L) a dose of 6.000 IU per day is used for the duration 8 weeks, but the duration of therapy can vary between 4 and 12 weeks, depending on the starting value of the concentration of 25(OH)D in the blood and risk factors. Patients with malabsorption syndromes, obesity or using pharmacotherapy that interfere with the metabolism of vitamin D, can apply doses of up to 10.000 IU per day over a longer period of time, under medical supervision.
References:
1 Sassi F, Tamone C, D'Amelio P. Vitamin D: Nutrient, Hormone, and Immunomodulator. Nutrients. 2018;10(11):1656.
2 Luthold RV, Fernandes GR, FrancodeMoraes AC, Folchetti LG, Ferreira SR.Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals. Metabolism. 2017;69:7686.
3 Fleet JC. Vitamin D and Gut Health. Adv Exp Med Biol. 2022;1390:155167.
4 Jones ML, Martoni CJ, Prakash S. Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25hydroxyvitamin D: a post hoc analysis of a randomized controlled trial. J Clin Endocrinol Metab. 2013;98(7):294451.
5 Miraglia Del Giudice M, Maiello N, Allegorico A, Iavarazzo L, Capasso M, Capristo C, Ciprandi G. Lactobacillus reuteri DSM 17938 plus vitamin D3 as ancillary treatment in allergic children with asthma. Ann Allergy Asthma Immunol. 2016;117(6):710712.
6 Ostadmohammadi V, Jamilian M, Bahmani F, Asemi Z. Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome. J Ovarian Res. 2019;12(1):5.
7 Ghaderi A, Banafshe HR, Mirhosseini N, Moradi M, Karimi MA, Mehrzad F, Bahmani F, Asemi Z. Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients. BMC Psychiatry. 2019;19(1):77.
8 Raygan F, Ostadmohammadi V, Bahmani F, Asemi Z. The effects of vitamin D and probiotic cosupplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, doubleblind, placebocontrolled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84(Pt A):5055.
9 Jamilian M, Amirani E, Asemi Z. The effects of vitamin D and probiotic co-supplementation on glucose homeostasis, inflammation, oxidative stress and pregnancy outcomes in gestational diabetes: A randomized, doubleblind, placebocontrolled trial. Clin Nutr. 2019;38(5):20982105.
10 Sun J. Dietary vitamin D, vitamin D receptor, and microbiome. Curr Opin Clin Nutr Metab Care. 2018;21(6):471474.
11 Sukik A, Alalwani J, Ganji V. Vitamin D, Gut Microbiota, and Cardiometabolic DiseasesA Possible ThreeWay Axis. Int J Mol Sci. 2023 Jan 4;24(2):940.
12 Trovato C, Zampino MG, Corso F, Bellocco R, Raimondi S, Rescigno M, Gandini S. Colorectal cancer, Vitamin D and microbiota: A doubleblind Phase II randomized trial (ColoViD) in colorectal cancer patients. Neoplasia. 2022;34:100842.
13 Vranešić Bender D, Giljević Z, Kušec V, Laktašić Žerjavić N, Bošnjak Pašić M, Vrdoljak E, et al. Smjernice za prevenciju, prepoznavanje i liječenje nedostatka vitamina D u odraslih. Liječ Vjesn 2016;138:121-132. 8.
14 Braegger, C., Campoy, C., Colomb, V., Decsi, T., Domellof, M., Fewtrell, M., Hojsak, I., Mihatsch, W., Molgaard, C., Shamir, R., Turck, D., van Goudoever, J. Vitamin D in the Healthy European Paediatric Population. J Pediatr Gastroenterol Nutr. 2013; 56 (6), 692701
15 National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment Osteoporosis. Developed by the NOF 2009, updated January 2010.
Enzymes are products of various digestive system organs such as the pancreas, small intestine, and stomach. Their tasks in the body can be different - from breaking down complex molecules from food and facilitating digestion and absorption to reducing inflammatory reactions and managing various physiological functions.
Amylase helps breaking down carbohydrates into simple sugars that can then be easily absorbed by the body. It is usually used to help digest starchy foods.
• Protease helps breaking down proteins into smaller peptides and amino acids and helps with digesting proteinrich foods.
• Lipase helps breaking down fats into fatty acids and glycerol and is used to aid in the digestion of fatty foods.
• Cellulase helps breaking down the cellulose found
in plant cell walls, making it easier for the body to digest plantbased foods.
• Lactase helps breaking down lactose, the sugar found in milk and dairy products, making it easier for lactoseintolerant people to digest this food.
Bromelain is found in pineapple, and it helps breaking down proteins. It is often used as a supplement to reduce inflammation and swelling.
• Papain is found in papaya and helps breaking down proteins and, like bromelain, is used to reduce inflammation and swelling.
They are the most numerous in the body and participate in all bodily processes such as breathing, speaking, moving, thinking, behaving, and maintaining the immune system. Systemic enzymes are commonly used to reduce inflammation, support cardiovascular health, and boost immune function. So far, they are less represented in the category of dietary
supplements, but they certainly offer application potential considering the indications for which they are used. The most famous ones used as dietary supplements are:
Serapeptase
Nattokinase
Lumbrokinase
Enzyme preparations are usually produced by a microbial fermentation process. This involves growing specific strains of bacteria, yeast, or fungi in a controlled environment and then extracting the enzymes. The specific organisms used to produce enzymes differ depending on the type of enzyme being produced. For example, lactase enzymes are often produced by strains of the Aspergillus fungus, while papain enzymes are usually obtained from the papaya fruit.
There are several key challenges in the production process. This includes proper selection and the optimization of microorganisms that can produce the desired enzyme. It also includes identifying microorganisms that have the ability to produce large amounts of enzymes and optimizing their growth conditions. After microorganisms produce an enzyme, it must be purified to remove any unwanted components and to ensure that the final product is of high purity. This can be a demanding process, as enzymes are often produced in complex mixtures and can be difficult to separate from other proteins and cellular components. Enzymes can be sensitive to changes in temperature, pH, and other environmental factors. This is a very important item in the production of enzyme supplements because the final product must be stable and retain its activity over time.
Enzyme supplements can come in a variety of pharmaceutical forms, including tablets, capsules, powders, and liquids. Each of these forms presents a unique challenge in terms of formulation, as the enzyme must be protected from degradation and must be delivered in a form that is easily absorbed by the body. Enzymes produced by microbial fermentation can find their application in various branches of industry pharmaceutical, cosmetic, food industry, and many others.1
Enzymes can be extracted from fruit and animal tissue. Many commonly used enzymes such as papain (from papaya fruit) and bromelain (from pineapple) are derived from fruit. While, for example, trypsin and chymotrypsin are obtained using the pancreas tissue of cows or pigs. Extraction of enzymes from fruit and animal tissue involves a process of tissue homogenization or maceration, followed by separation of the enzyme from the tissue by centrifugation or filtration. The enzyme extract thus obtained can then be purified and concentrated and used for various industrial or research applications. 2
Enzymes can also be produced by genetic engineering techniques. Thus, for example, proteases, amylases, lipases and cellulases3, and certain systemic enzymes can be produced.
The quality of enzymes can vary depending on the technology used for their production. Enzymes produced by modern fermentation technologies such
as microbial fermentation or recombinant DNA technology are usually of higher purity than those produced by traditional methods such as extraction from animal or plant sources. Also, modern technologies enable better control over conditions such as pH and temperature, can increase stability and activity, and ensure better microbiological purity. This results in a more effective and efficient enzyme.
When evaluating the quality of an enzyme, it is important to consider these factors in relation to the specific application for which the enzyme will be used. For example, an enzyme used in the food industry must meet strict purity and safety standards, while an enzyme used in a research laboratory must have certain activity or specificity characteristics. Overall, the technology used to produce enzymes can have a significant impact on their quality, and choosing the right production method can help ensure that the enzyme is efficient, safe, and consistent.
Given that both the stability and activity of enzymes are very sensitive to changes in temperature, pH, ionic strength, proteolysis, oxidation, aggregation, and other factors, production technology, formulation, and storage are key to choosing a quality enzyme. To ensure a long shelf life, enzyme supplements are usually formulated with stabilizing agents such as buffers, salts, sugars, and surfactants that can protect the enzyme from degradation and maintain its activity over time. Likewise, techniques such as microencapsulation and lyophilization can contribute to an extended shelf life.4
Supplementation with digestive enzymes is most often used to treat digestive problems such as flatulence, dyspepsia5, and abdominal pain because they reduce the load on the digestive system by the more efficient breakdown of food6. They are also used when the absorption of nutrients needs to be improved, for the same reason. Digestive enzymes can help people with food intolerances such as lactose intolerance7. They can also be used in various inflammatory bowel diseases, especially irritable bowel syndrome8. Also, indigestion that occurs in the state of pancreatic insufficiency can be alleviated by using digestive enzymes.
Proteolytic enzymes
Bromelain and papain are two proteolytic enzymes that are most often found in food supplements. The application of bromelain is diverse. It is most often used to reduce inflammation and swelling. Given that it has anti-inflammatory and analgesic effects in addition to antiedematous, antithrombotic, and fibrinolytic9 effects, it is used for various conditions from osteoarthritis, to sinusitis and sore throat. The mechanism of action of bromelain is mediated by the following factors: increasing fibrinolytic activity in serum10, decreasing fibrinogen levels in plasma11 , and decreasing bradykinin levels (resulting in reduced vascular permeability) and therefore reducing edema and pain12 by mediating prostaglandin levels (reducing PGE2 and thromboxane A2 levels).
The body can absorb bromelain to a significant extent without negatively affecting its proteolytic ac
tivity. Its many therapeutic benefits include wound debridement, improved drug absorption, and the treatment of sinusitis, bronchitis, angina pectoris, surgical trauma, and thrombophlebitis. In addition, it shows a beneficial effect on numerous cardiovascular conditions. Bromelain also promotes apoptotic cell death and exhibits some anticancer properties13
The use of papain is very similar to that of bromelain. Papain acts as a debridement without harmful effects on healthy tissues due to enzyme specificity, acting only on tissues lacking α1antitrypsin plasmatic antiprotease that inhibits proteolysis in healthy tissues14. Papain has proven to be extremely useful in dentistry during the process of dentin excavation15 and chemomechanical caries removal16. The enzyme papain has a long history of use in the treatment of sports injuries and other causes of trauma, where studies have shown that minor injuries are healed faster with papain proteases than with placebo17. Papain is also successfully used to treat allergies associated with the leaky gut syndrome, hypochlorhydria, and intestinal disorders such as gluten intolerance. It has also been noted that it finds its place in the treatment of symptoms of acute allergic sinusitis and toothache18
Serratiopeptidase is a metalloprotease with a molecular weight of 45–60 kDa. It belongs to the Serralysin group. It is originally obtained from Serratia marcescens isolated from the intestine of the mulberry silkworm BombyxmoriL. The clinical use of the enzyme has been recorded for many diseases such as arthritis, sinusitis, inflammatory bowel disease, and bronchitis19. Other applications in clinical practice mainly include breast diseases, atherosclerosis, Alzheimer's disease, sinusitis, hepatitis, lung disorders, and uterine fibroids20. As the demand for said enzyme has increased, certain safety issues arose. Given that the biomass used for enzyme production is considered dangerous, techniques for recombinant enzyme production in E. coli21 have been developed.
Nattokinase is a purified serine protease extracted from natto, a traditional Japanese food produced by the fermentation of soybeans with the bacterium Bacillussubtilis(natto). In 1980, Hiroyuki Sumi, a Japanese researcher, discovered that natto could dissolve
artificial fibrin. Further research revealed that it not only breaks down fibrin but also the substrate of plasmin22. Nattokinase can degrade blood clots by directly hydrolyzing fibrin and plasmin substrates, converting endogenous prourokinase to urokinase (uPA), degrading PAI1 (plasminogen activator inhibitor1), and increasing tissue plasminogen activator (tPA) which supports fibrinolytic activity23. As a dietary supplement, nattokinase is used for blood thinning, preventing the formation of blood clots, and improving blood circulation24. Studies also show that nattokinase can alleviate other diseases such as hypertension25, stroke26, Alzheimer's disease27, and atherosclerosis28. The use of nattokinase is considered to be safe, and the production by fermentation of the bacterium B. subtilis does not present a problem in the form of biomass toxicity. However, as the demands of the market grow, new ways of producing this enzyme using recombinant technologies are also being researched.
Lumbrokinase is a group of enzymes isolated and purified from different types of earthworms. They are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Advances in genetic technology have enabled the production of recombinant lumbrokinase and made it feasible to purify a single lumbrokinase enzyme for potential antithrombotic use29. Lumbrokinase is very specific for fibrin as a substrate and does not cause excessive bleeding30,31. It can dissolve fibrin itself or convert plasminogen to plasmin, by inducing the endogenous activity of tPA to dissolve fibrin clots32,31. This is precisely why lumbrokinase is used in various conditions such as the risk of thromboembolism33, thrombosis therapy34, cardiovascular diseases, stroke35,36, and all other conditions that require circulation support. The application also shows potential for reducing intraabdominal adhesions. It is a complication after abdominal surgery caused by suppression of fibrinolytic activity and increased invasion of fibroblasts into the injured area, which can lead to chronic diseases such as chronic pain, intestinal obstruction, and female infertility37.
Conclusion
The use of enzymes in food supplements offers a very wide range of indications. Many enzymes and their applications are already well known, while so
me new ones, especially systemic enzymes, are rising stars. Research is going in the right direction, so the future of this type of food supplement is certainly promising.
1 Singh R, Kumar M, Mittal A, Mehta PK. Microbial enzymes: industrial progress in 21st century. 3 Biotech. 2016 Dec;6(2):174. doi: 10.1007/s1320501604858. Epub 2016 Aug 19. PMID: 28330246; PMCID: PMC4991975.
2 Arshad ZI, Amid A, Yusof F, Jaswir I, Ahmad K, Loke SP. Bromelain: an overview of industrial application and purification strategies. Appl Microbiol Biotechnol. 2014 Sep;98(17):728397. doi: 10.1007/ s002530145889y. Epub 2014 Jun 26. PMID: 24965557.
3 Movahedpour A, Asadi M, Khatami SH, TaheriAnganeh M, Adelipour M, Shabaninejad Z, Ahmadi N, Irajie C, Mousavi P. A brief overview on the application and sources of αamylase and expression hosts properties in order to production of recombinant αamylase. Biotechnol Appl Biochem. 2022 Apr;69(2):650659. doi: 10.1002/bab.2140. Epub 2021 Mar 19. PMID: 33655550.
4 Flickinger, M.C., Rother, C. and Nidetzky, B. (2014). Enzyme Immobilization by Microencapsulation: Methods, Materials, and Technological Applications. In Encyclopedia of Industrial Biotechnology, M.C. Flickinger (Ed.). https://doi. org/10.1002/9780470054581.eib275
5 Banka N, Sawant P, Vartak M, Pawar D. Efficacy and Tolerability of Unienzyme MPS A Multienzyme Preparation with Simethicone in Patients with Nonulcer ,Dyspepsia. Indian Medical Gazette. 2001;135(7):294305.
6 Khandke DA, Shirsath PA, Jain SK. PostMarketing Surveillance Study to Assess the Efficacy and Tolerability of Al5zyme-A Multienzyme Preparation in Patients with Functional Dyspepsia. Indian Medical Gazette. 2013;18191.
7 Ojetti V, Gigante G, Gabrielli M, Ainora ME, Mannocci A, Lauritano EC, Gasbarrini G, Gasbarrini A. The effect of oral supplementation with Lactobacillus reuteri or tilactase in lactose intolerant patients: randomized trial. Eur Rev Med Pharmacol Sci. 2010 Mar;14(3):16370. PMID: 20391953.
8 Graham DY, Ketwaroo GA, Money ME, Opekun AR. Enzyme therapy for functional bowel diseaselike postprandial distress. J Dig Dis. 2018 Nov;19(11):650656. doi: 10.1111/17512980.12655. Epub 2018 Sep 21. PMID: 30101562; PMCID: PMC6910206.
9 Maurer HR. Bromelain: biochemistry, pharmacology and medical use. Cell Mol Life Sci. 2001 Aug;58(9):123445. doi: 10.1007/ PL00000936. PMID: 11577981.
10 Pirotta F, de Giuli-Morghen C. Bromelain: anti-inflammatory and serum fibrinolytic activity after oral administration in the rat. Drugs Exp Clin Res. 1978;4:1–20.
11 Livio M, Bertoni MP, De Gaetano G, Donati MB. Effects of bromelain on fibrinogen level, prothrombin complex and platelet aggregation in the rat—a preliminary report. Drugs Exp Clin Res. 1978;4:49–53
12 Kumakura S, Yamashita M, Tsurufuji S. Effect of Bromelain or kaolininduced inflammation in rats. Eur J Pharmacol. 1988;150:295–301
13 Agrawal P, Nikhade P, Patel A, Mankar N, Sedani S. Bromelain: A Potent Phytomedicine. Cureus. 2022 Aug 11;14(8):e27876. doi: 10.7759/ cureus.27876. PMID: 36110474; PMCID: PMC9463608.
14 Flindt, M.L., 1979. Allergy to alphaamylase and papain. Lancet, 1: 14071408. PMID: 87867
15 Piva, E., F.A. Ogliari, R.R.D. Moraes, F. Cora and S. Henn et al., 2008. Papain-based gel for biochemical caries removal: Influence on microtensile bond strength to dentin. Braz. Oral. Res., 22: 364370. PMID: 19148394
16 Lopes, M.C., R.C. Mascarini, B.M. de Silva, F.M. Florio and R.T. Basting, 2007. Effect of a papain-based gel for chemomechanical caries removal on dentin shear bond strength. J. Dent. Child (Chic), 74: 9397. PMID: 18477426
17 Dietrich, R.E., 1965. Oral proteolytic enzymes in the treatment of athletic injuries: a doubleblind study. Pennsyl. Med. J., 68: 3537. PMID: 5318158
18 Mansfield, L.E., S. Ting, R.W. Haverly and T.J. Yoo, 1985. The incidence and clinical implications of hypersensitivity to papain in an allergic population, confirmed by blinded oral challenge. Ann. Allergy., 55: 541543. PMID: 4051260
19 Tiwari M. The role of serratiopeptidase in the resolution of inflammation. Asian J Pharm Sci. 2017 May;12(3):209-215. doi: 10.1016/j.ajps.2017.01.003. Epub 2017 Feb 1. PMID: 32104332; PMCID: PMC7032259.
20 S.Ethiraj, S.Gopinath, Production, purification, characterization, immobilization, and application of Serrapeptase: a review, Front. Biol. 12 (5) (2017) 333–348. [6] C. De Duve, The significance of lysosome in pathology and medicine, Proc. Inst. Med. Chic. 26 (1966) 73–76.
21 Jadhav SB, Shah N, Rathi A, Rathi V, Rathi A. Serratiopeptidase: Insights into the therapeutic applications. Biotechnol Rep (Amst). 2020 Oct 17;28:e00544. doi: 10.1016/j.btre.2020.e00544. PMID: 33134103; PMCID: PMC7585045.
22 Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia. 1987 Oct 15;43(10):11101. doi: 10.1007/BF01956052. PMID: 3478223.
23 Yatagai C, Maruyama M, Kawahara T, Sumi H. Nattokinasepromoted tissue plasminogen activator release from human cells. Pathophysiol Haemost Thromb. 2008;36(5):22732. doi: 10.1159/000252817. Epub 2009 Dec 9. PMID: 19996631.
24 Weng Y, Yao J, Sparks S, Wang KY. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci. 2017 Feb 28;18(3):523. doi: 10.3390/ ijms18030523. PMID: 28264497; PMCID: PMC5372539.
25 Fujita M, Ohnishi K, Takaoka S, Ogasawara K, Fukuyama R, Nakamuta H. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats. Biol Pharm Bull. 2011;34(11):1696701. doi: 10.1248/bpb.34.1696. PMID: 22040882.
26 Chang YY, Liu JS, Lai SL, Wu HS, Lan MY. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med. 2008;47(5):4679. doi: 10.2169/ internalmedicine.47.0620. Epub 2008 Mar 3. PMID: 18310985.
27 Fadl NN, Ahmed HH, Booles HF, Sayed AH. Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model. Hum Exp Toxicol. 2013 Jul;32(7):72135. doi: 10.1177/0960327112467040. PMID: 23821590.
28 Dogné JM, Hanson J, de Leval X, Pratico D, PaceAsciak CR, Drion P, Pirotte B, Ruan KH. From the design to the clinical application of thromboxane modulators. Curr Pharm Des. 2006;12(8):90323. doi: 10.2174/138161206776055921. PMID: 16533159.
29 Wang KY, Tull L, Cooper E, Wang N, Liu D. Recombinant protein production of earthworm lumbrokinase for potential antithrombotic application. Evid Based Complement Alternat Med. 2013;2013:783971. doi: 10.1155/2013/783971. Epub 2013 Dec 12. PMID: 24416067; PMCID: PMC3876685.
30 Hrženjak T, Popović M, Božić T, Grdisa M, Kobrehel D, and TiškaRudman L, “Fibrinolytic and anticoagulative activities from the earthworm, Eisenia foetida,” Comparative Biochemistry and Physiology B, vol. 119, no. 4, pp. 825–832, 1998.
31 Cao YJ, Zhang X, Wang WH, Zhai WQ, Qian JF, Wang JS, Chen J, You NX, Zhao Z, Wu QY, Xu Y, Yuan L, Li RX, Liu CF. Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallelgroup and controlled clinical trial. Chin Med J (Engl). 2013 Nov;126(21):40605. PMID: 24229674.
32 Mihara H, Sumi H, Yoneta T, Mizumoto H, Ikeda R, Seiki M, Maruyama M. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol. 1991;41(3):46172. doi: 10.2170/jjphysiol.41.461. PMID: 1960890.
33 Jiang G, Zhang W, Peng M, Yan W. [Effect of lumbrokinase on patients with acute and moderate risk pulmonary thromboembolism]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Oct 28;42(10):11561162. Chinese. doi: 10.11817/j.issn.16727347.2017.10.005. PMID: 29093246.
34 Altaf F, Wu S, Kasim V. Role of Fibrinolytic Enzymes in AntiThrombosis Therapy. Front Mol Biosci. 2021 May 28;8:680397. doi: 10.3389/fmolb.2021.680397. PMID: 34124160; PMCID: PMC8194080.
35 Wang YH, Chen KM, Chiu PS, Lai SC, Su HH, Jan MS, Lin CW, Lu DY, Fu YT, Liao JM, Chang JT, Huang SS. Lumbrokinase attenuates myocardial ischemiareperfusion injury by inhibiting TLR4 signaling. J Mol Cell Cardiol. 2016 Oct;99:113122. doi: 10.1016/j. yjmcc.2016.08.004. Epub 2016 Aug 5. PMID: 27503317.
36 Chen Y, Liu Y, Zhang J, Zhou K, Zhang X, Dai H, Yang B, Shang H. Efficacy and safety of lumbrokinase plus aspirin versus aspirin alone for acute ischemic stroke (LUCENT): study protocol for a multicenter randomized controlled trial. Trials. 2022 Apr 11;23(1):285. doi: 10.1186/s13063022062004. PMID: 35410433; PMCID: PMC8996506.
37 Nguyen QTT, Rhee H, Kim M, Lee MY, Lee EJ. Lumbrokinase, a Fibrinolytic Enzyme, Prevents IntraAbdominal Adhesion by Inhibiting the Migrative and Adhesive Activities of Fibroblast via Attenuation of the AP1/ICAM1 Signaling Pathway. Biomed Res Int. 2023 Jan 12;2023:4050730. doi: 10.1155/2023/4050730. PMID: 36685669; PMCID: PMC9851794.
Today, in contrast to the beginnings of the development of the food supplements market, the dosage or galenic forms in which food supplements are available on the market are diverse. There is a large number of dosage forms, over time this number becomes larger, and the production technology is more and more sophisticated and complex. The direction in which this development is moving is guided by the needs of consumers.
With consumers, there is often a socalled pill fatigue especially in the elderly population, chronic patients, or patients who have difficulty swallowing. These groups of consumers need to take several types of medicine every day. Medicines are usually found in capsules or tablets that must be swallowed with
water or another liquid. In addition to medication, i.e., regular therapy, they often take nutritional supplements that support the therapy. In such cases, a person should swallow 7 or more types of tablets or capsules daily. It is no wonder that such a daily intake of a large number of medicines and/or food supplements can cause "pill fatigue".
Because of this, the food supplement market has moved in the direction of finding new solutions and developing new technologies. The main motive and direction of this development are to make the consumption of dietary supplements as pleasant as possible and thereby increase the cooperation of consumers. In addition to this motive, the simplicity of application is also important, the socalled onthego
The major concern in the development of dietary supplements is the requirement to obtain a stable finished product that releases the contents appropriately into the digestive system and at specific points of absorption and utilization.AUTHOR: Daria Šurić, M.pharm.
variants, consumption without the need to drink the liquid. In addition, one of the demands of consumers is that supplementation should be a pleasant and positive experience.
There are exact data available to the food supplement industry, which deal with the analysis of the representation of individual pharmaceutical forms in the food supplement market. The research conducted by Saldanha et al.1 on the American market showed that due to the different forms of food supplements, can affect not only the bioavailability of the ingredients they contain but also the methods needed for their analysis. Consumers may also prefer certain product forms, for example, powders and softgel capsules or gummies over tablets. The research results showed that 48% of all products on the market were in the form of capsules, followed by tablets (22%), powders (14%), and liquids (11%). All other forms accounted for 5% of the product, including 0.8% of gummies.
The PlantLIBRA2 consumer survey included a total sample of 2,359 adult herbal products consumers from Finland, Germany, Italy, Romania, Spain, and the United Kingdom. The popularity of herbal products in Europe is increasing, and consumers are using them
to supplement their diet or to maintain their health. The products are taken in many different forms (e.g., teas, juices, herbal medicines, and herbal dietary supplements). The aim of the survey was to provide an overview of the characteristics and usage patterns of herbal dietary supplements among consumers in six European countries. The survey showed that the most commonly used dosage forms are capsules (38.3%) and tablets/lozenges (36.8%). No significant difference was observed by gender or age (Table 1). In the six countries, solid forms were generally the most popular, although capsules were less frequently used in Romania (17.7%). Liquid forms were less common in Great Britain (8.2%) and Germany (9.9%), but more common in Finland (26.2%) and Italy (26.4%) (Table 2). There is a lack of data on the use of such products at the European level.
The word capsule is derived from the Latin word "capsula" which means a small box or container. The gelatin capsule was invented at the beginning of the 19th century as a result of the need to mask the unpleasant taste of many medicinal substances. 3
Hard capsules consist of two parts that "enter" each other and thus close the capsule. They can contain filling in the form of powder, granules, liquids, minitablets, pellets, microcapsules, or even smaller hard capsules in liquid filling. In the case of granules, pellets, and spherical microcapsules, the mass of active substances in the filling mass is reduced compared to the powder itself, because the lower density of the filling and the production of these forms require additional auxiliary substances.
Hard capsules as a galenic form are particularly suitable for vitamins and minerals as well as herbal powders and powdered extracts. They consist of two halves. The lower half, which is slightly smaller in diameter and is called the "body" - is filled, while the larger diameter "cap" is placed on the filled lower half as a cap or lid. The fine grooves ensure that the body and lid are tightly closed, which means that the capsule cannot break into two halves and that the powder cannot escape through the joint.
Capsule shells exist in different, internationally standardized sizes. When it comes to nutritional supplements, sizes from 1, 0, to 00 are most often used (Table 3). Depending on the density of the powder, hard capsules can generally contain between 288 to 1,080 mg of filling.
Hard capsules can be made of different basic materials. The most important of these are gelatin and HPMC (hydroxypropyl methylcellulose) as a vegetarian alternative (cellulose derived from plant material). HPMC capsules are also suitable for encapsulating hygroscopic active ingredients due to their low moisture content. Gelatin for the production of gelatin hard capsules is obtained by a production process from pig or beef collagen. There are also fish collagen capsules. Gelatin capsules are easily broken down in the body.
Products with prolonged release of active substances are often found in capsule form. For example, pellets or granules coated with polymeric substances that dissolve at different pH values can extend the time of the continuous release of the active substance.
An interesting option are HPMC capsules that are resistant to the acidic pH of the stomach and that allow the capsule shell to dissolve in the intestines.
Thus, a delayed release of the active substance is achieved. Probiotics and enzymes are sensitive to acids, so their effectiveness may decrease as they pass through the stomach and low pH on the way to the intestinal tract. Delayedrelease capsules are an ideal delivery method that can help maintain the maximum effectiveness of probiotics and food enzymes. Even organic products can be developed in hard capsules because according to Annex VIII of Regulation (EC), no. 889/2008 allowed the use of HPMC capsules as long as the capsule shells do not contain other excipients.
Consumers like hard capsules, because they are easy to swallow and mask the taste and smell of active substances. They can be transparent, and of different colors, and there is also the possibility of printing text, logos, and product names.
Soft capsules can be used for solid, liquid, and semiliquid ingredients. They can be round (pearls), ovoid, or cylindrical with rounded ends. They contain additives (e.g. sorbitol, propylene glycol, glycerin) that give them flexibility. They are usually filled with oil or suspensions. They may also contain dry substances, including compressed tablets (geltabs).
The primary types of gelatin used in soft gelatin capsules are usually from beef or pork sources. Depending on the filling, formulation, and target market group, producers have flexibility in the type of raw materials, with some opting for a combination of pork and beef options. Bovine bone gelatin, for example, contributes to the strength of the capsule. Pig options, on the other hand, offer the characteristics of flexibility.
Gelatin dissolves in the human body at normal body temperature, which makes it an ideal ingredient for soft gelatin capsules. The valuable active substances inside the capsule are protected from oxygen, light, moisture, and dust, and such a capsule allows consumers to easily swallow it. Soft capsules can be from a vegetarian source, starch, or, for example, based on carrageenan. It is a group of longchain carbohydrates (polysaccharides) found in the cells of various types of red algae.
Soft capsules are particularly suitable for encapsulating oils, emulsions, or other similar materials to a pastelike consistency. Unlike the two halves of a hard capsule, these capsules are not prefabricated. Instead, they are made directly during the filling process from two ribbons of capsule material running over each other via a socalled "rotary die" process, which uses rotating rollers. The material to be placed inside the capsule is then enclosed in two capsule shells of the same shape, which are firmly stitched together.
There are different shapes of soft capsules - round, oval, oblong, or so-called. twist-off capsules. They have a small extension that can be unscrewed by hand. This means that the material inside the capsule can be emptied and consumed through the opening thus created, without the need to consume the capsule itself. A wide range of sizes is also available, with fill amounts of around 1.200 mg typically representing the upper limit of what a person can reasonably be expected to ingest.
Gelatin capsules contain a certain percentage of
moisture. This can lead to unwanted interactions with highly hygroscopic ingredients, such as magnesium oxide or tannins. Hygroscopic powder binds moisture from the gelatin capsule shell. Because of this, the capsule shell loses its flexibility, so this should be taken into account when developing formulations for soft gelatin capsules.
Soft gelatin chewable capsules are one of the newer forms of dietary supplements. They are suitable for ingredients that are normally found in large capsules that are difficult to swallow, e.g., for omega-3 fatty acids. The development of technology strives for thinner shells in order to accelerate their dissolution in the mouth, for a more positive consumer experience. When chewing, there is a pleasant taste of the sweet, creamy liquid contained in the capsule.
Hard capsules consist of two cylindrical parts each closed at one end, which fit perfectly into a hermetically sealed unit. The hard capsule parts are manufactured before filling with the active ingredient. In the next manufacturing step, contract manufacturers or brand owners fill the active ingredient or drug into empty gelatin capsules.
Soft capsules are onepiece and hermetically sealed and contain a liquid or semi-solid filling. Unlike hard capsules, soft capsules are filled at the same time as the capsule is manufactured. They have a larger range of dimensions, and they differ from manufacturer to manufacturer, depending on the filling and production technology. The exact dimension of the capsule is known only after the production of the filled capsules is completed, unlike hard gelatin capsules, where the dimension is prestandardized since the empty capsules are produced before filling.
The biggest advantage of capsule production technology is that they can be filled without applying any pressure, or with relatively little pressure. Exposure of nutrients to heat stress is another aspect that can be minimized or avoided entirely. Moreover, the envelope not only protects the contents from environmental influences but also protects the taste receptors from a potentially unpleasant taste. For example, many people prefer fish oil capsules whose capsule shell prevents direct contact of the oil with the mucous membrane of the oral cavity, or hard capsules that envelop the active substances and thus give them a shape that can be easily swallowed. Hard capsules can be opened if necessary and the contents consumed without a capsule, e.g., probiotics for small children. A similar option is offered by the so-called twist-off soft gelatin capsules. An example of such a product is vitamin K1 capsules for infants.
Tablets are ingredients in powder form, which are mixed with auxiliary substances (additives) so that they retain a certain shape. They can be coated or uncoated. One of the advantages of tablets is that the ingredients are compressed, so in some cases, they can contain a larger amount of active substances than capsules.
Sometimes creating a formulation for a technically optimal tablet requires a complex development process. However, tablets allow for some variations that capsules do not. Effervescent tablets or tablets with a dividing line that allows breaking into smaller pieces are just one example. Coatings are another aspect that can be easily implemented on tablets, for visual or technical reasons, or to ensure the gastroresistance of the tablet. After being swallowed, the tablet breaks down very quickly into smaller and smaller units until it finally dissolves completely. According to the European Pharmacopoeia, a maximum decomposition time of 15 minutes is to be expected. With filmcoated tablets, this is extended to 30 minutes.
High pressure is required to press the tablets. For this reason, not all raw materials are suitable for tablets. For example, high pressure can have a negative effect on the structure of the oil matrix of most oil powders, leading to the release of free oils immediately, or after some time. This is a phenomenon that can be seen on the surface of the tablet in the form of a greasy stain.
The gentlest process is the socalled "direct compression". When the raw materials are suitable for this, they are directly mixed with the excipients of the tablet and pressed. This means that it is not necessary to carry out granulation in advance, which is timeconsuming, expensive, and potentially aggressive toward the content.
The entire tabletmaking process requires compression in a confined space, where the upper and lower punches are pressed from opposite directions within the die under a certain pressure, sometimes up to six tons, to produce the finished tablet. When choosing the ingredients for the formulation, it is important to consider the heat generated by such pressure. This heat is often harmful to the sensitive components in the tablets, so they sometimes need to be added in excess to ensure shelflife stability. Compounds that are sensitive to heat, moisture, or UV light must also be protected within the tablet, which is why many tablets go through an additional film-coating process, involving a protein or polymer, usually with a final thickness between 20 and 100 micrometers (very thin). The reason why tablets are often coated is to protect the ingredients from deterioration, to reduce tablet edges from erosion du
ring packaging and transport, and to mask the unpleasant taste or smell of the ingredients.
The advantage offered by the technology of multilayer tablets is the division into different layers of otherwise incompatible active ingredients, which should be released at different times and in different places of the gastrointestinal tract. An example is probiotics in combination with vitamins and minerals probiotics are in a separate layer from vitamins and minerals, protected from the harmful effects that certain minerals and vitamins can have. This ensures the stability of the product.
Products containing melatonin are another example. Namely, one layer enables the rapid release of melatonin, while the other enables a prolonged release, which ultimately ensures a continuous release during the night, important for the effect of such a dietary supplement.
The production of effervescent tablets is a particularly sensitive technology. Formulations generally include an agent capable of releasing CO2 (e.g., sodium carbonate and sodium bicarbonate) and an agent that promotes the release of CO2 (e.g., citric acid). The formation of carbon dioxide is the result of a chemical reaction that takes place between a carbonate or bicarbonate salt (e.g., sodium bicarbonate) and a weak organic acid (e.g., citric or tartaric acid) in the presence of water. That is why strict humidity control is mandatory in all production areas. Any packaging material used for effervescent tablets should protect them from external influences and keep as little air as possible in the package since moisture present in trapped air can lead to physical and/or chemical degradation of the tablet (Altomare et al., 1997). They are most often packaged in plastic tubes that contain desiccant in plastic caps.
The development process of the formulation may take longer in the phase of defining the organoleptic characteristics. It is necessary to make a suitable sample that meets the organoleptic requirements.
Effervescent tablets may contain higher dosage amounts compared to conventional tablets. There is no need to swallow, thus improving compliance, especially for elderly and pediatric users. Also, they enable improved dosing, and due to the generation of CO2, all ingredients are automatically mixed.
These are products designed to quickly disintegrate, or dissolve in the mouth on contact with saliva, eliminating the need to chew the tablet, swallow the tablet intact, or take the tablet with liquid. Initially, it was expected that this route of administration would be useful in the production of drugs for pediatric and geriatric patients, for people with conditions related to impaired swallowing, and for the treatment of patients who are difficult to cooperate with (e.g., in psychiatric disorders). Today, ODT appears more and more often in the category of food supplements, and products for better sleep in this form are especially interesting because they do not require additional liquid consumption before bedtime.
In the field of dietary supplements, sticks, and sachets are a newer and very "trendy" alternative to capsules and tablets. They cause great interest among consumers. Depending on the concentration, the sticks may contain approx. 110 grams of powder or granules. In this way, it is also possible to develop products that meet health claims and contain higher amounts of active substances. One stick can replace many capsules, and reducing intake to one serving per day makes the product less complicated and more popular among consumers. Stik powder can be taken according to the consumer's taste directly dissolved in the mouth (direct), dissolved in water, juice, or milk, mixed in yogurt, or in various other food.
Granules and powders have different advantages. While granules can be well mixed together and do not create fine dust, the advantage of powders is that they do not undergo expensive and timeconsuming preliminary treatments. Granulation burdens the contents due to the heat of drying. Moreover, it is necessary to add a carrier material usually sugars and to some extent solvents. However, granulate is much more suitable than powder for sticks that dissolve directly in the mouth (it is possible to achieve a better taste and less dusting when applied in the mouth).
As with other shapes, it is important that the finished mixture is uniform and flowable. Moreover, when it comes to them, the components should not have too strong an individual taste. If the basic mixture of ingredients is relatively neutral, it is easily combined with aromas and with sweet and fruitysour ingredients. This enables a wide range of product variety, which benefits the consumer.
A portion of powder or granules in stick form is the ideal dosage form for those who have problems swallowing capsules or tablets. Individual sticks or sachets are also easier to carry in your bag than a blister pack or a whole box of the product.
Sachets containing powder with probiotics are the most popular way of using probiotics because by dissolving them in water before consumption, the probiotics are reactivated before they are introduced into the body.
Recently, sticks with liquid or gel filling are gaining popularity. They are particularly interesting for use by athletes or, for example, for single doses of syrup.
Sachets with powder that dissolves in a liquid have been on the market for a long time and are the most common way of applying rehydration solutions.
Gummy candy is currently the star of the industry it's the most soughtafter and most popular new form of dietary supplement according to the Nutrition Business Journal's (NBJ) 2022 Report. Last year, when NBJ surveyed 1,005 consumers who preferred the pharmaceutical form—27.4% of respondents chose gummy candy, 25 .1% chose tablets, 19.7% opted for capsules, and 13.1% chose soft gelatin capsules as their choice.
These "crossbreeds" between the pharmaceutical form and sweets, the socalled "candyceuticals", cover various purposes, from sleeping to sports.
Key factors driving the gum products market include their availability in different flavors for cus
tomers looking for tasty health benefits, ease of use, variety of unique flavors, and tasty formulations offered by manufacturers to appeal to children and adult consumers.
Gummy candies can be produced with gelatin, and vegetarian variants with pectin.
Proponents of oral sprays point out that they enable faster absorption of nutrients. The study, published in the European Journal of Clinical Nutrition, was part of a threeyear research project that concluded that the oral spray method of vitamin D was as effective as taking capsules, and supported the same rate of improvement in vitamin D levels in subjects. Taking vitamin D in an oral spray is just as effective as taking a pill, according to research from the University of Sheffield.4
Nutrients are absorbed sublingually in larger quantities than with other forms that first pass through the digestive tract and are metabolized by the liver and kidneys. For this reason, nutrients should have better bioavailablity. This effect is especially pronounced when one of the organs is damaged, for example with leaky intestines. Several studies have provided results in support of this claim.5,6 However, since there are still many unknowns about the application and stability of the various ingredients in the spray, much more research is needed on this topic. For now, it looks like a promising form whose additional advantages are ease of application and a small number of additives.
In addition to the mentioned forms, there are many more classic galenic forms such as syrups, and modern ones such as lollipops. Dietary supplements are increasingly becoming attractive and at the same time a practical way to improve the quality of life by taking in nutrients. All the mentioned dosage forms enable the taking of nutritional supplements to be adapted to today's flexible and fast lifestyle. Despite this, classic forms such as capsules and tablets still have their important place on the market.
References:
1 Saldanha, Leila G et al. “Characteristics and Challenges of Dietary Supplement Databases Derived from Label Information.” The Journal of nutrition vol. 148,suppl_2 (2018): 1422S-1427S.
2 GarciaAlvarez A, Egan B, de Klein S, Dima L, Maggi FM, Isoniemi M, RibasBarba L, Raats MM, Meissner EM, Badea M, Bruno F, Salmenhaara M, MilàVillarroel R, Knaze V, Hodgkins C, Marculescu A, Uusitalo L, Restani P, SerraMajem L. Usage of plant food supplements across six European countries: findings from the PlantLIBRA consumer survey. PLoS One. 2014 Mar 18;9(3):e92265.
3 Kathpalia, Harsha and Gaurav Mahesh Doshi. “Recent trends in Hard Gelatin capsule delivery System.” (2014).
4 Claire E. Williams, Elizabeth A. Williams, Bernard M. Corfe. Rate of change of circulating 25hydroxyvitamin D following sublingual and capsular vitamin D preparations. European Journal of Clinical Nutrition, 2019.
5 Jacobson BH, Smith DB, Warren AJ, Glass RG, Kline C, Fedick JL, Stemm J. Assessment of the effectiveness of a sublingual, ergogenic spray on muscle strength and power. J Strength Cond Res. 2009 Nov;23(8):232630.
6 Satia, M., Mukim, A., Tibrewala, K. et al. A randomized two way cross over study for comparison of absorption of vitamin D3 buccal spray and soft gelatin capsule formulation in healthy subjects and in patients with intestinal malabsorption. Nutr J 14, 114 (2015).
Aholistic approach to health has always been our first choice when it comes to ways to support it. Nutritional supplements are an extremely important factor that can contribute to maintaining optimal health and are a good ally in the fight against various health disorders.
That is why professional path of Darmell is focused on developing new nutritional supplements and informing interested industry workers about ingredients, evidence of effectiveness, news, regulation and other relevant information in the field.
By combining many years of business experience, continuous acquisition of knowledge and cultivating business acquaintances, we are able to provide a variety of services.
Services we offer:
• Consulting in the elaboration of ideas and concepts for the development of new products - from the selection of ingredients to the launch of the finished product, with the help of finding the appropriate manufacturer of medicinal forms.
Consulting related to the registration of dietary supplements.
• Writing content for various purposes, in the field of dietary supplements and functional foods, related to individual ingredients and finished products.
• Help in finding a suitable distributor for finished products.
We also actively deal with:
Representing renowned companies producing branded ingredients/raw materials for nutritional supplements.
• Publishing professional publications in the field of nutritional supplements, functional food and cosmetics.
Darmell Ltd.
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.darmell.com
At Vitafoods and PLMA, functional food expert SternLife will present new Deluxe bars and powder supplements for improved gut health post-50.
Inhouse development using highquality formulations and ingredients allows SternLife to create flexible, private label product concepts. The German familyowned company will be presenting a new powder concept for the intestinal wellbeing of healthy agers, alongside its optimised vegan Grand Deluxe Protein Bars with extra cream filling, to the European trade public from 9 to 11 May 2023 at Vitafoods in Geneva (stand I191) and from 23 to 24 May at PLMA in Amsterdam (stand 5.B27).
"Gut Comfort", a powder supplement concept for improved intestinal health in later life, taps into current megatrends Healthy Ageing and Gut Health. It thus perfectly targets the needs of the growing 50plus market.
Older people, in particular, are often affected by digestive problems, as intestinal activity changes with inceasing age. The composition of the intestinal flora plays just as important a role as a functioning, impermeable intestinal mucosa. This is where the right nutrients can make a difference. Studies have shown that the superfood yellow kiwi has a positive effect on the intestines, which is why the extract forms the basis of this new supplement.
The powder, available in three on-trend flavours, has numerous application possibilities – for example, in shakes, yoghurt, muesli and water. It helps reduce inflammation in the intestine and has a positive influence on the microbiome, especially lactic acid and bifidobacteria which are both vital for good gut health. A healthy intestinal environment is further strengthened with a balanced nutrient complex of biotin, niacin, riboflavin and vitamin A to ensure the mainte
nance of the mucous membranes. It also contains soluble dietary fibres, which have a prebiotic effect.
SternLife has captured the mood of consumers in the creation of its "Grand Deluxe Vegan Bars", which promise great taste and mouthfeel, along with an impressive nutritional profile. Both concepts impress with a creamy, crunchy bite and soft texture, and contain up to 22% filling cream for extra smoothness. And that's not all: SternLife has also succeeded in finding a vegan alternative to milk chocolate coating using rice and coconut milk powder, and will be presenting it for the first time at Vitafoods and PLMA. The sustainable vegan bars also target the sports nutrition market, with a protein content of up to 24 per cent and a sugar content of less than 5 per cent. The new bars will be available to taste throughout the 2023 trade fair season, in Caramel Choco and Butter Cookie Peanut flavours. Soy-free and allergen-free varieties, as well as organic versions, are also available on request.
SternLife GmbH & Co. KG develops and manufactures functional foods and food supplements. The company’s portfolio ranges from powder preparations, functional bars and snacks to capsules and tablets. Brands and private labels benefit from its comprehensive know-how in the innovative health, sport and lifestyle nutrition sector and from its range of products tailored to specific target groups. SternLife is a member of the independent, ownermanaged SternWywiol Gruppe, one of the most successful enterprises with international operations in the world of food and feed ingredients. When developing new products, SternLife’s functional food experts have access to the pooled skills of eleven specialist companies and some 100 R&D experts in the Stern Technology Centre, with its broad range of applications technology. SternLife products are made in the group’s own stateoftheart manufacturing facilities located in various parts of Germany.
Curcumin C3 Complex®
• Yellow powder, standardized to min of 95% Curcuminoids
• Patented process and sold in Europe since 1996
• Used in most clinical studies (96) and scientific publications (246)
• Approved according to EFSA's Novel Food Catalogue
Awards:
NBJ Scientific Achievement Award 2007
NBJ Product Merit Award 2008
Functional Ingredients Editors Choice Award 2012
Winner of NutraIngredients Awards 2016
USP Donor Recognition Program, Silver Award 2020
USP Donor Recognition Program, Silver Award 2021
Curcumin C3 Complex® DC (Directly compressible)
• Same as Curcumin C3 Complex® but compacted for easier tabletting
Curcumin C3 Dispersible
• Blend of Curcumin C3 Complex® with gums of acacia, xanthan and guar that is completely dispersible in water
• Contains 630 mg of Curcumin C3 Complex® per gram
UC3 Clear®
• Water-soluble blend of Curcumin C3 Complex® with Licorice Extract and emulsifier (polyvinylpyrrolidone)
• Standardized to min of 10% Curcuminoids
Curcumin C3 Reduct®
• White powder, standardized to a minimum of 95% tetrahydrocurcuminoids
• The active, hydrogenated form in which curcuminoids are converted in to its metabolites
• Patented process
• High bioavailability
• Tested in 2 clinical studies and described in >27 scientific publications
• Approved according to EFSA's Novel Food Catalogue
Starmeric®
• Polysaccharide fraction standardized for resistant starch and difficult to digest carbohydrates
• Light brown powder
• Standardized for 40% resistant starch
Curcuma longa Turmeric Oil
• Volatile fraction (essential oil) of turmeric
• For cosmetic applications
SabiWhite®
• White powder, standardized to a minimum of 96% tetrahydrocurcumin
• The active, hydrogenated form in which curcumin is converted in to its metabolite
• For cosmetic applications
About the Bioavailability:
The clinical trials in which Sabinsa, among others, demonstrated the effectiveness of curcumin were carried out without the a ddition of emulsifiers and the like (which are sometimes assumed to improve the bioavailability) Any reference to these results fo r products with a lower content of curcuminoids combined with a high content of emulsifier that should improve bioavailability is therefore not scientifically justified The demonstrated improvement in bioavailability using BioPerine® is not based on solubility, but on the one hand optimizing thermogenesis and on the other hand limiting glucuronidation To improve the solubility of curcumin, if desired, we can offer excipients such as lecithin, phosphatidylcholine, galactomann ans from Fenugreek, etc
Vitafoods Europe 2023, booth B119: Omya presents exciting concepts for a new generation of orally disintegrating applications.
At Vitafoods Europe, Omya will present the Omyanutra® range of technologically advanced natural minerals that open up a wealth of opportunities for oral dosage forms. Omyanutra® 300OG, Omyanutra® 300 DC and Omyanutra® 300 Flash offer ultra-fast dissolution qualities that are suitable for supplements and nutraceuticals in directly compressed or free-flow powder form. Being highly porous while still of hard consistency, the nonnano and GMO free particles provide ultimate absorption qualities, no dusting, ideal glidance in powders and easy compressibility in solid tablets. Besides their extraordinary functionality, the particles add value as a natural source of calcium with optimal bioavailability, supporting bone health and making the use of health claims possible. When combined with other active ingredients such as vitamins, natural flavors and fibres, all offered in the company’s complementary distribution portfolio, manufacturers can meet current consumer demand both efficiently and effectively, and create market-differentiated products.
Omya will illustrate the range of options with unique prototype formulations such as Day & Night functional tooth tabs with vitamins and active ingredients for enhanced wellbeing. As tooth brushing usually happens early in the morning and last thing at night, these products are perfect for delivering an extra energy kick or late-night calming effect. While brushing, the supplements are absorbed through the mucosa to quickly deliver their beneficial effects. Taurine and Ltheanine are combined to provide an active start to the day, while tryptophan and Ltheanine support the body in winding down at the end of the day. Furthermore, the solid tabs give an authentic teeth-brushing effect thanks to the company’s mineral particles: porous Omyanutra® 300 Flash particles can carry actives and disintegrate ultrafast, while Omyacare® S95OG promises enamelsafe abrasivity and cleaning performance. Omyadent® 100 OG, meanwhile, delivers remineralization and whitening effects. Despite a minimalist INCI list, hydroxyapatite and calcium carbonate particles are ideal for fluoridefree products, and are environmentally friendly too: They save on water and can be packed in glass bottles or paper bags, which reduces transportation and storage costs, as well as CO2 emissions.
Further prototypes showcased will include Activfresh mint oilcontaining lozenges produced with
Omyanutra® 300 DC for instantly refreshed breath and mouthfeel, and Bone Boost Chewables, comprising a mix of Omyapure® 35 a highpurity, natural calcium source with 40% of bioavailable calciumplus vitamins D3 and K2, which are essential for optimal calcium absorption and deposition into bones. B12 Flash ODT are red berry-flavored tablets containing vitamin B12 which, thanks to Omyanutra® 300 Flash, orally disintegrate ultrafast regardless of the hardness of the tablet. Finally, LTheanine Flash ODTs with apple and mint flavour can quickly and effectively ease anxiety, while counteracting oxidative cellular stress.
Stefan Lander, Vice President Consumer Goods, Group Sales & Marketing at Omya, says: “Today’s consumers are increasingly demanding when it comes to best health support, but also want pleasant and effective application, as well as a safe and environmentally friendly profile of the end product. Our natural and safe minerals tick all the boxes, as they enable easy processing combined with a broad range of functional benefits.”
Omya is a leading global producer of industrial minerals mainly derived from calcium carbonate, dolomite and perlite and a worldwide distributor of specialty additives, premium services, and solutions. Founded in 1884 in Switzerland, Omya has a global presence extending to more than 160 locations in over 50 countries with 9,000 employees. Omya provides sustainable addedvalue products and services from responsibly sourced materials to meet current and future generations' needs. Omya offers innovative solutions based on high purity natural minerals and complementary ingredients that comply with the most stringent regulatory and quality standards in the Consumer Goods sector.
https://pharma-nutra.omya.com/
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New product development and collaboration with many renowned contract manufacturers of medicines, medical devices, dietary supplements, cosmetics and food products.
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Our advantages:
✓ Fast communication and short project deadlines
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Primrose has a long history of medicinal use, and today it is most commonly used as an expectorant and secretolytic, especially for coughs with difficult expectoration, chronic bronchitis, and asthma, due to its content of saponins, which stimulate the thinning of secretions in the respiratory tract and thus expectoration.
Common primrose or primrose (Primulavulgaris Huds.) is a perennial herbaceous plant of low growth. It is one of the first plants that begin to bloom in spring. It’s root is brown and short. The leaves are flat and arranged in a rosette. The flowers are bisexual, large, and about 3 cm in size. They are located on long stalks covered with protruding hairs. They have five petals and are light yellow in color, and closer to the middle are colored in bright yellow. The calyx is cylindrical, about 15 mm long, and made of 5 mutually fused lobes. The whole plant is covered with hairs. The fruit is a round cocoon containing brown, warty seeds about 23 mm long. 3
Primroses bloom for about a month, from the end of February until May.
Primrose naturally grows in the countries of southwestern and southern Europe, northern Africa, and southwestern Asia. It grows in sunny habitats, on fresh, loose, and nutritious, neutral to moderately acidic soils. We find it in dry meadows and clearings, in light forests, in orchards, next to bushes, and up to 1,200 m above sea level.
Primrose is a good honey plant because it provides pollen and some nectar to the bees. 3
For medicinal purposes, we use the root (Primulae radix) and the flower (Primulae flos) with or without a calyx (cum or sinecalycibus).
The root should be collected in autumn after the plant has grown for two or three years.
The underground part of the stem contains2:
• triterpene saponins
• phenol glycosides (primulaverin)
• salicylic acid
The flower contains2:
• saponins
• flavonoids
• carotenoids (in petals)
• a small amount of essential oil and trace enzymes
Primroses have a very long history of medicinal
use, and have been used to treat conditions that include colic and rheumatic pain in particular. However, they are considered less effective than the related plant Primula veris
Primrose contains saponins that promote the dilution of secretions in the respiratory tract, and thus expectoration.
It is used as an expectorant and secretolytic in the respiratory tract diseases, in the form of extracts, infusions, decoctions, and most often syrups. It is especially recommended for coughs with more difficult expectoration, chronic bronchitis, and asthma.
It is often included in various tea mixes and syrups on the market.
References:
1 Flora Croatica database, hirc.botanic.hr
2 Josip Gelenčir, Jasenka Gelenčir: Atlas ljekovitog bilja, Publisher:: Prosvjeta Zagreb 1991.
3 Izvor: https://www.plantea.com.hr/jaglac/
TAXONOMY
kingdom: Plantae
order: Ericales
family: Primulaceae
genus: Primula
species: Primulavulgaris
common name primrose, common primrose, English primrose
flowering time III, IV, V month
Kemin Industries, a global ingredient manufacturer that strives to sustainably transform the quality of life every day for 80 percent of the world with its products and services, will be exhibiting at Vitafoods Europe 2023 in Geneva, Switzerland on Monday, May 9, through Wednesday, May 11. Attendees of the nutraceutical industry trade show can visit Kemin Human Nutrition and Health at booth #I101 to learn about the latest healthforward functional ingredients.
Kemin Human Nutrition and Health’s sciencebacked ingredients support a range of wholebody solutions, including vision, cognition, immune and gut health, beauty from within, sleep, oral care and weight management.
“The Kemin team is excited to meet in Geneva with prospective and current customers to discuss our latest innovations in healthy solutions,” said Pedro Vieira, Vice President – EMEA, Kemin Human Nutrition and Health. “One ingredient we are highlighting is BetaVia™, our algaesourced beta glucan postbiotic with demonstrated immune and gutpromoting benefits derived from its triple-action mechanism: priming key immune cells, protecting intestinal barrier integrity and shaping the microbiome.”
Vitafoods Europe attendees who visit the Kemin Human Nutrition and Health at booth #I101 can learn more about Kemin’s innovative solutions, including:
• BetaVia™ – an algaesourced, postbiotic beta glucan, this nextgeneration immune and gut health solution provides the dietary support needed in Western diets.12
• DailyZz™ – a natural, proprietary, botanical blend of spearmint and green tea extracts promotes better quality sleep and improves nextday functioning in healthy adults who have occasional sleep complaints. 3
• Neumentix™ – naturally sourced from a patented line of spearmint4 high in polyphenols, this ingredient redefines the approach to cognition through improvements in agility, memory, focus and attention.57
“We will be displaying several prototype concepts we created, in partnership with key contract manufacturers, to help inspire customers in developing the next generation of healthpromoting formulations,” said Filipa Quintela, Marketing Manager – EMEA, Kemin Human Nutrition and Health. “One of these concepts includes our sleep quality ingredient, DailyZz, in an allnatural formula that gives consumers an
extra edge for better nextday performance. Prototypes will be available in formats ranging from tablets and stick packs to syrups, sprays and drops.”
Kemin Human Nutrition and Health offers an extensive portfolio of functional ingredients that have been used in over 100 studies to ensure they provide relevant health benefits to consumers and help improve their quality of life. Kemin is focused on delivering ingredients that are naturally sourced, environmentally friendly and proven to comply with the most stringent global quality standards.
1 Kemin, BetaVia Complete can prime key cells in the innate immune system. KHTL017150.
2 Kemin Proprietary Data TD-20-6867 “Effect of a Euglena gracilis (β1,3glucan) on Gut and Immune Health in Healthy Adults with Mild Gastrointestinal (GI) Issues.”
3 Tubbs AS, Kennedy KER, AlfonsoMiller P, Wills CCA, Grandner MA. A Randomized, DoubleBlind, PlaceboControlled Trial of a Polyphenol Botanical Blend on Sleep and Daytime Functioning. Int J Environ Res Public Health. 2021 Mar 16;18(6):3044. doi: 10.3390/ijerph18063044. PMID: 33809544; PMCID: PMC8000032.
4 US Patent #9,545,075; US Patent #9,545,076
5 Falcone, Paul H., et al. The attention-enhancing effects of spearmint extract supplementation in healthy men and women: a randomized, doubleblind, placebocontrolled, parallel trial. Nutrition Research 64 (2023): 2438.
6 Nieman, Kristin M., et al. Tolerance, bioavailability, and potential cognitive health implications of a distinct aqueous spearmint extract. Functional Foods in Health and Disease 5.5 (2015): 165187.
7 Herrlinger, Kelli A., et al. Spearmint extract improves working memory in men and women with ageassociated memory impairment. The Journal of Alternative and Complementary Medicine 24.1 (2018): 3747.
Studies show how bioactive collagen peptides can increase bone density in midlife women.
Osteoporosis affects about 22 per cent of European women over the age of 50, and about 7 per cent of men.1 In addition, the lifetime risk of osteoporotic fractures is about 46 per cent for women and 22 per cent for men. 2 The reason for the higher risk in women is the hormonal changes that occur after the menopause, which women experience on average between the ages of 45 and 55. Falling oestrogen levels lead to a decrease in bone mineral density, which is essential for maintaining bone health. However, as collagen is a major component of the organic bone matrix, supplementation with specific collagen peptides – in addition to known preventive measures such as a calcium and vitaminrich diet, weight management and adequate exercise – is a promising way to help prevent bone loss. Gelita, the leading collagen specialist, has developed Bioactive Collagen Peptides Fortibone® for this very purpose, with their effectiveness confirmed in clinical studies involving postmenopausal women.
Oestrogen plays an important role in bone metabolism as it impedes the activity of cells, known as osteoclasts, that break down bone mass. However, during the menopause, oestrogen levels fall, which means osteoclasts are no longer sufficiently inhibited. As a result, there is a decline in bone mineral density, which can result in bone loss and fractures, as well as postmenopausal osteoporosis.
There are several nonpharmacological approaches to preventing osteoporosis: daily physical activity, reducing alcohol consumption and quitting smoking. Although these measures can slow further loss of bone density, once osteoporosis has been diagnosed it is unlikely to improve. Taking calcium and vitamin D is often recommended, but there is no evidence that they make a significant difference to disease progression or fracture risk. Pharmacological treatments can have disadvantages too: Bisphosphonates, human monoclonal antibodies and selective estrogen receptor modulators are all associated with adverse side-effects.
The bone matrix of the human body consists of 70 per cent inorganic minerals such as calcium and phosphorus, and 20 per cent organic substances, with the remaining ten per cent being water. The organic part of the bone matrix consists of 95 per cent collagen fibres and 5 per cent bone cells, as well as other noncollagenous proteins. Collagen provides the scaffolding for mineralisation, which is important for bone formation because if the bone matrix is weak, there are not enough binding sites for calcium to ensure sufficient bone density. However, bone mass can be mineralised, and density and elasticity improved, by increasing collagen fibre content.
“At Gelita, we’ve spent years researching how the intake of Bioactive Collagen Peptides affects different areas of the body, such as joints, tendons or bones. In the area of bone health in postmenopausal women, in particular, we’ve been able to achieve convincing results with Fortibone®,” says Martin Walter, Category Manager Healthy Aging and Sports Nutrition at Gelita.
A doubleblind, randomised controlled trial conducted in 2018 evaluated 12 months of Fortibone® supplementation on bone mineral density at the spine and femoral neck in postmenopausal women with low bone density. The study involved 131 women aged 4680 who were divided into intervention and placebo groups. The intervention group took 5g of FORTIBONE® daily, while the placebo group took 5 g of maltodextrin. The study showed that bone densi
ty increased significantly after taking Fortibone® up by 4.2 per cent in the spine and 7.7 per cent in the femoral neck3 while it decreased in the placebo group.
The positive effect of Fortibone® on bone mineral density was also confirmed in a 2021 follow-up study, in which 31 female subjects from the 2018 study took 5g of Fortibone® daily for three more years. The subjects were from both the intervention and placebo groups. A longterm increase in bone density was observed, with subjects from the previous placebo group benefiting most from taking Fortibone®. Density increased between 5.79 and 8.16 per cent at the spine, and between 1.23 and 4.21 per cent at the femoral neck during the observation period. In addition, none of the participants suffered a fracture during the four years.4
Initial research into the mode of action of Fortibone® indicates not only a suppressive effect on bone breakdown but, more importantly, a distinct stimulatory effect on the bone-building osteoblast cells. This anabolic effect can increase collagen synthesis and support the development of a stable bone structure. This is in contrast to many pharmacological treatments that only aim to prevent further bone loss.
Gelita’s Bioactive Collagen Peptides are well tolerated and have no adverse side-effects. After oral administration, they pass through the intestinal mucosa and enter the bloodstream in partially intact form. They are easily digested, rapidly absorbed and highly bioavailable.
Gelita’s collagen peptides also offer many technological advantages: they combine well with vitamins, minerals and other nutrients, and have excellent cold water solubility. As they are tasteless and clear in colour, they are easy to incorporate into end products. They have high heat and acid stability, and low viscosity, making them ideal for blending with other substances. In addition to being fat and cholesterol free, they are completely natural, making them ideal for clean label formulations.
“Our range of specific collagen peptides offers almost unlimited possibilities for the development of dietary supplements, functional foods and beverages targeting women or the ageing population as a whole,” says Martin Walter. “They can be easily incorporated into a range of products, including dairy products, protein bars, drinks and dietary supplements that help maintain quality of life and keep people active for longer.”
References:
1 International Osteoporosis Foundation (IOF): A new scorecard for osteoporosis in the EU 27+2. 2021.
2 Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8(1):136. doi: 10.1007/s116570130136
3 König et al. (2018): Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women a randomised controlled trial. Nutrition. 2018 Jan 16;10(1):97. doi: 10.3390/nu10010097.
4 Zdzieblik et al. (2021): Specific bioactive collagen peptides in osteopenia and osteoporosis: Longterm observation in postmenopausal women. https://doi.org/10.11005/jbm.2021.28.3.207
5-7 May 2023, Bologna, Italy
https://www.cosmofarma.com/en/
6-7 May 2023, Hannover, Germany
https://www.cosmetica.eu/cosmeticahannover/
9-11 May 2023, Geneva, Switzerland
https://www.vitafoods.eu.com/
May 31 - June 2 2023, Istanbul, Turkey
https://chcistanbul.com/
14-15 June 2023, Munich, Germany
https://www.cosmeticbusiness.com/en/
7-8 September 2023, Stockholm, Sweden
https://www.hudochkosmetikmassan.se/
7-10 September 2023, Bologna, Italy
https://www.sana.it
27-29 September 2023, Istanbul, Turkey
https://beautyistanbul.com/
22-24 October 2023, Paris, France
https://natexpo.com
24-26 October 2023, Barcelona, Spain
https://www.cphi.com/europe/
15-16 November 2023, Malmo, Sweden
https://www.nordicorganicexpo.com/
28-30 November 2023, Frankfurt, Germany
https://www.figlobal.com
The skin is subject to two types of aging:
1. intrinsic aging is chronological aging caused by genetic inheritance and depends on the passage of time. It is characterized by skin atrophy, loss of elasticity and slowing down of metabolic activities. Signs of chronological aging are fine wrinkles, thin and transparent skin, loss of underlying fatty tissue and bone structure of the face, dryness of the skin, the inability of the sweat glands to sufficiently cool the skin, hair loss and the appearance of unwanted hair. Cell activity decreases, the skin becomes thinner. Subtle but constant skin changes result in progressive loss of its function. The main cause of aging is still considered to be the accumulation of damage. It has been proven that the speed of aging is genetically controlled, and by certain evolutionarily conserved biochemical processes.
2. extrinsic aging is caused by the influence of external factors. Among the numerous harmful environmental influences involved in this, the most
significant is long-term and repeated exposure to UV rays, which causes photoaging. It is a cumulative process that primarily depends on the degree of exposure to sunlight and skin pigment. UV radiation causes complex processes on specific molecules, the response of which causes damage to the connective tissue of the skin. UV radiation accelerates and intensifies the changes caused by intrinsic aging. Photoaging is manifested by the appearance of wrinkles, redness of the skin, dryness, loss of elasticity, appearance of telangiectasia, and pigmentary changes. Exposure to UV radiation increases the appearance of benign and malignant skin neoplasms on photoexposed parts.
Oxidative stress is a biological phenomenon that creates free radicals which damage cell structures such as membranes and proteins in DNA. The body naturally produces free radicals, and cells naturally have a defense mechanism. However, with age, the imbalance between external stressors (oxidation) and
They strengthen the protective function of the skin, hydrate it, reduce transepidermal water loss, enable antioxidant activity, and stimulate the renewal of cells and connective tissue...
the body's defense capabilities (antioxidants) grows. The number of potential causes of stress increases with age and life experiences (UV radiation, pollution, smoking, etc.), the body's defense mechanisms are overcome, and aging accelerates. That's why antioxidants play a key role in the fight against aging. They suppress free radicals or stop them (vitamins C and E), or strengthen the systems against free radicals in the skin (selenium, zinc, coenzyme Q10, and superoxide dismutase). They limit the harmful effect of oxidative stress on skin cells, which is responsible for skin aging. Other external factors that have a harmful effect on the skin are smoking, alcohol, improper diet, and lack of sleep.
Dermocosmetic products are complex formulations in which active substances with different mechanisms of action are incorporated into the appropriate base. Auxiliary substances that facilitate the permeation of active substances to the site of effect, ensure appropriate rheological and aesthetic properties and product stability. Antiaging ingredients in dermocosmetic products should strengthen the barrier function of the skin, increase skin hydration, and reduce transepidermal water loss in the epidermis; enable antioxidant action to remove free radicals responsible for the loss of skin elasticity and firmness as well as the formation of wrinkles; stimulate the renewal of cells of the epidermal (surface) layer of the skin; stimulate the production of connective tissue in deeper layers to prevent the loss of elasticity and firmness of the skin and the formation of wrinkles. Their regular use should alleviate dryness and the feeling of tightness, and maintain the elasticity, shine, and tone of the skin. Active substances that have proven to be effective for this purpose are certainly collagen, elastin, coenzyme Q10, peptides, vitamin C, vitamin E, retinoids, bakuchiol, and resveratrol.
Humectants (substances that bind water) and moisturizers (substances that supply the skin with moisture) in preparations for local application increase the water content in the SC, by attracting and binding it, so such products are often more effective in suppressing dry skin than those without a humidifier. Water is important for maintaining skin elasticity. Therefore, natural moisturizing factors (NMFs) such as urea and hyaluronic acid are important for SC function, as they ensure moisture retention, maintain acidic pH and buffer SC capacity, ensure appropriate epidermal maturation and removal of redness, and reduce pathogenic bacterial colonization. When their concentration in the SC decreases, the water in the products alone cannot restore elasticity.
Numerous studies show that the local application of physiological lipids containing cholesterol, ceramides and fatty acids can improve the reduced epidermal protective barrier of the skin and the homeostasis of its permeability.
Ceramides are a specific group of lipids in the stratum corneum of the skin. They are the most important structural element of the natural protective barrier of the epidermis. Numerous studies show that
their local application (phospholipids and sphingolipids, obtained from vegetable oils) in a very short time restores the damaged hydrolipidic barrier of the stratum corneum of the epidermis, thereby reducing the possibility of large transepidermal water loss. Ceramides used in cosmetic preparations are produced by a patented fermentation process and have the same structure as ceramides that are naturally present in the skin.
Collagen is a type of protein contained in the natural composition of the skin, i.e. in the dermis. Its role is to connect the skin with the structures beneath it. It gives the skin firmness, elasticity, and tone. The human body has the ability to constantly synthesize collagen, which is necessary for the growth and replacement of wornout tissues and for the healing and restoration of injured tissues. When the amount of collagen is sufficient, the skin is more resistant to the effects of external factors. However, due to the aging process, its renewal capacity gradually decreases over time. In youth, the loss of collagen is quickly replaced, but with age it becomes more pronounced. It negatively affects the appearance and function of the entire body, and leads to various degenerative changes, the formation of wrinkles, and fine lines. In order for it to penetrate the skin locally, the molecule must be extremely small, which is very difficult to achieve in preparations that are applied locally. However, the popularity of these products lies in the fact that collagen leaves a film on the skin that fills in irregularities on the surface. When the product dries, the protein film tightens, causing a subtle tightening of skin wrinkles.
Elastin enables the formation of elastic connective tissue, which allows the skin to stretch and return to its original state. Along with collagen, it gives the skin firmness and elasticity that is lost with aging.
Peptides are short chains of amino acids that act as cellular messengers. There are three categories present in antiaging cosmetic products: carrier peptides (eg palKTTKS or matrixyl), neurotransmitters (eg AcEEMQRR or argyrelin), and enzyme modulators (eg soy and rice proteins). Matrixyl is very potent because it provides positive effects even in the lowest doses. In a doubleblind, placebocontrolled study, it caused an improvement in the appearance of wrinkled skin. Peptides strengthen collagen and elastin, stimulate their further formation in the skin and stabilize the connection between the dermis and the epidermis so that the skin remains firmer.
Coenzyme Q10 is a liposoluble antioxidant naturally present in the body. Neutralizes free radicals that damage the cellular structure and protective function of the skin. There is in vitro evidence that it can suppress fibroblast-induced production of UVA-induced collagenases, thereby reducing collagen breakdown. It has also been shown to be effective against UVA damage caused by oxidative stress in human keratinocytes.
Vitamin C (ascorbic acid) participates in the synthesis of collagen and elastin, and in the binding of keratin fibers. As an antioxidant, it reduces skin damage from pollution, the sun, and other free radicals. It inhibits the enzyme tyrosinase, thereby reducing hyperpigmentation. In order to optimize percutaneous absorption and achieve vitamin C activity, it is very important to produce an adequate formulation for its
effective topical delivery. Namely, it is a very unstable molecule that loses its antioxidant capacity under the action of UV rays or in the air and becomes inactive. Some studies have shown that the esterification of the hydroxyl group solves the problem of instability within the formulation. New formulations for stabilizing vitamin C, such as microcapsules, liposomes and microemulsions, are being intensively researched, although many of them are already on the market.
Vitamin E (tocopherol) is an antioxidant and moisturizer, soluble in lipids. It prevents the oxidation of unsaturated fatty acids (membrane lipids) and neutralizes free radicals that accelerate the aging process. In addition to being used in dermocosmetic products for skin care and regeneration, it often has a role as an antioxidant and preservative. When applied topically, numerous studies have recorded its effect in protection against UVB radiation, and acute reduction of erythema in sunburns, tanning and photoaging has also been recognized. Out of a total of 32 vitamin E isomers, only dα-tocopherol is topically effective.
Retinoids are derivatives of vitamin A and the socalled gold standard among dermocosmetic products against skin aging. Their positive effects are visible in the area of the epidermis where they normalize the keratinocyte cell cycle, reduce keratinocyte atypia and normalize the distribution of melanosomes. They are also visible in the layers of collagen and elastic dermis, where they lead to an increase in collagen biosynthesis and an increase in the amount of elastin. It was recently discovered that they can also induce the deposition of fibrillin-rich microfibrils near the epidermal junction, which would reestablish the lost physical connection between the superficial layers of the skin and the mature elastic fibers in the deeper dermis. Most of the retinoids listed below, including vitamin A, have an antioxidant effect, the ability to whiten dark spots, and reduce the appearance of wrinkles on the face. However, retinoids can also be strong irritants, extremely unstable in the presence of oxygen and light, and their use as antioxidants in sun protection preparations is controversial because they do not provide any UV protection. Oral retinoids have been proven to be teratogenic, so they are not recommended for pregnant women and women planning to become pregnant, even as topical ones.
Retinoic acid or tretinoin, a non-aromatic firstgeneration retinoid, is considered one of the most powerful components for removing signs of skin aging such as wrinkles and age spots. However, due to a number of unwanted effects such as irritation and burning of the skin, it must be used with caution, and
newer systems for the delivery of the active substance should reduce side effects.
Retinol or vitamin A is the biologically active form of that vitamin, which in vivo studies have shown to have only moderate biological activity when applied topically compared to topical retinaldehyde and retinoic acid. On the other hand, two randomized controlled studies reported a significant improvement in fine lines during 12 and 24 weeks of application. Currently, retinol is the most commonly used component in antiaging cosmetic products and is better tolerated by the skin than transretinoic acid.
Retinaldehyde, an intermediate form during the conversion of retinol to retinoic acid, also works against signs of aging. Studies have shown that it causes significant correction of softer and deeper wrinkles.
Retinol esters, such as retinol propionate, retinyl propionate, and retinyl palmitate, are less commonly used retinoids, but there is evidence of their effectiveness. In doubleblind, placebocontrolled facial testing, retinol and retinyl propionate were highly effective in reducing wrinkles and hyperpigmentation. Retinyl palmitate has also been clinically tested, which, although it has a lower potential for causing irritation, has a lower effectiveness even in very high concentrations of 2%. However, in almost all studies, retinol esters have been shown to be more tolerable than retinol.
Bakuchiol is a natural antioxidant found in the seeds and leaves of the plant Psoralea corylifolia , commonly known as babchi, which grows in India, China and parts of Africa. It is a natural alternative to retinol, without any negative effects. It has been clinically shown to reduce hyperpigmentation and wrinkles as effectively as retinol, with better tolerance. It works directly in the skin cells, where it affects the production of several types of collagen useful for health, but also the youthful appearance of the skin, while not affecting the glands, which means that it does not lead to irritation or dryness. One of the most important advantages over retinol is that it does not make the skin more sensitive to UV rays.
Resveratrol is a natural polyphenol and a strong antioxidant. It is found in many foods, among which the most famous are black grapes, blueberries, cranberries, wine, cocoa, and dark chocolate. Plants produce it in response to injury, ozone exposure, UV radiation, and fungal or bacterial infections. It serves them for faster healing of damaged parts, cuts, and cracks. The vine produces resveratrol to protect itself from mold and regenerate itself; enabling it to live up to 100 years. Clinical studies have confirmed that it can also protect human skin from UV radiation. It also stimulates the production of collagen and elastin, and stops glycation, which is responsible for deep wrinkles.
Hyaluronic acid (HA) is a glycosaminoglycan, an integral part of the connective tissue of the dermis. It fills the space between collagen and elastic fibers, it is broken down and rebuilt during life. Its role is multiple it participates in the transport of nutrients, and hydration of the skin, but also as a defense against mechanical and chemical damage. A high concentration of HA is found in soft connective tissues, in the fluid surrounding the eyes, and in some cartilages, it is present in all living organisms. Even more than 50% of the total HA in the body is present in the skin.
It has been shown to be very effective in re-epithelialization processes and in controlling the proliferation and migration of keratinocytes from the epidermal basal layer. It is a strong humectant. In young skin, collagen fibers bind to glycosaminoglycans, forming proteoglycans that form a gelatinous mass, and like a sponge, it can bind large amounts of water and release it in the same way. Thanks to this ability, young skin is taut and shiny, without wrinkles. However, with age, collagen fibers ripple, and the ability to bind water decreases more and more, the skin dries out, loses volume and wrinkles appear. Therefore, HA is one of the most common components of dermal fillers. In dermocosmetic products, molecules are found in different sizes, which is important to know, because the skin will absorb them differently. High-molecular (longchain) HA consists of a long chain of molecules and therefore has a large molecular weight. It does not penetrate the skin, it creates a protective film on the surface of the epidermis where it improves hydration. Mediummolecular (mediumchain) HA works in a similar way to highmolecularweight HA. Lowmolecular (shortchain) HA consists of a short chain of molecules and therefore has a low molecular weight. It penetrates deep into the skin and helps to store moisture in the connective tissue of the skin, and stimulates its own production of hyaluronic acid. This makes the skin more supple and firmer, but also visibly reduces wrinkles.
Urea is a humectant and moisturizer. It maintains the desired level of moisture in the skin, softens it, and improves its elasticity. In this way, it prevents premature aging and the appearance of wrinkles, because they occur on dry skin with insufficient care. It is a common ingredient in creams for skin hydration, not only for cosmetic use but also for the treatment of dermatoses in which extremely dry, flaky skin occurs. In particular, its deficiency in the stratum corneum is associated with atopy, psoriasis, and xerosis in older people. It has a beneficial effect on the healing of wounds and skin damage. Concentrations of up to 25% are used in preparations for regular care and a mild keratolytic effect, and 5-15% for a more intense keratolytic effect. One placebo-controlled study showed that preparation with 5% urea was responsible for improving the barrier function of the skin. After repeated applications of this preparation, the transepidermal water loss in the SC decreased and the skin irritation induced by sodium lauryl sulfate (SLS) decreased.
Omega fatty acids are part of the hydrolipidic film and epidermis. Essential omega-3 and omega-6 fatty acids play an important role in the formation of lipids in the skin and have a positive effect on the prevention of aging, regeneration, and hydration of the skin. Their deficiency can lead to dry and irritated skin and various unwanted dermatological conditions. There is scientific evidence that shows that topical application of a combination of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid (e.g. from fish oil) and gamma-linolenic acid (GLA) (which is abundant in evening primrose oil, for example) can improve skin elasticity. Thanks to their anti-inflammatory effect, they can be of great benefit in inflammatory skin conditions such as psoriasis, acne, and atopic dermatitis. Their beneficial effects have also been proven in the reduction of signs of photoaging cau
sed by excessive exposure to UV radiation, and will also alleviate various hyperpigmentation and dark spots on the skin.
Panthenol is an alcohol analog of pantothenic acid (vitamin B5) and as such a provitamin of vitamin B5. In the body, it is quickly oxidized into pantothenate (pantothenic acid). Panthenol occurs in the form of two enantiomers, D and L. Only Dpanthenol (dexpanthenol) is biologically active, but both forms have hydrating properties. For dermocosmetic use, panthenol comes either in the D form or as a racemate (DLpanthenol). Dexpanthenol is a very viscous transparent liquid. It has emollient and humectant properties. It has an anti-inflammatory effect, removes itching and promotes epithelization of the skin. Glycerol is the simplest alcohol with three hydroxyl groups. It is easily absorbed into the skin and due to its ability to bind water, it maintains the hydration of the skin.
The pH5 citrate buffer restores the skin's natural pH level, so the skin's enzyme activities can return to normal, which enables hydration and strengthening resistance to irritants.
In modern times, more and more dermocosmetic products contain natural plant oils in their composition and less and less vaseline, paraffin and mineral oils. Paraffin and petrolatum are petroleum derivatives, and synthetic hydrocarbons are not related to skin lipids. In addition, their molecules are too large to penetrate the skin, so such products are not absorbed, but remain on the surface and interfere with the skin's natural functions such as absorption and elimination. Skincare with vegetable oils is a far more natural way to maintain youthful, hydrated, clean, and healthy skin because they are rich in essential fatty acids, vitamins, and minerals. When we talk about vegetable oils in cosmetics, the best quality oils are those obtained by cold pressing, because they contain all the naturally present ingredients. They are often similar to the composition of the skin, and as such are best preserved. Therefore, the skin recognizes and incorporates them into its cells, which is not the case with synthetic ingredients.
Dermocosmetic products contain different preservatives such as parabens. Nowadays, there are effective and at the same time harmless preservatives of natural origin, as well as ecopreservatives accepted by Ecocert, allowed for use in ecologically and organically certified cosmetics. There are two types of preservatives: antioxidants that prevent the oxidation of unsaturated fatty acids in vegetable oils (vitamin E, rosemary leaf extract...) and at the same time care for the skin, and microbiological preservatives that prevent the development of bacteria and mold (e.g. dehydroacetic acid and benzyl alcohol).
Wild rose fruit oil is goldenred to red in color due to the presence of carotenoids from the fruit. It contains essential fatty acids, vitamins and minerals, and smaller amounts of vitamin A acid derivatives, which are excellent for skin regeneration. It is extremely valuable in regenerative skincare and is very effective
in the treatment of burns, wrinkles, scars, eczema, hyperpigmented, and prematurely aged skin. It has natural antioxidant properties and a mild astringent effect. It is an ideal choice for formulations intended for mature and photodamaged skin, when it is necessary to restore and even out pigmentation. It has proven to be very effective in inflammatory skin diseases (psoriasis, seborrheic and atopic dermatitis).
Argan oil is rich in oleic and linoleic acid, carotenoids, and vitamin E. It is suitable for treating dry, mature, and wrinkleprone skin. Argan oil soothes and regenerates.
Wheat germ oil is rich in vitamins A, E, D and essential fatty acids. Due to the high content of vitamin E, it has a strong antioxidant effect, promotes the regeneration of skin cells, and at the same time promotes the maintenance of an optimal hydrolipidic barrier, thus preventing drying of the skin. It stimulates circulation while simultaneously softening the skin. It is excellent for the care of dry and damaged skin. Apricot seed oil is rich in vitamins and minerals. It is good for the care of dry, sensitive, and prematurely aged skin and for inflammatory skin processes. It softens, nourishes, and regenerates the skin. It is a very light oil, but at the same time extremely emollient, with a high content of oleic and linoleic acids.
Almond oil is rich in essential fatty acids and vitamins A, B1, B2, B6, and E, and is used as an emollient to soften sensitive skin and scalp. It is also suitable for children and pregnant women. It is traditionally used for various types of eczema, psoriasis, and dry and inflamed, itchy elephant skin, and it has been used for years in the prevention and treatment of stretch marks. It has a light texture that is easily absorbed by the skin.
Shea butter is a vegetable fat rich in stearic, oleic and linoleic acids. It contains a high proportion of unsaponifiable residue (up to 8%) and is made up of provitamin A, vitamin E, sterols, triterpene alcohols, and cinnamic acid esters (provide UVB protection). It protects the skin from external influences and drying, restores moisture and softness. It is suitable for the care of all skin types, especially dry and mature skin. It is used to treat sunburns, diaper rash, dermatitis, seborrhea, scars, wrinkles, and stretch marks. It is perfect for atopic skin care (neurodermatitis), especially in small children.
Coconut oil stands out for its high content of saturated fatty acids, and it also contains phytosterols, which are responsible for its anti-inflammatory and regenerative effects. It perfectly moisturizes and softens the skin. It is ideal for dry and sensitive skin.
Food supplements in the form of liquids or tablets also contain antiaging ingredients such as collagen, elastin, ceramide, hyaluronic acid, coenzyme Q10, and vitamins and minerals. They act on the skin in a similar way but from the inside.
Visible changes on the skin are the result of the aging of all parts of the skin. In the epidermis, there is a reduced synthesis of lipids, which breaks the skin barrier. This leads to transepidermal water loss (TEWL) resulting in dehydration and dry skin. This phenomenon can be even more pronounced on the skin of the face. Namely, in addition to the fact that the skin of the face is the most exposed to factors such as UV
rays, pollutants, and chemicals, the epidermis can also be very thin, only 0.02 mm (compared to the average thickness of 0.1 mm in other areas). Most dermocosmetic products intended for the care of aging skin try to improve the epidermal protective barrier by replenishing lipids, especially ceramides. Aging also leads to a reduced value of NMF concentration in the SC. Therefore, humectants and humectants in topical preparations may also improve epidermal barrier function. In the dermis, aging leads to the fragmentation of collagen and elastin fibers, while in the hypodermis, the deterioration of fat cells occurs.
Aging cannot be stopped, but with the regular use of dermatocosmetic preparations containing antiaging ingredients, aging processes in the skin can be delayed and alleviated. Protection from the sun and other damages, a healthy diet, and regular exercise can also contribute to this. When choosing dermocosmetic preparations, attention should be paid to the fact that they contain ingredients of natural origin and active substances that have clinically proven effects in slowing down aging.
References:
Šitum M, Buljan M, Čavka M, Kotrulja L, Pustišek N, Poduje S, et. al. Dermatovenerologija. Zagreb: Medicinska naklada; 2018. p. 11721. Jensen JM, Proksch E. The skin's barrier. G Ital Dermatol Venereol. 2009;144(6):689700.
Lipozenčić J, Murat-Sušić S, Šitum M, Skerlev M, Filipović V, Labar, et al. Dermatovenerologija. Zagreb:Medicinska naklada; 2004. p.16371.
Sahle FF, GebreMariam T, Dobner B, Wohlrab J, Neubert R H H. Skin Diseases Associated with the Depletion of Stratum Corneum Lipids and Stratum Corneum Lipid Substitution Therapy. Skin Pharmacol Physiol 2015;28:42–55.
Feingold KR. The role of epidermal lipids in cutaneous permability barrier homeostasis. J Lipid Res. 2007;48:253146.
Krakowski AC, Barrier Repair: Where Do We Stand? Practical Dermatology. December 2013:3840.
Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther. 2004;17:43–8. Dostupno na: http://doi.wiley. com/10.1111/j.13960296.2004.04S1005.x
Lodén M. Effect of moisturizers on epidermal barrier function. Clin Dermatol. 2012; 30(3):286–96.
SjerobabskiMasnec I, Šitum M. Skin aging. Acta Clin Croat 2010; 49: 515519. Dostupno na : https://hrcak.srce.hr/clanak/126404
Downie JB. Understanding Moisturizers and their Clinical Benefits. Pediatric Skincare. 2010 September/October:1922.
VerdierSévrain S, Bonté F. Skin hydration: a review on its molecular mechanisms. J Cosmet Dermatol. 2007;6(2):75–82.
Lee SH, Jeong SK, Ahn SK. An update of the defensive barrier function of skin. Yonsei Med J. 2006;47(3):293–306.
Ebner F, Heller A, Rippke F, Tausch I. Topical Use of Dexpanthenol in Skin Disorders. American Journal of Clinical Dermatology. 2002 August;3(6):427–33. Dostupno na: https://link.springer.com/article/1 0.2165%2F0012807120020306000005
Lodén M, Bárány E, Mandahl P, Wessman C. The influence of urea treatment on skin susceptibility to surfactantinduced irritation: a placebocontrolled and randomized study. Exog Dermatol 2004;3:16.
Kuštrak D. FarmakognozijaFitofarmacija. Zagreb: Golden marketing- Tehnička knjiga; 2005.
Marković S. Fitoaromaterapija. Zagreb: Centar Cedrus; 2005. Zadravec A. Kozmetički proizvodi protiv starenja kože. Diplomski rad, Sveučilište u Zagrebu, Farmaceutsko-biokemijski fakultet, Zagreb, 2018
Vugrinec M. Priprava i karakterizacija emolijentnoga gela za pranje i emulzije za njegu kože osoba s atopijskim dermatitisom. Specijalistički rad, Sveučilište u Zagrebu, Farmaceutsko-biokemij ski fakultet, Zagreb, 2019
https://vitamini.hr/blog/vitaminoteka/omega3masnekiselinelijepuizdravukozu13851/
https://www.plantagea.hr
The peer-review confirms: Bioiberica Dermial®, the first hyaluronic acid matrix formulated as an ingredient for skin and beauty innovations, has proven anti-aging, regenerative and antioxidant properties.
Anew peerreviewed paper, published in the International Journal of Molecular Sciences, has concluded that Bioiberica’s Dermial® ingredient - the first hyaluronic acid matrix ingredient for skin & beauty innovation presents antiageing, regenerative and antioxidant properties in skin cells. The peerreview further validates the promising potential of Dermial® in the development of cuttingedge products for the growing nutricosmetics spacecreating exciting opportunities for brands across the dietary supplement, functional food and cosmetic industries.
Glycosaminoglycans (GAGs), such as hyaluronic acid (HA), are an important component of the extracellular matrix found in the skin; proven to maintain skin hydration and regulate cell migration, proliferation and differentiation. With age, GAGs decrease, as well as th e concentration and quality of dermis collagen and elastin, leading to loss of skin moisture, dermal thickness and healthy appearance. The study aimed to extract, characterise and evaluate the benefits of Bioiberica’s hyaluronic acid matrix ingredient, Dermial®, at an invitro level, for skin and beauty innovation.
The findings of the study showed that Dermial® has a high concentration of hyaluronic acid (67%) and is also composed of other GAGs like dermatan sulfate and collagen. The invitro evaluation of the ingredient’s biological activity in keratinocytes and fibroblasts provided evidence that it induced cell proliferation and migration and increased the synthesis of collagen type I and III, elastin and GAGs. This suggests that it presents moisturising, regenerative and antiaging properties. The review also revealed Dermial®’s antioxidant properties in skin cells - the first time the ingredient’s protective role against oxidative stress has been exhibited. Furthermore, the hyaluronic acid matrix ingredient is easily absorbed in the intestine, signalling that it could be used in oral and topical applications for skin care.
Dermial® is a sciencebacked hyaluronic acid matrix solution with a difference. Its unique combination of three naturallyoccurring components hyaluronic acid, other GAGs such as dermatan sulphate and collagen work in synergy to nourish the skin at a low dose of 60 mg/day. In addition to the promising aforementioned results, Dermial® has shown a superior effect compared to pure hyaluronic acid from fermentation origin a wellknown ingredient in the skin care arena.
“The conclusions of this latest peerreviewed paper mark an exciting development in the research exploring Dermial® – further verifying the sciencebased benefits of the ingredient and its potential in nutricosmetics,” says Daniel Martínez Puig, Head of Human Health R&D, Bioiberica. “We can’t wait to unlock exciting opportunities for brands already in or considering entering this market. Following these promising outcomes, our next step will be to carry out a clinical trial to confirm the efficacy of Dermial® in humans.”
Antonio Vendrell, Marketing Director, Bioiberica adds: “The ‘beautyfromwithin’ market has witnessed rapid growth in recent years, fuelled by rising consumer interest in overall wellbeing, the holistic health movement and growing awareness that beauty can be achieved from the insideout via nutrition. Many consumers are taking a more proactive approach to their skin health, making them more open to trying nutritional solutions – including ingestible beauty products. This has created a new space for novel ingredients, like Dermial® our hyaluronic acid matrix ingredient.”
Photoprotective measures reduce the risk of skin cancer, photoaging and other skin damage. Important support for skin protection is also provided by certain nutrients whose the positive effects has been proven by numerous scientific studies.
Photoprotective behavior is extremely important for the prevention of malignant skin cancer, which, according to available data, is caused by excessive exposure to UV radiation in as many as 80% of cases. The term photoprotection refers to all protective measures that try to reduce the harmful effects of the sun on human skin. Photoprotective behavior reduces the risk of skin cancer, photoaging, and other skin damage. It includes the use of protective clothing and glasses, the use of sun protection products (topical and oral), as well as avoiding being outdoors during the period when UV radiation is strongest. Significant support for skin protection is also provided by certain nutrients, the positive effects of which are indicated by numerous scientific studies.
UV radiation causes complex processes on specific molecules, the response of which results in damage to the connective tissue of the skin. Photoaging is manifested by the appearance of wrinkles, skin redness, dryness, loss of elasticity, telangiectasia, and pigment changes.
In the chronological aging process, free radicals are formed during normal metabolism. Due to the influence of external factors such as UV rays, smoking, and alcohol consumption, the formation of free radicals also occurs, and according to today's knowledge, it is considered that at least 50% of UVinduced damage to the skin is due to the UVinduced formation of free radicals. Free radicals are highly reactive molecules with unpaired electrons that can directly damage various cell membranes, structural lipids, proteins, and DNA. The generation of free radicals increases with aging, while the endogenous defense mechanisms that oppose them decrease. This imbalance leads to progressive damage to cellular structures, and thus to accelerated aging.
The body has endogenous defense mechanisms such as antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) and nonenzymatic antioxidant molecules (vitamin E, vitamin C, glutathione, ubiquinone) that protect against free radicals, reducing and neutralizing them. Some of these antioxidant mechanisms can be inhibited by ultraviolet light. On this basis, it was hypothesized that the use of antioxidants can neutralize some of the effects of free radicals, thereby reducing and preventing the signs of skin aging.
Antioxidants can protect against endogenous and exogenous oxidative stress by removing free radicals and reducing their action. Some combinations of antioxidants, applied together, show synergistic effects and thus greater efficiency.
Properly dosed combinations of certain antioxidants, such as betacarotene, astaxanthin, lycopene, zeaxanthin, vitamin Bcomplex, selenium and zinc, vitamins C and E, vitamin B3, can certainly contribute to the photoprotective capacity of the organism. More recent ingredients that are thought to contribute to UV protection (systemic photoprotection) are certainly Polypodium leucotomos , green tea, pycnogenol, caffeine, genistein, and omega-3 fatty acids.
Carotenoids are a large group of lipophilic molecules, which act as powerful antioxidants. Some of the most famous representatives of these compounds are betacarotene, lycopene, lutein, and zeaxanthin.
Beta-carotene, the provitamin of vitamin A, accumulates in the skin, giving it a golden yellow color. Lutein and zeaxanthin accumulate mostly in the macula and protect the retina from oxidative damage caused by UV radiation. More recent studies talk about the impact of lycopene on atherosclerosis and its potential to lower LDL cholesterol in a similar way as statins do in patients with mildly elevated cholesterol levels. Carotenoids are synthesized in plants through the process of photosynthesis, and animals and humans must take them into the body through food.
Betacarotene is the bestknown representative of carotenoids. The results of a large number of studies show that it has a protective effect against damage caused by exposure to UV radiation. It reduces oxidative stress and promotes keratinocyte differentiation, leading to cell cycle arrest and apoptosis. Absorption of carotenoids in the human body ranges from 1030%. Fats from food stimulate it and dietary fibers reduce it.
Unlike other carotenoids, after absorption, betacarotene is metabolized into vitamin A, according to the body's needs. Therefore, by taking sufficient amounts of betacarotene, we provide the body with optimal amounts of vitamin A, which is very necessary for its many functions. There is a distinction between natural and synthetic betacarotene.
Synthetic consists of one molecule (transbeta
carotene), and natural consists of two molecules (transbetacarotene and 9cisbetacarotene). Betacarotene preparations of synthetic or natural origin can be in the form of powder, tablets, capsules, and dragees.
The recommended daily dose of betacarotene is 8-12 mg per day. To achieve the best effect, supplementation should be started 2 months before sunbathing. It can be taken alone or in combination with other antioxidants, for example with vitamin E (synergistic effect). It is harmful at doses of 30 mg or more, causing carotenodermia (yellowing of the skin and mucous membranes). By reducing the intake, the yellowness disappears. Also, studies have shown that high doses of betacarotene (greater than 30 mg) are associated with an increased risk of lung cancer in heavy, longterm smokers and people exposed to asbestos, so supplementation is not recommended for smokers.
Lycopene is a red carotenoid that is found in various fruits and vegetables, mostly in tomatoes, and in their skin. As much as 85% of lycopene is obtained from tomatoes and tomato products and in a much smaller amount from watermelon, red grapefruit, guava, and papaya. Absorption of lycopene is also higher and better when tomato products are consumed than when raw tomatoes are consumed. Compounds that bind lycopene in its raw form and thus make it more difficult for the body to access are destroyed by cooking, and it has been proven that it is absorbed more quickly from products obtained by heat treatment as well as with the addition of oil.
Due to the large number of conjugated double bonds, lycopene acts as a powerful antioxidant. The recommended daily intake is 5–10 mg. Studies have also shown the protective role of lycopene in the development of prostate cancer, stomach cancer, breast cancer, and skin cancer. It protects the skin from UV rays and is four times more effective than beta-carotene.
Astaxanthin is a redorange pigment present in plants, marine animals (salmon, shrimp, lobster), some bacterial species, and yeasts. The richest source of astaxanthin in nature is the microalgae Hematococcus pluvialis, which contains more than 80% of it in its cells. Thanks to its extremely fast growth and high content of astaxanthin, it is mostly used in industrial production for pharmaceutical purposes.
Given that astaxanthin, like vitamin E, is a lipophilic antioxidant, it exerts its positive effects on mem
branes and tissues that are rich in lipids. This is important for the protection of cells during exposure to UV radiation, when, due to the action of free radicals, cascading harmful reactions and lipid peroxidation are initiated. Astaxanthin has a preventive effect on photoinduced changes in the skin, as it prevents changes caused by UVA radiation, which are responsible for accelerated aging of the skin, as well as the development of malignant skin tumors. In dermatology often used as a dietary supplement due to suppression of hyperpigmentation induced by UV rays, inhibition of melanin synthesis, reduction of the overall consequences of skin photoaging, and reduction of visible wrinkles.
Studies have shown that astaxanthin can improve the health and appearance of the skin in several ways: it removes visible lines and wrinkles, maintains optimal skin moisture, reduces inflammatory processes in the skin, and optimizes melanogenesis. University studies have shown that astaxanthin is 1,000 times more effective than vitamin C, 500 times more effective than vitamin E, and 10 times more effective than betacarotene.
Astaxanthin is usually taken in doses of 48 mg. When taking larger doses, a slight orange coloration of feces may occur, while other unwanted or toxic effects have not been recorded so far.
Lutein protects the eyes especially well from negative changes caused by exposure to the sun, thanks to its strong antioxidant properties. However, with sufficient intake, lutein is also concentrated in the skin, where it shows numerous positive effects. It has been shown to successfully prevent oxidation and breakdown of skin lipids, and increase its moisture and elasticity.
Polyphenols are antioxidants present in fruits, vegetables, cereals, olive oil, and chocolate, but also in beverages such as coffee, tea, and wine. The most important polyphenols are flavonoids. It has been proven that an increased intake of polyphenols leads to a reduction in certain types of cancer and cardiovascular diseases.
Polyphenolic compounds have been extensively studied and are found in several plants, including green tea leaves, grape seeds (Vitis vinifera), blueberries (Vacciniummyrtillus), almond seeds (Prunusamygdalus), and pomegranate (Punicagranatum) extract. They suppress local and systemic immunosuppression caused by UVB rays and mediate the reduction of ROS in the skin.
Grapefruit seed extract taken orally is rich in procyanidins and has shown the effect of reducing hyperpigmentation in women with melasma.
Black grape extract contains resveratrol from the skin, proanthocyanidins from the seeds, and bisphenols that act synergistically, and reduce the disruption of glutathione levels caused by UV radiation, reducing the release of ROS in epidermal cells and thus inhibit the development of skin cancer induced by UV radiation.
Epicatechin and catechin flavonols from cocoa showed protective effects when administered oral
ly. In the group of subjects who received a higher dose of flavonols, UV-induced erythema was significantly lower. This group of subjects also had better blood supply to the cutaneous and subcutaneous tissues, increased skin density, and better hydration.
Polyphenols such as epigallocatechin gallate (ECGC), which is found in larger amounts in green tea, have been proven to protect against UVinduced DNA damage and immunosuppression with their ability to reduce oxidative stress and inhibit the NFKappaB factor.
Pycnogenol is an extract isolated from the bark of the maritime pine (Pinus pinaster) which grows in France, Spain, and Italy. It is considered to have antioxidant, anti-inflammatory, and anti-cancer effects. It contains numerous medicinal substances, the most important of which are flavonoids and monomeric phenolic ingredients including catechin, epicatechin, taxifolin, and proanthocyanidins.
Today, it is interesting for dermatology because of its photoprotective effect, as it is considered to reduce the possibility of burns and damage to the skin by UV rays. In vitro studies have shown that pycnogenol, depending on the dose, inhibits the NFKappaB factor, which is a pro-inflammatory component induced by UV radiation. Activation of NFKappaB factor in UVinduced erythema represents a possible explanation for the effect of polyphenols and pycnogenol on the reduction of hyperpigmentation caused by exposure to solar radiation.
Curcumin is also recognized as a polyphenol with photoprotective and chemo-preventive effects since it blocks reactive oxygen compounds induced by UV radiation and the expression of matrixmetalloproteinases (MMP1 and MMP3), which are essential for the breakdown of collagen and elastin.
Vitamin C or ascorbic acid acts as a powerful antioxidant, equally effective against UVB and UVA radiation. The oral combination of vitamins with antioxidant effect (C, E) had more significant photoprotective effects compared to their systemic monotherapy. In synergy, they protect both hydrophilic and lipophilic parts of cells and prevent their apoptosis (programmed cell death).
Vitamin C is also applied topically and significantly reduces UVinduced skin damage. Reduces erythema and formation of damaged socalled sunburn cells and thus reduce the incidence of tumors on the treated skin. Vitamin C products for topical application (creams, serums) are sensitive to air and light, so they must be properly manufactured and stored.
Polypodium leucotomos or tropical fern grows in Central and South America. It has been used for the treatment of various inflammatory conditions and skin diseases (vitiligo, psoriasis, dermatitis) since ancient times. The extract of this fern acts as an anti-inflammatory, photoprotective, and powerful antioxidant.
The protective effect against UV radiation has been proven in various studies with both oral and topical intake. The use of extract is particularly useful for people who are sensitive to the sun, as well as those who suffer from polymorphic light eruption and ot-
her photodermatoses.
Essential fatty acids play a key role in creating the lipid barrier of the skin and influence the response of skin cells to UV radiation. They also moisturize the skin and relieve skin irritations. Clinical research has shown that oral supplementation with omega3 fatty acids reduces UVB-induced burns and inflammatory processes, as well as UVAinduced changes in the skin.
Vitamin B3 or niacinamide (nicotinamide) belongs to the group of vitamins with an important physiological role in the processes of energy production, fat metabolism, and synthesis of nucleic acids. There is ample evidence of the photoprotective effect of orally administered vitamin B3. Also, many topical preparations for the skin, intended for care and hydration, contain this vitamin.
Niacinamide is a precursor of the coenzyme NAD, which is essential in the creation of ATP, which provides cells with energy that, among other things, is needed for DNA repair. In animal and human studies, niacinamide has been used topically and orally and has shown a significant effect in reducing actinic keratoses.
Silymarin, an extract of milk thistle, which is known for its strong hepatoprotective effect, also showed a photoprotective effect in studies. The main chemical components of silymarin that show antioxidant properties are silibinin A and silibinin B.
Despite the many undesirable effects of the sun's rays on the skin, with smart and responsible photoprotective behavior and preparation of the skin for sunbathing from the outside and the inside, every time spent with the sun's rays can still be joyful!
Huang HY, Caballero B, Chang S, et al. Multivitamin/mineral supplements and prevention of chronic disease. 2006;2:234
Werninghaus K. The role of antioxidants in reducing photodamage. In: Gilchrest B, ed. Photodamage. London, UK: Blackwell Science; 1995;249
Martin Guerin et al. Haematococcus astaxanthin: applications for human health and nutrition. TRENDS in Biotechnology Vol.21 No.5 May 2003.
Heinrich U, Moore CE, De Spirt S, Tronnier H, Stahl W. Green Tea Polyphenols Provide Photoprotection, Increase Microcirculation, and Modulate Skin Properties of Women. J. Nutr. 2011;141(6):12021208
McArdle F, Rhodes LE, Parslew RA, et al. Effects of oral vitamin E and betacarotene supplementation on ultraviolet radiationinduced oxidative stres sin human skin. Am J Clin Nutr. 2004;80:1270
Gonzalez S, Pathak MA, Cuevas J, et al. Topical or oral administration with an extract of Polypodium leucotomos prevents acute sunburn and psoraleninduced phototoxic reactions as well as depletion of Langerhans cells in human skin. Photodermatol Photoimmunol Photomed. 1997;13:50
González S, FernándezLorente M, GilaberteCalzada Y. The latest on skin photoprotection. Clin Dermatol. 2008; 26:614626
Saliou c, Rimbach G, Moini H, et al. Solar ultravioletinduced erythema in human skin and nuclear factorkappaBdependent gene expression in keratynocites are modulated by a French maritime pine bark extract. Free Radic Biol Med. 2001;30:154
With the daily application of the biological accelerator, the skin becomes tanned even in the season with a low level of sunlight, which enables its natural protection.
The literature on the effects of the sun on the human body can be summarized in a few key messages. So, for example, it is clear that without sunlight there is no natural process of creating vitamin D. The sun also affects the regulation of blood pressure, cholesterol levels, and mental health in general. So, it is important for human health. Unfortunately, excessive exposure to the sun and the longterm trend of tanning have resulted in premature aging of the skin and an increase in the number of melanomas in the population. Such a situation required a change of attitude. The media does everything it can to portray sun exposure as harmful and at least instill a fear of the sun. However, even in this case, the rule "the dose makes the poison" applies.
Today, products with SPF factors are common not only when sunbathing, but are recommended throughout the whole year. But this means that the higher the SPF in sun protection products, the longer it needs to be exposed to activate the natural protection mechanism. The same applies to biological processes, which are then also delayed. So, for example, in order to stimulate the formation of melanin, instead of 10 minutes of exposure to the sun without a product
with a protective factor, with the use of a product with SPF 30, it is necessary to be exposed for 300 minutes (6 hours) to stimulate this process.
It also remains unresolved to what extent products applied to the skin of the whole body to achieve protection of SPF 30 will affect the health of the skin, or even have a wider reach of action on the whole body and organism.
The yellowbrown to brownblack pigment melanin is produced in melanocytes through a biochemical reaction, starting with the amino acid tyrosine, which occurs naturally in proteins and oxidizes with the enzyme tyrosinase under the influence of light and oxygen. The later biochemical reactions that make up the melanin production pathway and the formation of melanoproteins mostly take place independently. The pigment formed in the melanocytes is then released into the epidermal cells and migrates with them to the surface of the skin. Thus, the skin becomes pigmented, and the skin is protected from further effects of solar radiation.
There are two types of pigmentation: direct and indirect.
Direct pigmentation occurs mainly under the action of UVA rays, but also by radiation of longer wavelengths and heat. In this process, colorless pigment precursors already present in the skin are converted into melanin. This pigmentation can appear within minutes of exposure to light. It gives the skin only a transient, relatively weak tan.
Indirect pigmentation takes place under the influence of UVB rays. They stimulate melanocytes for increased melanin synthesis. Thus, melanin is created in the cells and migrates with them through the entire layer of the epidermis to the surface of the skin. It develops over a few days and lasts from a few weeks to a few months. Given that pigmented skin has relatively weak inherent protection, it is exposed to the risk of sunburn in response to solar radiation. The desire behind every sunbathing is to achieve optimal tanning with minimal damage to the skin, after the shortest possible exposure to sunlight. That's why the main function of a cosmetic product for sun protection with UV protection is to protect the skin from burns caused by the sun, while at the same time ensuring that the skin is tanned as much as possible. The degree of protection, however, is inversely propor
tional to the darkening achieved, i.e., the higher the protection, the weaker and slower the darkening.
The use of skin tanning accelerators is particularly indicated to support the skin's natural protection, as more and more products with high SPFs are used. Using high SPFs works against the skin's natural protection mechanisms. The sun's rays are blocked and the mechanism cannot be formed, i.e., the natural protection mechanism is blocked.
In the case when a natural skin tanner is used, depending on the skin type, products with a lower SPF can consequently be used. This is the advantage brought by the daily application of tanning accelerators.
Tanning accelerators for skin care can provide certain benefits if used properly and in combination with appropriate sun protection measures. Some of the potential positives include:
1. Faster skin tanning accelerators stimulate melanin production, which can result in faster skin tanning with less exposure to the sun or artificial UV radiation.
2. Even Tanning Products with skincare accelerators usually contain moisturizing ingredients that allow for a more even tan. These ingredients soften and hydrate the skin, reducing the possibility of dryness, peeling, and uneven appearance.
3. More intense color skin care accelerators can help achieve a deeper and more intense skin tan. Improved melanin production can result in a darker and longerlasting color.
4. Skin care many accelerators contain an ingredient that nourishes and hydrate the skin, such as aloe vera, jojoba oil, or vitamin E which can help preserve the health and elasticity of the skin.
We can conclude that there is certainly great potential and scientific basis for using products with accelerators, but at least one month before exposure to the sun. With the daily application of the biological accelerator, the skin becomes tanned even in the season with a low level of sunlight, which enables its natural protection.
Source:
Alsins, J. et al. Acta DermatoVenerologica (Stockholm)
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This interesting review is bringing summarized information on the impact of blue light on the skin taking into consideration also blue light from electronic device screens.1
The growing use of electronic devices and other artificial light sources in recent decades has changed the pattern of exposure to blue light (400–500 nm). Although some progress has been made in the study of the biological effects of blue light on the skin, many questions in this field remain unexplored. The aim of this article was to review the currently available evidence on the deleterious effects of blue light on the skin as well as the methods and strategies designed to protect from the detrimental effects of blue light. The PubMed and ProQuest databases were searched in January 2022. Search results were supplemented by articles considered relevant by the authors.
Summary: The results of in vitro, in vivo, and clinical studies show that blue light produces direct and indirect effects on the skin. The most significant direct effects are the excessive generation of reactive oxygen and nitrogen species, and hyperpigmentation. Reactive oxygen and nitrogen species cause DNA damage and modulate the immune response. Indirect effects of blue light include disruption of the central circadian rhythm regulation via melatonin signaling and local circadian rhythm regulation via direct effects on skin cells. Antioxidants and sunscreens containing titanium dioxide, iron oxides, and zinc oxide can be used to protect against the detrimental effects of blue light as part of a strategy that combines daytime protection and nighttime repair.
Key Messages: Blue light produces a wide variety of direct and indirect effects on the skin. As exposure to blue light from artificial sources is likely to continue to increase, this area warrants further investigation.
The sun is the main source of blue light, which is also emitted by electronic devices, such as computer monitors, flat-screen televisions, smartphones, tablets, and fluorescent light bulbs. Changing lifestyles, with less time spent outdoors and increased use of light-emitting diode (LED) and fluorescent lighting and electronic screens via smartphones, televisions, computer monitors, and laptops, have changed the pattern of blue light exposure in humans2.
Conclusions: Blue light is capable of producing various effects on the skin, including deleterious direct effects, such as hyperpigmentation and photoaging, and complex indirect effects, such as circadian rhythm modulation. The precise nature of how blue light affects the circadian rhythm is not fully understood. However, increased exposure to blue light due to the widespread use of electronic devices warrants further research attention, particularly because longterm exposure to artificial sources of blue light has the potential to produce clinical effects by altering melatonin signaling. Progress in this field is hampered by a lack of standardized methods, including the use of different sources of blue light and measures of its biological effects. Several strategies designed to protect against the negative effects of blue light are being explored, of which the most promising include daytime protection and nighttime repair components.
1 Suitthimeathegorn O, Yang C, Ma Y, Liu W: Direct and Indirect Effects of Blue Light Exposure on Skin: A Review of Published Literature. Skin Pharmacol Physiol 2022;35:305318. doi: 10.1159/000526720
2 Cohen L, Brodsky MA, Zubair R, Kohli I, Hamzavi IH, Sadeghpour M. Cutaneous interaction with visible light: what do we know. J Am Acad Dermatol. 2020. https://doi.org/10.1016/j.jaad.2020.03.115.
The final, published version of this article is available at https://www.karger.com/?doi=10.1159/000526720
© 2022 The Author(s). Published by S. Karger AG, Basel
From the very beginning, the idea of producing Silvan soap had a strong foundation in the philosophy of providing the end user with quality and natural product, but also creating an interesting experience for each individual user, by introducing it to a story on the one hand, nostalgic, inspired by the lives of people who lived under this same sky several thousand years before us (inspiration in the cultural heritage of Croatia) and on the other hand the one that paves the way for a better and greener future for everyone (packaging that can be planted).
The packaging that turns into flowers is the finishing touch to the whole Silvan cosmetics story. Namely, the name of the brand comes from Silvan the divine protector of wild nature. Under its name, an untouched nature enters your home the soaps are packed in a biodegradable paper in which the seeds of meadow flowers are woven. It is only necessary to "plant" the cover...
All products are handmade from natural ingredients such as saponified or essential oils and additives such as ground coffee, sea salt, or activated carbon. They do not contain synthetic fragrances, col
ors, or alcohol, which could dry the skin. The products are made in small batches to ensure that they are always fresh and preserved in a natural way.
We talked about the company and its products with Jelena Bikić, owner of the Silvan brand.
NMC: How did it all start, what inspired you? And what was the initial idea?
The idea of making soaps was born in a very unusual way almost cinematic... My boyfriend and I were watching the series The Apprentice (the British version of Lord Sugar) in which the contestants were given the task to create their own cosmetic product and to sell it. We were fascinated by the idea and couldn't stop thinking about it. We started Silvan out of curiosity.
The process of making soaps really intrigued us and soon making soaps and mastering this skill became our hobby. As we liked the whole process, we soon spent every moment of our free time thinking about new recipes for soaps, and how to achieve different colors in a natural way. We also started making different macerates. We went so deep that at one point
we also made our own silicone molds for soap. We learned a lot during that first year and realized that we liked making soap so much that we decided to create our own business out of that hobby. Seven years later, I can say that we are still very pleased with it.
NMC: What has brought this idea to the realization?
When we decided to turn soapmaking into a "real" business, we had to research what criteria needed to be met to run such business. There were several requirements, and the most important ones were that I had to have a suitable education in the field and I had to have a suitable place for production. For the next year and a half, I devoted myself to acquiring the necessary qualifications and adapting the space where the production will take place. Acquiring new knowledge pushed me into a world diametrically opposed to my acquired humanistic education. But the story behind our brand was created precisely as a result of my unique educational background a master's degree in art history combined with the necessary retraining to run my own business for the production of natural cosmetics, which had more to do with chemistry. The end result is handmade, natural cosmetics, packed in a story inspired by the rich cultural heritage of Croatia.
NMC: What are you producing today and where and how do you market your products?
We currently offer four soaps and two gift boxes:
• Black & Pure, 60 g, activated charcoal and tea tree soap for facial cleansing;
• Sea Nymph, 80 g, sea salt and tangerine soap, for exfoliation when showering;
• Daydream, 60 g, soap based on five different vegetable oils and lavender, for hands and body;
• Coffee to GrOw, 60 g, coffee and orange soap, for shower peeling;
• All You Need is Soap, 105 g, gift box with 3 soaps for comprehensive skin care (for face, hands and body);
• Illyria's gift, 260 g, handwoven basket with a wo
oden bottom containing four Silvan soaps: Black & Pure, Daydream, Coffee to GrOw, Sea Nymph.
On the domestic market, we place our products on the shelves of the leading chain of drugstores in Croatia dm drogerie markt, in the natural cosmetics department. We also cooperate with numerous concept stores and souvenir shops that are always happy to sell quality Croatian products.
Since last year, we have also been present on the Italian market.
A special part of our offer consists of two products that can be branded with the partner's logo:
• All You Need is Soap, gift box, 105 g (3x35 g)
• Daydream, soap, 20 g.
In this way, we cooperate with a wide range of organizations and companies, as well as with the organizers of various events such as conferences and other business gatherings, for which we personalize the packaging. Silvan products have proven to be an excellent promotional material completely ecological and sustainable, for all business entities that want to further emphasize their innovation on the market and their commitment to environmental protection. We also cooperated with hotels, private accommodations, tourist associations, and other institutions whose goal is to promote cultural heritage and the desire to preserve nature. In such projects, in addition to the ecological aspect, we also emphasize cultural heritage as a key point in promoting sustainable tourism and community revitalization.
Our vision is to expand the production line and include new products in the future.
Given that we started from scratch, without a large capital (almost none), only with a crazy idea and the willingness to "roll up" our sleeves I would say that today we can be very satisfied. We are also grateful to all of our partners and clients for recognizing the quality of our work, and we are happy to have the opportunity of bringing a useful item into their lives. An item that has added value and into which a lot of effort has been invested.
Ever since we've been doing this business, many things that we couldn't even imagine at the very beginning have happened publication in Vogue magazine, cooperation with dmdorgerie markt, inclusion in the Infobip Startup Tribe program and expansion to the Italian market are some of them. We are grateful for all the opportunities we had and still have today.
SILVAN Jelena Bikić Miljci31, 22 322 Kljake,
Croatia info@silvan.hrT. +385 97 7587339
https://www.silvan.hr/
For more than 50 years, Cosmoprof Worldwide Bologna is the leading worldwide event which represents all sectors of the beauty industry under one roof. It consists of 3 exhibitions: Cosmopack, Cosmo perfumery and cosmetics i Cosmo hair & nail & beauty salon.
Cosmoprof is an excellent training ground for making business acquaintances and arranging deals, as well as the perfect stage for trendsetter product launches and the presentation of innovative cosmetic and beauty solutions. This year's edition was visited by 250,000 visitors from 153 countries, and the number of exhibitors increased to 2,984 from 64 countries.
“Cosmoprof is once again the reference showcase for the industry in the world. The results of this edition well represent the state of the industry", underlines Gianpiero Calzolari, President of BolognaFiere. “The presence of key players from the main markets, of more than 2,984 exhibitors (+11% compared to 2022), from 64 countries and of 29 country pavilions is the result of the efforts to strengthen the international profile and prestige of the event, thanks to the collaboration with Cosmetica Italia – Personal Care Association and the support of the Italian Ministry of Foreign Affairs and International Cooperation and ITA – Italian Trade Agency.
“In these days, in the pavilions of Cosmoprof Worldwide Bologna 2023, companies, experts and operators in the sector have interpreted the different aspects and novelties of our industry, highlighting its great re
activity and dynamism in Italy and abroad. The total turnover of the cosmetics sector in Italy is fully returning to prepandemic levels (13.3 billion euros in 2022), exceeding the values of 2019 by 10.5% and estimates by further growth (+7.7% compared to 2022) for 2023, commented Benedetto Lavino, President of Cosmetica Italia.
On international markets the Italian offer is increasingly appreciated for its high standards of quality, safety and innovation, with growing interest from nonEuropean destinations, and a trade balance that will reach record levels in 2022 exceeding 3.2 billion euros and a growth of over 500 million compared to 2021. These are the data which, once again, alongside the historic partner BolognaFiere Cosmoprof have allowed us to consolidate the story of cosmetics: an industry that is good for the country".
“Cosmoprof has once again proved to be an event of excellence with an international reach and ITA has contributed to this success by bringing 152 buyers from 50 countries, said Matteo Zoppas, President of Italian Trade Agency. It was a synergistic team effort, aimed at affirming the image of Italy, home of the culture of beauty.
This year there was an increase in the number of participants from North America, Europe, the Middle East, Asia and Oceania, and an elaborate matchmaking system helped in the organization of their visit.
The return of participants from China and Taiwan enabled companies and manufacturers to renew projects and cooperation in these distant markets, which continue to represent great potential and generate great value.
In addition to an exhibition area full of novelties and inspirations, the initiatives of Cosmoprof were very popular. The Cosmoprof & Cosmopack Awards once again decreed the best beauty products for the coming months, attracting the curiosity of insiders: over 1,000 attended the awards evening. The areas dedicated to CosmoTrends also aroused a lot of interest, with a vision of what the most current trends are, and to CosmoVision, the multisensory journey that revealed the future evolution of the beauty industry. The projects were created in collaboration with the international agency BEAUTYSTREAMS.
Great participation was registered also in the events scheduled during the event. The participants in the 12 CosmoTalks could follow analyses and round tables in the presence of international managers and experts.
The World massage Meeting dedicated to massage were also very popular, as well as the indepth sessions of Cosmo Onstage, which involved operators presenting the most current topics for the professional sector. The On Hair shows had a great success: 18 artistic teams presented new cut techniques and avantgarde colour proposals with engaging and exciting performances.
www.cosmoprof.co
BGG World has announced recognition from United States Pharmacopeia (USP) for its work with establishing standards for elderberry extracts. BGG received both a Certificate of Appreciation and a Donor Recognition Program award due to its extensive contributions to USP’s efforts, officially monographed as “European Elder Berry Dry Extract.”
USP noted that “BGG’s contributions add significant public benefit to the standards-setting process in support of the USP mission.” This latest achievement builds on several prior collaborations with USP involving other ingredients and represents another building block in BGG’s leadership in the Berry and Extract categories, according to the company.
“We were honored to participate and contribute to the development of this monograph, especially having our test methods validated and adopted. The monograph sets up the pharmacopeial standard of elderberry extract and will benefit all stakeholders of the elderberry industry to fight against adulteration and assure protection of public health,” said Christian Artaria, CEO of BGG Europe SA.
“At BGG, we believe that assisting thirdparty oversight organizations like USP comes with the territory of being market leaders. We’re always ready to pitch in and do our part to establish clear quality standards for the industry to follow.”
www.bggworld.com
