B2B Nutramedic&Cosmetics No. 12 by InPharma

Dry Eye Disease / Gut Microbiome and GERD / GERD Management / Biofilm in Chronic Infections / The Health Benefits of Pomegranate / Fermented Skincare

Editor's word

Dear Readers, Welcome to the September/October issue of B2B Nutramedic & Cosmetics

Although it is already the beginning of September, the weather is still scorching in some parts of the world. This proves that sustainability, a hot topic in the food supplements industry, is important as a way of caring for the environment and climate.

In this edition, we focus on a modern epidemic - dry eye disease. Another significant featured topic is gastroesophageal reflux disease – GERD from different angles and therapy approaches.

The cosmetics and cosmeceuticals sections feature fermented ingredients, bringing insight into prebiotics, probiotics and postbiotics in cosmetics. Additionally, we explore the forming of the biofilm and its role in chronic infections. We bring you updates on the Fi Europe 2024 event since the date is approaching.

In our Inspirational Success Story, we present Medardo, a Croatian honey and honey-based products producer and creator of Honey du cosmetics. The love for bees has been running in the family.

Our Medicinal Plants Photo Herbarium features the Pomegranate, a stunning plant packed with antioxidants and other healthy constituents.

Have a nice new start after the holidays,

Warm regards,

Daria Šurić, MPharm EDITOR-IN-CHIEF

B2B Nutramedic&Cosmetics Magazine

4 Dry Eye Disease - Emerging Ingredients in Managing a Modern Epidemic

10 GERD Management: The Role of Food Supplements

14 The Bidirectional Relationship Between Gut Microbiome and GERD

17 Levagen®+ and Immune Health Benefits

18 Botanicals for Holistic Health Support

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

Ingredients and raw materials / Contract manufacturing Equipment & Packaging / Services / Industry events

www.nmc-magazine.com

20 The Health Benefits of Pomegranate

info@nmc-magazine.com

Publisher: Darmell d.o.o.

Publisher: Darmell Ltd.

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

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

Supported by www.inpharma.hr

FDA: Whey Protein Hydrolysates in Infant

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.

Formula 24 MEDICINAL PLANTS PHOTO HERBARIUM: Pomegranate

Dry Eye DiseaseEmerging Ingredients in Managing a Modern Epidemic

Dry eye disease (DED) is a widespread condition marked by tear film hyperosmolarity and ocular inflammation, significantly impacting quality of life. Recent research suggests that dietary supplements like omega-3 fatty acids, lutein, hyaluronic acid and bilberry extract can improve tear quality and reduce DED symptoms by addressing underlying inflammation and supporting ocular health.

AUTHOR: Daria Šurić, Mpharm

Dry eye disease (DED) is common; its prevalence worldwide is up to 34%. Dry eye disease is seen with increased prevalence in patients with autoimmune diseases, which affect approximately 8% of the population, of whom 78% are women. Dry eye disease also more often affects postmenopausal women and the elderly, as well as younger population due to prolonged screen time. Its putative pathogenetic mechanisms include hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal gland.

Dry eye is clinically subdivided into subtypes: one with decreased tear secretion (aqueous-deficient DED), and one with increased tear evaporation (hyperevaporative DED). It can also be mixed in aetiology. Symptoms include dryness, excessive tearing, light sensitivity, and blurred vision. This leads to reduced

quality of life.

Managing DED focuses on enhancing tear quality, reducing inflammation, and implementing dietary and lifestyle modifications. Tear substitutes, commonly used as a first-line treatment, offer temporary symptom relief but do not address the underlying inflammation. While topical corticosteroids can effectively reduce inflammation, their long-term use is limited due to potential side effects such as cataracts and glaucoma. Another treatment option, topical cyclosporine A, faces challenges related to its variable efficacy and limited availability.

A dangerous vicious cycle ensures between ocular inflammation and dry eye, which in turn may lead to sight-threatening complications (Figure 1.)1. The underlying inflammation and symptoms of DED, are treated with various anti-inflammatory agents and

autologous and/or allogeneic serum drops. Considering the role of lifestyle in DED pathophysiology, lifestyle modifications, including diet, sleep, and physical activity are getting more attention. Among them, supplementation with omega-3 fatty acids shows the most promising results in alleviating subjective and objective measures of DED through a direct effect on the stability and production of the tear film, inflammation markers, and corneal nerve regeneration2

Microbiome and nutrients impact on DED

Emerging evidence suggests that the ocular surface and gut microbiomes play a significant role in the symptoms of dry eye disease (DED), with similarities to inflammatory diseases in other organ systems. Nutrient deficiencies, both micro- and macronutrient, are key in maintaining healthy microbiomes and have been linked to ocular surface disease. However, there is a lack of comprehensive reviews on how these deficiencies contribute to DED. The following review2 examines the composition of healthy ocular and gut microbiomes and explores how nutrient deficiencies may alter these microbial populations, thereby affecting ocular health. It highlights the connection between vitamin B1 and iron deficiencies with reduced butyrate levels - a fatty acid associated with inflammatory conditions like ulcerative colitis, which is known to be linked to ocular surface diseases. Vitamin B12 is recognized for its role in sustaining gut microbial balance and its association with the severity of dry eye symptoms. Similarly, vitamin A and omega-3 polyunsaturated fatty acids have shown positive effects on gut microbial balance.

Selenium and calcium interact complexly with the gut microbiome and are involved in the development of thyroid orbitopathy. Additionally, diabetes mellitus is connected with changes in both the ocular microbiome and ocular surface diseases. Understanding how alterations in the gut and eye microbiomes

impact DED could enhance our grasp of DED pathophysiology and lead to the development of more effective treatments.

There is emerging evidence that the ocular surface microbiome may be influenced by micro- and macronutrients such that diet may influence ocular surface disease (Figure 2)3.

This review highlights clear correlations between DED and the microbiomes of the gut as well as of ocular surface, and diet. The ocular surface microbiomes of patients with DED often displayed increased alpha diversity, with a predisposition to opportunistic and pathogenic bacteria. Furthermore, alterations in the gut microbiome, which are influenced by dietary intake, are associated with a wide spectrum of ophthalmic diseases that are not purely limited to the ocular surface.

Iron deficiency may lead to butyrate deficiency which decreases systemic inflammatory suppression, amongst other effects. Derangements in the intake of vitamin A, B1, B12, C, omega-3 fatty acids, calcium, and selenium are all associated with changes in the gut microbiome and linked to numerous ocular surface diseases. Associations of the translation between alterations of gut microbiota and those existing within the ocular surface need to be investigated, so that dietary or supplementation intervention may be a more objectively precise tool to utilize in managing dry eye. Beyond this, further investigation is warranted where individual dietary and supplementary factors are tested against the ocular microbiome and DED. Lastly, faecal microbiota transplantation for ophthalmic indications is an underresearched field, the exploration of which could lead to exciting discoveries in both the aetiology and treatment of ocular surface disease3

The following study4 also speaks in favour of supplementing different nutrient combinations for DED symptoms improvement.

To examine the effect of a combined dietary supplement containing fish oil, lactoferrin, zinc, vitamin

FIGURE 1 The vicious cycle of ocular surface inflammation1

C, lutein, vitamin E, γ-aminobutanoic acid, and Enterococcus faecium WB2000 on dry eye.

This study involved a preliminary rat model and a human clinical trial to evaluate the effects of a dietary supplement on dry eye disease. Forty volunteers, aged 22 to 59, were randomly assigned to either a supplement group or a placebo group and treated daily for 8 weeks. In rats, dry eye was mechanically induced, and they were given either the supplement or a placebo. Tear production was measured afterwards. In humans, various assessments, including tear production, keratoconjunctival epithelial damage, and subjective dry eye symptoms, were conducted at baseline and after 4 and 8 weeks.

The dietary supplement dose-dependently reduced the decline in tear production in rats. In humans with confirmed dry eye, clinical symptoms improved more significantly in the supplement group than in the placebo group at both 4 and 8 weeks. The increase in tear production was also greater in the supplement group, and no adverse events were reported.

Omega 3 and DED

Emerging clinical evidence suggests that dietary essential fatty acids (FAs), particularly omega-3 FAs, may effectively manage DED by modulating inflammatory responses. Studies have shown that omega-3 FAs can influence the composition of the lacrimal gland and improve tear secretion.

The following meta-analysis5 aimed to determine whether supplementing with omega-3 fatty acids improves dry eye symptoms. The study analyzed data from 4,246 participants, with an average age of 48, of whom 57% were women and 43% were men. All participants were diagnosed with dry eye disease. Researchers conducted a meta-analysis of 19 RCTs involving varying doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The daily intake of these omega-3 fatty acids ranged from approximately 227 to 3,000 mg, with EPA making up 60% to 80% of the dose. The intervention periods ranged from 1 to 12 months.

Omega-3 fatty acid supplementation significantly reduced dry eye symptoms compared to placebo, showing a large effect size. Participants reported noticeable relief from dryness and irritation. The analysis found a substantial improvement in Tear Break-Up Time (TBUT), indicating better tear film stability in those taking omega-3 supplements. Although the improvement in Schirmer test scores was modest (small effect size), it still suggested enhanced tear production with omega-3 supplemen-

tation. Omega-3 supplements reduced tear osmolarity to a medium effect size, implying better tear quality and reduced tear film hyperosmolarity. Improvements in Corneal Fluorescein Staining (CFS) were modest but present, indicating some level of reduced corneal surface damage.

The study found that longer duration interventions, higher doses of omega-3s, and higher percentages of EPA generally improved dry eye symptoms, TBUT, and osmolarity. However, this trend was less evident for CFS.

While the findings are promising, the analysis noted significant heterogeneity among the included studies. This variability stemmed from differences in diagnostic criteria for dry eye, participant demographics, and underlying causes of dry eye. Another limitation was the lack of assessment of participants' dietary intake of omega-3s, which could influence the outcomes.

The meta-analysis supports the potential benefits of omega-3 fatty acid supplementation in managing dry eye disease. By improving tear stability, reducing osmolarity, and alleviating symptoms, omega-3s offer a promising adjunctive treatment for DED. However, further research is needed to standardize dosing regimens and better understand the long-term effects and optimal formulations of omega-3 supplements.

For healthcare professionals and patients, incorporating omega-3 fatty acids into the dietary regime could be a valuable strategy in the comprehensive management of dry eye disease.

Omega-6

Omega-6 fatty acids, especially gamma-linolenic acid (GLA), have shown potential in managing dry eyes.

Omega-6 fatty acids, particularly GLA, are crucial for maintaining ocular health due to their anti-inflammatory properties and role in cell membrane function. They help manage dry eyes through several mechanisms:

1. Anti-inflammatory effects: GLA is metabolized into dihomo-gamma-linolenic acid (DGLA), which produces anti-inflammatory prostaglandins, reducing inflammation on the ocular surface.

2. Enhanced tear production: Omega-6 fatty acids support the production of the lipid layer of the tear film, helping to reduce tear evaporation and stabilize the tear film.

3. Cell membrane integrity: They contribute to the structural integrity of cell membranes in the eye, promoting overall ocular surface health.

The following study has investigated the efficacy of omega-6 combined with omega-3 in dry eye management.

Participants with moderate to severe DED were enrolled in a prospective, randomized, double-masked parallel group study6. Participants ingested either the treatment supplement containing omega-3 and omega-6 fatty acids (1200 mg eicosapentaenoic acid, 300 mg docosahexaenoic acid, 150 mg γ-linoleic acid) or the placebo (coconut and olive oil) daily for 3 months. To determine compliance, Omega-3 Index blood tests were conducted. At baseline and at 1 and 3 months, the following assessments were conduc-

ted: Ocular Surface Disease Index (OSDI) questionnaire and Symptom Assessment Questionnaire in Dry Eye, noninvasive tear breakup time, tear meniscus height, tear osmolarity, ocular redness, surface staining, Schirmer test, and meibography.

Fifty participants completed the study: 24 randomized to treatment and 26 randomized to placebo. Although there was an improvement in OSDI score at 3 months for both groups participants with baseline OSDI scores >52 demonstrated an even larger significant improvement in symptoms with the treatment at 3 months compared with baseline. There were no significant changes in any of the ocular assessments at 1 or 3 months. After 3 months, Omega-3 Index increased by 34% in the treatment group and did not change in the placebo group.

Conclusion of the study: supplementation with eicosapentaenoic acid, docosahexaenoic acid, and γ-linoleic acid resulted in a significant and clinically meaningful improvement of dry eye symptoms in extremely symptomatic participants with DED (OSDI ≥52).

Sea buckthorn (Hippophaerhamnoides)

Sea buckthorn (Hippophae rhamnoides) has been used in Asian traditional medicine for centuries, and SB berries are included in the Chinese Pharmacopeia. Sea buckthorn oil is rich in lipophilic antioxidants and SB seed oil especially contains high proportions of (n-3) and (n-6) fatty acids. Positive effects of SB oil on skin and mucous membrane have been reported.

In double-blind, randomized, parallel trial7, 20- to 75-y-old women and men experiencing dry eye symptoms consumed 2 g of SB or placebo oil daily for 3 months from fall to winter. Clinical dry eye

tests and symptom follow-ups were performed. Tear film hyperosmolarity is a focal factor in dry eye. There was a general increase in the osmolarity from baseline to the end of the intervention. Sea buckthorn oil attenuated the increase in tear film osmolarity during the cold season and positively affected the dry eye symptoms.

Lutein and zeaxanthin in the management of dry eyes

Lutein and zeaxanthin, carotenoids known for their role in eye health, have emerged as promising agents in the management of dry eyes. These nutrients are primarily recognized for their antioxidant properties and their role in protecting the macula, but recent studies suggest they may also alleviate symptoms of dry eye syndrome. This assay explores the potential benefits of lutein and zeaxanthin in dry eye management, providing a pharmacist's perspective on their application in patient care.

Lutein and zeaxanthin are deposited in the retina and are known to filter harmful blue light and reduce oxidative stress, which can have secondary benefits for ocular surface health. Both lutein and zeaxanthin help neutralize reactive oxygen species (ROS) that can damage the corneal and conjunctival cells, which are often implicated in dry eye disease. By mitigating oxidative stress, these carotenoids reduce inflammation on the ocular surface, a key contributor to dry eye symptoms. Lutein and zeaxanthin may enhance the stability and quality of the tear film by protecting the epithelial cells responsible for mucin production, which is crucial for tear film integrity.

Emerging research supports the role of lutein and

FIGURE 2 Visual graphic highlighting the complex relationship between diet, altered microbiomes, systemic inflammatory conditions, and DED3

Nutramedic &Cosmetics

zeaxanthin combined with other ingredients in managing dry eye symptoms.

Hyaluronic acid

Hyaluronic acid is a naturally occurring substance known for its excellent moisture-retaining properties. It is widely used in ophthalmology, particularly in artificial tears and eye drops, to provide lubrication and relief from dry eye symptoms.

When taken as an oral supplement, hyaluronic acid may also contribute to ocular surface hydration by supporting the body’s natural production of tears and improving the quality of the tear film. Clinical studies have shown that oral hyaluronic acid can reduce the severity of dry eye symptoms, particularly in individuals with mild to moderate dry eye disease.

The following study8 aimed to evaluate the effectiveness of oral hyaluronic acid (HA) in treating DED. It was a prospective randomized controlled trial with 54 participants, who were divided into a study group and a control group. All participants received topical HA treatment, while the study group also received oral HA supplementation. Key ocular surface parameters - ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescein staining (CFS), and Schirmer test results - were measured.

The study found that the group receiving oral HA showed significant improvements in OSDI, TBUT, and CFS scores after 1 and 3 months of treatment compared to baseline measurements. Specifically, OSDI scores decreased significantly, indicating reduced symptoms, while TBUT and CFS improved, showing better tear stability and corneal healing.

The conclusion is that a combination of oral and topical HA provides more effective relief and corneal healing in DED patients than topical HA alone.

Bilberry (Vacciniummyrtillus L.)

Herbal extracts like bilberry have a long history of use in eye health, particularly in managing dry eyes and other ocular conditions. Bilberry is rich in anthocyanins, which have antioxidant and anti-inflammatory properties that can support the health of the retina and improve circulation in the eyes. These properties may also contribute to better tear production and ocular surface health.

The study investigated the bioavailability, effectiveness in alleviating dry eye symptoms, and antioxidant potential of a standardized bilberry extract (Mirtoselect®) derived from fruits. The research involved both animal and human trials. In the animal study, rats were given either Mirtoselect® or a highly purified anthocyanin-rich bilberry extract, and their blood was analyzed for anthocyanoside levels. The results showed that Mirtoselect® had higher bioavailability despite a lower anthocyanoside dosage.

In the human trial9, 22 participants with dry eye symptoms were randomly assigned to receive either Mirtoselect® or a placebo for four weeks. Ophthalmological tests, including Schirmer’s test for tear production and antioxidant potential measurements, were conducted before and after the treatment period. The bilberry extract group showed significant improvements in tear secretion and antioxidant potential compared to the placebo group, especially in participants with more severe dry eye symptoms.

The study concluded that Mirtoselect® is a more bioavailable form of bilberry extract, enhancing tear production and antioxidant levels in patients with dry eye disease.

Conclusion

Recent research highlights the potential of dietary supplements and lifestyle modifications in managing DED. Omega-3 and omega-6 fatty acids, for example, have shown promise in improving tear quality, reducing inflammation, and stabilizing the tear film. Additionally, emerging studies suggest that the gut and ocular surface microbiomes play a role in DED, with nutrient deficiencies potentially altering these microbial populations and exacerbating the condition.

Various nutrients, including omega-3, lutein, zeaxanthin, and hyaluronic acid, have been studied for their effectiveness in DED management. Omega-3 supplements have been shown to improve tear stability and reduce symptoms. Similarly, lutein and zeaxanthin, known for their antioxidant properties, may enhance tear film quality. Oral hyaluronic acid has also been found to improve tear production and corneal healing when combined with topical treatments.

Herbal extracts like bilberry, rich in anthocyanins, have demonstrated benefits in improving tear production and antioxidant potential, particularly in patients with severe DED symptoms.

Overall, these findings suggest that dietary supplementation, particularly with omega-3 and specific micronutrients, could offer significant benefits in managing DED, potentially improving patient outcomes by addressing both symptoms and underlying causes.

References:

1 Bhavsar AS, Bhavsar SG, Jain SM. A review on recent advances in dry eye: Pathogenesis and management. Oman J Ophthalmol. 2011;4(2):50-56. doi:10.4103/0974-620X.83653

2 Hodžić, Nejra et al. “The Potential of Omega-3 Fatty Acids in the Treatment of Dry Eye Disease: A Narrative Review.” Al- Anbar Medical Journal (2024): n. pag.

3 Pilkington M, Lloyd D, Guo B, Watson SL, Ooi KGJ. Effects of dietary imbalances of micro- and macronutrients on the ocular microbiome and its implications in dry eye disease. Explor Med. 2024;5:127–47. https://doi.org/10.37349/emed.2024.00211

4 Kawashima M, Nakamura S, Izuta Y, Inoue S, Tsubota K. Dietary Supplementation with a Combination of Lactoferrin, Fish Oil, and Enterococcus faecium WB2000 for Treating Dry Eye: A Rat Model and Human Clinical Study. Ocul Surf. 2016;14(2):255-263. doi:10.1016/j.jtos.2015.12.005

5 Wang WX, Ko MLEfficacy of Omega-3 Intake in Managing Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.J Clin Med.(2023-Nov-10)

6 Ng A, Woods J, Jahn T, Jones LW, Sullivan Ritter J. Effect of a Novel Omega-3 and Omega-6 Fatty Acid Supplement on Dry Eye Disease: A 3-month Randomized Controlled Trial. Optometry and Vision Science : Official Publication of the American Academy of Optometry. 2022 Jan;99(1):67-75. DOI: 10.1097/ opx.0000000000001826. PMID: 34882608.

7 Larmo PS, Järvinen RL, Setälä NL, et al. Oral sea buckthorn oil attenuates tear film osmolarity and symptoms in individuals with dry eye. J Nutr. 2010;140(8):1462-1468. doi:10.3945/jn.109.118901

8 Kim, Yeseul et al. “Oral Hyaluronic Acid Supplementation for the Treatment of Dry Eye Disease: A Pilot Study.” Journal of ophthalmology vol. 2019 5491626. 25 Sep. 2019, doi:10.1155/2019/5491626

9 Riva, A et al. “The effect of a natural, standardized bilberry extract (Mirtoselect®) in dry eye: a randomized, double blinded, placebo-controlled trial.” European review for medical and pharmacological sciences vol. 21,10 (2017): 2518-2525.

WE CREATE VALUE

Fine Foods develops and manufactures contract products for the pharmaceutical, nutraceutical and cosmetics industries.

COMMITTED TO YOUR EXCELLENCE

GERD Management: The Role of Food Supplements

GERD, the most common gastrointestinal disorder, is influenced by lifestyle and dietary factors. However, lifestyle changes alone are often insufficient, necessitating the use of pharmaceuticals and supplements. Promising treatments include alginates, probiotics, melatonin, and other supplements like fenugreek, which offer potential benefits in managing GERD symptoms and warrant further research.

AUTHOR:

Lucija Sobotinčić, Msc Nutrition

GERD, or gastroesophageal reflux disease, is characterized by gastric content and gastric acid reflux into the oesophagus1. The prevalence of GERD in Europe is 4,5-10%2 and in the United States, it ranges between 18 and 28%, being the most prevalent gastrointestinal disorder1. The most common symptoms include regurgitation and/or heartburn3, but some others may be cough, laryngitis or noncardic chest pain2

Lifestyle factors are considered to be of great influence on symptom manifestation. Alcohol consumption (especially white wine and beer4), acidic foods (oranges, lemons etc.), coffee, spicy foods, tomatoes and chocolate may trigger GERD symptoms1 Obesity is a known risk factor for the initial development of GERD, as well as for the persistence of symptoms. BMI (Body Mass Index) is found to be independently connected with GERD, regardless of diet or energy expenditure, but central obesity as opposed to BMI, appears to be a better marker for the risks of GERD complications3. It is supposed that obesity increases upper abdominal pressure, thereby provoking an increase in gastroesophageal reflux. Another risk factor may be the size of a meal –

large and voluminous meals may provoke or worsen GERD symptoms4. It is interesting to mention the connection between GERD and physical activity, which is not really regarded as a beneficial measure for this disease. Some data suggest that physical activity may even provoke GERD symptoms4

Current treatments for GERD are lifestyle interventions, proton-pump inhibitors (PPIs), surgical therapy and H2-receptor antagonists2. Regarding lifestyle factors, meal timing and sleep position seem to be one of the most effective interventions. It is recommended to consume last meal in a day at least three hours prior to going to sleep or lying down1. It should be considered that lifestyle modifications, such as dietary factors, meal timing, sleep position or physical activity, have only a limited role in the management of GERD symptoms4, so some patients may experience better symptom control through pharmaceutical drugs or food supplements.

Drugs/supplements with potential in GERD treatment

Alginates

Alginates are polysaccharide polymers that, in an

acidic environment, precipitate into a low-density viscous gel of near-natural pH5. Their mechanism of action in preventing or reducing GERD symptoms is the formation of an already mentioned gel called the raft, a continuous layer formed when alginates react with gastric acid. Raft is a colloidal gel, which acts as a physical barrier for acid reflux, floating on the surface of the stomach.

The most frequently used alginate form is sodium alginate, a linear copolymer constituted of β-D-mannuronic acid and α-L-guluronic acid blocks, linked together through a 1,4-glycosidic bonds. It is a naturally pH-sensitive compound, stable in an acidic pH and unstable in an alkaline environment6. When the alginate formulation reaches the stomach, a change in pH triggers sodium bicarbonate in the formulation to release carbon dioxide, which then becomes trapped in the alginate gel. It causes the gel to float to the top of the gastric content, close to the esophagogastric junction, precisely where the acid pockets form5

Xu and Zhuang (2024) conducted a study testing the efficiency of proton-pump inhibitors (PPIs) combined with alginates in GERD symptoms treatment, in comparison with PPIs alone. Results showed that the change of heartburn score in the experimental group (PPIs + alginates) increased compared with the control group (PPI), but the difference was not statistically significant. The number of days without heartburn, during the 28-day treatment period, also increased, but the difference between test groups was not statistically significant7

A combination of alginates and antacid formulations shows promising results in GERD symptoms treatment. Acid reflux episodes are reducing more than 75% compared with antacid consumption only and reflux is being delayed for more than an hour after the meal (compared with 15 minutes after antacid consumption)5. Another study conducted by Ruigh et al. (2014) showed a significant reduction in postprandial esophageal acid exposure, and distal and

proximal acid reflux events, after alginate treatment (in comparison with antacid treatment)8

Takbirgou et al. showed great potential of aloe vera, in combination with alginates, in forming rafts that were voluminous, buoyant with greater floating time and stronger than formulations without aloe vera6

Probiotics

Human microbiota is every day, with every new research, showing more and more possible effects on human health overall, as well as on gastrointestinal health. With that in mind, new research is directed towards the potential positive effect of microbiota, through probiotics treatment, on the reduction of GERD symptoms.

New scientific evidence shows the influence of the composition of the oesophageal microbiota and the commensal bacteria from the oropharynx, stomach and colon on the beginning and progression of GERD. It is observed that the composition of the oesophageal microbiota of subjects with GERD symptoms is not the same as in healthy subjects. Analyses show the abundance of Gram+ bacteria in the healthy oesophagus, while in the reflux oesophagus, there is an abundance of Gram- bacteria9

Probiotics can be defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. They are often used with the intention of promoting gastrointestinal health, especially during dysbiosis (for example during antibiotic therapy) or weakened immune system10. It is assumed that probiotics may have the potential of restoring balance and composition of oesophageal, as well as gastric and intestinal microbiota, and through that mechanism of action, reduce and relieve GERD symptoms9

Results of the review paper carried out by Gopal and Shekhar (2021) showed that the majority (79%) of the science papers included in the comparison reported probiotic benefits on GERD symptoms (re-

Taken from: 13GanL,WangY,HuangS,ZhengL,FengQ,LiuH,etal.(2024)TherapeuticEvaluationofBifidobacteriumanimalissubsp. lactisMH-02asanAdjunctiveTreatmentinPatientswithRefluxEsophagitis:ARandomized,Double-Blind,Placebo-ControlledTrial. Nutrients16,342.https://doi.org/10.3390/nu16030342

FIGURE 1 Scheme of therapeutic improvements of combined probiotics (Bifidobacterium animalis subsp. lactis MH-02) and PPIs therapy for reflux esophagitis

gurgitation, heartburn, dyspepsia, nausea, abdominal pain and gas-related symptoms)11. Tursi et al. (2024) concluded that the administration of probiotics (Lactobacillus acidophilus LA14) and fermented soy proteins (fermented by Lactobacillusbulgaricus) was effective in reducing typical GERD symptom, heartburn, in a population of adults with mild-tomoderate GERD. It is important to mention that both heartburn severity and heartburn frequency were in decline9

PPIs are one of the most prescribed drugs for digestive disease treatment, as well as for GERD. Some data suggest changes in the microbiota of the gastrointestinal tract in patients who use PPIs as their therapy12. Additionally, after discontinuation of treatment, typical symptoms often recur13. Science paper conducted by Liu et al. (2022) shows that the administration of PPIs in combination with probiotics may be more suitable for GERD patients than PPIs therapy alone12. Another study observed the effects of combined therapy with PPIs and probiotics, specifically Bifidobacterium animalis subsp. lactis MH-02, and PPIs alone on reflux esophagitis (RE), a primary subtype of GERD. Results suggest that the combined supplementation can improve treatment outcomes of RE patients, including early relief of typical symptoms. This combined therapy approach may also help restore the balance and increase the diversity of gut microbiota13. Probiotics could therefore have potential as an adjunctive therapy that can support the action of primary prescribed drugs, often PPIs.

Melatonin

Melatonin is a hormone enzymatically derived from L-tryptophan. Its synthesis in humans is primarily set in pineal glands and its production is driven by the circadian rhythm with a peak at night. Even though the pineal gland contains the main melatonin-producing cells, entero-endocrine (EE) cells, present in mucosa covering the gastrointestinal tract, are also a major source of intestinal melatonin14. Some data even suggest up to 400 greater melatonin concentrations in the gastrointestinal system in comparison with the pineal gland15. After its biosynthesis in EE cells ends, melatonin is immediately being transported to the extracellular fluid, and gastrointestinal lumen and, consequently, its concentration in systematic circulation increases.

While the main melatonin production and its release from the pineal gland remains under photoperiodic control, its concentration in the gut depends mainly on food intake. Even though the highest concentrations of circulating melatonin have been re-

ported after oral application of L-tryptophan, some studies show that gastrointestinal mucosa contains melatonin even under fasting conditions14

Melatonin is an ubiquitous molecule with several functions, such as anti-oxidative and anti-inflammatory activities, as well as regulation of the circadian cycles and reproductive rhythms16. One of the GI-secreted melatonin's major functions is to strengthen the esophageal and gastric mucosa against different stressors and irritants, whether of endogenous or exogenous origin14. It has also been shown to inhibit secretion of HCl and pepsin15, so the topic of possible protective effect of melatonin on GI system, as well as on repressing GERD symptoms, has been of significant interest.

One of the suggested mechanisms of its action in relieving GERD symptoms is the inhibition of nitric oxide biosynthesis. Nitric oxide synthase inhibitors, among others, have been shown to reduce the rate of transient lower esophageal sphincter relaxation, a major mechanism of reflux in patients with GERD17

There are plenty of science papers showing positive effect of melatonin supplementation on relieving GERD symptoms14,15,17,18 and some studies even suggest lower melatonin concentrations in GERD patients compared to healthy subjects15. Melatonin has been shown to offer esophagoprotection against acute esophageal injury from acid and alkaline reflux in animals14 .

In a study conducted by Kandil et al . (2010), treatment of GERD with melatonin, omeprazole or both was shown to be duration-dependent. Patients treated with melatonin or omeprazole for four weeks showed incomplete improvement of GERD symptoms. On the other hand, in patients treated with melatonin for eight weeks and a combination of melatonin and omeprazole for four weeks, there was the complete improvement of GERD symptoms (heartburn and epigastric pain)15

A regression of GERD and NERD (non-erosive reflux disease) symptoms was noticed after using a supplement containing melatonin, vitamins (vitamin B12, B6 and folic acid) and amino acids (tryptophan, methionine and betaine) in a science research done by Pereira. In this study, patients, who used the supplementation, reported fewer side effects compared to patients who used omeprazole therapy. Therefore, these results suggest the inhibition of GERD symptoms by low levels of melatonin, as well as certain vitamins and amino acids17

Basu et al. (2014) conducted a study that suggests improvement of GERD's main symptom, heartburn, compared with nortriptyline or placebo in patients with functional heartburn who were receiving concomitant omeprazole. Melatonin was also shown to be a safe and well tolerable supplement and the only reported negative side effect was diarrhoea18

Other potential supplements

It is suggested that galactomannan, a water-soluble fibre found in fenugreek, can be effective in reducing GERD symptoms. Galactomannan's mechanism of action, through which it positively affects GERD, is still only hypothesized. Data proposes a mechanism very similar to the alginates one – the soluble fiber forming a raft, acting as a barrier to ameliorate the rise of gastric content, as well as acid,

into the esophagus19.

A number of food ingredients, as well as whole foods, have been shown to have an important role in managing GERD symptoms. Those can be named as functional foods, defined as food types that provide additional health benefits beyond their basic nutritional function. Aloe vera has soothing and beneficial effects on the digestive system, therefore it shows potential in relieving GERD symptoms as well, consuming small amounts of aloe vera juice before meals may reduce acid reflux symptoms. Bananas are considered alkaline foods and may help neutralize stomach acid. They are also rich in pectin, an important soluble fibre that helps keep food flowing through the digestive system, preventing food stasis in the stomach for prolonged periods. It helps in limiting acid production and reduces the probability of acid reflux. Almonds can also neutralize stomach acid, while research shows that ginger can help inhibit gastric acid production. Additionally, liquorice root should not be left out, containing compounds that can inhibit an enzyme H+/K+ ATPase, which is involved in acid secretion. Lastly, foods like yoghurt, kefir, kimchi and sauerkraut are a great source of probiotics, whose effect on relieving GERD symptoms has already been elaborated earlier in the article20

STW 5 is a liquid preparation sold in Europe as an over-the-counter medication, also known as Iberogast. It is a compound of nine herbal extracts – garden angelica root, caraway fruit, greater celandine, milk thistle fruit, liquorice root, bitter candy tuft, peppermint leaf, lemon balm leaf and chamomile flowers. Research suggests a positive effect on GERD symptoms, normalizing the stomach and intestinal motility, attenuating gastric acid secretion and reducing inflammation21,22

Conclusion

GERD, being the most prevalent gastrointestinal disorder, is influenced by various lifestyle and dietary factors. Even though lifestyle interventions are of significant importance in the treatment of GERD symptoms, their limited efficiency necessitates the exploration of pharmaceuticals and food supplements. Alginates, with their ability to form protective rafts, show promising results in reducing acid reflux. Probiotics restore gut microbiota balance and may be a great option as an adjunctive therapy, enhancing the efficiency of traditional treatments like PPIs. Melatonin offers esophagoprotection against acute esophageal injury caused by acid reflux. Additionally, other supplements like fenugreek or Iberogast, as well as functional foods, show promising results in repression of GERD symptoms. They have a great potential for further research, which should be conducted in order to learn more details about their effect on digestive health and GERD.

References

1 Ahuja A, Pelton M, Raval S, Kesavarapu K (2023) Role of Nutrition in Gastroesophageal Reflux, Irritable Bowel Syndrome, Celiac Disease, and Inflammatory Bowel Disease. Gastro Hep Advances 2, 860 – 872. https://doi.org/10.1016/j.gastha.2023.06.010

2 Ho CE, Goh YL, Zhao XX, Yu CY, Zhang C (2016) GERD: An Alternative Perspective. Psychosomatics 57, 142 – 151. https://doi. org/10.1016/j.psym.2015.10.007

3 Chang P, Friedenberg F (2014) Obesity & GERD. Gastroenterol Clin North Am 43, 161 – 173. 10.1016/j.gtc.2013.11.009

4 Meining A, Classen M (2000) The role of diet and lifestyle measures in the pathogenesis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 95, 2692 – 2697. 10.1111/j.1572-0241.2000.03175.x.

5 Rohof WO, Bennink RJ, Smout AJPM, Thomas E, Boeckxstaens GE (2013) An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 11, 1585 – 1591. 10.1016/j. cgh.2013.04.046.

6 Takbirgou H, Salami M, Askari G, Emam-Djomeh Z, Kennedy JF (2014) Characterization of novel alginate-Aloe Vera raft systems for treatment of gastroesophageal reflux disease. Int J Biol Macromol 257, 128686. https://doi.org/10.1016/j.ijbiomac.2023.128686

7 Xu X, Zhuang P (2024) A Meta-analysis of PPIs Plus Alginate Versus PPIs Alone for the Treatment of GERD. J Voice, In press. 10.1016/j.jvoice.2024.02.011.

8 De Ruigh A, Chen J, Pandolfino JE, Kahrilas PJ (2014) Gaviscon Double Action (Antacid + Alginate) Versus Equivalent Antacid for Postprandial Acid Reflux: A Double-Blind Crossover Study in GERD Patients. AGA Abstracts 103, S-27.

9 Tursi F, Benedetto E, Spina A, De Ponti I, Amone F, Nobile V (2024) Efficacy of a Food Supplement Containing Lactobacillus acidophilus LA14, Peptides, and a Multivitamin Complex in Improving Gastroesophageal Reflux Disease-Related Outcomes and Quality of Life of Subjects Showing Mild-to-Moderate Gastroesophageal Reflux Disease. Nutrients 16, 1759. https://doi.org/10.3390/nu16111759

10 Cheng J, Ouwehand AC (2020) Gastroesophageal Reflux Disease and Probiotics: A Systematic Review. Nutrients 12, 132. 10.3390/ nu12010132.

11 Gopal K, Shekhar S (2021) Role of Probiotics in Reducing GERD. Int J Contemp Surg 9, 13 – 16. 10.37506/ijocs.v9i2.3080

12 Liu W, Xie Y, Li Y, Zheng L, Xiao Q, Zhou X, et al. (2022) Protocol of a randomized, double-blind, placebo-controlled study of the effect of probiotics on the gut microbiome of patients with gastro-oesophageal reflux disease treated with rabeprazole. BMC Gastroenterol 22, 255. 10.1186/s12876-022-02320-y.

13 Gan L, Wang Y, Huang S, Zheng L, Feng Q, Liu H, et al. (2024) Therapeutic Evaluation of Bifidobacterium animalis subsp. lactis MH-02 as an Adjunctive Treatment in Patients with Reflux Esophagitis: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 16, 342. https://doi.org/10.3390/nu16030342

14 Majka J, Wierdak M, Brzozowska I, Magierowski M, Szlachcic A, Wojcik D, et al. (2018) Melatonin in Prevention of the Sequence from Reflux Esophagitis to Barrett's Esophagus and Esophageal Adenocarcinoma: Experimental and Clinical Perspectives. Int J Mol Sci 19, 2033. 10.3390/ijms19072033.

15 Kandil TS, Mousa AA, El-Gendy AA, Abbas AM (2010) The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterol 10, 7. 10.1186/1471-230X-10-7.

16 Tan J, Wang Y, Xia Y, Zhang N, Sun X, Yu T, et al. (2014) Melatonin protects the esophageal epithelial barrier by suppressing the transcription, expression and activity of myosin light chain kinase through ERK1/2 signal transduction. Cell Physiol Biochem 34, 2117 – 2127. 10.1159/000369656.

17 Pereira RS (2006) Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J Pineal Res 41, 195 – 200. 10.1111/j.1600-079X.2006.00359.x.

18 Basu PP, Hempole H, Krishnaswamy N, Shah NJ, Aloysius MM (2014) The effect of melatonin in functional heartburn: A randomized, placebo-controlled clinical trial. Open J Gastroenterol 4, 56 - 61. 10.4236/ojgas.2014.42010

19 Schulz RM, Ahuja NK, Slavin JL (2022) Effectiveness of Nutritional Ingredients on Upper Gastrointestinal Conditions and Symptoms: A Narrative Review. Nutrients 14, 672. https://doi.org/10.3390/ nu14030672

20 Herdiana Y (2023) Functional Food in Relation to Gastroesophageal Reflux Disease (GERD). Nutrients 15, 3583. https://doi.org/10.3390/nu15163583

21 Ahuja A, Ahuja NK (2019) Popular Remedies for Esophageal Symptoms: a Critical Appraisal. Curr Gastroenterol Rep 21, 39. 10.1007/s11894-019-0707-4

22 Kim YS, Kim JW, Ha NY, Kim J, Ryu HS (2020) Herbal Therapies in Functional Gastrointestinal Disorders: A Narrative Review and Clinical Implication. Front Psychiatry 11, 601. 10.3389/fpsyt.2020.00601

The Bidirectional Relationship Between Gut Microbiome and GERD: Cause or Consequence?

GERD is a chronic condition that causes stomac acid to flow back into the espophagus causing symptoms like heartburn. Emerging research suggests a complex relationship between GERD and the gut microbiome, where imbalances in gut bacteria may contribute to the development and severity of GERD. Understanding this bidirectional relationship opens new possibilities for treatment, including microbiome-targeted therapies that go beyond traditional acid suppression methods.

AUTHOR: Ira Renko, MSc, Master in Molecular biotechnology

Background information

Gastroesophageal reflux disease (GERD) is one of the most common chronic conditions affecting the digestive system, affecting around 8% to 33% of people globally and 10% to 20% of the population in Europe1,2 It is primarily driven by the dysfunction of the lower esophageal sphincter (LES), which acts as a barrier preventing the backflow of stomach contents into the esophagus. When the LES fails to function properly, it allows acidic gastric contents to reflux into the esophagus, causing irritation and inflammation3,4. This can lead to symptoms such as heartburn, regurgitation, and in severe cases, esophagitis. Several factors contribute to LES dysfunction, including obesity, diet, smoking, and certain medications. The chronic exposure of the esophagus to stomach acid can lead to complications like esophageal strictures, Barrett’s esophagus, and an increased risk of esophageal cancer5. While GERD has traditionally been attributed to mechanical and chemical factors, recent research suggests that the composition and functionality of the gut microbiome may also contribute to the pathogenesis of this condition6-8

Bidirectional

relationship: interplay between gut microbiome and GERD

The gut microbiome, comprising trillions of microorganisms residing in the gastrointestinal tract, plays a crucial role in maintaining overall health. Recent studies have begun to explore the connection between the gut microbiome and GERD. Although the exact nature of this relationship remains unclear9. Some research suggests that dysbiosis in the gut microbiome may contribute to the development of GERD10,11. For example, changes in the composition of the gut microbiota could affect gut motility, influence bile acid metabolism, or alter the production of short-chain fatty acids, all of which could impact the function of the LES and promote acid reflux12. Additionally, certain bacterial species have been found to influence the production of gases like hydrogen and methane, which can affect intra-abdominal pressure and potentially exacerbate GERD symptoms13,14

Gut microbiome as a potential cause of GERD

The gut microbiome plays a significant role in regulating gastrointestinal motility. Specific bacterial species produce metabolites such as short-chain

species effect

Lactobacillus reuteri

Lactobacillus acidophilus

Bifidobacterium bifidum

Bifidobacterium longum

Lactobacillus rhamnosus GG

Bifidobacterium breve

Enhances mucosal barrier and reduces inflammation, helping to manage GERD symptoms.

Improves gut motility and reduces GERD symptoms.

Reduces inflammation and improves gut barrier function, alleviating GERD symptoms.

Reduces gastrointestinal inflammation and improves motility, which can help with GERD symptoms.

Known for its ability to restore gut microbiota balance, reduce inflammation, and improve mucosal barrier function, potentially alleviating GERD symptoms.

Supports gut health by promoting a healthy microbiota balance and reducing inflammation, which may help in managing GERD symptoms.

fatty acids (SCFAs), which influence gut motility by interacting with the enteric nervous system15. Dysbiosis, or an imbalance in the gut microbiota, can disrupt these processes, potentially leading to delayed gastric emptying or altered esophageal motility, both of which are risk factors for GERD10,11. Impaired gut motility can increase intra-abdominal pressure, leading to the relaxation of the lower esophageal sphincter (LES) and promoting acid reflux.

Furthermore, gut microbiota is involved in the metabolism of bile acids, which are critical for digestion and the absorption of dietary fats. Bile acids also play a role in regulating gut motility and maintaining the integrity of the gut barrier16. What is more, dysbiosis can alter the composition of bile acids, leading to an increase in deconjugated bile acids that are more likely to reflux into the esophagus and cause mucosal damage. This bile acid reflux, in conjunction with gastric acid, can exacerbate the symptoms of GERD and contribute to esophageal inflammation. Since 70% of our immune system is in the gut, that has impact on overall health by modulation of inflammatory responses. Namely, dysbiosis can lead to an overproduction of pro-inflammatory cytokines and other mediators that can disrupt the esophageal mucosal barrier17,18. This disruption makes the esophageal lining more susceptible to acid damage and inflammation, both of which are characteristic of GERD. Additionally, certain microbial metabolites may directly affect the permeability of the esophageal epithelium, facilitating the penetration of acid and bile, thus worsening GERD symptoms19

Some gut bacteria even produce gases such as hydrogen and methane during fermentation processes which can increase intra-abdominal pressure, which may contribute to the relaxation of the LES and the subsequent development of acid reflux. Methanogenic bacteria have been associated with slower gastrointestinal transit times and increased gas retention, factors that could potentially promote GERD. Researchers have showed that there is a specific gut microbiome profile in individuals with GERD. Compared to healthy individuals, there is a reduced number of beneficial bacteria Lactobacillus and Bi-

references

31,32

34,35

36,37

fidobacterium and a higher abundance of pathogenic such as Escherichia coli and Clostridium difficile , which are known to induce inflammation and disrupt gut barrier integrity20,21

Following that, interventions aimed at modulating the gut microbiome have shown promise in managing GERD symptoms. Probiotic supplementation, for instance, has been reported to improve GERD symptoms by restoring the balance of the gut microbiota, reducing inflammation, and enhancing gut motility. These findings suggest that targeting the gut microbiome could be a viable therapeutic strategy for GERD.

GERD as a leader of gut microbiome alterations

While the gut microbiome may play a role in the development of gastroesophageal reflux disease (GERD), it is equally important to consider how GERD itself might lead to changes in the gut microbiome. The chronic acid reflux characteristic of GERD, as well as the treatments commonly used to manage it, can significantly impact the composition and function of the gut microbiota. The chronic exposure of the esophagus and upper gastrointestinal tract to stomach acid can create an unfavourable environment for certain bacterial species, leading to dysbiosis22. Moreover, the use of proton pump inhibitors (PPIs), a common treatment for GERD, has been shown to alter the composition of the gut microbiome23. By reducing stomach acidity, PPIs create conditions that favour the survival and overgrowth of bacteria typically suppressed by normal gastric acid levels. This can lead to conditions like small intestinal bacterial overgrowth (SIBO), which not only complicates GERD but also introduces a new set of gastrointestinal challenges24,25.

The acidic pH, combined with the presence of bile and digestive enzymes, can inhibit the growth of acid-sensitive microorganisms while allowing acid-resistant species to proliferate. This selective pressure can lead to a shift in the microbial composition of the esophagus and, potentially, the upper gastrointestinal tract26

What is more, the chronic reflux of gastric acid into the esophagus and, at times, into the pharynx

TABLE 1 presents some of the most known probiotics that showed a positive impact on the progression of GERD

and oral cavity, can disrupt the normal microbiota of the stomach and small intestine. This disruption can decrease microbial diversity and the overgrowth of pathogenic bacteria. The altered microbial environment may further impair digestive processes and contribute to the progression of GERD symptoms27,28.

A study by Nobile et al . (2020) found that patients with GERD exhibited significant differences in gut microbiota composition compared to healthy controls, with a reduction in the abundance of Lactobacillus species, known for their protective effects on the gut lining29. Conversely, research by Imhann et al. (2016) demonstrated that long-term use of PPIs in GERD patients was associated with a shift in the gut microbiome, including an increase in potentially pathogenic bacteria such as Enterococcus and Clostridium difficile30 .

Implications for treatment and management

The bidirectional relationship between the gut microbiome and GERD has significant implications for how the disease is treated. Traditional approaches that focus solely on acid suppression may not address the underlying microbiome imbalances that contribute to GERD. Integrative treatments that consider both the microbiome and GERD symptoms could offer more effective and long-lasting relief. For instance, combining PPI therapy with probiotics or dietary interventions aimed at restoring microbial diversity might help break the cycle of dysbiosis and reflux, leading to better outcomes for patients12 Specific strains of Lactobacillus and Bifidobacterium have been associated with improvements in gut motility, enhancement of the mucosal barrier, and reduction of inflammation31-41. These effects can help alleviate GERD symptoms and potentially reduce reliance on PPIs. Prebiotics, which are nondigestible fibers that promote the growth of beneficial bacteria, can also play a role in maintaining a healthy gut microbiome and supporting overall gastrointestinal health. Dietary interventions that emphasize the consumption of fiber-rich foods, fermented products, and foods low in refined sugars and fats can help support a diverse and balanced gut microbiome42 Additionally, dietary adjustments such as reducing the intake of trigger foods (e.g., fatty foods, caffeine, chocolate) can directly help manage GERD symptoms while also supporting microbiome health43,44

Conclusion

The relationship between the gut microbiome and GERD is a complex and dynamic interplay where each influences the other significantly.

It is unclear whether alterations in the gut microbiome contribute to the development of GERD or whether GERD itself leads to changes in the gut microbiome.

While the precise mechanisms by which the gut microbiome may cause GERD are still being elucidated, the evidence points to a significant role of microbial dysbiosis in the pathogenesis of this condition. Alterations in gut motility, bile acid metabolism, esophageal mucosal integrity, and intra-abdominal pressure are all potential pathways through which the gut microbiome could influence GERD development. Understanding these mechanisms not only enhances our knowledge of GERD but also opens up

new possibilities for treatment strategies that target the gut microbiome to alleviate GERD symptoms and prevent its progression.

Likely, future GERD management will increasingly incorporate microbiome-focused therapies, especially probiotics, leading to more comprehensive and personalized care. However, further research is needed to clarify the causal relationships and to explore how specific microbial interventions might be optimized for GERD management.

References:

1 Locke GR, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ. (1997). Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology, 112(5):1448-1456.

2 El-Serag HB, Sweet S, Winchester CC, Dent J. (2014). Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut, 63(6):871-880.

3 Kahrilas, P. J., Shaheen, N. J., Vaezi, M. F., & American Gastroenterological Association. (2008). AGA medical position statement on the management of gastroesophageal reflux disease. Gastroenterology, 135(4), 1383-1391.

4 Vakil, N., Van Zanten, S. V., Kahrilas, P., Dent, J., & Jones, R. (2006). The Montreal definition and classification of gastroesophageal reflux disease (GERD): a global evidence-based consensus. The American Journal of Gastroenterology, 101(8), 1900-1920.

5 Kahrilas, P. J. (2008). Gastroesophageal reflux disease. New England Journal of Medicine, 359(16), 1700-1707.

6 Nagrath, N., Gaur, P., & Panwar, R. (2021). The gut microbiome and gastroesophageal reflux disease: A complex relationship. Journal of Clinical Gastroenterology, 55(9), 750-759.

7 Chen, Y., Li, J., & Xia, L. (2020). Gut microbiota and gastroesophageal reflux disease: A review. World Journal of Gastroenterology, 26(28), 3683-3691.

8 Yang, J., Deng, Y., Chu, H., Cong, Y., & Zhao, J. (2020). Alterations in the gut microbiome of patients with gastroesophageal reflux disease. Gastroenterology Research and Practice, 2020, 7459157.

9 Akiyama, J., Matsuura, T., & Iizuka, Y. (2018). Role of the gut microbiome in the pathogenesis of GERD: A preliminary study. Journal of Gastroenterology and Hepatology Research, 7(3), 2324-2330.

10 Nyangale, E. P., Farmer, S., & Cash, H. A. (2016). Role of gut microbiota in the development of gastroesophageal reflux disease and its complications. Gut Microbes, 7(4), 341-351.

11 Chen, Y., Li, Z., & Yang, Y. (2019). The role of gut microbiota in the pathogenesis of GERD and its associated complications. Journal of Digestive Diseases, 20(2), 61-67.

12 Quigley, E. M. M. (2013). Gut microbiota and the role of probiotics in therapy. Current Opinion in Gastroenterology, 29(1), 84-91.

13 Basseri, R. J., Weitsman, S., Barlow, G. M., Rezaei, A., Dixit, R., & Pimentel, M. (2012). The association of methane and hydrogen-based breath testing in gastrointestinal conditions: A review. Gastroenterology Research and Practice, 2012, 1-8.

14 Pimentel, M., Mayer, A. G., Park, S., Chow, E. J., Hasan, A., & Kong, Y. (2003). Methane production during lactulose breath test is associated with gastrointestinal disease presentation. Digestive Diseases and Sciences, 48(1), 86-92.

15 Bohórquez, D. V., & Liddle, R. A. (2015). The gut connectome: Making sense of what you eat. Journal of Clinical Investigation, 125(3), 888-890.

16 Jones, B. V., & Begley, M. (2014). The gut microbiota and bile acid metabolism. Current Opinion in Gastroenterology, 30(3), 282-287.

17 Kamada, N., & Núñez, G. (2013). Regulation of the immune system by the gut microbiota. Nature Immunology, 14(7), 676-685.

18 Round, J. L., & Mazmanian, S. K. (2009). The gut microbiota shapes intestinal immune responses during health and disease. Nature Reviews Immunology, 9(5), 313-323.

19 Odenwald, M. A., & Turner, J. R. (2013). Intestinal permeability defects: Is it time to treat? Current Opinion in Gastroenterology, 29(2), 198-203.

20 Zhang, X., & Zhang, M. (2020). Gut microbiota alterations in patients with gastroesophageal reflux disease. Frontiers in Cellular and Infection Microbiology, 10, 408.

21 Yang, J., & Ding, Y. (2022). The gut microbiome in gastroesophageal reflux disease: A comprehensive analysis of bacterial diversity and abundance. Frontiers in Microbiology, 13, 789065.

22 Pimentel, M., & Lembo, A. (2020). Chronic acid exposure and the im-

pact on the gastrointestinal microbiota. Gastroenterology Clinics of North America, 49(1), 91-106.

23 Imhann, F., & Vich Vila, A. (2016). Proton pump inhibitors alter the gut microbiome of healthy subjects: A randomized, controlled study. Gastroenterology, 150(4), 1147-1156.

24 Gordon, H. M., & Kelleher, J. C. (2018). Impact of proton pump inhibitors on the gut microbiome and development of small intestinal bacterial overgrowth. Journal of Clinical Gastroenterology, 52(2), 113-121.

25 Lepage, P., & Bouter, S. (2017). Proton pump inhibitors and risk of small intestinal bacterial overgrowth: A systematic review. Digestive Diseases and Sciences, 62(10), 2815-2826.

26 Baines, A., & Koropatkin, N. M. (2020). Gastrointestinal pH and its impact on microbial communities in the upper gastrointestinal tract. Journal of Clinical Microbiology, 58(3), e01478-19.

27 Kumar, M., & Mendez, E. (2019). Effects of chronic acid reflux on the gut microbiota and implications for GERD. Gastroenterology Research and Practice, 2019, 1523942.

28 Wang, S., & Zhang, J. (2021). Gastric acid reflux and its impact on the microbiome: A comprehensive review. Journal of Digestive Diseases, 22(6), 393-402

29 Nobile, C. J., & Kothari, M. (2020). Gut microbiota composition in gastroesophageal reflux disease: Insights from a comparative study. Journal of Gastrointestinal & Liver Diseases, 29(4), 483-491.

30 Imhann, F., & Vich Vila, A. (2016). Proton pump inhibitors alter the gut microbiome of healthy subjects: A randomized, controlled study. Gastroenterology, 150(4), 1147-1156.

31 Miele, L., & Giorgio, F. (2013). Probiotics and their role in gut health: A comprehensive review. World Journal of Gastroenterology, 19(30), 4728-4742.

32 Lerner, A., & Jeremias, S. (2012). Lactobacillus reuteri for the treatment of gastroesophageal reflux disease. Pediatric Gastroenterology, Hepatology & Nutrition, 54(2), 153-159.

33 Ouwehand, A. C., & von Wright, A. (2008). Lactobacillus acidophilus: A probiotic with health benefits. Lactic Acid Bacteria: Microbiological and Functional Aspects, 247-269.

34 Morrow, L. E., & Duff, M. (2010). Probiotics in the management of gastrointestinal disorders: A review. Current Opinion in Gastroenterology, 26(2), 145-152.

35 Tannock, G. W. (2011). The role of bifidobacteria in gastrointestinal health. Beneficial Microbes, 2(1), 67-77.

36 O'Connor, M. M., & O'Connor, J. (2014). The role of probiotics in gastrointestinal diseases. Gastroenterology Clinics of North America, 43(3), 481-496.

37 Pérez, M. A., & Marzotto, M. S. (2017). Bifidobacterium longum: Probiotic potential and health benefits. Frontiers in Microbiology, 8, 370

38 Guarino, A., & Lo Vecchio, A. (2018). Probiotics in the treatment of functional gastrointestinal disorders: A review. Digestive and Liver Disease, 50(4), 404-412.

39 Makino, S., & Suzuki, T. (2019). Effects of Bifidobacterium breve on gastrointestinal disorders: A review. Journal of Digestive Diseases, 20(1), 19-26.

40Zhang, H., & Yu, Y. (2019). Effects of Bifidobacterium and Lactobacillus strains on gastrointestinal health: Insights from clinical trials. Journal of Gastroenterology and Hepatology, 34(8), 1390-1397.

41 Kumar, M., & Mendez, E. (2019). Probiotic strains in gut health: Benefits of Lactobacillus and Bifidobacterium. Alimentary Pharmacology & Therapeutics, 49(8), 1025-1034.

42 Roberfroid, M. B. (2007). Prebiotics: The concept revisited. The Journal of Nutrition, 137(3), 830S-837S.

43 van Mierlo, T., & Meinders, M. J. (2020). Dietary management of gastroesophageal reflux disease (GERD): A narrative review. Nutrients, 12(10), 3052.

44 Rokkas, T., & Pistiolas, D. (2007). Diet and gastroesophageal reflux disease. Annals of Gastroenterology, 20(3), 139-143

Centar Mikrobiom d.o.o.

Sky Office, Toranj B R. F. Mihanovića 9, Zagreb, Croatia

Mob.: + 385 98 13 73 344

Tel.: + 385 1 78 99 694

https://www.ccm.hr/

Gencor’s Levagen®+ Continues to Demonstrate Immune Health Benefits

Gencor has announced the publication of its recent human clinical trial, which demonstrated that its palmitoylethanolamide (PEA) ingredient, Levagen®+, is a safe, innovative, and effective supplement for immune health support.

PEA is an endocannabinoid-like lipid mediator naturally produced in the body in response to injury or stress. It is also found in lipid extracts of certain foods and plants, such as egg yolk, peanuts, and soybeans. Several studies have demonstrated that PEA may positively support immune health through its promising inflammatory response and unique mechanisms of action via proliferator-activated receptor-alpha (PPAR-alpha) and indirectly modulating the endocannabinoid system.

This study examined the effect of PEA supplementation (Levagen®+) on metabolic pathways through the microbiome. The 12-week randomized, double-blind, placebo-controlled study revealed Levagen®+ significantly altered gut microbiome cytokines, including IL-2 concentrations, and improved serum triglyceride levels. This suggests that PEA supplementation may influence metabolic pathways to support immune health.

“This study has initiated exploration into the potential effects of PEA on the microbiome and metabolic pathways and sheds light on the intricate relationship between PEA, the microbiome, and host health,” said R.V Venkatesh, co-founder and managing director of Gencor. “This study builds upon the previous research of PEA and its promising benefits for immune health.”

Levagen®+ is powered by the patented LipiSperse® delivery technology developed by Pharmako Biotechnologies. It offers a functional and bioavailable form of palmitoylethanolamide (PEA) with superior absorption. Levagen+ is manufactured in cGMP facilities and has been clinically tested to support joint health, sleep, recovery, immunity, discomforts, and inflammation. Levagen®+ is applicable for dietary supplements, food and beverages, and cosmeceuticals.

To review the published clinical data and for more information on Levagen+, visit www.levagenplus.com or www.GencorPacific.com.

Botanicals for Holistic Health Support

Vitafoods Asia 2024, booth G35: Euromed set to promote the power of Mediterranean fruit and vegetables extracts™ for a healthy body and mind.

At Vitafoods Asia 2024, Euromed will highlight the vast potential of herbal extracts for healthy ageing, beauty and wellness. Attendees will be able to explore groundbreaking clinical trial results of the company’s botanical extracts inspired by the Mediterranean diet, and their diverse effects on skin health, cardiovascular wellbeing, immunity, joint and muscle health, and the microbiome.

The focus will be on Euromed’s new cucumber extract CuberUp®, a potentially promising natural approach to the maintenance of healthy joints, which plays an important role in active and healthy ageing. In addition, Euromed is pleased to announce the completion of a clinical study on skin ageing with the pomegranate extract Pomanox®, which shows results consistent with those of a previously published in vitro study. This research underlines the scientifically supported benefits of Pomanox® for beautiful skin, with exclusive insights from the new study set to be revealed at pre-arranged meetings.

Visitors to the show will also be able to discover the power of lemon-based Wellemon® and its vast application possibilities for health and wellness offerings. Along with Cynamed® for a balanced gut flora, ABAlife® for blood sugar management and Spisar® for muscle fitness, the company is well-equipped to meet consumer and market demands for natural,

holistic healthy ageing solutions. Moreover, Euromed will introduce a new Mediterranean extract for weight management, supported by clinical data currently being prepared for publication, which will be formally launched towards the end of the year. Attendees will have the opportunity to get a first look at this innovative ingredient and its potential benefits.

Last but not least, Euromed will showcase Pygeum bark extract Prunera®, which is supported by a recently published in vitro study demonstrating its ability to modulate the inflammatory response, with potential implications for male urinary and hair health.1

Andrea Zangara, Head of Scientific Marketing & Medical Affairs, comments: “In an ever-ageing society, it is key to maintain health and overall wellbeing for as long as possible. Our Mediterranean fruit and vegetables extracts™ can contribute to that in a natural and efficient way. This allows manufacturers of dietary supplements, nutricosmetics as well as functional foods and beverages to offer safe, futureproof products for holistic healthy ageing needs. In addition, we have an extensive portfolio of premium botanical extracts featuring our flagship milk thistle and saw palmetto, as well as the Earth Harmony Organic Extracts®, a certified organic version of our botanicals.”

NEW CLINICAL STUDY

Fight allergies with Nigellin

We are thrilled to share the results of a recent clinical study that highlights the effectiveness of Nigellin®, Sabinsa’s standardized Nigella sativa extract, in managing seasonal allergy symptoms. This randomized, double-blind, placebo-controlled study evaluated the benefits of Nigella sativa oil containing 5% thymoquinone-Nigellin Amber with 2.5 mg PiperineBioperine. The results demonstrated that Nigellin® is both effective and well-tolerated, offering significant relief from allergy-related discomfort. This breakthrough reinforces Nigellin® as a promising natural solution for those suffering from seasonal allergies.

Nigellin® Amber is Sabinsa’s premium extract of Nigella sativa, standardized to contain 5% thymoquinone, the key active compound known for its potent health benefits. This high-quality extract is derived from carefully selected black cumin seeds and is designed to support immune health, respiratory function, and overall wellness. Nigellin® Amber stands out for its purity, consistency, and efficacy, making it an ideal ingredient for a wide range of health supplements. With Sabinsa’s commitment to scientific rigor and quality, Nigellin® Amber is a trusted choice for those seeking natural support for their health.

The Health Benefits of Pomegranate: A Review

The pomegranate, a fruit with a rich history, is packed with bioactive compounds that offer numerous health benefits. Recent research highlight its role in promoting cardiovascular and prostate health, as well as enhancing athletic performance.

AUTHOR: Valerija Pandža, MPharm

The pomegranate is a fruit that has been cultivated for thousands of years, with a rich history that spans across various cultures and regions. This versatile fruit, native to the Mediterranean region, has gained increasing attention in recent years due to its impressive array of health benefits.

The pomegranate tree belongs to the Lythraceae family and thrives in areas with long, hot, and somewhat dry summers, as well as cold winters. The fruit itself is a balausta, consisting of a hard pericarp and a spongy mesocarp containing juicy arils.

Pomegranates are renowned for their abundant antioxidant properties, which are primarily attributed to their rich content of phenolic compounds, flavonoids, and tannins. These bioactive molecules have been shown to possess anti-inflammatory, antioxidant, and cytotoxic activities, making pomegranates a valuable source of therapeutic potential. The fruit's unique composition extends beyond the edible arils, as the leaves, peels, and seeds also contain a wealth of these beneficial compounds, which are often discarded as waste.

The health benefits of pomegranate and its components have been extensively studied. Pomegranate juice, for instance, has been found to exhibit cardioprotective effects, potentially reducing the risk of cardiovascular diseases by improving blood flow and reducing blood pressure1,3.

The antioxidant capabilities of pomegranate have also been linked to neuroprotective properties, with

studies suggesting potential benefits in the prevention and management of neurodegenerative disorders, such as Alzheimer's disease. Furthermore, the anti-inflammatory effects of pomegranate components may play a crucial role in mitigating chronic inflammation, contributing to a lower incidence of diseases such as arthritis and certain types of cancer, thereby highlighting the importance of incorporating pomegranate and its extracts into dietary regimens. In addition to these benefits, the recovery and utilization of bioactive compounds from pomegranate waste, such as peels and seeds, not only enhances the nutritional value of processed products but also addresses environmental concerns related to agricultural waste management. Moreover, the extraction and valorization of these compounds from non-edible parts of the fruit present opportunities for their application in various industries, including food and pharmaceuticals, which can further promote sustainability and resource efficiency in agricultural practices1

Pomegranate's parts used

Pomegranate is a versatile fruit, and its various parts, including the arils, peels, leaves, and seeds, have been extensively studied for their bioactive compounds and potential health benefits (Figure 1.).

The pomegranate fruit can be consumed fresh or processed into various products, such as fresh or concentrated juice, infusions, or jam. Additionally,

Taken from: Kandylis,P.,&Kokkinomagoulos,E.(2020).FoodApplicationsandPotentialHealthBenefitsofPomegranateandits Derivatives.Foods(Basel,Switzerland),9(2),122.https://doi.org/10.3390/foods9020122

pomegranate peel, which accounts for a significant portion of the fruit's weight, has been recognized for its health benefits, including antibacterial activity, making it an important source of bioactive compounds that can be harnessed for both nutritional and functional applications.

Pomegranate processing generates large amounts of non-edible waste, including outer peels, seeds, pomace, and leaves, which constitute over 40-50% of the fruit. These leaves, typically discarded, could be valuable sources of biochemical compounds useful in various industries. Pomegranate leaves contain flavonols and flavones like catechin, epicatechin, and quercetin, which have been linked to protective roles in the plant. While most research focuses on pomegranate seeds, flowers, and juice, the therapeutic and functional properties of the leaves remain underexplored. Recovering bioactive molecules from these leaves could add value to the production process, as they possess potential antioxidant, anti-inflammatory, and other beneficial properties1

Furthermore, studies have shown that the nonedible fractions of the pomegranate plant, such as the leaves and seeds, also contain high amounts of specific nutritionally valuable and biologically active components, including phenolic acids, flavonoids, and alkaloids, which suggest their potential utility in enhancing health and wellness, thereby providing avenues for their incorporation into functional food products and dietary supplements aimed at improving overall health outcomes1,8. Moreover, the exploration of pomegranate waste as a source of bioactive compounds aligns with sustainable practices in the food industry, which increasingly aims to minimize waste and maximize resource recovery through the valorization of these by-products, thereby contributing to a circular economy1,2,5,8

Pomegranate for GERD

Pomegranate and its components have been studied for their potential benefits in the management of various health conditions, including gastro-

esophageal reflux disease. Research indicates that pomegranate juice may help alleviate symptoms associated with GERD by reducing inflammation and promoting mucosal healing in the gastrointestinal tract, which could lead to improved patient outcomes in managing this chronic condition8. Additionally, the anti-inflammatory properties of pomegranate components are believed to aid in the restoration of the oesophagal lining, providing patients with much-needed relief from the discomfort typically associated with GERD, thus making it a beneficial addition to dietary interventions aimed at managing this condition.

Pomegranate and prostate health

Studies have also explored the potential of pomegranate and its extracts in the context of prostate health. Research has shown that pomegranate extract may inhibit the proliferation of prostate cancer cells and promote apoptosis, thereby suggesting a possible protective effect against the progression of prostate cancer, which is particularly relevant given the rising incidence of this disease among men8 Furthermore, the incorporation of pomegranate extract in dietary regimens may provide a complementary approach to traditional therapies, potentially enhancing treatment efficacy and improving quality of life for patients diagnosed with prostate cancer, while also highlighting the necessity for further clinical studies to validate these promising findings.

Pomegranate oil and skin benefits

In addition to its internal health benefits, pomegranate has also garnered attention for its potential applications in dermatology and skincare.

The pomegranate seed oil, rich in punicic acid and other antioxidants, can improve skin hydration, reduce the appearance of fine lines, and protect against UV-induced damage, making it an attractive option for incorporation into various cosmetic formulations. The anti-inflammatory and wound-healing properties of pomegranate seed oil have also been

FIGURE 1 Major polyphenols, organic acids, alkaloids, and lignans of the pomegranate fruit

Taken from: Kandylis,P.,&Kokkinomagoulos,E.(2020).FoodApplicationsandPotentialHealthBenefitsofPomegranateandits Derivatives.Foods(Basel,Switzerland),9(2),122.https://doi.org/10.3390/foods9020122

explored, suggesting its potential utility in the management of skin conditions such as acne, and dermatitis.

Pomegranate extract and sports performance

Pomegranate and its bioactive components have also been investigated for their potential to enhance athletic performance. Several studies indicate that pomegranate juice can improve exercise performance and recovery, primarily due to its antioxidant properties, which help reduce oxidative stress and inflammation induced by intense physical activity. Moreover, the consumption of pomegranate juice before and after exercise has been associated with improved muscle recovery and reduced soreness. This highlights its role as a functional beverage for athletes aiming to optimize their performance and overall well-being. This has been evidenced by various experimental studies demonstrating its efficacy in enhancing exercise capacity and post-exercise recovery.

Pomegranate and its bioactive components have also been investigated in more depth for their potential to enhance athletic performance. Several studies indicate that pomegranate juice can improve exercise performance and recovery, primarily due to its abundant antioxidant properties, which help reduce oxidative stress and inflammation induced by intense physical activity. The antioxidant compounds

found in pomegranate, such as phenolics, flavonoids, and tannins, have been shown to mitigate the harmful effects of free radicals and reactive oxygen species generated during strenuous exercise.

Moreover, the consumption of pomegranate juice before and after exercise has been associated with improved muscle recovery and reduced soreness, highlighting its role as a functional beverage for athletes aiming to optimize their performance and overall well-being. This is further supported by various experimental studies demonstrating the efficacy of pomegranate in enhancing exercise capacity and post-exercise recovery, making it a promising natural supplement for athletes looking to enhance their athletic performance and support their body's recovery processes.

Several studies indicate that pomegranate juice can improve exercise performance and recovery, primarily due to its abundant antioxidant properties, which help reduce oxidative stress and inflammation induced by intense physical activity. The antioxidant compounds found in pomegranate, such as phenolics, flavonoids, and tannins, have been shown to mitigate the harmful effects of free radicals and reactive oxygen species generated during strenuous exercise.

FIGURE 2 A summary of pomegranate clinical trials in different diseases

overall well-being. Studies have further demonstrated the efficacy of pomegranate in enhancing exercise capacity and post-exercise recovery, making it a promising natural supplement for athletes looking to enhance their athletic performance and support their body's recovery processes.

Furthermore, pomegranate extracts may also offer additional benefits by promoting cardiovascular health, which is crucial for athletes engaging in rigorous physical activities, thereby contributing to an overall improvement in endurance and athletic performance as indicated by recent research findings6,8 Additionally, the role of pomegranate in supporting cardiovascular health can be attributed to its ability to improve endothelial function, reduce arterial stiffness, and lower blood pressure, all of which are essential factors that can enhance endurance and overall athletic performance in physically active individuals7,1

Conclusion

Pomegranate is a powerhouse of nutrition, offering a range of health benefits that extend far beyond its delicious taste. From cardiovascular health and cancer prevention to skincare and athletic performance, the bioactive compounds in pomegranate make it a valuable addition to any diet. The ongoing research (Figure 2.) into the therapeutic applications of pomegranate and its by-products highlights its potential to contribute to health and wellness in innovative and sustainable ways. As the understanding of this versatile fruit continues to grow, so does its role in promoting health across various domains.

References:

1 Marcelino S, Mandim F, Taofiq O, Pires TCSP, Finimundy TC, Prieto MA, Barros L. Valorization of Punica granatum L. Leaves Extracts as a Source of Bioactive Molecules. Pharmaceuticals. 2023; 16(3):342. https://doi.org/10.3390/ph16030342

2 García P, Fredes C, Cea I, Lozano-Sánchez J, Leyva-Jiménez FJ, Robert P, Vergara C, Jimenez P. Recovery of Bioactive Compounds from Pomegranate (Punica granatum L.) Peel Using Pressurized Liquid Extraction. Foods. 2021; 10(2):203. https://doi.org/10.3390/foods10020203

3 El Moujahed S, Dinica R-M, Cudalbeanu M, Avramescu SM, Msegued Ayam I, Ouazzani Chahdi F, Kandri Rodi Y, Errachidi F. Characterizations of Six Pomegranate (Punica granatum L.) Varieties of Global Commercial Interest in Morocco: Pomological, Organoleptic, Chemical and Biochemical Studies. Molecules. 2022; 27(12):3847. https://doi.org/10.3390/molecules27123847

4 Osama Mohamed Mabrouk, Omayma El-Sayed Shaltout, Wafaa Aly Amin, Thanaa Mustafa Ezz, Ahmed Mohamed Zeitoun. Evaluation of Bioactive Compounds in Pomegranate Fruit Parts as an Attempt for Their Application as an Active Edible Film. Journal of Biomaterials. Vol. 3, No. 1, 2019, pp. 7-17. doi: 10.11648/j.jb.20190301.12

5 Jiménez-Moreno, N., Esparza, I., Bimbela, F., Gandía, L. M., & Ancín-Azpilicueta, C. (2019). Valorization of selected fruit and vegetable wastes as bioactive compounds: Opportunities and challenges. Critical Reviews in Environmental Science and Technology, 50(20), 2061–2108. https://doi.org/10.1080/10643389.2019.1694819

6 Sood, Ankita & Gupta, Mahesh. (2015). Extraction process Optimization for bioactive compounds in pomegranate peel. Food Bioscience. 12. 10.1016/j.fbio.2015.09.004.

7 Nutrition and Athletic Performance. Medicine & Science in Sports & Exercise 41(3):p 709-731, March 2009. DOI: 10.1249/ MSS.0b013e31890eb86

8 Osama Mohamed Mabrouk; Omayma El-Sayed Shaltout; Wafaa Aly Amin; Thanaa Mustafa Ezz; Ahmed Mohamed Zeitoun. Evaluation of Bioactive Compounds in Pomegranate Fruit Parts as an Attempt for Their Application as an Active Edible Film. J. Biomater. 2019, 3(1), 7-17. doi: 10.11648/j.jb.20190301.12

9 Nutrition and Athletic Performance. Medicine & Science in Sports & Exercise 41(3):p 709-731, March 2009. | DOI: 10.1249/ MSS.0b013e31890eb86

FDA Confirms: Arla Foods Ingredients’ Whey Protein Hydrolysates Can Be Used in Infant Formula

Arla Foods Ingredients has secured US Food & Drug Administration approval for the use of whey protein hydrolysates, that support allergy management and gut comfort in infant formula.

The FDA agreed that four ingredients in the company’s Peptigen® and Lacprodan® ranges meet the definition of peptones in the US Code of Federal Regulations. As such, they are permitted for use in early life nutrition.

Anders Steen Jørgensen, Head of Arla Foods Ingredients’ Pediatric Business Unit, said: “We have over 30 years’ experience of developing and producing safe, high-quality whey protein hydrolysates for the infant formula market at our state-of-the-art manufacturing facilities. Our strategy is to ensure these scientifically backed ingredients are available all over the world. We are delighted that US infant formula manufacturers can now use four of our hydrolysates in infant nutrition products targeting cow’s milk allergy management or reduction of gut discomfort.”

It is estimated that 2-3% of infants in the US now suffer from cow’s milk allergy.1 In most cases where breastfeeding is not possible, hydrolyzed formulas backed by clinical proof of efficacy are recommended for them.

The four ingredients now permitted by the FDA for use in early life nutrition products are:

• Peptigen® IF-3032, an extensively hydrolyzed whey protein recommended for use in allergy management nutrition solutions. Multiple clinical studies support its suitability for infants with cow’s milk allergies. 2

• Peptigen® IF-3080, which is also suitable for allergy management nutrition solutions, and secured safety and suitability approval from EFSA for use in infant formula and follow-on milk in the EU in 2023.

• Peptigen® IF-3085, a partially hydrolyzed protein, which can be suitable in products for infants at high risk of developing milk allergies.

• Lacprodan® IF-3070, which is designed to support the reduction of gastrointestinal discomfort.

Anders Steen Jørgensen added: “We invest heavily in preclinical and clinical trials to provide scientific evidence for our ingredients’ benefits. Our whey protein hydrolysates have been shown to support the safe growth of formula-fed infants who are unable to tolerate traditional milk-based formulas.”

Arla Foods Ingredients has received approval for Lacprodan® IF-3070 and Lacprodan® DI-3072 for the Chinese formula market, and additional hydrolysate products are going through the country’s approval process.

1 Ward C.E., Greenhawt M.J. Treatment of allergic reactions and quality of life among caregivers of food-allergic children. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol (2015)

2 Halken, S., Host, A., Hansen, L. G. & Østerballe, O. Safety of a new, ultrafiltrated whey hydrolysate formula in children with cow milk allergy: a clinical investigation. Pediatric Allergy and Immunology 4, 53–59 (1993)

medicinal plants photo herbarium

Pomegranate (Punicagranatum)

Pomegranates are rich in antioxidants and anti-inflammatory properties, contributing to heart health, digestion, and cognitive function. They also have antimicrobial properties that aid in oral health and wound healing, while supporting hormonal balance and weight management.

TAXONOMY

kingdom: Plantae

order: Myrtales

family: Lythraceae

genus: Punica

species: Punica granatum

COMMON NAME

Pomegranate

FLOWERING TIME

V-IX month

Punica granatum L., commonly known as pomegranate, is a well-known member of the Lythraceae family. Pomegranate trees are native to the region from Iran to northern India and have been cultivated throughout the Mediterranean for millennia.

The pomegranate tree is a long-living tree that typically grows 2 to 5 meters high and lives over 200 years. The leaves are glossy and the flowers are red, white, large, or variegated and have tubular calyxes which finally become the fruit. The pomegranate fruit is grenade-shaped with a deep red, leathery skin and crown-shaped calyx. The seeds are surrounded by a small amount of tart and red juice and are separated via white, membranous pericarp1.

Habitat & cultivation

Pomegranate trees thrive in warm, dry climates typical of Mediterranean regions. They are well-suited to areas with hot, arid summers and mild winters. The tree is drought-tolerant once established but benefits from regular watering during fruit development. Depending on the variety, pomegranate fruits are typically ready for harvest 5 to 7 months after flowering. The fruit should be picked when it reaches full color and makes a metallic sound when tapped. Overripe fruit may crack open on the tree.

Use for medicinal purposes

Pomegranates have been proven to offer significant health benefits due to their high antioxidant content, particularly punicalagins and anthocyanins, which help reduce inflammation and oxidative stress. Studies have shown that pomegranate juice can lower blood pressure and improve cholesterol levels, supporting cardiovascular health. The fruit's antimicrobial effects contribute to better oral health by reducing dental plaque and fighting bacteria. Furthermore, pomegranate juice has been

linked to improved memory and cognitive function, particularly in ageing adults.

Traditional medicinal uses

Pomegranates have long been revered in traditional medicine for their diverse health benefits. Traditionally it was used medicinally to treat disorders of the circulatory system. Native Americans also used the blossoms in jewellery making. The fruit's rind and bark have been used as natural remedies for digestive issues, such as diarrhea and dysentery, due to their astringent properties. Pomegranate juice and extracts were also applied to promote wound healing and enhance skin health, while its seeds were consumed to regulate menstrual cycles and balance hormones. In many cultures, the fruit was regarded as a symbol of fertility and was used to boost sexual vitality. Additionally, pomegranate juice mixed with honey served as a traditional remedy to soothe coughs and sore throats.

Constituents

• punicalagins

• ellagic acid

• anthocyanins

• flavonoids (e.g., quercetin, kaempferol) tannins

vitamin C

• vitamin K

• fiber

• polyphenols (e.g., catechins, phenolic acids)

• potassium

Action and application

Pomegranates offer a range of health benefits due to their powerful antioxidant and anti-inflammatory properties. They are widely used to support cardiovascular health by lowering blood pressure, improving cholesterol levels, and preventing arterial plaque buildup. Their antimicrobial properties make them valuable in oral health and wound healing, while their digestive benefits help manage bowel movements and treat disorders like diarrhoea. Pomegranates are also consumed to boost cognitive function, support hormonal balance, and aid in weight management, demonstrating their versatility in promoting overall well-being.

Reference:

1 Jurenka, Julie S. “Therapeutic applications of pomegranate (Punica granatum L.): a review.” Alternative medicine review: a journal of clinical therapeutic vol. 13,2 (2008): 128-44.

Same Rules for Food Supplements in Europe: European Food Safety Authorities Present List of Critical Substances

Food supplements are to become even safer in Europe. To this end, the European Heads of Food Safety Agencies (HoA) unanimously adopted a list of critical substances at their meeting in Brussels.

The decision is based on a report by the working group on food supplements. This group consists of active members representing 26 European countries and has identified 117 substances that should not be used in food supplements or should only be used to a limited extent due to their possible hazardous properties which may lead to human health risks. The list can serve as an essential basis for the EU legislator to take further steps.

"Making food supplements safer is an important component of our daily work to protect the health of citizens in Europe. By drawing up the list of critical substances, the working group is making a significant contribution to this," emphasized Friedel Cramer, President of the Federal Office for Consumer Protection and Food Safety (BVL). "I would like to thank all members of the working group for their constructive work. For me, it is a successful example of the valuable and practical cooperation between food safety authorities in Europe."

Among other things, the working group collected information on possible risks associated with the consumption of the 117 listed substances. In particular, if these substances are ingested in concentrated form, for example in food supplements, they may pose a risk to human health. Existing official risk assessments were taken into account when evaluating the listed substances.

In its report, the working group prioritized 12 substances based on their risks for human health which

require a legally binding regulation. In the view of the working group, the European Commission should ask the European Food Safety Authority (EFSA) to assess these substances, as foreseen by the legislative procedure. If the EFSA confirms the conclusions of the HoA working group, the European Commission can restrict or ban the use of these substances by including them in Annex III of the EU fortification regulation (Regulation (EC) No 1925/2006). The report recommends further regulatory measures for the remaining 105 substances, for example through the requirements of the Novel Food Regulation (Regulation (EU) 2015/2283).

The "Heads of Food Safety Agencies" (HoA) is an informal committee of the leaders of the food safety authorities of European countries. This includes the member states of the European Union and Iceland, Liechtenstein, Norway and Switzerland. The main aim of the committee is to network and promote cooperation between state actors in the field of food safety. The committee meets once every six months at the invitation of the respective EU Council Presidency. The HoA sets up working groups and commissions them to draw up papers on proven and new risk management practices in Europe. The working group on food supplements has met since 2020 and has been chaired by Germany and co-chaired by the Netherlands since 2022.

Exploring the Impact of Crocus Sativus on Glycemic Control and Cardiometabolic Health

Metabolic syndrome and related disorders, such as type 2 diabetes, coronary artery disease, and diabetic nephropathy, pose significant health challenges. With the growing interest in herbal and natural remedies, saffron (Crocus sativus) stands out as a potential therapeutic agent.

This meta-analysis is pioneering in its examination of saffron's impact on metabolic syndrome, aggregating data from 840 adults aged 41–63 years across various randomized controlled trials (RCTs). The study's key findings include:

1. Improvement in fasting blood glucose (FBG): Crocin, a major active component of saffron, significantly lowered FBG levels compared to placebo. Notably, this effect was more consistent with crocin than with whole saffron extracts.

2. Reduction in hemoglobin A1c (HbA1c) and systolic blood pressure (SBP): Saffron supplementation, particularly over periods longer than eight weeks, resulted in significant reductions in HbA1c and SBP, suggesting a potential role in long-term management of glycemic control and hypertension.

3. Cholesterol reduction in metabolic syndrome patients: In individuals with metabolic syndrome, saffron significantly reduced total cholesterol (TC) levels, which could be beneficial in managing dyslipidemia and reducing cardiovascular risk.

Mechanisms of action

The hypoglycemic and cardiometabolic effects of saffron can be attributed to its anti-inflammatory and antioxidant properties. Crocin, in particular, helps in scavenging reactive oxygen species (ROS) and may support pancreatic beta-cell regeneration.

Additionally, saffron's influence on lipid metabolism, through the inhibition of lipid synthesis and the modulation of cholesterol homeostasis, contributes to its potential to reduce atherosclerosis risk.

Comparison with previous studies

Interestingly, this meta-analysis presents a nuanced perspective compared to earlier research. Previous studies suggested that saffron had a minimal effect on cardiovascular risk factors and HbA1c levels. However, the current analysis contradicts these findings, showing that saffron, especially crocin, has a significant impact on glycemic control and SBP, which may hold clinical relevance for patients with metabolic syndrome.

Clinical implications for pharmacists

Pharmacists should consider these findings when advising patients on complementary therapies for

managing metabolic syndrome and related disorders. Saffron's potential to lower FBG, HbA1c, and SBP could make it a valuable adjunct to conventional treatments, particularly for patients seeking natural alternatives.

However, we must also be aware of the limitations. The included studies varied in methodology, and some had small sample sizes, leading to heterogeneity in the results. Moreover, the availability and cost of saffron, driven by its high demand in various industries, may also affect its accessibility as a treatment option.

Conclusion

This meta-analysis underscores the potential of Crocus sativus in improving glycemic control and cardiometabolic parameters in patients with metabolic syndrome. While more extensive research is needed to confirm these findings, saffron may offer a promising complementary approach to managing this complex condition. Healthcare workers and industry members should stay informed about such emerging evidence to provide comprehensive care and advice to patients considering herbal supplements as part of their treatment regimen.

Reference:

Yan, X., Zhao, S., Feng, X., Li, X., Zhou, Q., & Chen, Q. (2024). Effects of Crocus sativus on glycemic control and cardiometabolic parameters among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Nutrition & metabolism, 21(1), 28. https://doi.org/10.1186/s12986-024-00806-y

AUTHOR: Darmell Ltd.

Fi Europe Startup Challenge: Time to Take the Centre Stage

Entries for the Fi Europe Startup Challenge are now open with a submission deadline of 6 September.

Now in its ninth year, the Fi Europe Startup Challenge 2024 – a unique competition for young companies championing ingredient innovations – is encouraging industry entrepreneurs to submit their applications. This year’s challenge will feature four exciting categories, including the new Most Innovative Foodtech Solution plus a special Jurys Choice award for the Most Innovative Sustainable Solution.

The awards recognise innovative products and ideas for the food and beverage ingredients sector, and inspirational young companies that are driving positive changes in the industry. The Fi Europe Startup Challenge also offers a unique platform for startups to gain exposure to a global audience, expand their networks and attract investment.

Just by entering the challenge, participants are guaranteed to catch the eye of the advisory board, who will be compiling the shortlist of entrants. All shortlisted startups will not only have the opportunity to pitch to an influential judging panel, but also showcase their innovation to more than 25,000 visitors who attend Fi Europe.

Entries are open to startups active for 5 years or less, with innovations focusing on groundbreaking additives and ingredients, technologies and digital

solutions.

This year’s categories are as follows:

Most Innovative Food or Beverage Ingredient

• Most Innovative Plant-based or Alternative Ingredient

• Most Innovative Foodtech Solution (NEW)

• Most Innovative Service or Digital Solution Supporting the F&B industry

Additionally, there will be a Jury’s Choice award for Most Innovative Sustainable Solution chosen from the finalists across all categories.

The winning startups in each category will be able to choose one prize from a selection up for grabs, including a free stand at next year’s Fi Europe, a digital marketing package for Ingredients Network and Fi Global Insights, or mentorship and support from one of the jury members.

This year’s panel and supporting companies include Michael Dovbish, Executive Director, Nutrition Capital Network; Kevin Camphuis, Co-Founder, ShakeUpFactory; Itziar Ortega, Senior VP Global Operations, Eatable Adventures; Thomas van den Boezem, Principal, PeakBridge; Albrecht Wolfmeyer, International Director of ProVeg Incubator; Sonia Huppert, Global Innovation Marketing Leader, IFF; and Nutrition Consultant Sandra Einerhand, Founder of Einerhand Science & Innovation and Co-founder of the Fi Europe Startup Challenge.

“Startups are defining and designing the innovative food ingredients of tomorrow, but often lack the scale and funds to bring their solutions to market,” says Yannick Verry, Brand Director, Food ingredients Europe & Americas. “Connecting with the right partners is therefore a fundamental part of any startup’s journey, and the Fi Europe Startup Challenge is the ideal place to do so.”

“Participating in an event like this is always positive, as other companies, potential clients and investors get to know you, thus reinforcing the brand,” adds David Ciudad Rodriguez, CEO and Co-founder of Deep Detection, one of the 2023 award-winning companies.

For more information on the Fi Europe Startup Challenge 2024, which will take place in Frankfurt at the Fi Europe Innovation Hub on 19 November, please click here.

Fi Europe Gears Up For Its Best Edition Yet

The unmissable ingredients show returns to Frankfurt with additional features.

Fi Europe is gearing up for its biggest and best year ever. From 19-21 November 2024, Messe Frankfurt will host the leading global event for food and beverage ingredients. More than 1,500 exhibitors and a programme of expert presentations will showcase innovation, share insights and foster business relationships. Over 25,000 visitors from 135 countries are expected to attend and exhibitors will include ABF Ingredients Group, Azelis, Brenntag Holding GmbH, Cargill, Fonterra and Prinova.

The main show arena will feature exhibitors from across the full F&B ingredients spectrum including, for the first time ever, a Petfood Suppliers Hub where visitors can explore the latest ingredients and technologies for pet nutrition. The health ingredients area is dedicated to functional F&B ingredients with proven health benefits. And the expanded Food Manufacturing Technologies & Solutions Area is a one-stop destination for those seeking practical and innovative ways to optimise their supply chain and future-proof their operations, from R&D to delivery.

Fi Europe has a strong track record of facilitating business partnerships that deliver successful products. As well as comprehensive exhibition halls offering an opportunity to meet with the best in the business, Exhibitor Showcases will allow innovators to share their unique ideas. All visitor passes also include free access to the Innovation Hub, which will run throughout the show, with a bustling programme of presentations and discussions covering a range of opportunities. Free access to the two-day Fi Europe Conference (19-20 November) is included with all visitor passes too. During a rich variety of expert-led sessions, speakers will focus on solutions for current industry challenges and immediate opportunities for R&D and product development.

Yannick Verry, Brand Director, Food ingredients Europe & Americas, says: “We’re excited to be back in Frankfurt for Fi Europe 2024. The event has been growing and evolving with the needs of the F&B ingredients industry and we’re constantly looking for new ways to offer a bigger and better platform for our exhibitors and visitors to connect. This year we have some great additions alongside our tried and trusted favourites that make the event even more unmissable than before.”

Exclusive insights will once again be shared at The Future of Nutrition Summit. This special event takes place at the Mövenpick Hotel Frankfurt City on 18 November, the day before Fi Europe opens its doors. Attendees can access the summit with a delegate

pass and will hear from industry leaders and visionaries who will give presentations and lead discussions on future trends and developments in health and nutrition. Topics will include Food As Medicine, AI and Food and Sustainable Solutions.

In fact, sustainability will be a key thread running throughout Fi Europe 2024. “Our partnership with international civil society organisation Solidaridad is part of our ongoing commitment to sustainability,” says Yannick Verry. “Throughout our Fi Europe features and content, we will highlight sustainable sourcing, transparency, regulatory compliance and more.”

With data-driven matchmaking and The Women’s Networking Breakfast also back this year, Fi Europe offers unrivalled networking opportunities. To help attendees plan their days, book meetings and optimise their time, the user-friendly Fi Europe event platform is available online now.

“Visitors and exhibitors can log into the event platform at any time,” says Yannick Verry. “They can browse products and suppliers and use our AI-driven matchmaking tool to connect with potential business partners. We’ve designed it to make planning easier for everyone before the event and we can’t wait for our F&B community to experience Fi Europe in person.”

For more information and to register your attendance, visit: https://www.figlobal.com/europe/en/home.html

Biofilm – Definition, Characteristics and Role in Chronic Infections

Infections associated with biofilm are a frequent problem in clinical practice and it is important to understand their etiology, epidemiology and pathogenesis so that they can be recognized in time and treated adequately. Microorganisms in the biofilm show high resistance to antimicrobial drugs, as well as disinfectants causing the therapeutic procedures in the treatment of biofilm infections to be limited.

AUTHOR: Kristina Harča, Mpharm

In nature, microorganisms can exist as planktonic organisms - individual cells in a liquid medium; or as a sessile community - biofilm. It is precisely the biofilm form which is a prevalent form of life in the environment, almost at every border of water and air, and land and water1,2. In the past two decades, the definition of biofilm has been constantly changing because each new research builds on the existing knowledge about the creation, structure, ripening, and resistance of biofilm. Today, biofilm is defined as a sessile community of microorganisms whose cells are irreversibly connected to the substrate and each other, and incorporated into the extracellular matrix of polysaccharide polymers that they created. Microorganisms within a biofilm exhibit a changed phenotype as a result of the change rates of reproduction and transcription of genes that we do not observe in planktonic organisms3

As shown in Figure 1, biofilm formation begins with

the conditioning of a surface with polymers from the aquatic environment, which enables the adherence of microorganisms. Surfaces on which biofilm can be found are, for example, metal, plastic, stone, soil particles, medical implants, and tissues. After the initial, reversible binding of planktonic cells to the surface of the substrate, the formation of a stable bond on the bacterial cell wall follows, followed by proliferation, and the accumulation of bacterial cells into multi-layered cell clusters and the formation of the extracellular polysaccharide matrix EPS (Extracellular Polymeric Substances). After the formation of a mature biofilm, there is a dispersion of microorganisms from the community in search of new surfaces, which presents a start of a new cycle of biofilm formation. These developmental stages are common to both bacterial and fungal biofilms2

The thickness of EPS ranges from 0.2 to 10 μm, and the total size of the biofilm does not exceed 10 mm.

Sessile communities of bacteria comprise only 5.35% of its total volume, while the remaining volume is EPS4

It was also discovered that microbial cells within the biofilm excrete chemical substances for mutual communication necessary for fluid exchange, nutrient supply, transfer of genetic material, synthesis of secondary metabolites, and more. This kind of communication system is called quorumsensing (QS).

Today, in biomedicine, it is an accepted fact that understanding biofilms is extremely important since 65-80% of infectious diseases are related to biofilm. In addition, microorganisms growing in biofilm show a higher level of drug resistance leading to clinical failure of applied therapy. Microorganisms in the biofilm show high resistance to antibiotics, antiviral, antimalarial, antifungal and anthelmintic drugs, as well as disinfectants and environmental stress5

Biofilm is associated with various infections of biomaterials such as catheters, prostheses, implants, and other medical devices made of metal or plastic polymers found in the human body6. According to estimates from the Centers for Disease Control and Prevention in Atlanta, biofilm is associated with almost two-thirds of bacterial infections7.

Biofilms may impact human health also positively. One example of a positive effect includes the biofilms of commensal bacteria such as Staphylococcus epidermidis , which can impede the colonisation of potentially pathogenic bacteria through the stimulation of host-cell immune defences and the prevention of adhesion.

However, biofilms are more often associated with many pathogenic forms of human diseases. One common example is cystic fibrosis, the most frequently passed genetic disorder in Western Europe. Cystic fibrosis (CF) patients suffer from chronic P. aeruginosa infections. When infecting the CF lung, P. aeruginosa undergoes a characteristic transition from an acute virulent pathogen to a CF-adapted pathogen, allowing it to persist in the lung for years or even decades. This is due to the overproduction of the matrix polysaccharide alginate, leading to the

formation of a mucoid biofilm that tolerates antibiotics and resists phagocytosis. The persistence of these mucoid biofilms within the CF lung leads to the development of a distinct antibody response. This prompts chronic inflammation mediated by granulocytes, and results in severe damage to the lung tissue of CF patients (Figure 2)8.

Biofilm is also thought to be responsible for preventing the normal wound-healing process, causing wounds to become chronic. A wound is considered chronic when under the influence of various internal or external factors factors cannot achieve anatomical and functional integrity through orderly and timely healing processes9. Wound healing on the skin is a complex process that includes cell proliferation, migration and tissue remodelling, which leads to the re-establishment of its primary function, which is the role of a barrier to the external environment. Failure to treat wounds can lead to further complications, including septicemia, chronic pain, prolonged hospitalization, amputation, and death.

In human medicine, chronic wounds include wounds of the lower extremities due to comorbidities such as diabetes, high blood pressure or venous hypertension, etc. Bacteria present in chronic wounds play a role in delayed tissue healing. It is believed that the bacteria present in chronic wounds do not exist only in planktonic form, but also as biofilm10 The presence of biofilms in chronic wounds leads to several common features: they prevent the action of antibiotics on bacteria and maintain the infected tissue in a persistent inflammatory state. Additionally, the presence of biofilms has been shown to induce chronic and/or "silent" inflammation and delay wound healing. A chronic wound is stopped in the inflammatory phase of wound healing and cannot progress further. While the biofilm is present in only about 6% of acute wounds, over 90% of chronic wounds contain bacteria and fungi incorporated into the biofilm. It has been observed that only seven to ten hours are enough for bacteria from wound samples of people with burn injuries to form a ma-

FIGURE 1

Taken from: https://www.immunology.org/publicinformation/bitesized-immunology/pathogens-disease/biofilms-and-their-role-pathogenesis

ture biofilm11

As the most common microorganisms responsible for two thirds of infections associated with a foreign body are bacteria that form a biofilm and belong to the genus Staphylococcus (S. aureus, S. epidermidis, S. lungdunensis) , followed by Pseudomonas aeruginosa and Enterococcus spp., and from fungal infections Candida sp . The polymicrobial nature of this pathogenic biofilm is key to understanding the chronicity of the lesion.

Bacteria that grow in biofilms are very tolerant to antibiotics and resistant to the immune system of the host, therefore they act as an important virulence factor that plays a key role in the persistence and pathogenesis of biofilm infection13. Infections associated with biofilm are a frequent problem in clinical practice and it is important to understand their etiology, epidemiology and pathogenesis so that they can be recognized in time and adequately treated accordingly. They pose a serious risk to patients with chronic diseases, such as those with cystic fibrosis, chronic obstructive pulmonary disease (COPD), chronic wounds or osteomyelitis. Also, one of the most vulnerable groups of patients are surgical patients because, in addition to being often immunocompromised due to the procedure itself, surgical implants and prostheses provide perfect surfaces for bacteria to accumulate and form biofilm. Due to increased tolerance and resistance to antimicrobial drugs, therapeutic procedures in the treatment of biofilm infections are limited and often include high doses of antibiotics, backup antibiotics or removal of prostheses14

Conclusion

The incidence, chronic course, and resistance to antimicrobial therapy are just some of the features of biofilm infections, which are one of the greatest

challenges of medicine in the 21st century. The study of biofilms, apart from biomedicine, has a significant role in biotechnology, industry, ecology and other diverse scientific fields4,5 .

References:

1 Davey ME, O’Toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev 2000; 64:847-67.

2 Donlan RM. Biofilms: microbial life on surfaces. Emerg Infect Dis 2002; 8:881-90.

3 Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbial Rev 2002; 15:167-93.

4 Rina Rani Ray, Nag M, Lahiri D. Biofilm-Mediated Diseases: Causes and Controls. Springer Nature; 2021.

5 Chaminda Jayampath Seneviratne. Microbial Biofilms. CRC Press; 2017.

6 Beech IB, Sunner JA, Arciola CR, Cristiani P. Microbially-influenced corrosion: damage to prostheses, delight

7 Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbial Rev 2002; 15:167-93.

8 https://www.immunology.org/publicinformation/bitesizedimmunology/pathogens-disease/biofilms-and-their-rolepathogenesis

9 J. Škrlin. Utjecaj biofilma na cijeljenje rane i postupak za identifikciju biofilma u rani. Acta Med Croatica, 70 (2016) 29-32

10 Marano RJ, Wallace HJ, Wijeratne D, Fear MW, Wong HS, O’Handley R. Secreted biofilm factors adversely affect cellular wound healing responses in vitro. Sci Rep 2015, 5: 13296.

11 Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz PM. A wound-isolated Pseudomonas aeruginosa grows a biofilm in vitro within 10 hours and is visualized by light microscopy. Dermatol Surg 2003; 29:631-5.

12 Valenzuela L, Chi A, Beard S, Orell A, Guiliani N, Shabanovitz J, Hunt DF, Jerez CA. Genomics, metagenomics and proteomics in biominimg microorganisms. Biotechnol Adv 2006; 24:197-211.

13 Vraneš et al. Biofilm i kronične infekcije. Med Glas 2009; 6(2):147-165

14 Kotur V. Infekcije povezane s biofilmom : diplomski rad. Rijeka: Sveučilište u Rijeci, Medicinski fakultet; 2023 [pristupljeno 19.08.2024.] Dostupno na: https://urn.nsk.hr/urn:nbn:hr:184:180614

FIGURE 1

Fermented Skincare

The skin is our largest organ and home to numerous microorganisms that make up the skin microbiome. This community of bacteria and fungi plays a crucial role in protecting the skin and the entire body from harmful microorganisms. The diversity and balance of the microbiome play a crucial role in skin health, and the cosmetic industry is increasingly exploring innovative ingredients to enhance its function and protect the body from harmful microorganisms.

AUTHOR: Gordana Gorinšek, MSc in Phytomedicine, Expert Cosmetic Safety Assessor, Expert Regulatory Affairs Consultant

The skin is our largest organ and the instrument through which we communicate with the external world, the environment that surrounds us. The skin is also a habitat for numerous species of microorganisms, bacteria, and fungi that make up the skin microbiome. It is estimated that the human body contains about ten trillion human cells and one hundred trillion bacterial cells, with one trillion bacterial cells on the skin alone.

Interestingly, each person has their unique microbiome with which they live in symbiosis. Microorganisms find a habitat in the skin and a source of nutrients, in return, they protect the skin and the body from the penetration of harmful microorganisms, which can cause various diseases. In fact, the microbiome and the skin create an acidic layer (pH around 5) that prevents the growth of most harmful microorganisms, which is a finely tuned mechanism for avoiding infections and other pathogenic changes. Therefore, the microbiome is considered an import-

ant part of the skin's barrier function and contributes to maintaining the skin in good condition. The diversity and balance between all species of microorganisms that make up the microbiome are key to its role.

The presence of sweat and sebaceous glands in the skin and the products they secrete determine which types of bacteria will dominate certain parts of the body. Species from the genera Propionibacterium and Staphylococcus dominate in sebaceous (oily) areas of the skin, such as the face and upper body, while the genera Corynebacteria, ß-Proteobacteria, and Staphylococcus dominate in moist areas such as the armpits, the inner side of the elbow, and the inner side of the knee. In dry skin areas, such as the forearm and buttocks, members of the genera ß-Proteobacteria,Corynebacteria,and Flavobacteriales can be found. The areas of the skin with the greatest bacterial diversity are dry regions, such as the skin of the forearm and legs.

The composition of the skin microbiome is variable, and the main factors influencing changes in its composition include gender, age, temperature, humidity, pH, availability of nutrients, host genetics, diseases and medications, hygiene habits (soaps and skin cleansing products with alkaline reactions can cause changes in the skin's pH), the external environment, interactions with other microorganisms, and the host's immune system.

Gender has a significant impact on the skin microbiome. Women have greater bacterial diversity within their microbiome compared to men. This is due to many differences between the female and male bodies, such as steroid production, skin thickness, sebaceous and sweat gland activity, the presence or absence of body hair, and skin pH.

The skin microbiome changes with age. It develops after birth during the first contact of the newborn with the external world, when colonization of the skin begins, and its composition is initially very simple. As we age, the skin microbiome becomes more diverse. Hormonal changes occur with puberty, leading to increased activity of sebaceous and sweat glands, and consequently to the development of so-called lipophilic bacteria, bacteria that inhabit oily areas of the skin. Additionally, with menopause, the skin loses lipids and elasticity, which also affects changes in the composition of the skin microbiome.

The axillary region (armpit) is the most important site for developing body odour. Due to the warm and moist environment, it is an ideal place for the growth of a large number of bacteria, and thus the creation of an unpleasant odour. The smell of axillary secretions becomes more intense as bacteria break them down. Body odours are associated with the dominance of "bad" bacteria in the axillary region. A new treatment called axillary bacteriotherapy is being developed worldwide, which is based on the transplantation of "good" bacteria, aiming to change the ratio of "bad" to "good" bacteria, of course in favour of the "good" ones. The transplantation results in an improvement in the body odor of the axillary areas.

In line with the role of the skin microbiome, the cosmetic industry, in its eternal quest for innovation, is developing cosmetic raw materials that are fermentation products and are likely to become a global trend of the future. The first steps have already been taken in South Korea. In this sense, the cosmetic industry is engaged in developing of probiotics, prebiotics, and postbiotics. Probiotics are considered to be live or inactive microorganisms (e.g., Lactobacillus casei, Lactobacillus acidophilus). Prebiotics are defined as nutrients necessary for the development of probiotics or the natural microbiome of the skin (e.g., niacinamide, minerals, thermal water, vitamins, oligosaccharides, natural oils, etc.). Postbiotics are defined as products or metabolic by-products secreted by live bacteria or released after the breakdown of bacterial cells (e.g., Bifida ferment lysate, Lactococcus ferment lysate, Bacilluscoagulans ferment, etc.). In cosmetic products, prebiotics can contribute to the development of the skin's natural microflora and increase microbiological activity, but very little is known about the effectiveness of topically applied prebiotics.

Preparations containing live microorganisms are extremely rare in the cosmetic raw material market.

Such raw materials would, by definition, be considered probiotics and would likely prove to be highly valuable active components. However, the cosmetic industry has shown little interest in developing cosmetic probiotics, as it has proven challenging to ensure the vitality of live microorganisms in a cosmetic product. Without the ability to remain alive, the expected effects of the microorganisms on the skin are lost, and with them, customer trust. Additionally, ensuring health safety, which is a legal requirement and an ethical obligation of manufacturers to make their products safe for consumer health throughout the product's lifespan, has proven difficult to achieve in such cases, despite the preservation process.

Moreover, the question of legal regulation of such a product remains open, as it could easily be classified as a borderline product between a cosmetic product and a drug due to unauthorized health claims that often accompany cosmetic products, usually out of ignorance or in an attempt to increase sales. All of the above complicates the marketing of cosmetic products with live microorganisms, and, likely, they will not become widespread anytime soon.

The cosmetic industry has chosen an alternative, safe approach and has shown interest in utilizing fermentation processes to obtain cosmetic ingredients rich in beneficial compounds such as proteins, ceramides, amino acids, and antioxidants. These raw materials are typically called "bioferments" and are considered postbiotics.

The main advantage of cosmetic ingredients obtained through fermentation is their compatibility with the skin, which tolerates and accepts them well. Fermentation enables the conversion of complex compounds into simpler ones. The simpler the compounds, the more easily they penetrate the skin, and thus their effectiveness at the site of action is greater.

Ferments from berries are characterized by their antioxidant properties, while ferments from red and black ginseng or tonka beans contribute to reducing visible signs of skin ageing. The last group includes ferments with moisturizing properties, such as aloe, seaweed, skim milk, and soy milk. These raw materials already have excellent skin moisturizing properties before fermentation, but the fermentation process significantly enhances this effect.

Conclusion

Fermentation is an efficient and interesting method of processing raw materials, but it requires further technological research, and the use of bioferments in the cosmetic industry is still minimal. However, it will likely find its enthusiasts among end consumers in the future.

Aromatični kutak Ltd.

Brune Bušića 21 Zagreb, Croatia https://pif.com.hr/ info@aromaticnikutak.hr T. + 385 98 1750 934

inspirational success story

Medardo

Medardo is such a fitting name for someone who has been passionate about honey from his early years... When a love for bees and excellent knowledge of honey and honey-based products come together, the result is a high-quality product, both fragrant and eco-friendly, organically grown.

To achieve this, it is essential to care for the bees, often referred to as 'the most important living beings on our planet'. The beehives of Medardo d.o.o., owned by Mr Medardo and his son Gordan, are located in a unique micro-locality between the Konavle hills and the valley. This specific location offers the bees access to a rich diversity of Mediterranean flora, resulting in a variety of honey types, from heather and sage to forest honey and multi-floral honey. Every few years, they manage to produce the rare Strawberry tree honey, considered the most bitter honey in the world, found only in a few other locations such as Montenegro, Sicily, and Corsica.

We spoke with Mr Gordan Delić, director of Medardo d.o.o., a visionary and passionate beekeeper, about this inspirational success story.

n Mr Delić, how did the 'Medardo d.o.o.' story begin what inspired you? What was the initial idea?

Our honey production started with the most basic, yet important element - a love for bees - which, in a romantic and somewhat cinematic way, has been passed down through generations. Today, several million bees work diligently at two apiaries in

the Dubrovnik-Neretva County, located in Konavle. The larger apiary in Zastolje consists of 120 bee colonies, while the smaller one in Komaji has 40 colonies. My father, Medardo, who has been beekeeping since childhood, instilled this love in me. Together with an excellent team in our production facility, we continue to develop numerous high-quality organic honey-based products, combining them with local ingredients. But honey is not our only focus...

n Yes, you also have an excellent line of natural cosmetics. What products do you offer, and where can we find them?

As a family of dedicated beekeepers and in addition to honey production, we decided to expand our offerings to include cosmetics, HoneyDu Cosmetics, based on bee products and precious natural ingredients, such as essential oils. The respect for nature that is part of our beekeeping practice has been carried over into our cosmetics line. Our products are pure, nourishing, and formulated with carefully selected ingredients, including bee products such as propolis, beeswax, honey, fermented honey, and other high quality ingredients such as cold-pressed and essential oils. Free from parabens and artificial fra-

grances, our products are not tested on animals. In 2022., we launched a new venture as part of the project 'Production of Natural Cosmetics Based on Bee Products and Mediterranean Herbs', significantly enhancing our business. This step was made possible with co-funding from the European Union through the European Agricultural Fund for Rural Development, where we received a subsidy of 50,000 EUR. With this subsidy, we invested 450,000 EUR from our funds into the production facility, development, and formulation of products.

Our goal was to create new products based on bee products. HoneyDu Cosmetics today includes hand creams, soaps, lip balms, face serums, and nourishing body lotions. All our products are made from high-quality ingredients and natural essential oils such as lavender, mandarin, and rosemary. We also offer gift sets featuring our most popular products, perfect for gifting, especially for under the Christmas tree: BeeAwaken Gift Set, BeeBuzzing Mandarin Gift Set, BeeCalm Lavender Gift Set, BeePresent Gift Set, BeePure Rosemary Gift Set. Also, at this moment, we are developing 20 new products that will be available by the end of the year.

In addition to high-quality natural cosmetics, through our brand Dubrovnik Manufaktura, we also offer a range of gastronomic delicacies from the region, including homemade spreads and marmalades. Our spreads and marmalades are made exclusively with ingredients from the region, such as lemons from Lopud island or dried figs from Vrgorac, and famous Dubrovnik bitter oranges. Our products are available through our online store and in selected artisan shops. The products we offer include marmalade from Dubrovnik bitter orange, marmalade from Dubrovnik lemon, a spread made from Dubrovnik bitter orange and dried Vrgorac figs, and a dried fig spread. Soon, we will introduce a muscat squash and apple spread, along with several other marmalades and spreads that we plan to launch in 2025. These products have been well received in hotels and restaurants as part of locally-inspired breakfasts, which is a key part of our promotion and market placement as a 100 per cent local product. Our customers are also very interested in our liqueursDubrovnik honey brandy and a bitter orange liqueur with Dalmatian honey. This production line goes by the brand name Ragusa Spirits. As passionate, organic beekeepers, we also offer a wide range of over 500 products for beekeeping – from packaging to various beekeeping tools. All our products can be found on our official website.

n From idea to realization: What actions were, let's say, necessary?

It took five years to go from the idea to the realization of natural cosmetics production. The biggest challenge was finding a suitable space - which is always a significant challenge in Dubrovnik - we had four failed attempts before we found the space we are in today, and the second biggest challenge was finding energetic and qualified staff as the field is quite specific and highly regulated. The challenge of financing the interim period, which is extremely long, along with the process of developing and certifying products, is the challenge 'per se'. During all those years, we had to arm ourselves with patience and

stable income from other sources. Of course, there was also the challenge of choosing equipment, selecting and defining packaging, and 'locking' the product formula at the right time - in short, all of these were challenges, each bigger than the one before.

n Are you satisfied with what you’ve achieved? What are you most proud of?

We are very satisfied with what we’ve achieved, but we always believe there is more place for further growth and development. Our philosophy is not focused on quantitative production, but rather on uncompromising quality. We carefully design each product and pay attention to every detail in the production process. Along with our investments in space and equipment, our plan – which we have successfully realized – was to hire highly qualified staff.

Today, our expert team in production includes Kazimir Antunović, mag.ing.techn. aliment., the main production manager, as well as two food technologists, Irena Šabić and Tena Silađi, both mag.ing.techn. aliment., and Ivana Roković, mag.ing.chem.ing., head of cosmetics production. Their expertise and dedication are crucial in maintaining the high quality of our products.

n What are your future plans?

Our commitment to quality has been recognized by both tourists and locals, as well as throughout Croatia in general. All our products have already reached satisfied customers. Of course, we never lack of ideas, plans and dreams. It’s essential to follow them but to stay as realistic as possible. As I mentioned earlier, our plan is to develop 20 new natural cosmetics products, new spreads, and soon bring them to market while further strengthening our established market presence. Foreign visitors love and appreciate us, and we are always happy to open our production facility to locals, visitors, nature lovers...

We also plan to further strengthen our brand presence in the market. In addition, we continue to nurture a close relationship with our customers and visitors, both foreign and locals, and we are always open to sharing our stories and products. Besides online and at our production facility iz Župa dubrovačka, you can also find us in our artisan HoneyDu Store Dubrovnik Old Town. Visit us!

Medardo d.o.o.

20207 Mlini, Put Dr. Ante Starčevića 145, Croatia Mobile: +385 (98) 344951 e-mail: mia@dubrovnikmed.com https://www.dubrovnikmed.com/

Cell-based Evidence Supports the Bioactivity of Collagen Peptides for Skin Firmness and Elasticity

An in vitro study recently published in the scientific journal Frontiers in Medicine provides cell-based evidence for the beneficial effects of exposure to collagen peptides on the skin’s collagen content and on the molecules that provide skin firmness and elasticity. This may support the hypothesis that collagen peptides are biological messengers for maintaining extracellular matrix (ECM) structure and skin regeneration.

Unraveling anti-aging dermal cell mechanisms

Collagen is one of the major proteins of the skin and it is particularly important for the skin’s strength and resilience. Skin aging is a natural process that is characterized by the decrease and fragmentation of collagen in the dermis. A previously conducted double-blind clinical study carried out at the Cosderma Institute in France over a period of 56 days has already proven the positive effects of the oral intake of 5-10 g/day of Solugel® collagen peptides on skin anti-aging. However, the underlying mechanisms of senescence-associated molecules synthesized by collagen-exposed cells remain unclear.

The effect of collagen peptides on cell behavior

In a recent in vitro study conducted by Bionos Biotech*, the mechanisms associated with collagen, elastin, and versican in human dermal fibroblasts were investigated after exposure to collagen peptides. The effects of different concentrations of collagen peptides on cell viability and metabolism were analyzed and this resulted in the following findings: Solugel® collagen peptides increased the expression of the collagen (COL1A1), elastin (ELN), and versican (VCAN) genes in human dermal fibroblasts (p<0.005);

• Higher collagen expression was detected by confocal microscopy in the dermal fibroblast culture after treatment with the collagen peptides (p<0.005);

• The exposure to collagen peptides in dermal cells affects the skin’s collagen content and the molecules that provide firmness and elasticity.

Implications and conclusion

These data provide scientific, cell-based evidence for the potential beneficial effects of the exposure

of collagen peptides on skin-firming and anti-aging properties, which suggests that they may trigger the cell signaling and gene expressions to maintain the structure of the dermis and ECM.

Expert insight

Dr. Reyhan Nergiz Unal, Health & Nutrition Science Lead at PB Leiner and co-author of the study: “This novel data shows that SOLUGEL® triggers the fibroblasts to produce skin anti-aging molecules. The study proves that collagen is a biological messenger, which means that exposure to collagen changes the dermal cell behavior to provide firmness and elasticity, and also increases collagen production. Moreover, collagen positively changes gene expressions, which results in skin cells producing more anti-aging molecules.”

The study results were published in the peer-reviewed scientific journal Frontiers in Medicine (Sec. Dermatology). Read the article online.

* This study was conducted by Bionos Biotech and funded by PB Leiner, part of Tessenderlo Group, which also provided the tested product: Solugel® collagen peptides.

Stephenson Stands by RSPO-certified Palm Oil

A leading manufacturer in the personal care industry, is committed to using only RSPO-certified palm oil to ensure sustainable practices. The company supports responsible palm oil cultivation to protect the environment, communities, and wildlife.

Stephenson is a leader in the manufacture and supply of a wide range of solid and extruded soap bases, syndets, and sustainable esters for the personal care and beauty industry.

As a responsible manufacturer of vegetable oilbased products, the Yorkshire-based company recognises that there are often valid sustainability and environmental issues linked to the use of conventional palm oil and palm oil-derived ingredients in the manufacture of these products.

Putting its weight behind the need for transformation in the palm oil industry, Stephenson has reiterated its support for RSPO-certified palm oil and palm oil derivatives during all its manufacturing processes.

Rob Carr, Managing Director of Stephenson says, “When grown sustainably, palm oil can be a force for good, protecting the environment, communities, employees, and wildlife. This is why the Stephenson team is so committed to enabling the positive impact of sustainable palm oil through our Roundtable on Sustainable Palm Oil (RSPO) certification.”

RSPO certification is a set of environmental and social criteria that guarantees the sustainable cultivation of palm oil during the entire supply chain.

“Rather than prohibit palm oil use, Stephenson has taken the position to only source and use palm oil that is grown and managed sustainably and certified by RSPO. Palm oil is a highly productive crop versus other vegetable oils, which often uses more land and natural resources which could lead to further negative environmental impacts,” Rob points out.

A strict set of criteria

Stephenson is committed to only sourcing ingre-

dients from suppliers who are aligned with its key sourcing principles, and the strict criteria set out by the RSPO regarding the cultivation, harvest, and supply of palm oil to the manufacturing industry.

These include:

• No deforestation

Protecting high conservation values and carbon stock areas

• No planting of new crops on or the development of peatland

• Prohibits the exploitation of people and local communities

• Smallholder inclusion

• Promotes the fair treatment of smallholders in the supply chain,

Since joining RSPO in 2010, Stephenson has further increased its commitment to the responsible sourcing of palm and palm kernel oil as a member of the Palm Oil Innovation Group (POIG) in conjunction with high-profile brands such as L’Oreal. POIG also shows its support for NGOs including WWF, Greenpeace, Rainforest Action Network, and Orangutan Land Trust.

“We expect our partners and supply chains to remain compliant with all applicable legislation while adhering to voluntary sustainability standards that support responsible practices to protect the natural world and the communities that we source our raw materials from,” Rob concludes. “After all, we only have one earth, and we must protect it.”

To read Stephenson’s Sustainability Policy in full, click here or visit the website at www.stephensonpersonalcare.com

How GC Rieber VivoMega™ is Utilizing AI to Boost Efficiency, Reliability

and Sustainability

Its Intelecy no-code industrial AI solution prevents disruptions and optimizes operations.

GC Rieber VivoMega™ is excited to share its use of Intelecy’s no-code AI solution, which creates machine learning models for real-time predictions to drive efficiency, quality, and improved sustainability.

The AI platform identifies real-time deviations or anomalies for its state-of-the-art processing facilities and provides a cloud-based, comprehensive, centralized data reporting system. By evaluating the anomalies, GC Rieber VivoMega can proactively plan maintenance and reduce unexpected downtime. The technology also allows the company to analyze energy consumption in real-time, identifying ways to decrease its energy use. For example, the company has identified 500,000 kw/h per year of energy waste in relation to its steam usage, equivalent to twenty-two Norwegian households’ yearly electricity use. The company’s energy management team is now working diligenttly to reduce this inefficiency.

“With Intelecy’s platform, we can significantly improve our production process and strengthen our environmental initiatives. Previously, we focused on addressing faults as they occurred and took preventive measures based on those time intervals. Now, we have increased focus on predictive maintenance, which enables us to anticipate future issues and address them before they become a concern,” said Torbjørn Saltkjelvik, Process Optimizer at GC Rieber VivoMega. “Combining the extensive knowledge of our plant operators with AI technology, we reduce downtime, mitigate the risks of contamination, and ensure the high standards set for our platinum-grade omega-3 oil.”

The no-code AI tool creates anomaly detection machine learning models without the need for manual coding. Historical data from successful production runs is fed into the Intelecy platform, enabling

the models to learn and understand the patterns of a well-functioning production process. When a deviation is detected in the real-time production data, an anomaly is generated in the Intelecy platform.

“This proactive approach enables strategic planning and predictive scheduling of the plant’s downtime, avoiding unexpected shutdowns triggered by high pressure or excessive heat, which boosts efficiency, reliability, and sustainability. Additionally, the cloud-based platform enables our team to monitor and manage our systems from anywhere at any time, which is evermore important as we continue to expand,” Torbjørn Saltkjelvik continued.

"At Intelecy, we're incredibly impressed by GC Rieber VivoMega's commitment to using our no-code AI platform to improve efficiency, reliability, and sustainability in their operations. Their proactive approach to predictive maintenance sets a new standard in the omega-3 industry, showcasing the impact of innovation and sustainable practices. We're honored to contribute to their pursuit of excellence in production and environmental responsibility,” said Camilla Gjetvik, CEO of Intelecy.

Tosla Nutricosmetics Teams Up with Foodpairing AI to Elevate Velious™ Flavor Technology

Tosla Nutricosmetics is proud to announce a collaboration with Foodpairing AI to elevate Velious™ Flavor Technology and to create evergreen flavors that the consumers will be repurchasing for years.

Tosla Nutricosmetics, a leader in liquid supplement solutions for the beauty and wellness sector, is proud to announce its collaboration with Foodpairing AI, a cutting-edge technology company specializing in flavor optimization. This partnership enhances Tosla’s patented Velious™ flavor technology, bringing a new era of taste innovation to nutricosmetics.

Enhancing Velious™ flavor technology with AI precision

Velious™, Tosla’s proprietary flavor technology, has been pivotal in setting new standards for taste in liquid nutricosmetics. Tosla relies on Foodpairing's advanced flavor profiling capabilities to elevate the sensory experience, aligning them perfectly with consumer preferences. This synergy promises to offer unparalleled flavor profiles that enhance consumer enjoyment and satisfaction, crucial factors in driving higher repurchase rates and building brand loyalty.

Uroš Gotar, Chief Innovation Officer at Tosla, commented: "In the world of nutricosmetics, flavor is the missing element that has often been overlooked. By leveraging Foodpairing AI’s expertise with our Veli-

ous™ technology, we are addressing a critical aspect of consumer satisfaction: taste. This collaboration is a breakthrough for Tosla and our clients, as it ensures our products not only deliver on their beauty and wellness promises but also delight the palate. This innovation will significantly boost our clients' retention strategies, as superior taste is crucial in forming lasting consumer habits."

Why does the taste matter

“Taste is the first and most important competitive driver when developing premium nutricosmetic products,“ is a quote from Foodpairing AI. Recent insights have highlighted the importance of taste in consumer retention strategies. Market analyses suggest that products that deliver a superior sensory experience are more likely to foster repeat purchases. In the context of liquid supplements, taste can be a decisive factor in habit formation and continued product use.

The combination of Foodpairing AI’s technology allows Tosla to harness detailed flavor data and consumer insights to develop products that not only meet but exceed taste expectations.

Spins to Wins –Smartcore Celebrates Success at the Eventex Awards 2024

Smartcore, a leading global B2B food and nutrition marketing solutions provider based in the Netherlands, triumphs at the Eventex Awards 2024.

Nominated for their gamified lead generation tool, Spin-to-Win, Smartcore received the People’s Choice Marketing, Communications, & Strategy (Bronze) honour. This achievement reflects their passion for creativity and smarter digital marketing solutions - as evidenced by the brand’s many success stories.

Smartcore launched Spin-to-Win in 2023 at Fi Europe, Informa Markets’ leading global event for food ingredients. As the official digital marketing provider of the event, Smartcore was determined to bring digital innovation into the physical world. Spin-to-Win empowers both participants and organisers with a win-win solution. It addresses the time constraints of busy exhibitors, providing them with an entertaining onsite experience and the opportunity to walk away with a guaranteed top-notch prize. At the same time, it sparks promising business conversations between them and Smartcore’s team about the brand’s smarter digital solutions for brand awareness, lead generation, thought leadership, and more.

Its success has led Informa Markets to replicate Spin-to-Win at Vitafoods Europe, the world’s nutraceutical event, and other global trade shows. Dimitrios Kales, Head of Commercial Marketing, Informa Markets, says, “Spin-to-Win has truly revolutionised our approach to engagement at events, and the Smartcore team is truly deserving of this award.”

The Eventex Awards, founded in 2009 to recognise stars in the world of events and experiential marketing, highlight the best events, brand experiences, tech, suppliers, and venues from the world of events. This year’s 14th edition saw a record-breaking 1,207 entries from 62 countries and six continents. Out of these, the Netherlands has 24 winners, and Smartcore takes centre stage as one.

View the complete list of Eventex Awards 2024 winners here

Oleon Health & Beauty Launches Radiastar 1436

Oleon Health and Beauty is excited to announce the launch of Radiastar 1436, a vegetable-based multibranched Guerbet alcohol for beauty & cosmetic applications.

Radiastar 1436 offers remarkable performance across a wide range of applications in the beauty and cosmetics industry, delivering great film-forming properties, a sensational sensorial profile, and a soft, cushioning touch with fantastic gloss.

“With its unique skin feel, good oxidation stability, and excellent pigment dispersion properties, Radiastar 1436 is a superior film-forming emollient for use in a broad range of color cosmetic & personal care formulations,” Ine Matthè, product manager at Oleon Health & Beauty explains.

Due to its branched structure, Radiastar 1436 is liquid at room temperature - an exceptional characteristic for a molecule of C36 carbon chain length. In addition, its occlusivity is comparable to mineral oil and better company to octyldodecanol, making it an ideal green alternative to synthetic film-forming properties.

When used as an ingredient in lipstick formulations, Radiastar 1436 assists in creating a solid, uniform layer on the lips that does not flake or break even as the solvent evaporates. It leaves a firm deposit after application to the lips, with good adhesion, for a flexible covering that is sturdy enough to flex with lip movements.

“Radiastar 1436 was shown to increase the break strength of the lipstick without increasing lipstick hardness too substantially. This Guerbet alcohol can therefore be used to create a more resilient lipstick without compromising the payoff. And, with its high refractive index, Radiastar 1436 gives a nice gloss to the lipstick together with a high color intensity,” Ine concludes.

For more information on Radiastar 1436 or formulation advice for a wide range of color cosmetics and personal care items, contact the Oleon Health & Beauty team at info@oleonhealthandbeauty.com

Denes Consulting Named Official Ambassador for Coptis

Denes Consulting is now an official ambassador for Coptis, aiming to expand the brand's influence in the cosmetics industry by promoting its innovative software solutions and collaborating on industry events.

Denes Consulting is proud to announce its new role as an official ambassador for Coptis, a leading provider of cosmetic formulation and regulatory software solutions. This partnership marks a significant step in Denes Consulting's mission to enhance industry collaboration and innovation within the cosmetics sector.

As part of this ambassadorship, Denes Consulting will actively promote Coptis and introduce the brand to new audiences, expanding its reach and visibility, highlighting collaborative projects, product features, and training milestones associated with Coptis.

“We are thrilled to partner with Coptis and take on the role of an ambassador. Coptis is renowned for its cutting-edge software solutions that significantly streamline cosmetic formulation and regulatory processes. We look forward to showcasing their innovations and continuing to contribute together to the growth and success of the cosmetic industry. We are confident that this collaboration will drive innovation, enhance customer experience, improve efficiency, and offer greater value." said Dr. Agi Denes. Marie Thadal, VP of Sales & Operations, Americas of Coptis, stated, "At Coptis, we are very proud to partner with Dr. Agi Denes as she has a long history of successful experiences in the cosmetic industry and is recognized as an expert in the Coptis solutions. This partnership will undoubtedly strengthen our presence and influence within the industry."

Both companies have committed to collaborating on trade shows and presentations, further cementing their commitment to industry excellence. They will also actively participate in relevant industry groups and forums, promoting knowledge sharing and best practices.

The Effectiveness of Tosla's Formulations Reconfirmed: Second Clinical Study Just Published in the Nutrients MDPI Journal

The study results showed the beneficial effects of both interventions on the skin, improving dermis density, as well as reducing skin roughness and wrinkle severity.

An article featuring a clinical study comparing the efficacy of test products by Tosla Nutricosmetics was published in the Nutrients MDPI Journal. A randomised, double-blind, placebo-controlled study investigated the effect of 16-week daily dietary supplementation with collagen, vitamin C, and hyaluronic acid on skin health.

The study led by prof. Katja Žmitek investigated different collagen-based formulations. The results showed that participants using the supplements experienced improved dermis density and reduced skin roughness and wrinkle severity.

The study was conducted with 87 healthy female participants, aged between 40 and 65, all of whom were recruited from Slovenia. Prior to their inclusion, adherence to the study's specific inclusion and exclusion criteria was verified, and each participant gave their formal consent. Participants were then divided evenly, with 28-30 subjects per group, through a computerized randomization process.

The results of the study showed several beneficial effects on the skin. The test products improved dermis density, reduced skin roughness, and lowered wrinkle visibility.

"Having been published in the Journal of Functional Foods last year, has set a clear vision for the future. Today, we are proud to announce the publication of our second clinical study in the Nutrients journal. It underscores our commitment to scientific excellence and innovation in the field of beauty supplements," says Uroš Gotar, Chief Innovation Officer at TOSLA. "The positive results reaffirm the effectiveness of our collagen products, and we are excited to continue pushing the boundaries of skin health solutions."

Interested individuals can find the study details in the latest edition of Nutrients MDPI Journal here: https://www.mdpi.com/2072-6643/16/12/1908

IFF to Develop New Nutrient-dense, Great-tasting Solutions for the Evolving Weight Management Landscape

New research shows an increase in consumer conversations about mindful eating. With the new research indicating a rapidly evolving health and weight management landscape, IFF, a global leader in food and beverage, home and personal care and health, is working towards helping the nutrition-conscious consumer, by extending it's range.

IFF currently offers a range of products that can help manufacturers support consumers on their weight management journeys. In addition to studying consumers’ needs in this landscape, the Company is now partnering with experts in nutrition, metabolic health, and obesity to create new concepts to meet the growing demand for tasty and nutrient-dense options.

“We believe IFF technologies and expertise in nutrition science are best positioned to co-create with our customers to offer new products and formulations that win in the marketplace and help consumers achieve and maintain a healthy and sustainable lifestyle,” said Erik Fyrwald, IFF chief executive officer. “Consumers increasingly want nutritious choices that fit their weight management journeys but offer the best quality and flavor.”

Social listening research by IFF shows that conversations around developing a healthier relationship with food grew by 242 percent in the U.S., while conversations about mindful eating grew by 190 percent globally in the last year .

Further results have shown that conversations related to anti-obesity medications (AOMs) have increased in volume by 48 percent but decreased in sentiment by 11 percent, suggesting that consumers are interested but less receptive to the idea of taking AOMs1. Meanwhile, the number of consumers trying to consume protein is rising rapidly - from 59 percent in 2022 to 71 percent in 20242

Anti-obesity medications reduce appetite and help people feel fuller for longer. An estimated 7 percent of American adults (24 million people) will be on an AOM by 2035, according to study conducted by Mattson. 92 percent of Americans taking AOMs were eating less, with overall consumption dropping by as much as 1000 calories a day3. The use of AOMs has allowed consumers to prioritize healthier choices. They are commonly advised to focus on nutrient density, increasing protein and fiber intake and reducing calories by avoiding sugary beverages and alcohol4.

With demand for healthier and high-protein options set to accelerate, IFF is committed to enhance the existing suite of solutions for healthier, flavorful and nutrient-dense products which include:

• Proteins – a broad portfolio of proteins from different sources. IFF protein solutions are designed to deliver great taste and texture with high-quality nutrition and sustainability benefits. High-quality proteins have been shown to increase satiety and help maintain muscle mass on a calorie-restricted diet.

Flavors – a suite of high impact top notes and consumer-preferred tonalities to make every sip and mouthful a genuine sensorial delight. IFF Flavorfittm modulation technologies enable creation of healthier products with natural flavors, supporting manufacturers by improving perception in sweetness and saltiness, enhancing mouthfeel and masking undesirable off-notes like bitterness. IFF Flavorfit™ can also bring juiciness and freshness to applications like healthier protein bars and help in reducing the dryness.

• Fiber – Litesse® fiber solutions offer great functionality for healthy weight management in formats like powders, beverages, bars and gummies. Litesse® Ultra™ can support metabolic health and help manage weight by promoting satiety and controlling overall appetite and caloric intake. Additionally, in combination with the probiotic Howaru® B420™, it can further help to control fat mass and increase lean body mass.

Manufacturers can now tap into a world of exciting possibilities with IFF, by co-creating innovative food and beverage solutions to support consumers as they strive to achieve and maintain a healthier weight. With the IFF Product Design™ AR Experience, it allows companies to experiment with ingredients, explore technologies and build their own concepts, ranging from healthy baked goods and snack bars to gourmet dishes: https://iffapps.com/product-design/

References:

1 IFF Consumer Intelligence Social Listening Insights, 2024

2 2024 IFIC Food & Health Survey

3 Mattson Webinar ‘Obesity Medications: Understanding their impact on Food and Beverage Behavior’, May 2024

4 Watchmethink - The GLP-1 Journey: Lifestyle changes and effects of medication use