B2B Nutramedic&Cosmetics No. 11

Editor's word

Dear readers,

Welcome to the July/August issue of B2B Nutramedic & Cosmetics. In this edition, we focus on maintaining kidney health and addressing related disorders. Our comprehensive examination sheds light on the latest research and practical insights into how supplements can support renal function.

Another significant featured topic is diabetic neuropathy, a prevalent complication of diabetes. We explore potential food supplement interventions.

On the regulatory front, we provide an update on fragrance allergens in cosmetics and their INCI names. Other cosmetics and cosmeceuticals sections are dedicated to pigmentation disorders, offering a deep understanding of these conditions and strategies for prevention. Additionally, we highlight the remarkable efficacy of spruce resin as a natural solution for treating all types of wounds, emphasizing the power of nature in skincare.

For those involved in new product development, we present a guide to selecting a reliable contract manufacturer (CMO) for your food supplements. This crucial decision can significantly impact the quality and success of your products.

In our Inspirational Success Story, we present Luminos Mod, a Croatian food supplements producer, and their Hug Your Life brand. Their journey is a testament to innovation, dedication, and success.

As you enjoy this issue, we wish you a relaxing and interesting summer.

Warm regards,

Daria Šurić, MPharm EDITOR-IN-CHIEF B2B Nutramedic&Cosmetics

Magazine

4 Examining the Influence of Nutritional Supplements on Kidney Health and Disorders

8 Diabetic Neuropathy and Potential Food Supplement Interventions

12 Can Berries Boost Diabetes Treatment?

13 Research Links Pomegranate Extract With Improved Liver Health

14 Regulation of Appetite and Probiotics

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19 News in the Gut-Brain Area

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19 Stance on Probiotics

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The publisher does not assume responsibility for the opinions and data that the authors present in the magazine, as well as for the data and materials provided by companies for publication in texts and advertisements. It is not allowed to reuse any part of the content without the prior consent of the publisher.

20 New Experimental Research About Improves of Cholesterol Levels

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Examining the Influence of Nutritional Supplements on Kidney Health and Disorders

Nutraceuticals such as vitamin C, coenzyme Q10, resveratrol and others are being investigated for their potential benefits in slowing the progression of chronic kidney disease and improving overall renal function.

Maintaining optimal kidney health is a critical global priority, as the kidneys play a vital role in various physiological processes, such as filtering blood, regulating fluid and electrolyte balance, and producing essential hormones.1 Chronic kidney disease (CKD) is a growing concern, and researchers are investigating the potential of dietary components, known as nutraceuticals, to manage and potentially delay the progression of renal injury.

The normal structure and function of the kidneys are crucial for overall health. Genetic, metabolic, and inflammatory diseases can target various components of the nephron, the functional unit of the kidney. In addition to their filtration functions, the kidneys play a crucial role in maintaining blood pressure, calcium homeostasis, and the production of hormones like erythropoietin and active vitamin D. 2

Renal disease is an indication that the kidneys' normal functions have been compromised, leading to the accumulation of water and waste materials in the body.3

Acute insults to the kidney can result in acute renal injury, which may resolve over time or progress to chronic renal disease, a growing health concern globally. Unfortunately, few pharmaceutical agents currently exist that can effectively delay or prevent the progression of renal injury, making the investiga-

tion of dietary components for renal health management an active area of research.

Nutraceuticals, or dietary supplements, have been the focus of ongoing studies exploring their potential benefits in managing renal health. These substances may offer promising therapeutic approaches, although more research in the form of prospective, controlled, randomized clinical trials is needed to demonstrate their clinical usefulness.4

Intervention in the conservative phase of chronic kidney disease is likely to be more effective if performed as early as possible in the course of the disease, as early and regular nephrology care has been shown to be beneficial. Primary care clinicians play a vital role in the identification, monitoring, and management of chronic kidney disease, as it often occurs alongside other conditions, requiring a holistic, patient-centered approach.

Vitamin C

Vitamin C, also known as ascorbic acid, is an essential nutrient with a wide range of physiological functions, including its role in maintaining kidney health.

Vitamin C is a potent antioxidant, and its supplementation has been investigated for its potential benefits in chronic kidney disease. Oxidative stress

AUTHOR:

Kristina Harča, Mpharm

and inflammation are believed to be major factors contributing to the progression of renal injury, and vitamin C's antioxidant properties may help mitigate these processes.

Studies have suggested that vitamin C supplementation may help slow the decline in glomerular filtration rate, a measure of kidney function, in individuals with chronic kidney disease.5 Additionally, vitamin C may also help reduce the risk of end-stage renal disease in this population.

However, it is important to note that the optimal dosage of vitamin C for kidney health is still being investigated, and excessive intake of vitamin C may potentially have adverse effects, particularly in individuals with impaired renal function.

Other supplements for kidney health

In addition to vitamin C, other dietary supplements have been explored for their potential benefits in kidney health.

Selenium, a trace mineral with antioxidant properties, has been associated with improved kidney function in observational studies.6 Supplementation with selenium has been investigated as a potential intervention for chronic kidney disease, although the results have been mixed.

Coenzyme Q10, an essential cofactor in the mitochondrial electron transport chain, has also been studied for its potential renal benefits. Some studies have suggested that coenzyme Q10 supplementation may help improve kidney function in individuals with chronic kidney disease.7

Moreover, the importance of maintaining adequate levels of other essential minerals, such as zinc and potassium, has been highlighted in the context of kidney health.

In summary, the investigation of dietary supplements for the management of chronic kidney disease is an active area of research.

Astragalus

Astragalus is a herb that has been used in traditional Chinese medicine for centuries. In recent years, astragalus has garnered attention for its potential benefits in the context of kidney health.

Astragalus is believed to possess antioxidant and anti-inflammatory properties, which may be particularly relevant in the context of chronic kidney disease.8 Studies have suggested that astragalus may help slow the progression of renal dysfunction and reduce the risk of end-stage renal disease.

While the evidence on the use of astragalus for

AKT: protein kinase B; PDK: pyruvate dehydrogenase kinase; PIP3: phosphatidylinositol-3,4,5-triphosphate; PIP2: phosphatidylinositol 4,5-bisphosphate; ERK: extracellular signal-regulated kinase; PI3K: phosphoinositide 3-kinase; Grb: growth factor receptor-bound protein; PDGF: Platelet-derived growth factor; EMT: extracellular matrix transition; JNK: c-Jun N-terminal kinase; AMPK: AMP-activated protein kinase; SIRT: sirtuin; PGC: Peroxisome proliferator-activated receptor gamma coactivator; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; TGF-β: transforming growth factor beta.

Adapted from Den Hartogh DJ, Tsiani E. Health Benefits of Resveratrol in Kidney Disease: Evidence from In Vitro and In Vivo Studies. Nutrients.2019;11(7):1624.Published2019Jul17.doi:10.3390/nu11071624

FIGURE 1 Effects of resveratrol on cellular signaling molecules

kidney health is promising, more high-quality, welldesigned clinical trials are needed to establish its efficacy and safety in the management of chronic kidney disease.

Dandelion

Dandelion is a common weed that has been used in traditional medicine for its potential health benefits, including its potential effects on kidney function.

Dandelion is believed to possess diuretic properties, which may help increase urine output and potentially improve kidney function. Additionally, dandelion is rich in antioxidants, which may help mitigate the oxidative stress and inflammation associated with chronic kidney disease.9

Some studies have suggested that dandelion extracts may have a protective effect on the kidneys, potentially reducing the risk of kidney stone formation and improving overall renal function.10 However, the evidence on the use of dandelion for kidney health is still limited, and more research is needed to confirm its efficacy and safety.

Glutamine

Glutamine is a non-essential amino acid that has been investigated for its potential benefits in the context of kidney health.

Glutamine has been proposed to play a role in the regulation of acid-base balance, which is important for maintaining normal kidney function.11 Additionally, glutamine has been suggested to have anti-inflammatory and antioxidant properties, which may be relevant in the management of chronic kidney disease.

NAC

N-acetylcysteine (NAC) is a derivative of the amino acid cysteine and has been studied for its potential benefits in the context of kidney disease.

NAC is believed to have antioxidant and anti-inflammatory properties, which may be particularly relevant in the management of chronic kidney disease. Results of metanalyses suggested that NAC appears to be safe without obvious adverse events, which can also benefit kidney function, relieve inflammation and reduce cardiovascular events among people with chronic kidney desease.12

Some studies have investigated the use of NAC in individuals with chronic kidney disease, with some suggesting potential benefits in slowing the progression of renal dysfunction and reducing the risk of end-stage renal disease.13

The proposed mechanisms by which NAC may exert its protective effects on the kidneys include:

1. Reducing oxidative stress and inflammation

2. Improving endothelial function and renal blood flow

3. Modulating pathways involved in the development of fibrosis and renal injury.

Resveratrol

Resveratrol is a polyphenol compound found in various plants, including grapes and red wine.

Resveratrol has been investigated for its potential benefits in the context of kidney health.

Studies have suggested that resveratrol may possess antioxidant, anti-inflammatory, and anti-fibrotic properties, which may be relevant in the manage-

ment of chronic kidney disease. Available in vitro and in vivo animal and human studies examining the effects of RSV in kidney disease indicate that it can reduce fibrosis, mesangial expansion, oxidative stress, and inflammatory cytokine levels, while improving kidney structure and function (Figure 1).14

Some research has indicated that resveratrol may improve markers of kidney function, such as glomerular filtration rate, and potentially slow the progression of kidney disease.15

Conclusion

Research into the potential role of dietary supplements in managing kidney disease is both active and promising. Maintaining kidney health is crucial and should be prioritized consistently.

References:

1 Fraser, S., & Blakeman, T. (2016, August 1). Chronic kidney disease: identification and management in primary care. Dove Medical Press, Volume 7, 21-32. https://doi.org/10.2147/por.s97310

2 Akilesh, S. (2014, January 1). Normal Kidney Function and Structure. Elsevier BV, 2716-2733. https://doi.org/10.1016/b978-0-12-3864567.05402-2

3 Pillai, A., & Fulmali, D G. (2023, January 1). A Narrative Review of New Treatment Options for Diabetic Nephropathy. Cureus, Inc.. https:// doi.org/10.7759/cureus.33235

4 Locatelli, F., Vecchio, L D., & Pozzoni, P. (2002, November 1). The importance of early detection of chronic kidney disease. Oxford University Press, 17(suppl 11), 2-7. https://doi.org/10.1093/ndt/17.suppl_11.2

5 Wang, C., Zhao, J., Zhou, Q., & Li, J. (2024). Serum vitamin C levels and their correlation with chronic kidney disease in adults: a nationwide study. Renal Failure, 46(1). https://doi.org/10.1080/0886022X.2023.2298079

6 Wang, T., Zhang, L., Liu, Y., Li, J., Chen, G., Zhou, H., Ling, Y., Wan, Z., Dong, C., Qin, L., & Chen, J. (2023, March 17). Combined Exposure to Multiple Metals and Kidney Function in a Midlife and Elderly Population in China: A Prospective Cohort Study. Multidisciplinary Digital Publishing Institute, 11(3), 274-274. https://doi.org/10.3390/toxics11030274

7 Bakhshayeshkaram M, Lankarani KB, Mirhosseini N, et al. The Effects of Coenzyme Q10 Supplementation on Metabolic Profiles of Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Curr Pharm Des. 2018; 24(31):3710-3723. https://doi.org/10.2174/1381612824666181112112857

8 Yoshino T, Horiba Y, Mimura M, Watanabe K. Oral Astragalus Root Supplementation for Mild to Moderate Chronic Kidney Disease: A Self-Controlled Case-Series. Front Pharmacol. 2022;13:775798. Published 2022 Mar 1. https://doi.org/10.3389/fphar.2022.775798

9 Clare BA, Conroy RS, Spelman K. The diuretic effect in human subjects of an extract of Taraxacum officinale folium over a single day. J Altern Complement Med. 2009;15(8):929-934. https://doi.org/10.1089/acm.2008.0152

10 Yousefi Ghale-Salimi, M., Eidi, M., Ghaemi, N., & Khavari-Nejad, R. A. (2018). Inhibitory effects of taraxasterol and aqueous extract of Taraxacum officinale on calcium oxalate crystallization: in vitro study. Renal Failure, 40(1), 298–305. https://doi.org/10.1080/0886022X.2018.1455595

11 King, P A., Goldstein, L., & Newsholme, E A. (1983, November 15). Glutamine synthetase activity of muscle in acidosis. Portland Press, 216(2), 523-525. https://doi.org/10.1042/bj2160523

12 Ye M, Lin W, Zheng J, Lin S. N-acetylcysteine for chronic kidney disease: a systematic review and meta-analysis. Am J Transl Res. 2021;13(4):2472-2485. Published 2021 Apr 15.

13 Hsu, S., Chiang, C., Yang, S., & Chien, C. (2010, July 2). N-Acetylcysteine for the Management of Anemia and Oxidative Stress in Hemodialysis Patients. Karger Publishers, 116(3), c207-c216. https://doi.org/10.1159/000317201

14 Den Hartogh DJ, Tsiani E. Health Benefits of Resveratrol in Kidney Disease: Evidence from In Vitro and In Vivo Studies. Nutrients. 2019;11(7): 1624. Published 2019 Jul 17. https://doi.org/10.3390/nu11071624

15 Saldanha, J F., Leal, V D O., Stenvinkel, P., Carraro-Eduardo, J C., & Mafra, D. (2013, January 1). Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?. Hindawi Publishing Corporation, 2013, 1-6. https://doi.org/10.1155/2013/963217

Diabetic Neuropathy and Potential Food Supplement Interventions

Diabetic neuropathy is the most frequent chronic complication of diabetes and may attack sensory, motor or autonomous fibres. Researchers have explored various dietary interventions, including food supplements, as potential therapeutic strategies.4

AUTHOR:

Daria Šurić, Mpharm

Diabetic neuropathy, a debilitating complication of diabetes, is a significant public health concern affecting millions of individuals worldwide. This condition arises from the metabolic and vascular disturbances associated with prolonged hyperglycemia, leading to nerve damage and impaired function.1,2 Diabetic neuropathy is a clinical condition that can significantly impact the quality of life, presenting as numbness, tingling, and burning in the extremities. Current treatment options focus on symptom alleviation and reducing exposure to risk factors as treating the pathophysiological causes of diabetic neuropathy remains a significant challenge. Novel studies have proposed that the use of antioxidants, including alpha-lipoic acid, may represent a beneficial intervention for treating neuropathic pain in diabetic patients. 3

One promising approach involves the use of functional foods and their bioactive compounds. A comparative in vitro study has shown that certain food supplement ingredients, such as quercetin, ascorbic acid, caffeine, and ellagic acid, may be efficient in targeting the underlying mechanisms of diabetic neuropathy.5

Alpha-lipoic acid and diabetic neuropathy

Alpha-lipoic acid (ALA), a potent antioxidant, has demonstrated beneficial effects in the management of diabetic neuropathy. Supplementation with alpha-lipoic acid has been found to improve nerve conduction, reduce oxidative stress, and alleviate neuropathic pain in individuals with diabetes. ALA has been shown to play a significant role in

mitigating the oxidative stress and nerve damage associated with diabetic neuropathy.

Alpha lipoic acid is a potent lipophilic antioxidant in vitro and in vivo conditions, which plays a main role as a cofactor in many mitochondrial reactions, is easily absorbed from the gastrointestinal tract and can easily cross the blood-brain barrier. Apoptosis is an important mechanism of degenerative diseases, which is induced by some factors like hyperglycemia toxicity. In vivo and in vitro studies showed that hyperglycemia affected cell survival and induced apoptotic changes in dorsal root ganglion neurons and Schwann cells. Experimental studies have demonstrated the protective effects of ALA on the loss of myelin sheath in the sciatic nerve, a hallmark of diabetic neuropathy.6 Furthermore, clinical trials have indicated that alpha-lipoic acid supplementation can improve glucose control and lipid profiles in individuals with type 2 diabetes and coronary heart disease.7 In a review study from 2021, randomized controlled trials investigated ALA treatment in diabetes mellitus patients with neuropathic pain and made an appropriate comparison. The reduction of neuropathic symptoms was the primary outcome, and the secondary outcome was the incidence of adverse events. Eight studies comprising 1,500 diabetic patients were evaluated in this systematic review. The findings were inconsistent among the literature concerning the effectiveness of ALA in the treatment of diabetic neuropathy, with three trials (37.5%) observing significant improvements in symptoms and five trials (62.5%) not observing any notable results. The doses used were from 600 mg to 1600 mg per day. All studies found ALA to be a safe and tolerable intervention, with no reported adverse effects. The administration of ALA may result in symptom reduction and offers a safe and tolerable treatment option. 3

Research on alpha-lipoic acid has delved into its mechanisms of action in the context of diabetic neuropathy. In addition to its antioxidant properties, alpha-lipoic acid has been shown to exert anti-inflammatory effects, modulate intracellular signalling pathways, and enhance glucose metabolism. These multifaceted actions contribute to its potential in addressing the complex pathophysiology of diabetic neuropathy. Moreover, the ability of alpha-lipoic acid to improve nerve conduction and mitigate neuropathic pain underscores its role as a promising therapeutic agent for this condition.

The role of B vitamins

In addition to alpha-lipoic acid, B vitamins have shown promise in addressing diabetic neuropathy. Specifically, vitamin B12, B6, and folic acid have been the focus of several studies due to their potential role in nerve function and regeneration. Vitamin B12, also known as cobalamin, is essential for the maintenance of myelin, the protective sheath surrounding nerve fibres. Deficiency in vitamin B12 has been linked to neuropathy and nerve damage, particularly in diabetic individuals. Supplementation with vitamin B12 has shown improvement in nerve conduction and neuropathic symptoms in diabetic patients. Similarly, vitamin B6, or pyridoxine, plays a crucial role in neurotransmitter synthesis and regulation. Studies have suggested that vitamin B6 supplemen-

tation may alleviate neuropathic pain and improve nerve function in diabetic individuals.

Folic acid, another B-vitamin, is involved in DNA synthesis and repair, which are crucial for nerve cell development and function. Research has indicated that folic acid supplementation may have a protective effect against diabetic neuropathy by promoting nerve regeneration and reducing oxidative stress.

Incorporating alpha-lipoic acid and B-vitamins through food sources and supplements may offer a multifaceted approach to managing diabetic neuropathy, addressing both oxidative stress and supporting nerve health. Further exploration of these potential interventions could provide valuable insights into improving the quality of life for individuals living with diabetic neuropathy.

Potential of berberine and curcumin

Besides alpha-lipoic acid and B vitamins, other nutraceuticals such as berberine and curcumin have garnered attention for their potential in treating diabetic neuropathy.

Berberine, a plant-derived compound, has been shown to possess anti-inflammatory, antioxidant, and neuroprotective properties.8 Berberine is a bioactive constituent that displays effects on blood glucose; however, the mechanism underlying the role of BBR during the development of diabetic retinopathy is not completely understood. Berberine reversed the high glucose-induced effects by decreasing the phosphorylation of IκB, inhibiting NFκB nuclear translocation and deactivating the NF-κB signalling pathway. The results suggested that berberine protects against diabetic retinopathy by inhibiting oxidative stress and cell apoptosis via deactivation of the NF-κB signalling pathway; therefore, suggesting that BBR may serve as a promising therapeutic agent for diabetic retinopathy.9

Curcumin, the active compound in turmeric, has also been explored for its ability to modulate oxidative stress, inflammation, and neural function in the context of diabetic neuropathy. The Banafshe et al . study was designed to investigate the effect of curcumin on diabetic peripheral neuropathic pain and the possible involvement of the opioid system. Study results suggest that curcumin can be considered as a new therapeutic potential for the treatment of diabetic neuropathic pain and the activation of opioid system may be involved in the antinociceptive effect of curcumin.10

The role of nucleotides, vitamin D and magnesium

In addition to the well-studied food supplements, emerging evidence suggests that other dietary components, such as nucleotides, vitamin D, and magnesium, may also play a role in the management of diabetic neuropathy.

Nucleotides are the building blocks of DNA and RNA, and they have been found to have neuroprotective properties. Further investigation into the potential role of nucleotides in managing diabetic neuropathy in human subjects is warranted to validate these findings and understand the underlying mechanisms.

Vitamin D, known for its crucial role in bone health,

has also been associated with neurological function. Research has suggested that vitamin D deficiency may contribute to the development and progression of diabetic neuropathy. Supplementation with vitamin D has shown potential in improving nerve conduction and reducing neuropathic pain in diabetic individuals. The relationship between vitamin D status and neuropathy warrants deeper exploration to determine the extent of its impact and the optimal strategies for supplementation in this context.

Magnesium, an essential mineral involved in various physiological processes, has been implicated in neuropathic pain modulation. Studies have proposed that magnesium supplementation may help alleviate neuropathic pain by regulating N-methyl-D-aspartate receptor activity and calcium ion influx in nerve cells. Understanding the role of magnesium in diabetic neuropathy and its potential as a therapeutic adjunct could offer new insights into comprehensive dietary interventions for individuals with this condition.

Chromium, a trace mineral, has been studied for its potential role in improving insulin sensitivity and glucose metabolism, which are crucial factors in the development of diabetic neuropathy. Chromium supplementation has shown promise in reducing neuropathic pain and improving nerve conduction in individuals with diabetes.

The potential of other ingredients

L-carnitine and coenzyme Q10 are also food supplements that have been investigated for their potential benefits in diabetic neuropathy. L-carnitine plays a crucial role in the metabolism of fatty acids, and it has been found to improve nerve conduction and reduce neuropathic pain in individuals with diabetes. Coenzyme Q10, an essential component of the electron transport chain in mitochondria, has also demonstrated neuroprotective effects in animal studies.

In addition to the aforementioned food supplements, bitter melon and omega-3 fatty acids have also shown promise in the management of diabetic neuropathy.

Bitter melon, a popular vegetable in many Asian cuisines, has been studied for its antioxidant, anti-inflammatory, and hypoglycemic properties. Re-

search has suggested that bitter melon may help alleviate neuropathic pain and improve nerve function in individuals with diabetes.

Omega-3s have been shown to possess anti-inflammatory and neuroprotective effects, which could contribute to their ability to mitigate the progression of diabetic neuropathy.

The synergistic effects of food supplements

The synergistic effects of combining different food supplements have become a focal point in ongoing research. By investigating the interactions between bioactive compounds, researchers aim to develop comprehensive dietary strategies tailored for the management of diabetic neuropathy. Understanding how these compounds work in tandem and their impact on individual variations in nutrient metabolism could help to find a better way for personalized dietary interventions that address the diverse needs of individuals with diabetic neuropathy.

In conclusion, the exploration of food supplements and bioactive compounds as potential interventions for diabetic neuropathy has gained significant attention in the scientific community.

References:

1 Wooton, A K., & Melchior, L M. (2018, November 1). Diabetic autonomic neuropathy resulting in sexual dysfunction. Lippincott Williams & Wilkins, 43(11), 39-45. https://doi.org/10.1097/01.npr.0000546447.94226.53

2 Ma, J., Jiang, C., Fu, X., Chen, J., Hu, W., & Ye, L. (2023, March 1). Editorial: Novel insights into the pathophysiology of diabetes-related complications: Implications for improved therapeutic strategies. Frontiers Media, 14. https://doi.org/10.3389/fendo.2023.1157807

3 Abubaker SA, Alonazy AM, Abdulrahman A. Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review. Cureus. 2022;14(6):e25750. Published 2022 Jun 8. https://doi.org/10.7759/cureus.25750

4 Mirmiran, P. (2014, January 1). Functional foods-based diet as a novel dietary approach for management of type 2 diabetes and its complications: A review. 5(3), 267-267. https://doi.org/10.4239/wjd.v5.i3.267

5 Mehta, V., Verma, P., Sharma, N., Sharma, A., Thakur, A., & Malairaman, U. (2017, June 1). Quercetin, ascorbic acid, caffeine and ellagic acid are more efficient than rosiglitazone, metformin and glimepiride in interfering with pathways leading to the development of neurological complications associated with diabetes: A comparative in-vitro study. 55(1), 115-121. https://doi.org/10.1016/j.bfopcu.2016.12.002

6 Taşçı, İ., Demir, C F., & Kuloğlu, T. (2018, January 1). Effects of Alpha Lipoic Acid on Loss of Myelin Sheath of Sciatic Nerve in Experimentally Induced Diabetic Rats. Academy of Medical Sciences of Bosnia and Herzegovina, 72(3), 178-178. https://doi.org/10.5455/medarh.2018.72.178-181

7 Akbari, M., Ostadmohammadi, V., Lankarani, K B., Tabrizi, R., Kolahdooz, F., Khatibi, S R., & Asemi, Z. (2018, October 1). The effects of alpha-lipoic acid supplementation on glucose control and lipid profiles among patients with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials. Elsevier BV, 87, 56-69. https://doi.org/10.1016/j.metabol.2018.07.002

8 Gupta R. Active phytoconstituents for diabetes management: A review. J Complement Integr Med. 2018;15(3):/j/jcim.2018.15.issue-3/jcim-2017-0123/jcim-2017-0123.xml. Published 2018 Jan 19. https://doi.org/10.1515/jcim-2017-0123

9 Zhai J, Li Z, Zhang H, et al. Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF-κB signaling pathway. Mol Med Rep. 2020;22(5):4227-4235. https://doi.org/10.3892/mmr.2020.11505

10 Banafshe HR, Hamidi GA, Noureddini M, Mirhashemi SM, Mokhtari R, Shoferpour M. Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement of opioid system. Eur J Pharmacol. 2014;723:202-206. https://doi.org/10.1016/j.ejphar.2013.11.033

lnflamrnation in the body can result from physical or athletic exertion. And while a crucial and useful biologica I proces�, such chronic respon�es can damage tissue and cause injuries, leading to various conditions. Because it's composed exclusively of THC s - the major active metabolites of curcumin - C3 Reduct ® delivers anti-inflammatory properties that hold significant promises in protecting and soothing joints and muscles.

Can Berries Boost Diabetes Treatment?

Type 2 diabetes affects millions worldwide, often requiring a multifaceted management approach involving medication and lifestyle changes. While metformin stands as a common and effective drug, it can come with side effects. Now, a new study published in Journal of Diabetes Research explores a promising avenue: combining metformin with the power of polyphenols found in certain berries.

The study, conducted by Zima et al., focused on the synergistic potential of a polyphenol-rich blend AP029 derived from three specific fruits: black currant (Ribes nigrum L.), chokeberry (Aroniamelanocarpa (Michx.) Elliott), and black elderberry (Sambucus nigra L.) extracts, alongside metformin. The researchers conducted both in vitro (cell-based) and in vivo (animal model) experiments to investigate the combined effects.

In cell cultures, the polyphenol blend demonstrated positive effects on key metabolic parameters. It effectively reduced cholesterol and triglyceride levels while simultaneously enhancing glucose uptake, suggesting improved cellular response to insulin. These effects are likely linked to the blend's influence on the AMPK pathway, a crucial regulator of energy metabolism.

Moving to the in vivo phase, the researchers observed even more compelling results. The combination of the polyphenol blend and metformin significantly outperformed either treatment alone in reducing both insulin levels and fasting glucose concentrations. This synergistic effect suggests that

these natural compounds could amplify the effectiveness of metformin, potentially leading to better blood sugar control for patients.

While these findings are preliminary and require further investigation through large-scale clinical trials, they offer a beacon of hope for improved diabetes management.

The potential implications are significant:

Enhanced treatment efficacy: The synergistic relationship between the polyphenol blend and metformin could lead to more effective blood sugar management and potentially slow down the progression of the disease.

Reduced metformin dosage: The enhanced effects might allow for lower metformin doses, potentially minimizing side effects like gastrointestinal issues that some patients experience.

Dietary interventions: This research strengthens the argument for incorporating specific polyphenol-rich extracts like black currant, chokeberry, and elderberry as part of a holistic diabetes management plan.

The synergistic interaction of these polyphenols with metformin not only aids in glucose metabolism but also provides cellular protection from oxidative stress and reduces inflammatory pathways, which are critical in the pathogenesis of type 2 diabetes. These findings suggest that incorporating polyphenols could enhance the therapeutic efficacy of metformin, potentially allowing for lower dosages and improved treatment adherence by mitigating side effects.

However, further extensive clinical research is needed to fully understand the mechanisms, determine the appropriate dosages, and confirm the long-term safety and efficacy of this combined therapeutic strategy.

Reference:

Zima, K., Khaidakov, B., Banaszkiewicz, L., et al. (2024). Exploring the Potential of Ribes nigrum L., Aronia melanocarpa (Michx.) Elliott, and Sambucus nigra L. Fruit Polyphenol-Rich Composition and Metformin Synergy in Type 2 Diabetes Management. Journal of Diabetes Research, 2024, 1092462. https://doi.org/10.1155/2024/1092462

Research Links Pomegranate Extract With Improved Liver Health

Pre-clinical study with Pomanox® shows beneficial effects on metabolism after fructose consumption and reduced risk of obesity-related harm.

Arecently published pre-clinical study reveals the potential effects of pomegranate extract supplementation on the health issues associated with high fructose consumption. In an animal model, Pomanox® from botanical ingredients producer Euromed was able to counteract lipid deposition, dyslipidemia and fatty liver. Therefore, it could work synergistically with pharmacological treatments aimed at controlling obesity, liver steatosis and metabolic syndrome.1

Non-alcoholic fatty liver disease and obesity are major non-communicable diseases with high mortality rates worldwide. While dietary sugars are known to be responsible for insulin resistance and metabolic syndrome, the underlying pathophysiological effects of sustained fructose consumption require further clarification. The recent study aimed to elucidate both the molecular mechanisms involved in the pathophysiology associated with fructose intake and the effect of punicalagin-rich Pomanox® from Euromed as a nutritional strategy to alleviate fructose-induced metabolic impairments. The researchers hypothesized that punicalagin and ellagic acid from dietary pomegranate could counteract the harm caused by both obesity and liver damage. Therefore, nineteen Wistar rats were supplemented with either 30% fructose in drinking water or 30% fructose solution plus 0,2% Pomanox® for ten weeks. The results were compared to those from a control group provided with pure drinking water. As expected, fructose promoted an increase in fat depots, he-

patic fat content and glycoxidative stress, as well as inflammatory and immunological responses in the rats that consumed fructose in drinking water for 10 weeks. In contrast, Pomanox® supplementation decreased fat depots, counteracted the dyslipidemia caused by fructose and improved markers of liver injury including steatosis. It could thus be a useful supplement to pharmacological therapies aimed at controlling obesity, fatty liver and metabolic syndrome. Andrea Zangara, Head of Scientific Communication and Medical Affairs at Euromed, explains: “Fructose consumption has increased in recent decades, despite the efforts of governments and health organisations to alert people to the health risks linked to sustained sugar intake. Metabolic syndrome, obesity, dyslipidemia, non-alcoholic fatty liver disease, diabetes mellitus and cardiometabolic diseases are just a few examples of fructose-induced health problems. The current study, which received no funding from Euromed, is part of a comprehensive investigation into the efficacy of punicalagin-rich pomegranate extract in mitigating the adverse metabolic effects associated with various ailments, including diabetes, inflammatory bowel disease (IBD), and cardiovascular diseases.”

Reference:

1 Sánchez Terrón, Mª Guadalupe & Martínez, Remigio & Morcuende, David & Caballero, Víctor & Estévez, Mario. (2024). Pomegranate Supplementation Alleviates Dyslipidemia and the Onset of Non-Alcoholic Fatty Liver Disease in Wistar Rats by Shifting Microbiota and Producing Urolithin-like Microbial Metabolites. Food & Function. 10.1039/D4FO00688G.

Regulation of Appetite and Probiotics

Probiotics are promising natural tools for regulating appetite by modifying gut microbiota and producing metabolites that act on the gut-brain axis. Studies on animals and humans have shown that probiotics can influence appetite-regulating molecules such as GLP-1, leptin, and ghrelin, reducing hunger and food intake. Specific probiotic strains, like Lactobacillus rhamnosus and Hafnia alvei HA4597, have demonstrated significant anorexigenic effects.

AUTHOR:

Ira Renko, MSc, Master in Molecular biotechnology

Thanks to the success of GLP-1 agonists such as liraglutide and semaglutide in regulating appetite and body weight, incretins have become a field of great interest. Today, incretins as hormones are not only studied by endocrinologists and pharmacists but also by other medical specialties such as gynaecologists, neurologists, and cardiologists, as well as nutritionists and physiotherapists. Their effectiveness fascinates the entire healthcare sector, which has recognized their role in addressing one of the biggest problems in modern society – excessive body weight. A review of current literature gives the impression that modern humans, whose lives are characterized by the intake of energy-rich food and reduced expenditure due to inactivity, are relatively deficient in GLP-1. In other words, the amounts of endogenously produced GLP-1 are not sufficient to adequately regulate both appetite and glucose metabolism in the body, given their diet and physical activity. But are drugs the only way to increase GLP-1 levels in the body? Are there any natural and less harmful alternatives?

The regulation of appetite at the central level is closely linked to the conditions within the gut.15 Recent discoveries have highlighted the significant ro-

le of the gut microbiome in regulating appetite through the gut-brain axis. This has sparked interest in developing gut microbiome-targeted therapies for managing appetite. Probiotics, in particular, have emerged as promising tools for modulating gut microbiota composition and function.8 Could therefore probiotics potentially regulate appetite by influencing GLP-1 levels?

Appetite and appetite regulation

Appetite is the neurological impulse that drives us to eat. It varies in intensity, signalling us when to eat or stop eating based on feelings of hunger and satiety. When we feel full, our appetite levels are low; when we feel hungry, our appetite increases.1

The global rise in obesity and an ageing population means more people are experiencing appetite dysregulation. This has led the scientific community to focus on understanding the molecular mechanisms of appetite regulation, aiming to develop potential treatments for these conditions.4

Appetite regulation is a complex process involving neurohormonal and metabolic signals. It depends on the balance between compounds that stimulate ap-

petite (orexigenic) and those that suppress it (anorexigenic).4 These signals interact within the central nervous system and the digestive tract through neuropeptide hormones.

Key hormones and compounds in appetite regulation include leptin, insulin, GLP-1, amylin, ghrelin, omentin-1, nesfatin-1 and adropin. Leptin is regarded as a master regulator of appetite. In obese people visceral adiposity is associated with increased levels of leptin.5 It is interesting that levels of ghrelin, also called the “hunger hormone” rise before meals and decrease after meals hence it has been associated with meal initiation and food intake.6 Another novel appetite-modulating compound is nesfatin-1 which is mainly produced by a subcutaneous fat tissue. Nesfatin-1 regulates appetite and body weight as an anorexigenic adipokine and its levels are increased in obesity and decreased by food deprivation.7 In Table 1 anorexigenic and orexigenic neuronal and hormonal pathways are presented. Understanding these pathways is crucial for exploring how probiotics might influence appetite. The mechanisms of appetite regulation are intricate and rely on a delicate balance of various signals and hormones. Considering that, probiotics may play a role in this process by interacting with these pathways, potentially offering new avenues for managing appetite-related disorders.

Probiotics and appetite

Beyond these benefits, probiotics are known for their anti-inflammatory, pain-relieving, and antioxidant effects. Interestingly, emerging research suggests that probiotics may also have appetite-suppressing (anorexigenic) effects.

Supplementing with probiotics alters the gut microbiota composition, which in turn influences molecules that regulate appetite and satiety. This connection has led to increased interest in developing next-generation, or precision, probiotics. These advanced probiotics are designed to have specific, targeted effects, particularly by producing metabolites that influence the gut-brain axis.14

While the potential of probiotics is promising, there is still a gap in knowledge regarding their anorexigenic effects.

How to probiotics regulate appetite? Probiotics have emerged as promising agents for modulating appetite and weight management through a variety of mechanisms.

Neurohormonal compounds, such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), are produced by enteroendocrine cells (EECs) in the gut. These intestinal hormones play a crucial role in both the digestive system and the central nervous system, influencing various brain regions involved in appetite regulation.

The gut microbiome is the one that interacts closely with these EECs (Figure 1). EECs have nutrientsensing receptors that detect available nutrients and the composition of the gut microbiome, prompting the release of specific neurohormonal compounds.

Current studies

In order to investigate this effect, various studies on both animals and humans have been performed.

Animal studies have confirmed that the gut microbiome plays a crucial role in the physiological modulation of hunger and satiety regulating various metabolic pathways. As probiotics target the gut micro-

FIGURE 1 Central and peripheral pathways of appetite modulation and the role of the gut microbiome

Original from: (Han et al., 2021)

CENTRAL APPETIE REGULATION

PERIPHERAL APPETITE MODULATION

Orexigenic pathway

neuropeptide Y (NPY)

agouti-related protein (AGRP)

PYY

Mechanism (secretion/site of action)

hypothalamusnucleus arcuatus (ARC)

pathways

Anorexigenic pathway

proopiomelanocortin (POMC)

hypothalamus cocaine-andamphetamine related tract (CART)

colon (EEC?) – NPY/ AGRP hypothalamus

ghrelin stomach-NPY/ AGRP neurons

omentin-1 fat tissue (visceral stroma cells)hypothalamus (CART, NE) (Brunetti et al., 2013)

adropin fat tissue –hypothalamus (POMC, CART, NPY, orexin)

biome, they can influence this process in several ways. They can alter the gut microbiome composition, change the metabolite profile, and secrete metabolites like short-chain fatty acids (SCFAs), which impact metabolic pathways related to appetite regulation. Probiotics exert their regulatory action on both the peripheral and central levels of appetite modulation. Additionally, by affecting gut microbiome alterations, they can influence digestion and nutrient absorption, further impacting appetite regulation.

A study from Falcinelli et al. demonstrated that administering Lactobacillus rhamnosus at 106 CFU/ mL to 6-day-old zebrafish larvae changed the gut microbiota by increasing Firmicutes and Proteobacteria abundance. These changes were associated with a downregulation of orexigenic genes like cb1 and npy and an upregulation of anorexigenic genes like leptin and mc4r, leading to a significant reduction in food intake.16 In a study by Lee et al. eight weeks of supplementation with Lactobacillus rhamnosus PL60 in obese mice led to reduced leptin levels and adipose tissue mass, attributed to the probiotic's production of conjugated linoleic acid.17 What is more, a controversial 2008 study found that direct administration of Lactobacillus supernatant into the central nervous system of rats increased leptin expression in the brain and fat tissue, reducing body mass.18 A study from Korea investigated a multi-

Mechanism (secretion/site of action)

hypothalamus

hypothalamus

leptin gut/brain axis, vagus?

insulin

pancreas –ghrelin/POMC/ CART

hypothalamus

glucagon-like peptide 1 (GLP-1)

colon (EEC)pancreas

adiponectin fat tissue – POMC, NPYY

hypothalamus (N. Tang et al., 2021)

nesfatin-1 fat tissuehypothalamus amylin

gastric inhibitory polypeptide (GIP)

strain formulation consisting of Bifidobacterium pseudocatenulatum, Bifidobacterium longum, and Bifidobacterium longum SPM 1207 on rats for seven weeks. The probiotic treatment was associated with reduced serum leptin levels, indicating potential anorexigenic effects.19

Further research by Falcinelli et al.16 on zebrafish fed a high-fat diet found that supplementation with Lactobacillus rhamnosus altered gut microbiota composition and appetite-modulating compounds' secretion. It also changed the expression of anorexigenic and orexigenic genes, favouring appetite suppression.

Most studies on central appetite control pathways have been performed in rodents, but pigs offer a more comparable model to humans due to physiological similarities. 20,21 Valent et al. studied the effect of a high-fat diet on brain neuropeptides in pigs, finding that Bifidobacterium breve supplementation, especially with omega-3 fatty acids, partially reversed high-fat diet effects on regulatory neuropeptides and the dopaminergic system. 22

Both Forssten etal.and Bagarolli etal.(2013) found out that probiotic administration resulted in reduced feed intake. 23,24

Future prospects for probiotics in appetite regulation include biotechnological modifications to deliver or produce anorexigenic compounds. Chen et

TABLE 1 Overview of anorexigenic and orexigenic neuronal and hormonal

al. demonstrated that genetically altered Escherichia coli secreting N-acyl-phosphatidylethanolamines (NAPEs) reduced food intake and improved metabolic health in mice on a high-fat diet. 25

Human studies on probiotics and appetite modulation show varying outcomes due to the complexity of human physiology and study designs, although they have confirmed the appetite modulation mechanisms of probiotics observed in animal studies. While some studies indicate beneficial effects on appetite and metabolism, others show limited or no significant impact, highlighting the need for further research to clarify the mechanisms and efficacy of probiotics in appetite regulation and weight management.

A randomized, controlled, double-blind trial investigated the effect of Lactobacillus plantarum 299v supplementation over 6 weeks in 36 healthy, heavy smokers. Besides reducing cardiovascular disease risk factors, the probiotic treatment led to decreased leptin levels and interleukin-6 (IL-6) in 42% of the probiotic group, and reduced monocyte adhesion to endothelial cells. The authors suggested that short-chain fatty acid production by the probiotic was the mechanism behind these effects. 26

A 2021 randomized trial tested whether a multistrain probiotic formulation (Bifidobacterium, Lactobacillus, and Enterococcus) could mitigate weight gain and appetite changes due to antipsychotic therapy with olanzapine. No significant differences in appetite levels were found between the probiotic and control groups after 4, 8, and 12 weeks. However, there was a slight delay in appetite increase (19.8 vs. 25.6 days), and weight gain was delayed in the initial treatment phase (4 weeks). 27 A multicenter doubleblind randomized placebo-controlled trial on patients with higher body mass and abdominal visceral fat area found that supplementation with Lactobacillus gasseri SBT2055 (LG2055) for 12 weeks significantly increased adiponectin levels. 28 One other bacteria species that gained lot of attention when it comes to research on anorexigenic (apetite suppressing) is Hafnia alvei . According to the research, Hafnia alvei produces a molecule called ClpB, which mimics the human anorexigenic hormone α-melanocyte-stimulating hormone (α-MSH). This mimicry can help reduce appetite and thus support weight management. A commercial product utilizing Hafnia alvei, particularly the strain HA4597, is available and represents one of the first probiotics developed through biotechnology to aid in weight loss. This innovation combines the natural benefits of probiotics with targeted biotechnological enhancements to influence satiety and body weight regulation. The research supports that the ClpB produced by Hafnia alvei HA4597 has functional anorexigenic properties, making it an effective supplement for those seeking to manage their weight through dietary means.

34

On the other hand, a double-blind, randomized, placebo-controlled study on obese adolescents found that 16-week treatment with commercially available supplement VSL#3 had no significant effects on appetite-regulating hormones or other obesity-associated outcomes. This highlights the importance of specific probiotic strains and their unique mechanisms in influencing metabolic and appetite-related pathways. 29

Clinical applications and implications

Based on our brief scoping review, probiotics have demonstrated anorexigenic properties, which are strain-specific. Not all probiotic strains improve appetite suppression, and their efficacy depends on genetic and metabolic characteristics. Probiotics must produce short-chain fatty acids or other essential metabolites to regulate appetite. 30 They should also modulate gut microbiota and metabolome to reduce gut permeability, endotoxemia, and inflammation, crucial for appetite control. Additionally, effective probiotics induce enteroendocrine cells to produce anorexigenic metabolites and affect lipid metabolism, from absorption to adipose tissue function.16,31,32

Our review highlights that the anorexigenic effect is dose-dependent and more pronounced with long-term supplementation, typically lasting at least 12 weeks. Also, short-term treatments have shown limited efficacy. 30,33

Conclusion

Appetite regulation involves a complex interplay of hormones and neuropeptides that signal hunger and fullness.

Probiotics hold great potential not only for general health but also for regulating appetite through their impact on the gut microbiome. Based on these findings, probiotics do not seem to consistently affect key appetite-related hormones in overweight and obese populations. However, the variability in study outcomes underscores the complexity of probiotic interactions with human physiology, necessitating further research to elucidate their mechanisms and potential therapeutic applications in managing weight and metabolic health. Regarding the application, we recommend long-term probiotic supplementation with a high-dose regimen, using either a multi-strain formulation as supported by various studies or a next-generation probiotic known for its anorexigenic effects, such as Hafnia alvei HA4597. Finally, continued research in this area could lead to new, effective treatments for appetite-related disorders, offering hope for those struggling with issues like obesity or undernutrition.

References:

1 Watterson, K. R., Bestow, D., Gallagher, J., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2013). Anorexigenic and orexigenic hormone modulation of mammalian target of rapamycin complex 1 activity and the regulation of hypothalamic agouti-related protein mRNA expression. NeuroSignals, 21(1–2), 28–41. https://doi.org/10.1159/000334144

2 Dixon, J. B. (2010). The effect of obesity on health outcomes. In Molecular and Cellular Endocrinology (Vol. 316, Issue 2, pp. 104–108). https://doi.org/10.1016/j.mce.2009.07.008

3 Thaler, J. P., Choi, S. J., Schwartz, M. W., & Wisse, B. E. (2010). Hypothalamic inflammation and energy homeostasis: Resolving the paradox. In Frontiers in Neuroendocrinology (Vol. 31, Issue 1, pp. 79–84). https://doi.org/10.1016/j.yfrne.2009.10.002

4 Blüher, M. (2019). Obesity: global epidemiology and pathogenesis. In Nature Reviews Endocrinology (Vol. 15, Issue 5, pp. 288–298). Nature Publishing Group. https://doi.org/10.1038/s41574-0190176-8

5 Fantuzzi, G. (2005). Adipose tissue, adipokines, and inflammation. In Journal of Allergy and Clinical Immunology (Vol. 115, Issue 5, pp. 911–919). Mosby Inc. https://doi.org/10.1016/j.jaci.2005.02.023

6 Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. E., & Weigle, D. S. (2001). A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans. Diabetes, 50(8), 1714–1719. https://doi.org/10.2337/diabetes.50.8.1714

Nutramedic &Cosmetics

7 Ramanjaneya, M., Chen, J., Brown, J. E., Tripathi, G., Hallschmid, M., Patel, S., Kern, W., Hillhouse, E. W., Lehnert, H., Tan, B. K., & Randeva, H. S. (2010). Identification of nesfatin-1 in human and murine adipose tissue: A novel depot-specific adipokine with increased levels in obesity. Endocrinology, 151(7), 3169–3180. https://doi.org/10.1210/en.2009-1358

8 Bagarolli, R. A., Tobar, N., Oliveira, A. G., Araújo, T. G., Carvalho, B. M., Rocha, G. Z., Vecina, J. F., Calisto, K., Guadagnini, D., Prada, P. O., Santos, A., Saad, S. T. O., & Saad, M. J. A. (2017). Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice.

Journal of Nutritional Biochemistry, 50, 16–25. https://doi.org/10.1016/j.jnutbio.2017.08.006

9 Carvalho, B. M., Jose, M., & Saad, A. (2013). Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance. Mediators of Inflammation, 2013, 13. https://doi.org/10.1155/2013/986734

10 Bagarolli, R. A., Tobar, N., Oliveira, A. G., Araújo, T. G., Carvalho, B. M., Rocha, G. Z., Vecina, J. F., Calisto, K., Guadagnini, D., Prada, P. O., Santos, A., Saad, S. T. O., & Saad, M. J. A. (2017). Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice.

Journal of Nutritional Biochemistry, 50, 16–25. https://doi.org/10.1016/j.jnutbio.2017.08.006

11 Falcinelli, S., Picchietti, S., Rodiles, A., Cossignani, L., Merrifield, D. L., Taddei, A. R., Maradonna, F., Olivotto, I., Gioacchini, G., & Carnevali, O. (2015). Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism. https://doi.org/10.1038/srep09336

12 Ghosh, S., van Heel, D., & Playford, R. J. (2004). Probiotics in inflammatory bowel disease: Is it all gut flora modulation? In Gut (Vol. 53, Issue 5, pp. 620–622). https://doi.org/10.1136/gut.2003.034249

13 Pražnikar, Z. J., Kenig, S., Vardjan, T., Bizjak, M. Č., & Petelin, A. (2020). Effects of kefir or milk supplementation on zonulin in overweight subjects. Journal of Dairy Science, 103(5), 3961–3970. https://doi.org/10.3168/jds.2019-17696

14 Ejtahed, H. S., & Hasani-Ranjbar, S. (2019). Neuromodulatory effect of microbiome on gut-brain axis; new target for obesity drugs. In Journal of Diabetes and Metabolic Disorders (Vol. 18, Issue 1, pp. 263–265). Springer. https://doi.org/10.1007/s40200-019-00384-4

15 Pizarroso, N. A., Fuciños, P., Gonçalves, C., Pastrana, L., & Amado, I. R. (2021). A review on the role of food-derived bioactive molecules and the microbiota–gut–brain axis in satiety regulation. In Nutrients (Vol. 13, Issue 2, pp. 1–18). MDPI AG. https://doi.org/10.3390/nu13020632

16 Falcinelli, S., Rodiles, A., Hatef, A., Picchietti, S., Cossignani, L., Merrifield, D. L., Unniappan, S., & Carnevali, O. (2017). Dietary lipid content reorganizes gut microbiota and probiotic L. rhamnosus attenuates obesity and enhances catabolic hormonal milieu in zebrafish. Scientific Reports, 7(1). https://doi.org/10.1038/s41598-017-05147-w

17 Lee, H. Y., Park, J. H., Seok, S. H., Baek, M. W., Kim, D. J., Lee, K. E., Paek, K. S., Lee, Y., & Park, J. H. (2006). Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1761(7), 736–744. https://doi.org/10.1016/j.bbalip.2006.05.007

18 Sousa, R., Halper, J., Zhang, J., Lewis, S. J., & Li, W. I. O. (2008). Effect of Lactobacillus acidophilus supernatants on body weight and leptin expression in rats. BMC Complementary and Alternative Medicine, 8(1). https://doi.org/10.1186/1472-6882-8-5

19 An, H. M., Park, S. Y., Lee, D. K., Kim, J. R., Cha, M. K., Lee, S. W., Lim, H. T., Kim, K. J., & Ha, N. J. (2011). Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids in Health and Disease, 10. https://doi.org/10.1186/1476-511X-10-116

20 Bassols, A., Costa, C., Eckersall, P. D., Osada, J., Sabrià, J., & Tibau, J. (2014). The pig as an animal model for human pathologies: A proteomics perspective. In Proteomics - Clinical Applications (Vol. 8, Issue 10, pp. 715–731). Wiley-VCH Verlag. https://doi.org/10.1002/prca.201300099

21 Koopmans, S. J., & Schuurman, T. (2015). Considerations on pig models for appetite, metabolic syndrome and obese type 2 diabetes: From food intake to metabolic disease. In European Journal of Pharmacology (Vol. 759, pp. 231–239). Elsevier B.V. https://doi.org/10.1016/j.ejphar.2015.03.044

22 Valent, D., Arroyo, L., Fàbrega, E., Font-I-Furnols, M., Rodríguez-Palmero, M., Moreno-Muñoz, J. A., Tibau, J., & Bassols, A. (2020). Effects of a high-fat-diet supplemented with probiotics and ω3-fatty acids on appetite regulatory neuropeptides and neurotransmitters in a pig model. Beneficial Microbes, 11(4), 347–359. https://doi.org/10.3920/BM2019.0197

23 Forssten, S. D., Korczyńska, M. Z., Zwijsen, R. M. L., Noordman, W. H., Madetoja, M., & Ouwehand, A. C. (2013). Changes in satiety hormone concentrations and feed intake in rats in response to

lactic acid bacteria. Appetite, 71, 16–21. https://doi.org/10.1016/j.appet.2013.06.093

24 Bagarolli, R. A., Tobar, N., Oliveira, A. G., Araújo, T. G., Carvalho, B. M., Rocha, G. Z., Vecina, J. F., Calisto, K., Guadagnini, D., Prada, P. O., Santos, A., Saad, S. T. O., & Saad, M. J. A. (2017). Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice. Journal of Nutritional Biochemistry, 50, 16–25. https://doi.org/10.1016/j.jnutbio.2017.08.006

25 Chen, Z., Guo, L., Zhang, Y., Walzem, R. L., Pendergast, J. S., Printz, R. L., Morris, L. C., Matafonova, E., Stien, X., Kang, L., Coulon, D., McGuinness, O. P., Niswender, K. D., & Davies, S. S. (2014). Incorporation of therapeutically modified bacteria into Gut microbiota inhibits obesity. Journal of Clinical Investigation, 124(8), 3391–3406. https://doi.org/10.1172/JCI72517

26 Naruszewicz, M., Johansson, M.-L., Zapolska-Downar, D., & Bukowska, H. (2002). Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers 1-3. In Am J Clin Nutr (Vol. 76). https://academic.oup.com/ajcn/article-abstract/76/6/1249/4689562

27 Yang, Y., Long, Y., Kang, D., Liu, C., Xiao, J., Wu, R., & Zhao, J. (2021). Effect of Bifidobacterium on olanzapine-induced body weight and appetite changes in patients with psychosis. Psychopharmacology, 238(9), 2449–2457. https://doi.org/10.1007/s00213-021-05866-z

28 Kadooka, Y., Sato, M., Imaizumi, K., Ogawa, A., Ikuyama, K., Akai, Y., Okano, M., Kagoshima, M., & Tsuchida, T. (2010). Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. European Journal of Clinical Nutrition, 64(6), 636–643. https://doi.org/10.1038/ejcn.2010.19

29 Jones, R. B., Alderete, T. L., Martin, A. A., Geary, B. A., Hwang, D. H., Palmer, S. L., & Goran, M. I. (2018). Probiotic supplementation increases obesity with no detectable effects on liver fat or gut microbiota in obese Hispanic adolescents: a 16-week, randomized, placebo-controlled trial. Pediatric Obesity, 13(11), 705–714. https://doi.org/10.1111/ijpo.12273

30 Déchelotte, P., Breton, J., Trotin-Picolo, C., Grube, B., Erlenbeck, C., Bothe, G., Fetissov, S. O., & Lambert, G. (2021). The probiotic strain h. Alvei ha4597® improves weight loss in overweight subjects under moderate hypocaloric diet: A proof-of-concept, multicenter randomized, double-blind placebo-controlled study. Nutrients, 13(6). https://doi.org/10.3390/nu13061902

31 Takemura, N., Okubo, T., & Sonoyama, K. (2010). Lactobacillus plantarum strain No. 14 reduces adipocyte size in mice fed high-fat diet. Experimental Biology and Medicine, 235(7), 849–856. https://doi.org/10.1258/ebm.2010.009377

32 Zarrati, M., Raji Lahiji, M., Salehi, E., Yazdani, B., Razmpoosh, E., Shokouhi Shoormasti, R., & Shidfar, F. (2019). Effects of Probiotic Yogurt on Serum Omentin-1, Adropin, and Nesfatin-1 Concentrations in Overweight and Obese Participants Under Low-Calorie Diet. Probiotics and Antimicrobial Proteins, 11(4), 1202–1209. https://doi.org/10.1007/s12602-018-9470-3

33 NabizadehAsl, L., Sendur, S. N., Ozer, B., Lay, I., Erbas, T., & Buyuktuncer, Z. (2022). Acute and short-term effects of Lactobacillus paracasei subsp. paracasei 431 and inulin intake on appetite control and dietary intake: A two-phases randomized, double blind, placebo-controlled study. Appetite, 169, 105855. https://doi.org/10.1016/J.APPET.2021.105855

34 Legrand R, Lucas N, Dominique M, Azhar S, Deroissart C, Le Solliec MA, Rondeaux J, Nobis S, Guérin C, Léon F, do Rego JC, Pons N, Le Chatelier E, Ehrlich SD, Lambert G, Déchelotte P, Fetissov SO. Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice-a new potential probiotic for appetite and body weight management. Int J Obes (Lond). 2020 May;44(5):1041-1051. https://doi.org/10.1038/s41366-019-0515-9

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News in the Gut-Brain Area

The increased focus on healthy aging – to live longer and stay healthy – drives consumers to seek ways to improve their health in general but also in specific health areas like digestive, immune and mental health. Probi® strengthens the Gut-Brain offering with new study in older adults.

Inflammaging, a newer term used to describe chronic inflammation that accompanies aging, was investigated in a recently published study. The UN has estimated that the population aged 65 years and older will continue to rise during the coming years, eventually doubling by 20501. With an increased older population, the demands on the healthcare system will ultimately increase, driving higher costs and longer wait times. The increase in expected lifespan can also be seen on an individual and marketing level, as more and more people are actively searching for ways to improve their longevity and healthy aging.

The new study is the 4th clinical study performed on the proprietary strain Lactiplantibacillus plantarum HEAL9 (HEAL9™) investigating its benefits in the GutBrain area. The study included older adults (>70 years) with chronic low-grade inflammation and investigated the anti-inflammatory effects of HEAL9, alone or in combination with berries. The results showed significantly decreased levels of inflammation, which could play a role in chronic conditions such as cardiovascular disease, diabetes and Alzheimer's disease.

Intake of HEAL9 was shown to decrease inflammatory levels, with significantly decreased calprotectin overall compared to placebo. Significantly fewer participants had elevated calprotectin at the study's end compared to placebo. There was also a tendency of decreased CRP within the HEAL9 group not seen with placebo, and of reduced pro-inflammatory marker TNF-alpha in the HEAL9 group compared to placebo. Cognitive assessment using the Trail Making Test also showed improvement with HEAL9 consumption. The combination of HEAL9 with berries seemed not to be more beneficial for improving low-grade inflammation than the HEAL9 alone.

“With the findings of this 4th clinical study, showing the benefits of our HEAL9 strain in the gut-brain area, Probi is cementing our status as pioneers also within this growing new health area for probiotics. The new data obtained in older adults follows a previous study, published in 2023, in which the HEAL9 strain was shown to support and improve cognitive performance, as well as memory, mood and sleep in adults at the age of 21-52 years. Supporting cognitive functions and healthy aging is relevant for everyone who wants to live healthier lives for a longer time, and we are confident that our Probi Sensia concept is relevant for many age groups seeking to lay the foundation for better health later in life” says Anita Johansen, CEO Probi AB.

The study “Probiotic-Reduced Inflammaging in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial” was published in the journal Probiotics and Antimicrobial Proteins (June 2024) and can be found here

1 Nations U (2020) World population ageing 2019 (st/esa/ser. a/444). Department of Economic and Social Affairs PD, editor New York, USA2020

Stance on Probiotics

In a significant development for the probiotic industry, a formal request for investigation has been submitted to the European Ombudsman, questioning the European Commission's stance on probiotics.

International Probiotics Association Europe (IPA) argues that the European Commission has inadequately addressed the concerns raised by the industry and provides sufficient elements to support this request.

In response, the Ombudsman has initiated an inquiry to scrutinize the Commission's handling of the complainant’s issues, highlighting the need for the Commission to consider new evidence and requested that the Commission provide a more detailed explanation of its rationale for categorizing probiotics as a health claim only. The inquiry is currently ongoing, and further developments are anticipated as the Ombudsman seeks to ensure that the Commission’s decisions are transparent and evidence based.

This investigation brings renewed hope to the probiotic industry, which has long awaited for more clarity and the recognition of the probiotic category of products and ingredients.

New Experimental Research About Improves of Cholesterol Levels

Ingredients by Nature announce the publication of its experimental research in the International Journal of Molecular Sciences - the investigation assessed the antioxidant capacity of Eriomin®, a multi-patented citrus flavonoid blend, and its impact on cholesterol metabolism in the context of healthy aging.

Cholesterol is critical to countless bodily functions, from vitamin D synthesis, steroid hormones, cell wall stability, bile acid production, and more. On the other hand, excess cholesterol in the blood can lead to the formation of atheromatous plaques in the arteries, which is very harmful. Thus, it is vital to strike a balance between endogenous synthesis plus dietary intake, along with the body's clearance of cholesterol, to ensure balanced biochemical and physiological functions as we age.

The four-week study treated aged male lab rats with Eriomin (40 mg/kg body weight) suspended in sunflower oil, and the Control group in the same age received only sunflower oil. After the four-week period, the antioxidant activity, cholesterol biosynthesis and degradation, and the absorption markers of Eriomin were measured in the blood serum, liver, jejunum, and ileum in both groups.

The results found that Eriomin significantly reduced total oxidant status (TOS) and the oxidative stress index (OSI) (p < 0.05) compared with the controls, indicating consistent antioxidant action across the liver and small intestine. Additionally, Eriomin significantly lowered the biosynthetic hepatic precursor of cholesterol, desmosterol (p < 0.05), and reduced the levels of 7α-hydroxycholesterol and 24-hydroxycholesterol in the liver and ileum (p < 0.01).

“These products - oxygenated derivatives of cholesterol 7α-hydroxycholesterol and 24-hydroxycholesterol - also known as oxysterols, are crucial for maintaining cholesterol balance and ensuring proper digestive and metabolic functions,” said Dr. Thais Cesar, lead researcher and scientific advisor to Ingredients by Nature. “7α-hydroxycholesterol regulates bile acid synthesis and cholesterol homeostasis in the liver, as well as bile acid reabsorption in the ileum. Meanwhile, 24-hydroxycholesterol facilitates cholesterol transport from the brain to the liver for detoxification and clearance, contributing to overall cholesterol homeostasis.”

“This study showed that Eriomin exerted potent antioxidant effects to help maintain serum cholesterol levels,” said Rob Brewster, president at Ingredients by Nature. “Flavonoids are well-known for antioxidant properties and our proprietary blend, Eriomin, continues to demonstrate its potent antioxidant effects through our clinical research.”

FIGURE 1 Illustration of the Eriomin effect on cholesterol metabolism in aging

Probi® Launches at Denmark's Leading Health Retail Chain

Probi AB is proud to announce that its products are now also available in Matas, Denmark's leading health-oriented retail chain.

Through this collaboration, Probi® - the Swedish market leader in probiotic supplementscan offer scientifically proven probiotic solutions to a wider audience and strengthen our commitment to improving people's health and well-being in the Nordic region.

In recent years, consumers' views on health have changed significantly, with an increased focus on preventive health measures and overall well-being. Interest in gut health is growing, driven by greater awareness of the importance of gut health for overall health. This in turn has led to an increase in the demand for probiotics, live bacteria that promote a healthy gut.

Probi offers high-quality food supplements with lactic acid bacteria, supported by extensive research and clinical studies. The range, which consists of products for various health areas such as gut health, immune health and women's health, contributes to a healthy lifestyle.

The products are currently sold mainly through pharmacies, both in physical stores and online, in the Swedish, Norwegian and Icelandic markets. Through the collaboration with Matas, the chain's e-commerce customers will initially have access to Probi's range.

"We are very excited about our collaboration with Matas, and that Probi's scientifically well-documented products are now also available to Danish consumers who want to improve their health and quality of life with lactic acid bacteria" says Anita Johansen, CEO of Probi.

Matas has a long tradition of offering quality health and beauty products and enjoys strong trust among Danish consumers. Matas' e-commerce platform is the second largest in Denmark with a high level of customer satisfaction.

With this collaboration, Probi AB looks forward to giving Matas' customers the opportunity to experience the benefits of our probiotic supplements.

Significant Exercise Performance Improvements

The randomized double-blinded placebo-controlled clinical research demonstrated Levagen®+, a highly bioavailable form of palmitoylethanolamide (PEA), significantly improved lower body power and did not interfere with skeletal muscle hypertrophy gains.

Gencor has announced the publication of its recent human clinical trial in the high impact factor journal (9.8), Sports Medicine. Over-the-counter (OTC) medications have been shown to negatively affect skeletal muscle adaptations to strength training. PEA has demonstrated great potential as a suitable alternative to OTCs due to its analgesic and healthy inflammatory response properties. Therefore, the study aimed to investigate the effects of daily Levagen+ supplementation combined with eight weeks of resistance training in healthy, active male and female participants.

The results indicated that a daily dose of 350 mg of Levagen+ significantly improved lower body power and isometric strength compared to the placebo group (17% vs 5%). It also showed that, unlike NSAIDs and other analgesics, the PEA supplementation did not inhibit strength training adaptations.

“To our knowledge, this is the first study to investigate the effects of PEA on the adaptive responses to strength training, and it is a great honor to have this data published in the Sports Medicine Journal,” said R.V. Venkatesh, Co-Founder and Managing Director at Gencor. “This is our second study investigating Levagen+ for active nutrition, and it continues to show great promise in this category.”

Levagen®+ is a highly bioavailable form of PEA due to its award-winning delivery technology, LipiSperse®, developed by Pharmako Biotechnologies. It is manufactured in cGMP facilities and has been clinically shown to support joint health, sleep, recovery, immunity, aches and discomforts, and a healthy inflammation response. Levagen®+ is applicable to dietary supplements, food and beverages, and cosmeceuticals.

Fragrance Allergens and Their INCI Names in the Cosmetics

We remind you of the updated naming conventions for essential oils and extracts of popular plant species to minimize discrepancies and prevent errors between the names of extracts derived from different parts of the same plant.

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

In the light of the latest addition to the list of fragrance allergens in the year 2023., here is a short reminder for cosmetics manufacturers about the name change of essential oils; actually, extracts of some of the most popular plant species used in cosmetics. This name change reduces the differences between the names of extracts and essential oils obtained by extraction from different parts of the same plant, as well as the confusion and possibility of mistakes.

Apart from their presence being indicated in the list of ingredients on the product label, in cases where the concentration of the substance exceeds 0,001% in leave-on products and 0,01% in rinse-off products, they should be indicated with the „new“ INCI name. This completes compliance with Regulation (EC) No 1223/2009 on cosmetic products.

A simplified overview of the names of plant extracts as stated in Annex III of Reg. 1223/2009:

Aromatični kutak Ltd.

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

109

114

122

Pinus Mugo Leaf Oil; Pinus Mugo Twig Leaf Extract; Pinus Mugo Twig Oil

Pinus Pumila Needle Extract; Pinus Pumila Twig Leaf Extract; Pinus Pumila Twig Leaf Oil

Cedrus Atlantica Bark Extract; Cedrus Atlantica Bark Oil; Cedrus Atlantica Bark Water; Cedrus Atlantica Leaf Extract; Cedrus Atlantica Wood Extract; Cedrus Atlantica Wood Oil

347 Cananga Odorata Flower Extract; Cananga Odorata Flower Oil

350 Citrus Aurantium Amara Flower Oil; Citrus Aurantium Dulcis Flower Oil

351

354

Citrus Aurantium Amara Peel Oil; Citrus Aurantium Dulcis Peel Oil; Citrus Sinensis Peel Oil

Cymbopogon Schoenanthus Oil; Cymbopogon Flexuosus Oil; Cymbopogon Citratus Leaf Oil

355 Eucalyptus Globulus Leaf Oil; Eucalyptus Globulus Leaf/Twig Oil;

356

357

Eugenia Caryophyllus Leaf Oil; Eugenia Caryophyllus Flower Oil; Eugenia Caryophyllus Stem Oil; Eugenia Caryophyllus Bud Oil

Jasminum Grandiflorum Flower Extract; Jasminum Officinale Oil; Jasminum Officinale Flower Extract

358 Juniperus Virginiana Oil; Juniperus Virginiana Wood Oil

358 Juniperus Virginiana Oil; Juniperus Virginiana Wood Oil

360

366

Lavandula Hybrida Oil; Lavandula Hybrida Extract; LavandulaHybrida Flower Extract; Lavandula Intermedia Flower/Leaf/Stem Extract; Lavandula Intermedia Flower/Leaf/Stem Oil; Lavandula Intermedia Oil; Lavandula Angustifolia Oil; Lavandula Angustifolia Flower/Leaf/Stem Extract

Rosa Damascena Flower Oil; Rosa Damascena Flower Extract; Rosa Alba Flower Oil; Rosa Alba Flower Extract; Rosa Canina Flower Oil; Rosa Centifolia Flower Oil; Rosa Centifolia Flower Extract; Rosa Gallica Flower Oil; Rosa Moschata Flower Oil; Rosa Rugosa Flower Oil

Mugo

Cananga Odorata Oil/Extract

Aurantium Flower Oil

Aurantium Peel Oil

Oil

Eucalyptus Globulus Oil

Eugenia Caryophyllus Oil

Jasmine Oil/Extract

Juniperus Virginiana Oil

Juniperus Virginiana Oil

Lavandula Oil/Extract

Rose Flower Oil/Extract

Pinus

Pinus Pumila

Cedrus Atlantica Oil/Extract

Citrus

Citrus

Lemongrass

Pigmentation Disorders: Understanding and Prevention

Pigmentation disorders are conditions that affect skin, hair, and eye color due to variations in melanin production, leading to either hypopigmentation (reduced pigment) or hyperpigmentation (increased pigment). These disorders can be influenced by genetic, environmental, and physiological factors.

AUTHOR: Valerija Pandža, Mpharm

Skin pigmentation, which refers to how much melanin the body generates, determines the colour of the skin. The two main types of melanin (Figure 1), eumelanin and pheomelanin, are produced by melanocytes in the epidermal layer of the skin. Pheomelanin causes lighter skin tones, while eumelanin is responsible for darker skin tones.

Pigmentation disorders are a diverse group of conditions that affect the coloration of the skin, hair, and eyes. These disorders can arise from various genetic, environmental, and physiological factors, leading to either hypopigmentation (reduced pigment) or hyperpigmentation (increased pigment). Proper understanding of the different types of pigmentation disorders and their underlying causes is crucial for effective prevention and management.

Hypopigmentation

One of the primary types of pigmentation disorders is hypopigmentation, characterized by a decrease or absence of melanin pigment in the skin. This can manifest as localized or generalized conditions, such as vitiligo, albinism, and piebaldism. Vitiligo, for instance, is an autoimmune disorder that destroys melanocytes, leading to the development of white patches on the skin1. Albinism, on the other hand, is a genetic disorder that causes a complete or partial lack of melanin pigmentation, affecting not only the skin but also the hair and eyes.

One of the most common forms of acquired hypopigmentation is post-inflammatory hypopigmentation (PIH), which can occur as a result of various inflammatory skin conditions, such as acne, eczema,

or psoriasis. Hereditary disorders such as albinism, melasma, fungal infections, pityriasis versicolor, pityriasis alba, and vitiligo can result in hypopigmentation (Figure 2). In these cases, the inflammatory process can disrupt the normal function of melanocytes, leading to a reduction in melanin production and, consequently, a loss of pigmentation. The severity and duration of the inflammatory process can influence the extent and persistence of the hypopigmentation3

Hyperpigmentation

In contrast, hyperpigmentation disorders involve an excess of melanin production, resulting in darker patches or areas of the skin. These can be attributed to various factors, including hormonal changes, sun exposure, inflammation, and certain medications1 Melasma, a common type of hyperpigmentation, is often triggered by hormonal fluctuations, particularly during pregnancy or with the use of birth control pills2. Additionally, post-inflammatory hyperpigmentation can occur as a result of skin injuries, such as acne, eczema, or even insect bites3

Understanding the underlying causes of pigmentation disorders is crucial for effective prevention and management. Genetic factors play a significant role in many congenital pigmentation disorders, and genetic testing can help identify the specific muta-

tions responsible3. Similarly, environmental factors, such as sun exposure and certain medications, can contribute to the development of acquired pigmentation disorders1. By recognizing the various triggers and risk factors, individuals can take proactive steps to mitigate the occurrence or progression of these conditions3

Prevention for pigmentation disorders

Prevention strategies for pigmentation disorders involve a multifaceted approach. For those with genetic predispositions, regular skin examinations and genetic counselling can help identify the underlying cause and guide appropriate management1,4. Individuals with a family history of pigmentation disorders should be vigilant in monitoring their skin and seeking early medical attention.

Protecting the skin from excessive sun exposure is crucial in preventing both hypopigmentation and hyperpigmentation disorders. The use of broadspectrum sunscreen, protective clothing, and seeking shade during peak UV hours can significantly reduce the risk of developing sun-induced pigmentation changes1,4

For those with existing pigmentation disorders, proper skin care and the use of depigmenting or lightening agents may help manage the condition. Medications such as topical corticosteroids, retino-

Source: Ricciardo,B.,&Kumarasinghe,P.(2018,January1).AClinicalClassificationofPigmentaryDisorders.SpringerInternational Publishing,1-26.https://doi.org/10.1007/978-3-319-70419-7_1

FIGURE 1 Schematic representation of the melanin synthesis pathway

Nutramedic &Cosmetics

Source: Ricciardo,B.,&Kumarasinghe,P.(2018,January1).AClinicalClassificationofPigmentaryDisorders.Springer InternationalPublishing,1-26.https://doi.org/10.1007/978-3-319-70419-7_1

ids, and hydroquinone have been employed to inhibit melanin production and reduce the appearance of discolored skin. However, it is essential to consult with dermatologists to ensure appropriate and safe use of these treatments, as they can have potential side effects.

Alongside medical interventions, lifestyle modifications can also play a crucial role in preventing and managing pigmentation disorders5. Stress management, a balanced diet rich in antioxidants, and the avoidance of irritants or triggers may help mitigate the severity of these conditions4,5

Food supplements in preventing pigmentation disorders

Certain food supplements, such as vitamin C, vitamin E, and carotenoids, have been shown to have a beneficial effect on pigmentation disorders. Vitamin C, for instance, is a potent antioxidant that can inhibit the activity of tyrosinase, the enzyme responsible for melanin production5. Vitamin E, on the

other hand, has been found to have a protective effect against UV-induced pigmentation changes. Poliphenols have also been studied for their potential to reduce the appearance of age spots and other forms of hyperpigmentation3,4,6

Conclusion

In conclusion, pigmentation disorders are a complex and diverse group of conditions that can significantly impact an individual's appearance and self-confidence. Understanding the underlying causes, risk factors, and preventive measures is crucial for effectively managing these conditions. By combining medical interventions, lifestyle modifications, and the judicious use of food supplements, individuals can take proactive steps to maintain healthy and even-toned skin, thereby enhancing their overall well-being and quality of life.

Ultimately, a comprehensive understanding of the diverse range of pigmentation disorders, their underlying causes, and a multifaceted approach to prevention and management are essential for maintaining healthy, even-toned skin.

Ongoing research in the field of pigmentation biology continues to unveil new insights and treatment strategies, offering hope for individuals affected by these often challenging and complex disorders.

References:

1 Fistarol, S K., & Itin, P. (2010, February 24). Disorders of Pigmentation. Wiley-Blackwell, 8(3), 187-202. https://doi.org/10.1111/ j.1610-0387.2009.07137.x

2 Tailor, R. (2019, June 2). Pigmentation disorders: types, aetiology and treatment options. Mark Allen Group, 8(5), 235-239. https://doi.org/10.12968/joan.2019.8.5.235

3 Ricciardo, B., & Kumarasinghe, P. (2018, January 1). A Clinical Classification of Pigmentary Disorders. Springer International Publishing, 1-26. https://doi.org/10.1007/978-3-319-70419-7_1

4 Spritz, R A., & Hearing, V J. (1994, January 1). Genetic Disorders of Pigmentation. Springer Nature, 1-45. https://doi.org/10.1007/978-1-4757-9062-7_1

5 Engin, R İ. (2015, January 1). Pigmentation Disorders: A Short Review. OMICS Publishing Group, 02(06). https://doi.org/10.4172/2376-0427.1000189

6 Couteau, C., & Coiffard, L. (2016, July 25). Overview of Skin Whitening Agents: Drugs and Cosmetic Products. Multidisciplinary Digital Publishing Institute, 3(3), 27-27. https://doi.org/10.3390/cosmetics3030027

FIGURE 2 The mechanisms involved in some types of hypopigmentation

Givaudan Active Beauty Tackles OxInflammation to Uphold Skin Health

Of 100% natural origin ISO 16128 and vegan suitable, Silybidiol™ complies with global standards. It unlocks new perspectives to protect and reverse the consequences of the exposome for all consumers of beauty products.

Givaudan Active Beauty unveils Silybidiol™, the first globally compliant alternative to the iconic CBD (cannabidiol) molecule. Designed to combat the harmful effects of urban photo-pollution and promote skin health, Silybidiol™ is extracted from the fruit of the milk thistle with ‘green fractionation’. It offers a new, holistic approach to ageing, leveraging the emerging concept of OxInflammation, the vicious cycle connecting oxidative stress and inflammation.

In recent years, the perception of skincare and ageing has evolved towards a more positive and resilient approach known as ‘pre-ageing’. This approach emphasises the importance of self-care, focusing on prevention and overall wellbeing. It recognises the link between positive emotional wellbeing and skin condition, promoting skin health and longevity. The exposome – the set of extrinsic aggressors to which our skin is exposed - is an important factor challenging skin health and longevity. It encompasses UV radiation and pollution, which disrupt the skin’s delicate OxInflammation balance - the interconnection of two key biological pathways. These factors can have a damaging cumulative effect on skin health and emotional balance.

Silybidiol™ binds to cannabinoid receptors in the skin and activates cellular crosstalk leading to the activation of skin defences and detoxification pathways to effectively maintain OxInflammation balance and promote wellbeing. Clinically tested versus placebo and CBD, on volunteers exposed to photopollution, Silybidiol™ offers:

a drastic improvement in skin homogeneity (2.7x better than CBD);

• enhanced skin radiance (1.6x better than CBD);

• an improvement in volunteers’ wellbeing (equivalent to CBD).

“We discovered that Silybidiol™ specifically activates CB2 cannabinoid receptors and delivers the same benefits as the hero CBD molecule. As such, not only does it reduce inflammation, which improves skin tone, but it also stimulates the production of beta-endorphins, feel-good peptides that contribute to overall wellness. This dual-action mechanism underlines Silybidiol™’s efficacy in promoting healthy, radiant skin while supporting emotional wellbeing.” stated Romain Reynaud, Research & Development Director.

Measurable, Inclusive Results for Skin Health and Appearance

Lycomato® drove significant improvement across a variety of ages, ethnicities, and skin types, as evaluated by expert grading, instrumental measurement, and, most importantly, user perception.

Daily supplementation with Lycomato®, Lycored’s tomato-derived nutrient complex, delivers beauty results that are scientifically measurable as well as noticeable by consumers after just 4 weeks of use, a new clinical study has found.

The anti-inflammatory properties of carotenoids mean they can support the skin from within, balancing the effects of aging. Sourced from tomatoes, Lycomato® contains standardized levels of carotenoids, which includes lycopene (15 mg), phytoene and phytofluene to support skin health and appearance.

In the clinical trial, 50 healthy women of different ages (35-58), ethnicities (Asian, Black, Caucasian and Latino), and skin types (Fitzpatrick II-V) took Lycomato® soft gels containing 15 mg of lycopene daily for 12 weeks.

Their skin condition was assessed using three methods: expert visual grading of facial markers, instrumental measurement (including assessment of firmness, elasticity and skin barrier via trans-epidermal water loss) and consumer perception viaquestionnaires.

The visual grading identified significant improvement to a range of parameters after both four weeks and 12 weeks of supplementation. These included fi-

ne lines, wrinkles, pore appearance, brightness/radiance, skin tone evenness, dark spot intensity, smoothness and firmness. The instrumental measurement found significant improvement to skin firmness after the fourth and 12th weeks and significant skin barrier improvement after 12 weeks.

The self-assessment stage of the study also revealed significant results. After 12 weeks of supplementation, 86% of subjects said that using Lycomato had improved the overall appearance of their skin. 88% said it had improved their skin’s elasticity, 86% said their skin felt smoother and 84% said it felt younger or healthier.

Elizabeth Tarshish, Ph.D., Head of Claims and Clinical Affairs at Lycored, said: “In this study we see that Lycomato drove a significant improvement across a variety of ages, ethnicities and skin types, as evaluated by expert grading, instrumental measurement and most importantly – user perception. We strive to empower people to feel comfortable in their own skin, so it’s exciting to know that participants reported feeling a difference and feeling good about themselves.”

View the full study at:

https://onlinelibrary.wiley.com/doi/10.1111/jocd.15650

Spruce Resin as an Effective Natural Solution for Treatment of all Types of Wounds

Conifer resin and the salve produced from this resin have strong antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria, also antifungal activity against yeasts and against the most common dermatophyte fungi.

Nature has an incredible power as being the source of medicinal substances that people have used for centuries in traditional folk medicine to treat various conditions and diseases. The Norway spruce (Picea abies) resin represents such an example. For more than 4 centuries, the population of northern Finland was collecting dried resin from the spruce trunk surface, dissolving it in butter by cooking, and with such salve they were treating wounds and skin infections. The effectiveness of such salve was documented long ago in 1578. in an ancient Nordic textbook by Benedictus Olai1, which is also the only record of the use of resin in medicine until 2003.

A doctor (A. Sipponen) from Finnish Lapland faced one case of a patient with a long-term heel decubitus where none of the wound care therapies applied until then led to an improvement in the condition of the wound and healing. In the end, he listened to the advice of an experienced senior nurse and used home-made ointment according to a traditional recipe. The wound was completely healed after a few months. Prompted by this and additional positive experiences of using home-made ointment with spruce resin, he decided to investigate the mecha-

nism of action of such a product from a scientific point of view.

Active components of Norway spruce resin

Spruce resin is a mixture of hundreds of compounds produced by coniferous trees. The purpose of the resin is to protect the tree from external influences, including various microbes (bacteria, fungi, yeasts, molds) and insects, as well as from dehydration and other physical stress. Wood first produces physiological resin, which provides a physical barrier, and later other components that are important for long-term protection and healing of bark and wood wound.

In general, the resin is mainly composed of volatile and non-volatile terpenes and essential oils2. Some resins, especially in conifers, have a high content of mixtures of diterpenic, organic carboxylic acids, called resin acids3,4. Many terpenes and terpenoids have been proven to have antimicrobial activity against bacteria and fungi, and even against viruses and protozoa5. Several papers have documented the strong antimicrobial activity of resin acids6,7, among which dehydroabietic acid has shown the most po-

AUTHOR: Daria Šurić, MPharm

tent antibacterial activity, including its effect on Gram-positive bacteria6,8.

Mechanism of action

Conifer resin and the salve produced from this resin have strong antimicrobial activity against a wide range of bacteria including Gram-positive (S. aureus, MRSA, B. subtilis) and Gram-negative bacteria (E.coli,P.aeruginosa), also antifungal activity against yeasts, such as C. albicans , and against the most common dermatophyte fungi (genus Trichophyton)9

A change in the structure of the cell wall, adhesion property, appearance of the cells (formation of a partition-like structure), decrease in the production of cellular energy (ATP) and destruction of the cell wall of hyphae are cited as the assumed mechanism of antimicrobial action.

The use of salve with spruce resin promotes the healing of infected wounds and the aforementioned antimicrobial effect against a wide range of microorganisms is a key factor in this process10,11. Also, such salve has been shown to be effective for healing wounds that are not infected, suggesting that the resin has other mechanisms of action besides being antimicrobial. Such an effect is attributed to lignans and coumarin acid from the composition of the resin with its anti-inflammatory and antioxidant effects12,13,14. The action of skin bacteria on lignans produces metabolites that show hormonal activity and improve molecular and cellular mechanisms in wound healing, such as the synthesis of collagen and hyaluronic acid and the stimulation of re-epithelialization. An in vitro test also proved the anti-inflammatory effect of the resin, similar to the effect of medium-strength corticosteroids (dexamethasonum)9

Wounds and stages of wound healing

According to the definition, a wound is an interruption of the anatomical and functional continuity of tissue. The types of wounds can be defined with regards to the cause of their occurrence and the healing time of the wound, and according to the latter we distinguish between acute and chronic wounds. Chronic wounds are those that do not heal within the expected period in correlation with the etiology and localization of the wound, which means a period of 4 to 6 weeks15

The healing process of wounds that affect both the epidermis and the dermis takes place in several time-dependent phases16,17:

1. Hemostasis in which blood clotting and immune response mechanisms are activated in response to the presence of foreign bodies and microorganisms;

2. Inflammatory phase in which infection is prevented and the wound is cleaned;

3. Proliferation phase in which the damaged epidermis is restored by the process of re-epithelialization. Also, fibroplasia (collagen synthesis) and angiogenesis (creation of new blood vessels) occur;

4. Remodeling in which complete normalization of the epithelial layer occurs, formation of new tissue and scar tissue.

Given that all phases of wound healing are timedependent and partially are overlapping, the inter-

ruption or extension of one of the phases can have negative consequences on the success of the entire healing process16,17. It has been proven that spruce resin with its active components accelerates processes in all phases of wound healing and thus enables these time-dependent processes to take place without interruption or prolongation, which is essential for successful wound healing. The main reasons for such an effect are: broad-spectrum antibacterial action, destruction of existing biofilm and prevention of new biofilm formation, antifungal action, anti-inflammatory action, stimulation of epithelialization and tissue renewal9

The role of biofilm in difficult healing of wounds18

Antibiotic-resistant and biofilm-forming microorganisms cause serious infections that threaten the health and lives of millions of patients worldwide. An analysis carried out in 2019 in 204 countries shows that 4.95 million people die annually because of infections caused by resistant bacteria, of which almost a million are caused by 6 types of resistant microorganisms: Escherichiacoli,Staphylococcusaureus,Pseudomonasaeruginosa,Klebsiellapneumoniae,Streptococcuspneumoniae and Acinetobacter baumannii . In addition to antibiotic resistance, an important cause of unsuccessful therapy is the formation of a biofilm - a colony of bacteria adhered to the surface and surrounded by an extracellular polymer matrix. The biofilm matrix has a protective and nutritional function and provides an environment for the exchange of genes encoding resistance to antimicrobial agents. The result is that cells in the biofilm are characterized by a significantly higher tolerance to antimicrobial agents compared to cells outside the biofilm.

Biofilms cause, among other things, skin infections and difficult-to-heal wounds, where there is mostly a biofilm consisted of two to ten types of microorganisms. Over time, one of the species begins to dominate the number of cells, which is characteristic of the species P.aeruginosa and S. aureus . Biofilm is present in almost 90% of chronic and 6% of acute wounds.

According to existing guidelines for the management of chronic wounds, topical products containing antibiotics should not be used in the treatment of infected chronic wounds. Topical agents for treating chronic wounds, where the presence of an infection caused by biofilm is suspected, should have a broad spectrum of action (multiple types of microorganisms) and be able to penetrate through the biofilm matrix to the cells located in the lowest (basic) layers, lead to their eradication and prevent biofilm reformation.

Scientific work has proven that the salve containing purified spruce resin, thanks to the composition of resin acids and lignans, shows high activity against the types of bacteria in the biofilm, S. aureus and P. aeruginosa , and does not have a cytotoxic effect on fibroblasts and keratinocytes responsible for tissue renewal and wound healing. As a follow-up to this scientific work, a study was conducted whose aim was to evaluate the effect on the biofilm of an salve containing 10% resin acids and lignans com-

pared to an ointment containing bacitracin, neomycinandpolymyxinB(BNP).

The conclusion of the study is that salve containing 10% spruce resin, compared to ointment with BNP composition, shows significantly greater:

• antimicrobial action; ability of active components to penetrate through biofilm layers and reduce the number of microorganism cells;

• the ability of active components to penetrate to the base layer of the biofilm.

It is indicated that spruce resin salve is suitable for treatment of both acute and chronic infected and noninfected wounds, thus can be used at home for any minor injury but also for the professional wound treatment.

References:

1 Olai, B. Een Nyttigh Läkare Book, 1578. Benedictus Olain lääkärikirja vuodelta 1578. Translated by Sakari Härö. Publisher Suomen Lääkäriliitto (Finnish Medical Association) 150, 2008

2 Langenheim, JH Plant resins: Chemistry, Evolution, Ecology and Ethnobotany. Timber Press; Portland, Cambridge, 2003

3 Kimland, B, Norin, T. Wood extractives of common spruce, Picea abies (L.) Karst. Svensk Papperstidn 10:403-409, 1972

4 Holmbom, T, Reunanen, M, Fardim, P. Composition of callus resin of Norway spruce, Scots pine, European Larch and Douglas fir. Holzforschung 62:417-422, 2008

5 Cowan, MM. Plant products as antimicrobial agents. Clin Microbiol Rev 12:564-582, 1999

6 Smith, E, Williamson, E, Zloh, M, Gibbon, S. Isopimaric acid from Pinus nigra shows activity against multidrug-resistant and EMRSA strains of Staphylococcus aureus. Phytother Res 19:538-542, 2005

7 Savluchienske-Feio, S, Curto, MJ, Gigante, B, Roseiro, JC. Antimicrobial activity of resin acid derivates. Appl Microbiol Biotechnol 72:430-436, 2006

8 Söderberg, TA, Gref, R, Holm, S, Elmsros, T, Hallmans, G. Antibacterial activity of rosin and resin acids in vitro. Scand J Plast Reconstr Hand Surg 24:199-205, 1990

9 Sipponen, A, Coniferous resin salve, ancient and effective treatment for chronic wounds : laboratory and clinical studies. University of Helsinki, Doctoral thesis, 89 p, 2013

10 Clark, RA. Wound repair: overview and general considerations. In: The Molecular and Cellular Biology of Wound Repair. Clark RAF, editor. London: Plenum Press, 3-50, 1996

11 Broughton, G 2nd, Janis, JE, Attinger, CE. The basic science of wound healing. Plast Reconstr Surg 117:12-34, 2006

12 Kangas, L, Saarinen, N, Mutanen, M, Ahotupa, M, Hirsinummi, R, Unkila, M, Perälä, M, Soininen, P, Laatikainen, R, Korte, H, Santti, R. Antioxidant and antitumor effects of hydroxymatairesinol (HM-3000,HMR), a lignan isolated from the knots of spruce. Eur J Cancer Prev 11:48-57, 2002

13 Dragsted, LO. Antioxidant actions of polyphenols in humans. Int J Vitam Nutr Res 73:112-119, 2003

14 Cosentino, M, Marino, F, Maio, RC, Delle Canne, MG, Luzzani, M, Paracchini, S, Lecchini, S. Immunomodulatory activity of the lignan 7-hydroxymatairesinol potassium acetate (HMR/lignan) extracted from the heartwood of Norway spruce (Picea abies). Int Immunopharmacol 10:339-343, 2010

15 Batičić Pučar L., Grčić A., Pernjak Pugel E., Detel D., Varljen J. Wound healing process and dipeptidyl peptidase IV, Medicina fluminensis 2017, Vol. 53, No. 1, p. 4-15

16 Witte MB, Barbul A. General principles of wound healing. Surg Clin North Am 1997;77:509-28.

17 Braiman-Wiksman L, Solomonik I, Spira R, Tennenbaum T., Novel insights into wound healing sequence of events. Toxicol Pathol 2007;35:767-79.

18 Efficacy assessment of sutriheal® forte 10% against Pseudomonas aeruginosa and Staphylococcus aureus mixed biofilm displaying high tolerance to bacitracin, neomycin and polymyxin B, A. Junka, M. Dzięgielewska, M. Worek, M. Bartoszewicz, FORUM ZAKAŻEŃ 2023;14(1):1–8

Completion of $75M Facility Expansion

GC Rieber VivoMega™ is thrilled to announce the completion and grand opening of its new omega-3 manufacturing facility campus in Norway.

The grand opening ceremony took place on May 24, 2024, where its chairman and GC Rieber group CEO, Jan Roger Bjerkestrand, cut the ribbon and introduced the new facility, which will enable GC Rieber VivoMega to double the output of their high-end triglyceride form of marine omega-3s EPA and DHA and certified vegan EPA & DHA algal oils.

“This is an exciting time for GC Rieber VivoMega and our customers,” said Snorre Glærum Strand, CEO at GC Rieber VivoMega. “With the supply of fish oils starting to normalize somewhat thanks to improvements in ongoing fishery, and the growing demand for sustainable, traceable, high-quality omega-3 increases, this new facility allows us to meet the varying consumer needs, including a vegan alternative EPA & DHA.”

The $75M expansion investment also included:

• A 38,000 metric ton storage tank park;

• An electric steam boiler which allows its three facilities to run on 100% renewable energy;

• Additional heating capabilities to help maintain the quality of the oils and allow for easier extraction in winter;

Additional nitrogen to remove oxygen for improved sensory profiles.

Snorre Glærum Strand continued, “To further minimize our eco-footprint, we utilized much of the existing infrastructure, including docks, tanks, and laboratories. We are also proud to announce that this addition will bring new jobs to GCRV as we continue to grow.”

The manufacturing campus fully aligns with the EU Green Deal initiatives and the UN Global Compact guidelines. GC Rieber VivoMega is also SEDEX-certified. The new facility makes GC Rieber VivoMega one of the world’s largest fish and algae manufacturing and storage facilities, putting sustainability and quality first.

CosmofactoryFrom Ideas to Innovation

The new podcast dedicated to innovation in the beauty industry will highlight ideas, initiatives, and new solutions on the most strategic segments of the supply chain: product development, logistics and operations, ingredients, cutting-edge machinery and automation systems, sustainable packaging materials, and design.

Cosmoprof Worldwide Bologna, the leading b2b event for the cosmetics industry, is launching its first podcast series, CosmoFactory – From Ideas to Innovation. The project, created in collaboration with Deanna Utroske, an expert in the beauty industry supply chain, aims to highlight the evolution of the sector by involving key players from around the world and sharing experiences and initiatives that are revolutionizing the sector.

The podcast "CosmoFactory – From Ideas to Innovation" traces its origins back to the inception of CosmoFactory in 2013, originally conceived as a project to represent specific steps of the supply chain processes with dedicated setups on the show floor. Over the years, the initiative has showcased to attendees at Cosmoprof Worldwide the production processes of iconic cosmetic products, such as lipstick, perfume, bb-cream and powder, spotlighting the high level of technology integrated throughout the supply chain. Thanks to the new project, CosmoFactory evolves from a "product factory" to an "ideas factory," showcasing the most extraordinary innovations that are transforming the industry.

“The cosmetics industry plays a pivotal role in the research and development of new solutions, technologies, and sustainable strategies. As organizers of Cosmoprof Worldwide Bologna, the leading b2b event for international stakeholders in the sector, it is our duty to give voice to the most disruptive novel-

ties and experiences which are transforming the sector day by day,” says Enrico Zannini, General Manager of BolognaFiere Cosmoprof. “With the CosmoFactory Podcast we hope to create a common platform for our community where they can share motivating case-histories, discover what’s new in beauty, and get inspired.”

“Cosmoprof Worldwide Bologna is the cornerstone event of our industry. And the launch of the CosmoFactory podcast brings inspiring innovations, business leadership insights, and supplier discovery opportunities off the show floor and into your work week,” says CosmoFactory host Deanna Utroske. “Being invited to collaborate on the development of the CosmoFactory podcast and having the privilege of interviewing leading beauty industry experts for a new episode every week is a true honor.”

The podcast

In the months leading up to the 2024 edition of Cosmoprof Worldwide Bologna, Deanna Utroske engaged key players in the supply chain to report on industry news through articles and interviews published on Cosmoprof official channels. The storytelling now evolves in podcast format, with a series of interviews involving disruptive companies, suppliers, brand owners, distributors, and international experts who are literally shaping the future of the industry. The podcast will highlight ideas, initiatives,

and new solutions on the most strategic segments of the supply chain: product development, logistics and operations, ingredients, cutting-edge machinery and automation systems, sustainable packaging materials, and design. Each episode will showcase the most sensational discoveries for cosmetics.

The launch of the new series includes the release of the CosmoFactory Trailer and the first four fulllength episodes, which have been recorded during the latest edition of Cosmoprof Worldwide Bologna featuring specialists in AI technology, ingredients, packaging, and manufacturing.

• Episode One: manufacturing Makeup with AI, featuring SEA Vision Cosmetic Business Development Manager Francesco Ringressi

Episode Two: sourcing a Zero-Waste Skincare Ingredient, featuring Macro Oceans Founder and CEO Matthew Perkins

• Episode Three: advancements in Packaging and Dispensing, featuring President at Aptar Beauty EMEA Xavier Susterac and Marketing Manager Aptar Beauty EMEA Delphine Bony

Episode Four: transparency and Sustainability in Contract Manufacturing, featuring Ancorotti Cosmetics Communication Manager Arwen Imperatori

Subsequently, the editorial plan includes continuous publication of one podcast every Tuesday, available on Transistor, Spotify, Amazon Music, Google Podcast, Apple Podcasts, and many more.

The podcast series will be accompanied by a communication plan with online articles, EDMs, and social media posts on Cosmoprof Worldwide Bologna channels.

The voice of Cosmofactory:

Deanna Utroske

Deanna Utroske is one of the most well-respected critical thinkers in the cosmetics and personal care industry today. She is Editor of the Beauty Insights newsletter and a supplyside positioning consultant. Deanna writes the Global Perspectives column for EuroCosmetics magazine, and is a former Editor of CosmeticsDesign.

As a public speaker, Deanna has presented to beauty industry audiences in Bologna, Paris, London, Barcelona, Amsterdam, New York City, and LA as well as via live video. She’s been a guest lecturer at FIT, Manhattan College, and Columbia College. She often serves as a judge for both beauty industry and media awards, and is commonly invited to share her observations with market research and intelligence companies.

Deanna’s writing and commentary have been featured in Cosmetics & Toiletries, Luxe Packaging Insight, BeautyMatter, NewBeauty Magazine, Beauty Store Business Magazine, Natural Beauty News, Beauty Industry Report, Beauty Independent, CEW, Stylist France, Yahoo! Finance, The Huffington Post, PBS Media Shift, and AdWeek (Publishing Executive) as well as cited on Wikipedia, in peer-reviewed journals, and in several books on cosmetics and personal care, wellness, and business.

For more information visit: CosmoFactory

B2B Events Calendar

An overview of live B2B events that will take place during 2024.

5-6 September 2024, Stockholm, Sweden https://www.hudochkosmetikmassan.se/

18 - 20 September 2024, Bangkok, Thailand https://www.vitafoodsasia.com/en/home.html

2-4 October 2024, Istanbul, Turkey https://beauty-istanbul.com/

8-10 October 2024, Milan, Italy https://www.cphi.com/europe/

9-10 October 2024, Stockholm, Sweden https://www.nordicorganicexpo.com/

9-12 October 2024, Munich, Germany https://www.expopharm.de/messe/apotheken/ event.php?pg=main&setlang=en

13-14 October 2024, Birmingham, UK https://www.thepharmacyshow.co.uk/

28 October - 1 November 2024, Las Vegas, NV, United States https://west.supplysideshow.com/en/home.html

19-21 November 2024, Frankfurt, Germany https://www.figlobal.com

20-21 November 2024, Milano, Italy https://www.in-vitality.it/

New Product Development: Selecting a Reliable Contract Manufacturer (CMO)

A reliable CMO can be the difference between a high-quality product that meets market demand and a disappointing venture that fails to gain traction.

AUTHOR: Darmell

When it comes to developing new food supplements, choosing the right contract manufacturer (CMO) is crucial for success. A reliable CMO can be the difference between a highquality product that meets market demand and a disappointing venture that fails to gain traction.

First and foremost, it is essential to assess the CMO's experience and expertise in the field of food supplement development. Look for a CMO with a proven track record in producing similar products to your ideas. Consider their level of knowledge regarding regulatory requirements, formulation development, and packaging options specific to food supplements. A CMO with experience in your niche will understand the unique challenges and opportunities that come with it.

Reliability is another crucial factor to consider. A reliable CMO should have a strong reputation in the industry for delivering consistent, high-quality products. Look for certifications and accreditations that demonstrate their commitment to quality control and compliance with regulatory standards. Additionally, consider their capacity and ability to handle your production volume requirements and meet deadlines consistently. A reliable CMO will have efficient production processes in place to ensure timely delivery. Cost is another consideration that cannot be ig-

nored. While it may be tempting to choose the cheapest option, it is essential to strike a balance between cost and quality. Consider the CMO's pricing structure, including any additional fees or charges that may apply. It is advisable to request quotes from multiple CMOs and conduct a thorough costbenefit analysis to determine the best fit for your budget and requirements.

Communication and transparency are vital in any business relationship, and selecting a CMO is no exception. Evaluate the CMO's communication channels, responsiveness, and willingness to provide updates and progress reports. A reliable CMO should be open to collaboration, actively involving you in the development and production process. Clear lines of communication will help prevent misunderstandings and ensure that your vision is accurately translated into the final product.

In conclusion, selecting a reliable contract manufacturer is a critical step in the new product development process for food supplements. By considering factors such as experience, reliability, cost, and communication, B2B food supplement producers, CMOs, and brand owners can make an informed decision that sets the foundation for a successful partnership. Remember, the right CMO will not only produce high-quality products but also contribute to

the growth and success of your brand in the market. Communication is also a very important point. It should be a „two-way street“, so ideas and information should be easily exchanged between you and the chosen CMO.

Managing the production process and quality control

In the competitive world of food supplement development, managing the production process and ensuring quality control are crucial aspects that can make or break a product's success.

The production process begins with the conversion of raw materials into finished products. It is essential to establish a well-defined manufacturing plan that outlines each step, from ingredient sourcing to packaging and labeling. By having a clear roadmap, producers can streamline operations, minimize errors, and optimize efficiency. The production plan should also consider factors such as equipment selection, production capacity, and workforce management to ensure smooth operations.

Quality control plays a pivotal role in the production process. It involves implementing measures to monitor and evaluate the quality of ingredients, intermediates, and finished products. Producers must establish quality control protocols to verify that all materials meet specified standards and ensure consistent product quality. This includes conducting regular inspections, testing for purity and potency, and adhering to regulatory requirements. By implementing a robust quality control system, producers can identify and rectify any deviations promptly, preventing potential product recalls or customer dissatisfaction.

To manage the production process effectively, it is essential to adopt advanced technologies and automation wherever possible. Modern software solutions can streamline inventory management, production scheduling, and quality control documentation. Automation can also minimize human errors and enhance overall efficiency, allowing producers to focus on innovation and new product development. Furthermore, collaboration with reliable suppliers and their regular audit is crucial for successful production management. By partnering with trusted suppliers, producers can ensure the consistent availability of high-quality raw materials. CMOs can offer specialized expertise, state-of-the-art facilities, and scalability, enabling producers and brand owners to navigate complex production challenges and meet market demands.

If you are using CMO as your production partner or if only outsourcing part of the production process, it is important to make the first audit before starting the collaboration. Also, audits have to be performed regularly, as long as a partnership exists. In conclusion, managing the production process and implementing quality control measures are vital for B2B food supplement producers, CMOs, and brand owners. By establishing a well-defined production plan, implementing robust quality control systems, adopting advanced technologies, and collaborating with reliable partners, producers can enhance operational efficiency, ensure consistent product quality, and ultimately succeed in the competitive market of new product development for food supplements.

Darmell Expert in the Nutritional Supplements Field

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

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

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

Services we offer:

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

• Consulting related to the registration of dietary supplements.

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

• Help in finding a suitable distributor for finished products.

We also actively deal with:

• Representing renowned companies producing branded ingredients/raw materials for nutritional supplements.

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

Darmell Ltd.

20+ years of experience in developing new concepts for food supplements

Mob: + 385 91 68 12 444 darmell@protonmail.com www.dar-mell.com

Fi Europe 2024 Registration Opens With Early Bird Offer

F&B industry tastemakers from around the world can start planning their participation in Fi Europe 2024, which returns to Messe Frankfurt from 19-21 November 2024.

Registration has opened for Fi Europe 2024, allowing forward planners to lock this unmissable food & beverage industry event into their schedules and benefit from an early bird discount. Those who register before 14 July qualify for an introductory rate of €49, which includes entry to the Fi Europe Conference. The 2024 edition will offer a host of new features, including an expanded Food Manufacturing Technologies & Solutions Area and the Pet Food Suppliers’ Hub.

A vast and vibrant show floor is the core of Fi Europe’s value proposition and the format is constantly evolving in line with market trends. Informa is expanding the Food Manufacturing Technologies & Solutions Area for 2024, dedicating a larger space to solutions that can help food & beverage businesses secure their supply chains and future-proof their operations. This year will also see the introduction of the Pet Food Suppliers’ Hub – a new area showcasing ingredients and technologies that can support the pet food industry in developing nutritious, safe and innovative products. In addition, there will be a number of new country pavilions, providing visibility for products and solutions from markets

around the world. Denmark, Thailand and Latin America will be among the countries participating in this capacity for the first time this year.

Fi Europe’s content programme is always a highlight, with expert speakers offering exclusive insights on the challenges, trends and technologies shaping the food & beverage industry. This year, for the first time, entry to the Fi Europe Conference will be free of charge for visitor pass holders, making this knowledge gathering forum accessible to all.

Yannick Verry, Brand Director, Food ingredients Europe & Americas, at Informa Markets, says: “The food & beverage industry never stands still; there are always new narratives unfolding. We strive to evolve the Fi Europe platform to reflect these changes and challenges, whilst constantly looking for ways to enrich the experience and add value for visitors and exhibitors alike. We look forward to seeing how attendees use the different facets and features of this year’s event to support innovation, solve problems and develop profitable connections.”

Click here to register for Fi Europe 2024.

Nagoya BioTrade Permit for Sustainable Honeybush Sourcing

Nektium has secured its first BioTrade permit in accordance with the Nagoya Protocol for the sustainable and ethical sourcing of honeybush from South Africa.

Honeybush (Cyclopia spp.) is a naturally sweet, caffeine-free tea from the highly biodiverse Cape Floral Kingdom in South Africa. It is rich in antioxidants and the health-promoting bioactive compound mangiferin and has been shown to demonstrate anti-diabetic1, anti-obesity2, and immunomodulatory3 properties.

Nektium has now secured a BioTrade permit from South Africa’s Ministry of Forestry, Fisheries and the Environment to source honeybush in line with the principles of the Nagoya Protocol. The international legal framework, which came into force in 2014, promotes biodiversity and sharing benefits with communities in the raw materials’ sourcing areas in a fair and equitable way.

With the permit in place, Nektium’s R&D team is now working to develop a honeybush ingredient with the potential for use across supplements, food and beverages.

Adriana Regidor, Sustainability & Corporate Affairs Director at Nektium, said: “Sustainability is a key priority for Nektium. We had already integrated the Nagoya Protocol’s principles in our product development strategy to promote conservation, biodiversity and fair trade. When we started exploring honeybush’s potential as a nutraceutical, we soon discovered that South Africa had the whole legal framework in place for the Protocol. We are delighted to have obtained our first BioTrade permit, which we believe is the first issued to an extract manufacturer for honeybush in South Africa.”

She added: “This important milestone demonstrates our strong commitment to sustained and sustainable sources of raw materials for our customers. They can rest assured that we will act responsibly, delivering secure supplies that align with their own environmental and social commitments.”

To secure the permit, it was essential to recognize and reward the traditional knowledge of relevant indigenous groups as determined by the South African Government. Spain-based Nektium therefore worked with South African distributor Parceval (Pty) Ltd to consult and negotiate with the San Council of South

Africa and the National Khoisan Council. Parceval has already secured a number of BioTrade and Bioprospecting permits to supply natural resources from the country in a responsible and sustainable manner.

As a result of the negotiations, Nektium will share the profits from any honeybush ingredients with both councils and provide their members with internships at the company’s facilities on the island of Gran Canaria.

Nektium will also work with local raw material supplier Agulhas Honeybush Tea, which secured a permit demonstrating its compliance with the Nagoya Protocol in December 2023. The parties will cooperate to ensure sustainable cultivation that preserves wild honeybush stocks, encourages agricultural biodiversity, and promotes carbon sequestration.

Adriana Regidor said: “Securing the permit was a long journey, but Parceval helped guide us every step of the way. We were able to identify a raw material supplier that is committed to our values as well as the two local councils that represent the traditional knowledge holders. We’ve been able to establish a firm relationship built on trust with the San and Khoisan councils. The communities they represent have existed for thousands of years and we are hugely grateful for their depth of knowledge on sustainable honeybush use. In turn, the internship program we are offering means they will be able to acquire new skills and knowledge. This will allow them to return home and uplift their own communities in a variety of ways.”

References:

1 Malongane, F. et al. 'Anti-Inflammatory, Anti-Diabetic, Anti-Oxidant and Cytotoxicity Assays of South African Herbal Teas and Bush Tea Blends' Foods (2022)

2 Jack, B.U. et al. 'Cyclopia intermedia (Honeybush) Induces Uncoupling Protein 1 and Peroxisome Proliferator-Activated Receptor Alpha Expression in Obese Diabetic Female db/db Mice' International Journal of Molecular Sciences (2023)

3 Garcia, D. et al. 'Modulation of rat macrophage function by the Mangifera indica L. extracts Vimang and mangiferin' International Immunopharmacology (2002)

inspirational success story

Hug Your Life

The Hug Your Life brand currently includes 25 high-quality dietary supplements that are available in a large number of pharmacies and specialized stores in Croatia and are distributed in several countries.

n How did it all begin, what inspired you, and what was the initial idea?

It officially began 11 years ago, but a few years before starting the company, we started to intensely think about "what to do." At that time, the global crisis had also hit Croatia so we were searching for ideas and how to proceed. We did not see the light at the end of the tunnel in the companies where we worked, so we were looking for new opportunities. And then, somewhere around 2012, we managed to secure some capital and simultaneously started a business with food supplements. We surrounded ourselves with good partners and with immense experience from previous companies set off on new ventures. Today, we are present in a large number of retail locations, in pharmacies and health food stores, and we also have about 10 international B2B customers.

n What was needed from idea to realization?

We certainly had to be extremely cautious at the very beginning. Of course, we can't say that we are careless now, but when you have only one product and everything is new without established customers, there is a great "respect" towards the unknown or rather a positive fear. Given our previous work experience, we certainly had the knowledge in development and implementation, and that was a great relief for us. Without such background, we most

definitely would not have entered the private sector. In those early days, the hardest part was watching our savings dwindle while the business (still) did not grow fast enough. Everything needed to be financed in advance and we had to wait for the wheel to start turning. Simultaneously, we had to develop new products, devise approaches to customers, and seek sources of supply. Then there was the risk of payment, the risk of product shelf life, large minimum production quantities, and so on. Quite challenging.

n What products do you offer today, and where and how do you market them?

The current assortment includes 25 high-quality products, available in a large number of pharmacies and specialized stores in Croatia and distributed in several countries. Our products range across dietary supplements for immune support, cardiovascular health, focus and memory, skin, hair and nail health, stress and insomnia reduction, bone and joint health, weight loss assistance, beauty and women's health. Our distribution is primarily done through wholesalers and direct customer processing but lately we’ve been investing more and more in online sales through our new webshop.

n Are you satisfied with what you've achieved? Absolutely. We can proudly say that in these 11

years of operation, we have sold more than one million units, and we have only discontinued one product (back in 2014; perhaps due to our inexperience).

Considering that the entire development, procurement, sales, and marketing concept takes place within the company, we have the ability to ensure our products contain high amounts of active ingredients, while at the same time being very competitive in the market and matching international players.

We are especially thrilled by the feedback we receive, both from end customers and from pharmacists or managers about the quality, effectiveness, and positive impact of our products. This has become an integral part of our mission and vision through our promise to end customers: "Top quality available to everyone."

n What are you most proud of?

The main feature of all our products is absolute quality. There is no compromise here. Ingredients must be verified, standardized, health-compliant, and the finished products are tested for pesticides, heavy metals, and microbiology in authorized laboratories. For us, there is no better feeling than when a customer contacts us and enthusiastically says how our product has helped them. The average rating of independent reviews on our web shop is 4.91/5.

n Is there anything else you would like to add... wishes, plans...

Recently, we were awarded the title of Best Web Shop in Croatia in the Best Analytics category by eCommerce Croatia. This recognition is a significant encouragement for us to continue expanding our business.

Although all of this may sound great, we must admit that we approach every new month with immense respect. Certainly, we would not have achieved any of this without an excellent team, both within the company and among our long-term partners. There’s no giving up, always move forward while staying positive (although that’s sometimes easier said than done). As the famous quote goes: "A ship is safe in harbor, but that's not what ships are for."

Hug Your Life

Luminus Mod Ltd.

Dankovecka 12, 10000 Zagreb, Croatia www.HugYourLife.hr info@luminusmod.hr

Driving Sustainable Practices and Achieving Net Zero Goals

ACG announced a strategic partnership with EYParthenon aiming to enhance ACG's sustainability initiatives through a comprehensive Net Zero strategy and implementation roadmap aligned with the Science Based Targets initiative (SBTi).

ACG, the world’s largest integrated supplier and service provider to the pharmaceutical industry, has announced a strategic partnership with EY-Parthenon, one of the largest professional services networks in the world, aiming to enhance ACG's sustainability initiatives through a comprehensive Net Zero strategy and implementation roadmap aligned with the Science Based Targets initiative (SBTi). Combining ACG’s industry expertise with EY-Parthenon’s sustainability consultancy, the partnership seeks to significantly reduce carbon emissions and promote sustainable practices across ACG’s operations has already initiated its journey by conducting a comprehensive greenhouse gas emissions (GHG) emissions inventory and carbon footprint assessment for their most prominent products. This assessment has provided critical insights into ACG’s emissions profile, identifying priority areas for targeted sustainability efforts.

ACG, in collaboration with EY-Parthenon, is developing a comprehensive Net Zero Roadmap. This roadmap will set specific targets and actions aligned with the Science Based Targets initiative (SBTi), a globally recognized framework for companies to set science-based emissions reduction targets in line with the latest climate science.

Given ACG’s significant export of aluminium-based films and foils to the European Union, EY Parthenon has also conducted a comprehensive assessment of the Carbon Border Adjustment Mechanism (CBAM) implications for ACG and preparing it for 100% CBAM compliance.

Shivshankar S.R, CEO of ACG Packaging Materials, said, “Adherence to the Science Based Targets initiative (SBTi) underscores our unwavering commitment to conscientious corporate stewardship. We are pro-actively setting targets and focusing on long-term initiatives that will provide value realization and business transformation towards creating a more sustainable and resilient future. “Our alliance with EY Parthenon marks a pivotal advancement in our sustainability pursuit.

Leveraging their esteemed expertise in industrial decarbonization, we are poised to expedite our Net Zero objectives, thereby effectuating a meaningful reduction in our carbon emissions.”

Kapil Bansal, Partner and Leader of Industrial Decarbonization, EY-Parthenon India, added, “EY-Parthenon is proud to announce its collaboration with ACG as they advance towards achieving SBTi aligned Net Zero strategy and roadmap. With our extensive expertise in strategic decarbonization and CBAM impact mitigation, we are committed to guiding ACG in meeting the company’s emission reduction goals, optimizing costs, minimizing risks, and driving meaningful transformation in the sector. As global efforts intensify to meet the goals set by the Paris Climate Accord, partnerships like this enable businesses and industry leaders to set the standard for environmental stewardship and contribute to a more sustainable future.”

medicinal plants photo herbarium

Red Clover

Red clover Trifoliumpratense is a versatile and valuable plant with a wide range of applications in agriculture, medicine, and beyond. Its ability to fix nitrogen, improve soil quality, and provide nutritious forage makes it an important component of sustainable agricultural systems.

TAXONOMY

kingdom: Plantae

order: Fabales

family: Fabaceae

genus: Trifolium

species: Trifolium pratense

COMMON NAME

Red clover, purple clover, purple glover, peavine glover

FLOWERING TIME

V-IX month

Trifoliumpratense , commonly known as red clover, is a perennial that has been an integral part of agricultural systems worldwide for centuries. Trifolium pratense is characterized by its distinct trifoliate leaves, each leaflet containing a white crescent marking. Red clover is a creeping perennial with a taproot system that can grow up to 50 cm in depth1 The plant's flowers are typically pinkish-purple in colour and arranged in dense, spherical clusters2

Habitat & cultivation

Red clover is native to Europe, western Asia, and northwest Africa, and has been introduced to many other regions. It thrives in meadows, pastures, and disturbed areas with well-drained, fertile soils3. The plant is cultivated extensively as a forage crop, cover crop, and green manure, particularly in North America, New Zealand, and Northern Europe2

Nitrogen fixation & soil improvement

An important attribute of red clover is its ability to fix atmospheric nitrogen through a symbiotic relationship with Rhizobium bacteria. This nitrogen fixation process was first discovered in the late 19th century3. Legume cover crops like red clover can contribute significant amounts of nitrogen to the soil, reducing the need for synthetic fertilizers. Additionally, red clover improves soil structure and water-holding capacity, which can enhance the effectiveness of applied nitrogen fertilizer4

Use for medicinal purposes

Beyond its agricultural applications, T. pratense has a long history of medicinal use. The flowers and aerial parts of the plant have been used to treat a variety of ailments, including respiratory issues, skin conditions, and menopausal symptoms. The plant is rich in isoflavones, which have been associated with potential health benefits1.

Traditional medicinal uses

In traditional medicine, red clover has been used for centuries to treat various ailments. The flowers are often used to make teas, tinctures, and extracts that are believed to have therapeutic properties. The plant has been used to alleviate respiratory problems, such as bronchitis and asthma, as well as skin conditions like eczema and psoriasis

Constituents

• isoflavones

• coumarins

• alkaloids saponins

• organic acids

Action and application

Numerous studies have investigated the potential health benefits of red clover. The isoflavones present in the plant, such as genistein and daidzein, have been the focus of much research due to their estrogen-like effects and potential to alleviate menopausal symptoms. Red clover has also been studied for its potential to reduce the risk of cardiovascular disease, osteoporosis, and certain types of cancer5. However, the clinical evidence for these potential benefits remains mixed, and more research is needed to establish the efficacy and safety of red clover-based interventions.

References:

1 Tundis, R., Marrelli, M., Conforti, F., Tenuta, M C., Bonesi, M., Menichini, F., & Loizzo, M R. (2015, August 21). Trifolium pratense and T. repens (Leguminosae): Edible Flower Extracts as Functional Ingredients. Multidisciplinary Digital Publishing Institute, 4(4), 338-348. https://doi.org/10.3390/foods4030338

2 Frame, J., & Newbould, P. (1986, January 1). Agronomy of White Clover. Elsevier BV, 1-88. https://doi.org/10.1016/s0065-2113(08)60280-1

3 Burton, G W. (2015, October 26). Legume Nitrogen Versus Fertilizer Nitrogen for Warm-Season Grasses. , 55-72. https://doi.org/10.2134/asaspecpub28.c3

4 Lu, Y., Watkins, K B., Teasdale, J R., & Abdul‐Baki, A A. (2000, May 15). COVER CROPS IN SUSTAINABLE FOOD PRODUCTION. Taylor & Francis, 16(2), 121-157. https://doi.org/10.1081/fri-100100285

5 Piersen, C E., Booth, N L., Sun, Y., Liang, W., Burdette, J., Breemen, R B V., Geller, S E., Gu, C., Banuvar, S., Shulman, L., Bolton, J L., & Farnsworth, N. (2004, June 1). Chemical and Biological Characterization and Clinical Evaluation of Botanical Dietary Supplements: A Phase I Red Clover Extract as a Model. Bentham Science Publishers, 11(11), 1361-1374. https://doi.org/10.2174/0929867043365134

GOED Publishes Two New Reports

The Global Organization for EPA and DHA Omega-3s (GOED) recently published two reports on the EPA and DHA omega-3 industry: a biennial report on the global finished products market for EPA and DHA omega-3s and a scientific report on Attention Deficit Hyperactivity Disorder (ADHD) and omega-3s.

The 2024 Finished Product Report offers a comprehensive overview of six key markets: dietary supplements, pharmaceuticals, food and beverage, pet nutrition, infant formula and clinical nutrition/medical foods. Together, these categories reached US$52.4 billion in sales in 2023, primarily influenced by inflation and higher prices.

Some key takeaways from the report:

The pet nutrition segment exhibited strong growth of 8.8% annually, reaching US$1.5 billion in sales in 2023.

• The supplement category also grew, but the dollar increase was driven primarily by increased prices as a result of fish oil shortages.

The DHA-fortified infant nutrition market is by far the largest of the consumer product categories, although birth rates across the globe are on the decline, resulting in a growth of 2.9% in 2023.

• Looking ahead, sales of EPA and DHA finished products are poised to increase an average of 3.3% annually through 2025.

The report encompasses market statistics and trend analyses across 11 regions for 2022 and 2023, with forecasts extending through 2025. Click here to request a sample of the report.

Note: Sales are based on consumer cost to purchase the finished product

The second report, EPA and DHA Supplementation and Attention Deficit Hyperactivity Disorder, explores the latest research on the impact of EPA +DHA omega-3 supplementation on ADHD and associated ADHD outcomes. The report was created using GOED’s Clinical Study Database (CSD), a powerful tool that catalogs all human clinical studies on EPA and DHA omega-3s.

EPA+DHA have been suggested to play a potential role in reducing the symptoms associated with ADHD and the report analyzes the studies conducted on people who have been diagnosed with ADHD, or people who have been assessed using ADHD criteria for symptoms. The report also provides key takeaways and suggests next steps for research.

The ADHD report is available for purchase on the GOED website for US$199. GOED members have free access to the report.