Obesity is a complex disease and a growing health problem. Being overweight or obese increases the risk of developing other health conditions such as diabetes and heart disease. In 2020, it was estimated that around 38% of the world's population aged five years and older were overweight or obese; this figure is expected to reach 51% by 2035. As well as reducing quality and length of life among populations, the pressure it puts on healthcare systems comes at a huge cost: the annual healthcare cost of obesity-related illness in the USA alone is $147 billion. Global obesity rates have been on the rise for decades. More recently, widespread disruption to routines and lifestyle deterioration caused by the COVID-19 pandemic challenged diets and exercise regimes, prompting cases of food addiction and binge eating behavior in some regions.
In the aftermath of the pandemic, there has been a focus on weight management by those seeking to lose weight or maintain a healthy weight. The good news? Obesity is preventable through exercise and diet management, and this growing awareness around healthy eating is driving the global diet market and opportunities for manufacturers. This article explores DNF-10®, a yeast hydrolysate ingredient gaining recognition for its potential role in weight management.
What is DNF-10®?
DNF-10® is a hydrolysate fraction from Saccharomyces cerevisiae, commonly known as baker's yeast. It is manufactured by Neo Cremar since 2008. Saccharomyces cerevisiae occurs naturally in nature and plays a key role in human food and nutrition, being rich in minerals, vitamins, amino acids and proteins. It is made by extracting the contents of Saccharomyces cerevisiae (baker’s yeast, a key ingredient in baking, wine making and brewing for thousands of years), and hydrolyzing the proteins and isolating peptides with average molecules below 10,000 DA. This proprietary ingredient by Fytexia is a protein hydrolysate peptide blend derived from food-grade yeast protein.
Protein hydrolysates are obtained by decomposing proteins using acids, enzymes, and other physicochemical methods, and are used as food additives. They are categorized into hydrolysed vegetable proteins, which are made mainly from soybeans and hydrolysed animal proteins, which are mostly derived from fish and meat. Protein hydrolysates are composed of complexes such as peptides and amino acids with small molecular weights due to protein breakdown. Therefore, they are quickly absorbed, easily digested, and used for various food-related purposes. Research into single-cell proteins as a protein source has been undertaken, and yeast has attracted attention as the most suitable protein supply.
Manufacturing Process
The manufacturing of DNF-10® involves enzymatic proteolysis and the use of ultrafiltration to select peptides with a molecular weight <10 kDa. Saccharomyces cerevisiae was cultured according to a previously described method to recover the cells. To the recovered cells was added 50 mM phosphate buffer (pH 7.0) 10 times the amount of the cells. Then, protease was added to 0.5% of the cells, and hydrolysis was performed at 30°C for 6 h. To inactivate the enzyme, the supernatant obtained by centrifugation at 8,000 g after standing for 10 min in a water bath maintained at 100°C was passed through a 10 kDa Hydrosart membrane (Sartorius Stedim Biotech GmbH, Göttingen, Germany).
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How Does DNF-10® Work?
DNF-10® regulates appetite by acting on the gut-brain axis. The low molecular weight peptides (<10kDa) from DNF-10® downregulate the ghrelin, the inner hunger promoter produced by the stomach before food intake, and lower the hypothalamic expression of the neuropeptide Y. It is a natural, safe and effective weight loss ingredient, backed by a raft of clinical studies to support its efficacy in promoting the feeling of fullness and reducing inclination for food intake, in turn promoting weight loss and reduction in accumulation of abdominal fat. Its mechanism in the body decreases ghrelin and increases leptin and improves lipid metabolism and inhibits fatty acid synthesis (the creation of fatty acids).
Eating behavior is complex, affected by a myriad of external and emotional factors, but recognising ‘fullness’ is key in order to regulate appetite. Leptin and ghrelin are hormones produced by the body that can influence appetite and satiety. Leptin, an anorexigenic, suppresses food intake, thereby promoting weight loss. Ghrelin, on the other hand, is an orexigenic and fast-acting hormone, and plays a role in meal initiation. The mechanisms by which these ‘hunger hormones’ have an influence on energy balance has been widely studied. Medical research has examined yeast hydrolysate as a way to promote physiological activity with anti-obesity effects.
Mechanistic studies demonstrated that DNF-10 is efficient to decreasing appetite signalling by modulating the central and peripheral mediators. Thanks to the inhibition of DPP-4 activity by DNF-10, GLP-1 has better chance to remain effective longer in the metabolism. The combined effect-enhanced GLP-1 release and reduced degradation-amplifies appetite regulation, contributing to decreased energy intake as demonstrated in clinical studies.
Scientific Evidence and Clinical Studies
More than 10 years of research have been conducted to support the mechanism of action and clinical benefits of DNF-10® on body composition. Several articles supporting the mechanism of action and health benefits of DNF-10® have been published and are available upon request.
Among the body of research is a randomised, placebo-controlled study of obese female adults aged 20-28 years. It found those in the two groups who consumed pouches containing yeast hydrolysate (HY-1 and HY-2) experienced a significant decrease in body weight and BMI after six weeks of treatment - an outcome which suggests yeast hydrolysate can have beneficial properties as a weight-loss supplement. The study also found that weight loss was evenly distributed throughout the body. As well as reduction on abdominal fat, there was reduced skinfold thickness in areas including hips, waist and arm triceps.
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Another study which examined the effects of yeast hydrolysate on body weight and abdominal fat accumulation in obese adults found that yeast hydrolysate reduced body weight, BMI and the accumulation of abdominal fat by week 10, without an adverse effect on lean body mass in obese adults, via the reduction of energy intake.
A study into the effects of DNF-10® in eight-week-old mice found that it increased leptin and decreased ghrelin concentrations in the blood, and dietary intake significantly decreased one hour after administration. Another study in obese-induced mice for eight weeks measured the effects of orally administered DNF-10® at high concentration with a high fat diet, compared to a general diet test group. Weight gain was shown to decrease in the intake group, despite the high fat diet, and showed that lipogenic enzymes were at a low level and fat-digesting steatolytic enzymes were at a high level. Consequently, lipogenesis was more suppressed in the DNF-10® intake group than the general diet group.
Meanwhile in humans, clinical studies have shown that the average dietary intake of obese male and female adults consuming capsules containing DNF-10® of 1g for six weeks was 392.38kcal per day lower than that of the control group over a 10-week period. The total abdominal fat area in the yeast group was significantly lower than in the control group after the 10 weeks (P < 0.01), with significant decrease in the abdominal fat thickness and abdominal circumference compared to the control group. Furthermore, the CT scan in this study showed a reduction in not only abdominal fats but also visceral fats, stored around the organs including the liver and intestines, and typically harder to reduce than abdominal fats. Even low dose of yeast hydrolysate supplementation (0.5g per day) may induce a significant reduction in weight and body mass index in obese women via the reduction of calorie intake, another 8-week study concluded.
Weight loss is significant after one month of supplementation with DNF-10®. The change in body composition is confirmed by computed tomography. The subjects’ total abdominal fat mass is significantly reduced by 5% with DNF-10®.
Key Studies
- Hong K. et al.; Progr. Nutr., 2015, 17:3:262-264
- Jung E. et al.; Phytother. Res., 2009, 3(5):619-23
- Jung E. et al.; Nutrition; 2014, 30:25-32
- Jung E. et al.; Prev. Nutr. Food Sci. 2017 Mar;22(1):45-49. doi: 10.3746/pnf.2017.22.1.45. Epub 2017 Mar 31. PMID: 28401087; PMCID: PMC5383141.
- Park Y. et al.; Food Chemistry, 2013
- Jung E.Y. et al., Ann. Nutr. Metab. 2012; 61(2):89-94
Safety and Regulatory Status
In May 2023 DNF-10® manufactured by Neo Cremar received a No-Questions Letter issued by the Food and Drug Administration (FDA) for Generally Recognized As Safe (GRAS). The ingredient’s safety is a significant competitive advantage over other products. A toxicity evaluation by single dose (5,000 mg / kg) and repeated administration (1,000 mg/kg for 90 days) of DNF-10® in rats was found to be comparatively non-toxic; an earlier safety study found that yeast hydrolysate with below 10kDA molecular weight had very low toxicity.
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DNF-10® has been shown to have no side effects - such as diarrhoea and headaches - commonly associated with weight loss products, thereby offering peace of mind to both manufacturers and consumers.
This study aimed at investigating the acute and subacute oral toxicity of yeast hydrolysate (DNF-10) in Sprague-Dawley rats. To determine the acute toxicity of DNF-10, it was orally administered to rats at a dose of 5,000 mg/kg. Furthermore, to determine subacute toxicity of DNF-10, it was orally administered to female and male rats at a dose of 1,000 mg/kg for 90 days. In the acute toxicity test, the experimental group did not show changes in body and organ weights compared to the corresponding weights in the control group. When compared to female controls, the DNF-10-treated female rats showed decreased red blood cell counts, haemoglobin, and total bilirubin levels; however, the parameters remained within the normal range. In the subacute toxicity test, DNF-10 administration significantly reduced body weight among male rats, which appears attributable to the anti-obesity effect of the compound. In the experimental groups, significant differences in some haematological parameters were considered as non-toxic because the results were within the normal range.
Detailed Toxicity Study Results
- Acute Toxicity: No death was observed 2 weeks after the administration of a single dose of DNF-10 at 5,000 mg/kg in the experimental group. No unusual pathological findings were found in the organs of the female and male rats in any experimental group.
- Subacute Toxicity: No death occurred 2 weeks after the repeated administration of DNF-10 at 1,000 mg/kg for 90 days in the experimental group. The weight of DNF-10-treated male rats at 6 weeks after oral administration of DNF-10 significantly differed from the male controls. Furthermore, the weight of DNF-10-treated female rats differed from the female controls. However, the intergroup difference was not significant. In the male experimental group, brain weight increased significantly compared to male controls. However, the increased brain weight was still within the normal range (brain weight: 0.39∼0.84 g/100 g of body weight).
Haematological Parameters
Changes in haematological parameters after single administration of 5,000 mg/kg DNF-10 and repeated administration of 1,000 mg/kg were measured to ascertain toxicity.
- Acute Toxicity: For female rats in the experimental group, the RBC count and Hb level significantly decreased relative to the corresponding parameters in the female controls (P<0.05).
- Subacute Toxicity: However, the WBC and RBC counts, and Hct level for female rats in the experimental group significantly decreased relative to the corresponding values in the control group (P<0.05). The three parameters showed changes within the normal range (WBC count, 3.0∼14.3; RBC count, 6.69∼8.92; Hct level, 36.9∼51.8).
Blood Biochemical Parameters
The acute and subacute toxicity of DNF-10 was assessed by analysing blood biochemical parameters in this study.
- Acute Toxicity: The ALT level in male rats of the experimental group was significantly lower than that of male controls (P<0.05). However, the change was within the normal range (ALT level: 26.0∼97.0). The BIL level in female rats of the experimental group was significantly lower than that in the female controls. Nevertheless, the change was within the normal range (BIL: 0.2∼1.0).
- Subacute Toxicity: The ALB level in male rats of the experimental group increased significantly compared to that of male controls (P<0.05). However, the change was within the normal range (ALB level: 3.70∼5.00). The CRE level in female rats of the experimental group significantly decreased compared to the level for female controls (P<0.05).
Both tests showed no specific abnormalities in body weight, general symptoms, feed intake, negative volume, hematologic examination, and visual findings. In summary, the acute toxicity test, in which 5,000 mg/kg DNF-10 was orally administered once to Sprague-Dawley rats, and the subacute toxicity test, in which 1,000 mg/kg DNF-10 was orally administered for 90 days, showed no toxicity.
DNF-10® and Muscle Mass
DNF-10® has been found to help reduce weight by reducing body fat while maintaining muscle weight (lean body mass). This is important because preserving muscle mass during weight loss is essential. Muscle not only keeps the body fit and strong, it also protects against disease and boosts mortality. It can even help to prevent rebound weight gain since losing muscle can slow the metabolism and reduce the body’s ability to burn calories and therefore prevent the ‘yoyo effect’ of gaining weight after dieting.
A study evaluated the effects of yeast hydrolysate YH on muscle differentiation and muscle atrophy inhibitory activity in C2C12 cells and atrophy inhibitory activity in a dexamethasone (DEX)-induced muscle atrophy mouse model. Although further research is needed, in this study yeast hydrolysate was shown to promote muscle cell differentiation and inhibit DEX-induced muscle atrophy through in vitro and in vivo experiments. Yeast hydrolysate prevented skeletal muscle loss and concluded that yeast hydrolysate can be used for the development of functional foods that inhibit muscle atrophy while promoting muscle differentiation.
Applications and Formulations
Today DNF-10® is manufactured on a large scale, its efficacy supported by a growing body of clinical studies and technical data. Formulation options for manufacturers include pills and capsules, as well as potential opportunities to explore and expand into applications across the functional snack bar and beverage sectors. The GRAS status allows DNF-10 to be used as an ingredient in food and beverage products like crackers, chips, popcorn, snack bars, meal replacements, and dry protein powders.
DNF-10 is water soluble and heat resistant, with a recommended dose of 500 mg/day for formulating dietary supplements and functional foods, says the company.
Global Presence and Future Directions
DNF-10® has long been exported from Korea to countries including the USA, UK, Japan, China, Europe and to South East Asia where the ingredient has been used to create a range of products, appreciated by consumers for reliable effects that are underpinned by science. Neo Cremar continuously strives to improve the efficacy and quality of DNF-10®. As well as receiving GRAS No question letter from FDA, Neo Cremar is investing into research and studies to understand more about the ingredient's profile, mechanism and health benefits. A new study - much anticipated by Neo Cremar’s entrusted partners who have used DNF-10® over the years - is expected to be published towards the end of 2023.
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