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    Features

    Formulating for Weight Loss Products

    Developers of weight loss nutraceuticals have a wide range of mechanisms to target with safe, efficacious ingredients.

    Formulating for Weight Loss Products
    By Mike Montemarano, Associate Editor09.08.22
    Product developers are leaning into the personalized nutrition trend today, incorporating emerging, research-backed, proprietary ingredients that offer benefits for a healthy weight, body composition, and other related health needs.

    “Ready-to-drink beverages, gummies, and shots seem to be leading the area with regard to growth,” said Maggie McNamara, marketing director at Gencor. “People are seeking products with convenience that can easily fit into their daily lives. Pill fatigue is very real.”

    This has spurred development and use of “water-soluble, neutral-tasting ingredients that are easy to formulate with and are pleasing to the consumer,” said Steve Fink, vice president of marketing for PLT Health Solutions. 

    Fortunately, several functional ingredients lend themselves to positive sensory profiles, according to Vaughn DuBow, global director of marketing, microbiome solutions, ADM. “Functional botanicals are helpful in developing dietary supplements that target wellbeing and the sensory experience,” DuBow said. “Our high-quality botanical extracts pair well with biotics, fiber, and other functional ingredients to create offerings that are both nutritious and delicious.”

    With many unique dietary approaches trending in the weight loss/management market, supplements that complement a particular diet could help target an audience with unique nutritional needs.

    For example, with plant-based diets trending, product manufacturers can help fill nutrient gaps. “Essential fatty acids are important here,” McNamara said. “While omega-3s often come with side effects or challenges with formulating, finding ways to make them easier to digest and absorb while expanding the formulation capabilities is key. Technologies such as AquaCelle work great for these two problems. AquaCelle omega-3 helps with the digestion, absorption, and formulating woes.”

    Advances in natural low- and no-sugar sweeteners are creating high flavor expectations in functional foods that address cravings or act as meal replacements.

    “Foods and beverages that aim to support weight management often fall short in this regard,” said Carla Saunders, senior marketing manager for high intensity sweeteners, Cargill. “Many of these products struggle with bitterness, off-notes, and aftertastes, but advances in sweetener technology offer remedies for these flavor challenges. Cargill’s newest sweetener system, EverSweet + ClearFlo, is a great example. It brings together our premier stevia sweetener with a natural flavor. The resulting sweetener system offers wide-ranging benefits that include flavor modification and enhanced mouthfeel, along with improved solubility and stability in formulations, and faster dissolution.”

    Research Targets

    There are many factors that contribute to the formation of fat cells, and many mechanisms of action by which that formation can be slowed down, said Jeremy Appleton, ND, director of medical and scientific affairs for PLT Health Solutions.

    “Aspects of our physiology help to conserve energy when times are hard,” he said. “But modern life interacts negatively with these, increasing risk of disease. There are many mechanisms of action by which nutraceuticals can influence fat metabolism.”

    For example, he noted a range of ingredients have been shown to: control calorie intake by decreasing appetite or increasing satiety; control the availability of substrates by interfering with their metabolism or absorption; influence the expenditure of energy through thermogenesis; or treating fat reserves by decreasing adipogenesis (the formation of fat-laden cells) or increasing lipolysis (the process by which triacylglycerols in fat cells break down into their constituents, glycerol and free fatty acids).

    There is much more to uncover in the space of bioactives—compounds that confer non-food-related health effects. “Bioactives in the weight space often act through blocking absorption of macronutrients like fat or carbs, increasing general energy expenditure and/or metabolic rate, increasing burn of specific macronutrients, and/or suppressing appetite,” said Jim Flatt, CEO and co-founder of Brightseed, a company  that has developed an AI platform called Forager to build a library of proprietary bioactive compounds. “There is so much more potential to uncover as we open up the solution space of novel bioactive discovery for the natural products industry. The plant kingdom has been vastly under-explored to address high-need health areas.”

    Flatt said there is a shortfall in nutrition research when it comes to how long weight loss can be sustained, as most studies are not longitudinal. Likewise, there are many characteristics of clinical trial participants that get under-examined, including: dietary record, physical activity, thyroid function, genetic makeup, microbiome composition, family history, physical (in)activity, satiety or absence thereof, inflammatory markers, and hormones such as leptin, ghrelin, and cortisol.

    Breaking Barriers

    Stress and poor sleep are among the top barriers that consumers cite when it comes to weight loss, and products with stress and sleep benefits are prevalent in today’s weight loss market.

    “Snacking, also known as emotional eating, is a phenomenon we are seeing on the rise,” said Fink. “PLT’s Supresa Crave Control is derived from the stigmas of a special cultivar of Crocus sativus L flowers. Supresa supports weight loss by reducing the desire to snack between meals. Unlike some products, Supresa does not work by promoting a feeling of ‘fullness.’ Rather, it induces a feeling of wellbeing and stress reduction over time, to address the source of stress-related overeating and snacking.”

    A randomized, double-blind, placebo-controlled clinical trial showed that in subjects considered to be snackers, daily Supresa consumption helped to change behavior, with significant reductions in snacking starting within 14 days.

    Stress plays an enormous role in weight through multiple metabolic pathways, McNamara noted. “Stress increases cortisol levels, which cause other hormones to become out of balance and lead to insulin resistance, fat storage, and decreased metabolic rate. Additionally, stress is linked to poor food choices, cravings, and decreased satiety. While under acute stress, cortisol is a positive hormone. Under extended periods it becomes harmful by increasing blood sugar levels, decreasing sex hormones, increasing insulin resistance, triggering metabolic syndrome, decreasing satiety, and causing more fat storage.” 

    “Through multiple lenses, including endocrinological systems in the body, the gut-brain axis, and the neuromodulation of behaviors related to weight, there is tremendous overlap between mental wellbeing and healthy weight,” said Flatt. “Decreased sleep can cause appetite dysregulation through altering levels of the hormones leptin and ghrelin, which can increase hunger, and altering food preferences toward more calorie-dense foods. Sleep deprivation can also contribute to metabolic syndrome.”

    Expect future research to evaluate ingredients that overlap between weight management and digestive health, blood sugar management, and blood cholesterol management, said Sid Shastri, director of research and business at Kaneka Probiotics.

    “This bodes well for many other product categories not directly associated with weight management, including formulations of probiotics strains, ingredients for healthy energy synthesis such as ubiquinol, for glucose management such as alpha lipoic acid, berberine, and gymnema, and healthy aging, such as resveratrol and carnosine, to name a few.”

    On the digestive health front, “we believe that a prime gap exists in offering a clinically-researched postbiotic for healthy weight management,” Shastri said. “To give some context to this nutritional approach, it’s important to note that an altered gut microbiome is evident in people with obesity. Specifically, it’s been seen that people with obesity have lowered gut microbiota diversity and the ratio of firmicutes/bacteroides decreases significantly.”1

    Satiety and Metabolism

    Reduction of food cravings can be a difficult endpoint to calculate objectively. Still, it is a benchmark where many ingredients thrive. Consumers seem more attuned to how they feel than how they look, so there is a strong focus on products and diets that address appetite control and carbohydrate cravings, according to Katie Emerson, manager of scientific affairs for Nutrition21.

    Research is still elucidating the connection between blood sugar control and cravings, she added. “When our bodies utilize the insulin system properly, you can see changes in lowering appetite, burning more calories, and improving overall body composition.”

    Nutrition21’s Chromax chromium picolinate ingredient is well established in the weight management space, “having a strong foothold when it comes to issues of blood sugar control and how that relates to various aspects of weight management,” Emerson said. Chromium is integral to the function of insulin, and Chromax has been substantiated for its potential to improve carbohydrate metabolism, blood sugar metabolism, carbohydrate cravings, and appetite, she added. These mechanisms together influence positive weight changes.

    For those with prediabetes, there is still hope to normalize blood glucose levels, said Rob Brewster, president of Ingredients by Nature. “Lemon flavonoids—including eriocitrin, hesperidin, and naringin—are able to take a triple-pronged approach by supporting normal insulin sensitivity, helping manage a healthy inflammation response, and supporting healthy cell function through increased antioxidant activity.”

    Several human clinical studies show that high intensity sweeteners, when used in place of sugar and calories, support weight loss and can aid in overall weight management, noted Corey Scott, principal nutrition scientist at Cargill.2

    Eyes on the Gut

    Fiber has long been a crucial component of many weight loss formulas, thanks to the feeling of fullness and improved digestion it often confers. Many fiber types can reduce blood sugar spikes after a meal and may reduce the risk of several obesity-related diseases, according to a 2019 meta-analysis appearing in The Lancet. Researchers concluded that the highest tiers of fiber consumption were linked to a 15-30% reduction in all-cause and cardiovascular mortality.3

    “With Matsutani LLC, we have created Fibersol, a line of soluble prebiotic dietary fiber ingredients supported by over 30 years of extensive clinical research,” DuBow said. “Fibersol is shown to minimize blood sugar spikes after a meal in healthy individuals, and it may delay hunger by stimulating appetite-regulating hormones.4,5 It also promotes the growth of gut microbes positively associated with health.6-7 Fibersol is shown to be well-tolerated at up to 68 grams per day.8 Fibersol, at 3.75 grams per serving, may help nourish the intestinal flora and maintain a healthy intestinal tract environment. It also ferments more slowly in the large intestine, reducing the risk of rapid onset of bloating or other digestive discomfort associated with some fibers.”

    A major trend in probiotics and postbiotics is formulation in gummies, beverages, and functional foods, DuBow noted. Postbiotics do not contain live cultures, so they are able to remain stable in gummy, quick-melt, and beverage formulations. “Our award-winning BPL1 probiotic and its postbiotic counterpart BPL1 HT were designed to target factors relevant to metabolic health.9 We also use spore-forming probiotics such as DE111 which can withstand formulation environments that would otherwise damage conventional lactic acid bacteria-based probiotics.” 

    Shastri said that Kaneka’s Lipigo product is a postbiotic form of Saccharomyces cerevisiae, and it has been tested in a randomized, parallel, double-blind, placebo-controlled format. “A study on the postbiotic demonstrated that 3 grams per day of Lipigo promoted the reduction of body weight and reduced the rebound effect on overweight people after 52 weeks.10 In another randomized, double-blind, placebo-controlled clinical study, overweight and obese subjects exhibited reduced body weight without any other dietary intervention.11 In that study, it was seen that body weight increased in the placebo group.”

    Emerging Ingredients

    Bioavailable forms of essential nutrients offer a point of differentiation,  according to Emerson. “The superiority of Nutrition21’s Chromax over other forms of chromium can be seen in its stable chemical structure and superior absorption profile,” she said. “It is 15 times more bioavailable than other forms of chromium.”

    Recent research on Slendacor, a complex of turmeric, moringa, and curry leaf extracts from PLT Health Solutions, “set new standards for communicating efficacy to consumers and regulatory agencies in the weight management category,” according to Appleton, “because of its size, its length, its use in healthy non-obese men and women, and its design and execution. Consistent body weight reductions were observed throughout the 16-week trial starting with statistically significant weight loss at two weeks.12 Participants averaged a total weight loss of nearly 12 pounds by the end of the study. The subjects taking Slendacor lost two inches in waist circumference and had no reduction in lean body mass.”

    Further, a series of clinical and pre-clinical studies elucidated Slendacor’s dual mode of action for controlling fat reserves and managing energy expenditure.13 The human clinical study found that a single daily dose of Slendacor was associated with a 15.2% increase in resting energy expenditure at day 7, with no effects on heart rate or blood pressure, unlike what has been seen in other thermogenic ingredients.

    “The two recent pre-clinical studies on energy expenditure showed that the mechanisms of action are related to the effect of Slendacor on white adipose tissue increasing UCP1 expression to resemble what occurs in more metabolically active brown adipose tissue,” said Fink.

    Sabinsa’s ForsLean (Coleus forskohlii) has been shown to mediate white fat to beige or brown fat conversion, along with stimulating lipolysis which leads to a decrease in fat storage, according to Kalyanam Nagabhushanam, president of R&D at Sabinsa.14

    Researchers with Sabinsa are also investigating its recently-launched CurCousin ingredient, an extract of curcumin that is standardized in Calebin-A, a compound found in very small quantities in Curcuma longa. “Our research scientists studied this molecule comprehensively and found it has a great potential to balance cholesterol, support healthy blood sugar levels and circulation, and that it is an excellent metabolic support compound,” Nagabhushanam said. “Because the amounts present in natural sources are prohibitively small for commercial purposes, we developed CurCousin with 99% Calebin-A synthetically as a nature-identical compound. The product has self-affirmed GRAS status and it has been clinically studied with a dosage of 25 mg twice a day and has 65 U.S. and international patents.”

    Product developers should note ingredients that can support a healthy inflammatory response, Brewster said. “Excess weight can increase the production of pro-inflammatory cytokines, resulting in an inflammation imbalance. This can start a chain of reactions that affect the body’s ability to manage proper blood glucose levels and oxidative stress as well,” he said. “In two recently published studies, the citrus flavonoid eriocitrin was shown to support healthy blood glucose function by addressing insulin sensitivity, generate potent antioxidant activity to balance a rise in reactive oxygen species, and inhibit cytokine production to help manage the inflammation response within a healthy range.”15,16 

    References

    1. Duan, M. et al. (2021). Characteristics of gut microbiota in people with obesity. PLOS One 16(8): e0255446. doi.org/10.1371/journal.pone.0255446
    2. Rogers, P. et al. (2020). The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies. International Journal of Obesity 45, 464-478. https://doi.org/10.1038/s41366-020-00704-2
    3. Reynolds, A. et al. (2019). Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. The Lancet. 393, 434-445. https://doi.org/10.1016/S0140-6736(18)31809-9
    4. Livesey, G. et al. (2009). Interventions to lower the glycemic response to carbohydrate foods with a low-viscosity fiber (resistant maltodextrin): meta-analysis of randomized controlled trials. Am J Clin Nutr. Jan;89(1):114-25. doi: 10.3945/ajcn.2008.26842.
    5. Ye, Z. et al. (2015). Soluble dietary fiber (Fibersol-2) decreased hunger and increased satiety hormones in humans when ingested with a meal. Nutr Res. May;35(5):393-400. doi: 10.1016/j.nutres.2015.03.004.
    6. Burns, A. et al. (2018). In healthy adults, resistant maltodextrin produces a greater change in fecal bifidobacteria counts and increases stool wet weight: a double-blind, randomized, controlled crossover study. Nutr Res. Dec;60:33-42. doi: 10.1016/j.nutres.2018.09.007.
    7. Ukhanova, M. et al (2012). Gut microbiota correlates with energy gain from dietary fiber and appears to be associated with acute and chronic intestinal diseases. Clinical Microbiology and Infection. 18(4) 62-66 https://doi.org/10.1111/j.1469-0691.2012.03859.x
    8. Kishimoto, Y. et al. (2013). The Maximum Single Dose of Resistant Maltodextrin That Does Not Cause Diarrhea in Humans. J-STAGE. 59(4)352-387. https://doi.org/10.3177/jnsv.59.352
    9. Pedret, A. et al. (2019). Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial. Int J Obes (Lond). 43(9):1863-1868. doi: 10.1038/s41366-018-0220-0.
    10. Valero-Pérez, M. et al. (2020). Regular Consumption of Lipigo® Promotes the Reduction of Body Weight and Improves the Rebound Effect of Obese People Undergo a Comprehensive Weight Loss Program. Nutrients. Jun 30;12(7):1960. doi: 10.3390/nu12071960.
    11. Santas, J. et al. (2017). Effect of a polysaccharide-rich hydrolysate from Saccharomyces cerevisiae (LipiGo) in body weight loss: randomised, double-blind, placebo-controlled clinical trial in overweight and obese adults. J Sci Food Agric. Sep;97(12):4250-4257. doi: 10.1002/jsfa.8301.
    12. Dixit, K. et al. (2018). Efficacy of a novel herbal formulation for weight loss demonstrated in a 16-week randomized, double-blind, placebo-controlled clinical trial with healthy overweight adults. Diabetes Obes Metab. Nov;20(11):2633-2641. doi: 10.1111/dom.
    13. Kundimi, S. et al. (2020). Combined extracts of Moringa oleifera, Murraya koenigii leaves, and Curcuma longa rhizome increases energy expenditure and controls obesity in high-fat diet-fed rats. Lipids Health Dis. Aug 28;19(1):198. doi: 10.1186/s12944-020-01376-7
    14. Henderson, S. et al. (2005). Effects of Coleus Forskohlii Supplementation on Body Composition and Hematological Profiles in Mildly Overweight Women. Journal of the International Society of Sports Nutrition. 2:2 doi: 10.1186/1550-2783-2-2-54
    15. Thais Borges, C. et al. (2022). Nutraceutical Eriocitrin (Eriomin) Reduces Hyperglycemia by Increasing Glucagon-Like Peptide 1 and Downregulates Systemic Inflammation: A Crossover-Randomized Clinical Trial. Journal of Medicinal Food. http://doi.org/10.1089/jmf.2021.0181
    16. Ribeiro, C. et al. (2019). Effectiveness of Eriomin® in managing hyperglycemia and reversal of prediabetes condition: A double-blind, randomized, controlled study. Phytother Res. Jul;33(7):1921-1933. doi: 10.1002/ptr.6386
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