Mark Tallon, PhD

March 1, 2008

23 Min Read
Sports nutrition goes natural

Past nutritional products in the sports world have focused on synthetic ingredients in relation to the enhancement of sports performance. However, the push for 'natural' within mainstream markets is crossing over to the sports category. Mark J Tallon, PhD, covers the latest movers and shakers across the sports-nutrition and weight-loss categories, including the emerging trend for natural performance enhancers

Highly processed dietary supplements are beginning to give way in the minds of consumers to products perceived as more natural. A study conducted by AC Nielsen in the UK in 2006 reported that 60 per cent of consumers preferred to get health benefits not from fortified foods, but from foods that are as natural as possible. Clearly, there is a need to understand how relevant this survey is when trying to gauge the response of the typical weekend warrior. However, given the growth of the energy-beverage market (primarily from food, drug and mass-market retailers), the ability to deliver similar performance effects gained from natural sports supplements is an attractive proposition.

Superfruits for sports
The rise of superfoods, in particular superfruits, has been pushing many segments within the natural-products market for some time. The greater awareness of fruits as being 'good for you,' due to their so-called beneficial antioxidant capacities, has helped power the superfruit phenomenon. Although the concept of superfruits as a natural way to better health has influenced consumer sales, over time more hard-hitting claims and novelty regarding beneficial effects will be needed. Questions relating to sustainability and fair-trade aside, the popularity of these products are now beginning to penetrate the sports-nutrition market. Although many are nutrient dense and fulfil 5-A-Day guidelines, it is the actives and associated research on these products that are fuelling their story in the sports market. Fruits and berries are typically the domain of the health-and-wellness market; however, recent studies by the likes of Hort Research (New Zealand) and others are about to shake up the sports market with some interesting trials on these superfruits and muscle recovery.

Blueberry: Researchers from Hort Research investigated the influence of blueberry fruit on stress-induced muscle damage.1 Fruits, especially blueberries, are dense carriers of antioxidants such as polyphenols. The premise of this work is that the quenching of excessive reactive oxygen species (ROS) will reduce oxidative muscle damage.

Following the preparation of an aqueous extract from three fruit extracts (not disclosed by the study's authors), an in vitro study commenced consisting of cultured muscle cells that were exposed to chemicals, representing an oxidative insult. Muscle damage was also assessed by release of cellular enzymes.

The results clearly showed a protective effect of blueberry extract on oxidative damage as indicated by a reduction in cellular enzymes. Of the fruits tested, blueberry showed the greatest protective effect, even though there seemed to be no correlation between antioxidant capacity (determined by ORAC and FRAP) and the ability of the extracts to inhibit damage. This could be suggestive of many factors such as how physiologically relevant the dose of extract was to the insult. If the oxidant damage was well above what is generally experienced in vivo, it may be that the correlation between damage and antioxidant capacity was hidden due to the magnitude of damage. Although the potential within the sports market is obvious, clearly more human and in vitro work is needed to elucidate not only the mechanism, but also a transferable dose level.

Grape: In a study presented at the Third International Conference on polyphenols in October 2006, researchers from Advantage Nutrition and the French Agronomic Research Institute (INRA) investigated the effect of 400mg/day grape extract or placebo on a selection of biochemical markers of oxidative stress in competitive soccer.2 The aim of the study was to determine if grape supplementation is able to decrease the oxidative stress generated during competition.

Eleven professional soccer players during the competitive season were assessed for plasma markers of antioxidant capacity before and following 21 days of grape supplementation. After three weeks of supplementation, antioxidant capacity, vitamin C and co-Q10 levels were significantly increased by 14, 60 and 96 per cent, respectively. This study suggests supplementation with grape extract rich in flavanols enhances antioxidant capacity during intense training and performance.

Although this study provides some external validity, we know that dietary variation in food intake (especially those high in antioxidants) will markedly influence markers of oxidative stress. We also have no idea about the intensity and frequency of the exercise these athletes were exposed to. A design that incorporated a placebo control group would have been a good starting point to address some of these issues, as well as dietary records and exercise diaries.

In a personal communication with the study organizers, details were provided of a recent study that was recently carried out integrating a performance test and supplementation with the same grape extract (400mg/day for two months). The study seems to indicate that the use of this extract can enhance recovery capacity and power output, and decrease urinary markers of oxidative stress (isoprostans). Further details will become available upon submission to peer review in 2008.

Mangosteen: The southeast Asian superfruit mangosteen (Garcinia mangostana) has become popular over the last few years thanks to the push of information from companies such as Xango regarding the potential benefits of the mangosteen actives, xanthones. In a recent study, presented at the 62nd annual meeting of the Northwest Region of the American Chemical Society, researchers investigated the influence of a liquid dietary mangosteen supplement containing concentrated xanthones (alpha-mangostin).3

The in vitro study assessed the liquid supplement's ability to stimulate adrenergic receptors known to relate the rate of lipid mobilisation and breakdown when exposed to different concentrations of mangosteen. The results demonstrated a clear concentration-dependent binding, and stimulation, of ß-1 and ß-3 adrenergic receptors. It is these receptors that accelerate metabolic rate and caloric expenditure (uncouples oxidative phosphorylation), but also increase the rate of fat utilisation as an energy source.

Adrenergic stimulation mechanism is active in the presence of mangosteen, and therefore has the potential to increase energy production from lipids/fat sources. However, the receptors stimulated in the cell study may not be effective in humans (ie, B2 receptors), and as such further studies are warranted to assess the dosage and efficacy concerning energy and weight managements in humans.

Cherry: A study published in the British Journal of Sports Medicine focused on not only the antioxidant benefits of these superfruits, but also their potential anti-inflammatory role.4 The study aimed to test the efficacy of tart cherry juice in preventing the symptoms of exercise-induced muscle damage.

In a randomised, placebo-controlled, crossover design, 14 males drank 12fl oz cherry juice or a placebo twice daily for eight days. On day four of supplementation, subjects carried out a bout of eccentric elbow-flexion contractions known to elicit muscle damage. Two weeks later subjects crossed over.

Strength loss (cherry: four per cent, placebo: 22 per cent) and pain were significantly reduced in the cherry-juice users vs placebo. This study again highlights the efficacy of fruit-based extracts in decreasing some of the symptoms related to exercise-induced muscle damage.

From these studies on grape, mangosteen and cherry, the potential is clear despite the study's design flaws. Much more work is needed to make sure that the actives are present in the same concentration each time a commercialised juice drink is made.

Got milk?
Any talk of a milk product for performance is usually on whey protein, which is a mixture of some of the proteins naturally found in milk. Whey protein has one of the highest protein digestibility-corrected amino-acid scores (PDCAAS; a measure of protein bioavailability), and is more rapidly digested than other proteins, such as casein (another milk protein).5 Whey protein has been shown to increase gains in lean body mass resulting from exercise.6

But the news on milk-derived products is not on any derivative, but on milk itself. Since the publication of four research papers highlighting milk and its ability to enhance performance, there has been some push back from the dietary-supplements market on their results and conclusions.7,8,9,10 The following gives a quick overview of these latest studies and potential issues with their design.

Study 1 (Milk and endurance performance): The first of the most recent milk studies is one that has received a significant degree of exposure within the media, thanks to sponsorship from Mars and Runner's World.8 Researchers from Northumbria University investigated the effect of consuming a chocolate-milk drink during recovery, and endurance capacity, following prolonged cycling exercise.

Nine male, endurance-trained cyclists completed three trials in a randomised, double-blind, crossover design. Subjects completed an exercise session in an attempt to reduce the stores of carbohydrate in muscles. Following this, subjects consumed one of three drinks during the first two hours of a four-hour recovery period, after which they completed a cycle ride to exhaustion. Drinks were provided as either an isocaloric or a chocolate-milk drink (CMD), a carbohydrate-replacement sports beverage (CRB), or an isovolumetric amount of a fluid-replacement sports beverage (FRB).

During the depletion ride, there were no significant differences between the trials in 'time to exhaustion,' heart rate or the subjects' perception of effort. However, during the 'time to exhaustion' ride, subjects who took the CMD drink rode significantly longer than when using CRB and FRB. No differences in blood lactate, total body water or body mass were observed in either trial. The authors concluded that the CMD drink was more effective in enhancing endurance capacity following prolonged exercise.

A whole host of design flaws are present within this study, including the compositions of the drinks being all significantly different and designed for different purposes beyond enhancement of endurance performance; the test protocol did not mimic a real competitive environment; and no measurements of muscle glycogen were made so we have no idea how depleted each subject was before each ride. This could have made a significant difference in the performance outcome.

Study 2 (Milk and hydration): As mentioned, a selection of studies has investigated the potential of milk-based products in regard to sports nutrition. However, most of the research has focused on potential effects related to macronutrient intake (ie, carbohydrates, proteins, fats), but little work has been done on micronutrient intake. This study has focused on just that and the related influence on hydration post-exercise.9

UK researchers assessed the effectiveness of low-fat milk, alone or with additional sodium chloride, at restoring fluid balance compared to a sports drink and water. Subjects completed multiple 10-minute cycle rides until they lost 1.8 per cent of their body mass, and then they consumed one of three drinks equivalent to 150 per cent of their sweat loss in volume. Urine samples were collected before and for five hours after exercise to assess fluid balance and the degree of exercise-induced hypohydration.

Urine excretion over the recovery period did not change during the milk trials, whereas there was a marked increase in output between one and two hours after drinking water and the sports drink. Cumulative urine output was less after both milk drinks compared to water and the sports drink. Subjects remained in net-positive fluid balance throughout the recovery period after drinking the milk drinks, but returned to net-negative fluid balance one hour after drinking the sports and water-only drinks.

The results suggest that milk can be an effective post-exercise rehydration drink beyond that of water and the selected sports beverage used in the study. However, this study, like the endurance trial on chocolate milk, was flawed in that the intermittent exercise protocol was not reflective of the competitive environment. Additional issues relating to lactose intolerance also were ignored, and the spin put on these studies by the media was to damn sports-nutrition beverages as ineffective and expensive imitations. Failure to recognise the limitations in the study design, and other beverages with much better composition, raises questions to the reporting of these studies.

Study 3 (Muscle building): This final milk study, from the Exercise Metabolism Research Group, McMaster University (Canada), examined the effects of acute protein consumption of fat-free fluid milk or soy after resistance exercise.10 Fifty-six healthy young men carried out a resistance-training protocol (five days/week) for 12 weeks, and were randomly assigned to consume either fat-free milk, fat-free soy protein (isoenergetic, isonitrogenous and macronutrient ratio matched to milk), or a maltodextrin drink that was isoenergetic with milk and soy. Drinks were consumed immediately prior to and one hour after exercise.

Muscle-fibre size, maximal strength and body composition were measured before and after training. No differences were seen in strength between each drink. Further work looking at the explosive (Type II) and endurance (Type I) muscle-fibre types was carried out with the greater increases in milk than soy and maltodextrin groups. Fat and bone-free mass increased in all groups, with a greater increase in the milk group than in the soy or maltodextrin groups. The authors concluded that post-exercise consumption of milk promoted greater muscle growth during the early stages of resistance training compared to soy or carbohydrate-based drinks. The authors of this study, although matching based on energy and nitrogen content, failed to highlight that when comparing the soy to milk, the protein content was 37 per cent lower in the soy. Given that the premise of the study was adaptation and related to the rise in plasma amino-acid concentrations, a comparison based on protein levels (not accounted for fully in this study) may have been more appropriate.

The take-home of this work is that, in many cases, studies are biased, and set up to make milk look like it can compete and, in some cases, outperform functional sports beverages. However, it is clear that these trials should have carried out tighter-controlled designs using products designed specifically for the hypothesis at hand — milk vs a functional beverage designed for hydration and not energy delivery (see Study 2, above). Additional factors, such as performance trials, should be just that, and provide outcomes relevant to the sport. How many sports do you know have the goal of going until exhaustion? Only then will we have the data that highlight the benefits or disadvantages of milk vs the functional sports beverage.

Losing weight naturally
With the recent clamp down on claims by nutrition companies offering novel and unsubstantiated weight loss, the use of natural products with peer-reviewed evidence behind their use is becoming more advantageous for companies wanting to avoid potential litigation from regulatory government bodies.

HCA: A recent study presented at the 48th annual meeting of the American College of Nutrition highlighted the impact of the tropical-fruit extract hydroxycitric acid (HCA) on weight loss in humans.11,13 HCA is a well-known plant extract often harvested from plants such as Garcinia cambogia and Hibiscus subdariffa. Its use as a weight-loss aid has been known for some time, and the following study enhances that evidence base.

This clinical trial evaluated the effects of supplementing HCA or an HCA-based botanical matrix (HCA+) as compared to placebo (PL) for weight loss in overweight/obese healthy adults. Subjects were randomised into the following groups: 39 HCA, 39 in HCA+, and 38 in PL. The HCA was composed of a four-salt hydroxycitric acid (Ca, Mg, K, Zn), while HCA+ additionally contained banaba leaf, green-tea leaf and green coffee-bean standardized extracts. All subjects were instructed to eat a 1,500kcal/day, and received counselling.

After 12 weeks, those on the HCA lost 2.42kg compared to 5.21kg for HCA+, there was a weight gain of 0.35kg for PL. Additionally, the HCA+ group lost more fat weight than either the HCA or PL group, demonstrating a significant benefit as a dietary supplement for overweight and obese subjects looking to accelerate their weight loss during a calorie-controlled diet.

Cinnamon: Metabolic syndrome is characterised by insulin resistance, the ability to manage blood-glucose levels and increased oxidative stress. The polyphenols found in the bark of the cinnamon tree have been reported to act as an insulin-potentiating factor and as antioxidants. As such, the use of cinnamon may help alleviate many of the symptoms of metabolic syndrome and enhance weight loss.

In another study, also presented at the 48th annual meeting of the American College of Nutrition, researchers assessed the effects of cinnamon on fasting glycaemia and oxidative stress, using an animal model of the metabolic syndrome.14 Wistar rats were split into three groups, and fed a high-fructose diet for six weeks to induce the metabolic syndrome, or the same high-fructose diet plus either 2g or 20g cinnamon/kg diet.

The rats receiving cinnamon at 20g/kg of diet, but not rats fed 2g cinnamon/kg of diet, had a significant decrease in fasting glucose levels, lipid peroxidation and DNA oxidative damage. Antioxidant capacity was enhanced (as determined by the FRAP assay), as was lean-muscle mass. Study authors concluded that cinnamon might act in preventing metabolic syndrome through glucose regulation and its antioxidant functions, and suggest that it may be of benefit for people with metabolic syndrome and diabetes. Further human work is under way by this group with results expected in late 2008.

Clearly, a large market exists in the emerging natural sports-nutrition category, although this work is still in its early stages and more definitive criteria need to be used in determining what is, and what is not, natural. As an example, we could say ingredient X and ingredient Y are both natural, as they are extracts from the same fruit. However, if one had been extracted using chemicals and alcohols, and the other by only hot water, the latter would likely be considered more truly natural. This article only explores the tip of the iceberg in natural sports products, yet ongoing research related to Momordica charantia juice and raspberry extract are beyond the scope of this article.15,16,17

As the use of truly natural products such as superfruits moves from the fad and trend categories to permanent features within the FDM market, the potential for products offering a true performance benefit is huge. In this market, issues relating to novel-foods law are more easily bypassed, as is the ease of conferring a healthy functional benefit to the consumer. Superfruits and associated products are here to stay, but their sustainability and product-cycle time frame may lie in the hands of proven health claims in sports and wellness nutrition.

Mark J Tallon, PhD, is chief science officer of NutriSciences, a London-based consultancy firm specialising in health-claim substantiation, product development and technical writing.
www.NutriSciences.net.
Respond: [email protected]

For more on sports nutrition, see 'Formulations' on energy beverages and 'Ingredient Focus' on amino acids, including carnitine.

Borderline naturals stay strong
'Borderline natural' ingredients naturally occur in foods but may be processed or synthesised by chemical methods. One such ingredient is beta-alanine, found naturally in chicken, which of late has been touted as the next creatine.

This is still in the future, due to the amount of time before performance effects are experienced, and the lack of consumer education on exactly how it works. Despite these challenges as a natural product, the market is growing, and in 2007, further peer-reviewed work has surfaced.

Muscle fatigue can occur as a result of excess hydrogen ion build-up in the muscle and a subsequent fall in pH (acidosis). Increasing the concentration of compounds that delay or slow this decline in muscle pH can prolong exercise performance and/or enhance performance intensity.

In a research trial in Belgium, the carnosine precursor beta-alanine was investigated to increase carnosine stores and also improve 400-metre sprint performance in competitive athletes.1 Fifteen male athletes in a placebo-controlled, double-blind study supplemented for four weeks with either 4.8g/day beta-alanine or placebo. Performance was evaluated by five bouts of 30 maximal voluntary knee extensions, and by the indoor 400-metre running time.

Beta-alanine significantly increased muscle carnosine content. Dynamic knee-extension torque during the fourth and fifth bout was significantly improved. Isometric endurance and 400-metre race time, however, were not affected.

In sum, beta-alanine increases muscle carnosine, which attenuated fatigue in repeated bouts of exhaustive dynamic contractions. Although some benefits were shown, the duration of treatment may have been too short to enhance all performance measures taken.

— MJT


Select Suppliers: Sports & weight-loss suppliers

Bioenergy
Ribose accelerates energy recovery, useful in foods and supplements.
www.bioenergy.com

Core Naturals
Salba is available as a seed or oil for foods, and its high-quality protein content, as well as stores of magnesium, potassium, calcium and iron make it a novel ingredient to replenish minerals used in muscle contractions and lost in sweat.
www.salbausa.com

Danisco
Litesse polydextrose is a 1kcal/g carbohydrate that replaces sugar and fat in cookies, cakes, beverages and more. Lactitol is a reduced-calorie sweetener for formulating sugar-free products.
www.danisco.com

Draco Natural Products
Pomegranate is one of a bevy of full-spectrum fruit and vegetable extracts.
www.dracoherbs.com

DSM
PeptoPro was the original protein entrant to the sports-drink market, good for making clear, stable peptide drinks that are not bitter. Fabuless, available for select European markets, has applications in supplements as well as dairy because it adds creamy texture attributes.
www.dsm.com

Gencor Pacific
Slimaluma, an extract of Caralluma fimbriata, acts as an appetite suppressant.
www.gencorpacific.com

Glanbia Nutritionals
This Ireland-based global supplier has an extensive line of branded whey-protein concentrates, isolates and fractions.
www.glanbianutritionals.com

Integrity Nutraceuticals
Cinnulin PF is the company's flagship weight-management ingredient, a water-soluble cinnamon extract that modulates blood-sugar levels. Other ingredients in the portfolio include iFAS503, Lipolide-SC, Razberi-K, ThermoDiamine and RC-NOS.
www.integritynut.com

InterHealth
Super Citrimax is an all-natural plant extract containing hydroxycitric acid, which helps suppress appetite and inhibit fat production without stimulating the central nervous system.
www.interhealthusa.com

Kerry Americas
Nutriant Soy Ingredients provide natural and organic soy ingredients. Dairy proteins provide functional and nutritional milk proteins for bars, beverages, desserts, confections, baked goods, cereal and dairy applications.
www.kerryamericas.com

Lipid Nutrition
PinnoThin is an appetite suppressant for use in supplements and foods such as nutritional bars and yoghurts.
www.lipidnutrition.com

Lonza
Carnipure is a grade of L-carnitine produced via fermentation, and includes Carnipure crystalline, Carnipure tartrate, Carnipure Mg citrate and Carnipure ALC.
www.lonza.com

Naturex
Svetol, a water-soluble extract of decaffeinated green coffee beans, works as a fat burner by decreasing the glucose intestinal absorption and by inhibiting the glucose-6-phosphatase (G-6-Pase) in the liver. MacaTonic is a water-soluble extract of maca that promotes energy and endurance with no caffeine or stimulants.
www.svetol.com
www.naturex.com

Nutraceuticals International
For weight management, Cha' de bugre acts as a stimulant while Hoodia gordonii acts as an appetite suppressant.
www.nutraceuticalsintl.com

Nutratech
Advantra Z is Citrus aurantium, a thermogenic ingredient for weight loss and sports nutrition.
www.nutratechinc.com

Orafti
Beneo Synergy1, an FOS-enriched inulin prebiotic, has been shown to help curb excessive weight gain in healthy adolescents.
www.orafti.com

Phase 2
The starch blocker food supplement derived from the white kidney bean has attained GRAS status for integration into foods.
www.phase2info.com

Roquette
Maltisorb crystalline maltitol replaces sucrose on a weight-for-weight basis, especially useful in chewing gum, chocolate and baked goods.
www.roquette.com

Sabinsa
CitrinK is a Garcinia cambogia extract used to help maintain healthy body weight and energy balance. Cococin is a proprietary composition of freeze-dried coconut-water solids that delivers a high amount of electrolytes. ForsLean increases lean body mass and improves overall body composition.
www.sabinsa.com

Sigma-tau
AminoCarnitines are an innovative line of distinct forms of L-carnitine, along with a specific amino acid in one distinct molecule, such as Acetyl-L-Carnitine Arginate Dihydrochloride and Acetyl-L-Carnitine Taurinate Hydrochloride.
www.aminocarnitines.com

TSI Health Sciences
Peak ATP provides the exact molecule the body needs to create energy. HMB is the company's patented leucine metabolite for enhancing muscle mass and strength. Promilin promotes healthy glucose levels and insulin utilisation.
www.tsiinc.com


All-natural functional ingredients for performance and weight management

  • Superfruits

  • Blueberries

  • Grapefruit

  • Mangosteen

  • Cherries

  • Raspberries

  • Momordica charantia juice

  • Milk

  • Whey

  • Hydroxycitric acid (HCA)

  • Garcinia cambogia

  • Cinnamon


References
1. Hurst RD, et al. Blueberry fruit extracts suppress oxidative stress induced damage in skeletal muscle cells. 3rd International Conference on Polyphenols Applications in Nutrition and Health : Stalellite Symposium on Natural Antioxidants and Polyphenols : Valorization from Fruit & Vegetable Wastes, 26-27 October 2006, St Julian, Malta. Pp. 95. (Poster.)
2. S. Lafay. Powergrape, a grape extract rich in procyanidins, reduce exercise-induced oxidative stress of professional soccer player. 3rd International Conference on Polyphenols Applications in Nutrition and Health : Stalellite Symposium on Natural Antioxidants and Polyphenols : Valorization from Fruit & Vegetable Wastes, 26-27 October 2006, St Julian, Malta.
3. Palu AK, et al. The potential fat burning effects of the liquid supplement Mango.Xan?. Abstract 149. 62nd annual meeting of the Northwest Region of the American Chemical Society. 2007.
4. Connolly DA, et al. Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage. Br J Sports Med 2006; 40(8):679-83;
5. Dangin M, et al. Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr 2002;132:3228S—33S.
6. Bouthegourd JC, et al. A preexercise alpha-lactalbumin-enriched whey protein meal preserves lipid oxidation and decreases adiposity in rats. Am J Physiol Endocrinol Metab 2002;283:E565—72.
7. Karp JR, et al. Chocolate milk as a post-exercise recovery aid. Int J Sport Nutr Exerc Metab 2006;16(1):78-91.
8. Stevenson EJ, et al. (2007) The effects of consuming chocolate milk on recovery of endurance capacity in cycling. J Int Soc Sports Nutr Abstract 17.
9. Shirreffs SM, Watson P, Maughan RJ. Milk as an effective post-exercise rehydration drink. Br J Nutr 2007;98(1):173-80.
10. Hartman JW, et al. Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. Am J Clin Nutr 2007;86(2):373-81.
11. Derave W, et al. beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. J Appl Physiol 2007;103(5):1736-43
12. Suzuki Y, et al. Carnosine and anserine ingestion enhances contribution of nonbicarbonate buffering. Med Sci Sports Exerc 2006;38(2):334-8.
13. Kalman DS, et al. Hydroxycitric Acid (HCA) and an HCA combination for weight loss in overweight/obese adults. 48th Annual Meeting of the American college of nutrition. Florida USA.2007. Abstract 65.
14. Roussel AM, et al. Beneficial effects of cinnamon on oxidative stress, muscle mass and glycemia in rats with metabolic syndrome. 48th Annual Meeting of the American college of nutrition. Florida USA.2007. Abstract 73.
15. Chan LL, et al. Reduced adiposity in bitter melon (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. J Nutr 2005;135(11):2517-23.
16. Sridhar MG, et al. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats. Br J Nutr 2007; 17:1-7.
17. Morimoto C, et al. Anti-obese action of raspberry ketone. Life Sci 2005 27;77(2):194-204.

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