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This post was originally published on New Hope 360. It is republished with the author's permission.
The one pharmaceutical solution to weight loss - GSK's Alli - is going off the market later this year. Can you say “opportunity?” Douglas S. Kalman, Ph.D., RD, rounds up the science on some promising ingredients in the ever-growing category of weight management and blood sugar control.
Douglas Kalman, PhD, RD: It is no surprise that the weight-control category for dietary supplements and foods grows each year. It's startling to note that approximately 68 percent to 72 percent of Americans are now classified as either overweight or obese; but it provides an impetus for the concomitant growth of the sales of these foods and products. Accessed 4-19-2011.Flegal KM, Carrroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity amongst US Adults 1999 - 2008. JAMA 2010;303(3):235-241. When looking at the data, we see that African-Americans had 51 percent higher prevalence of obesity, and Hispanics had 21 percent higher obesity prevalence compared with Caucasians - data that further indicate a larger risk of developing diabetes and other cardiovascular-related co-morbidities.1,2 In adults, the rate of obesity (classified as a body mass index of > 27) was 32.2 percent for men and 35.5 percent for women. Being overweight and/or obese increases risks for many quality-of-life issues as well as medical disorders and conditions.Shin JY, Lee HR, Lee DC. Increased arterial stiffness in healthy subjects with high-normal glucose levels and in subjects with pre-diabetes. Cardiovasc Diabetol. 2011 Apr 15;10(1):30
Diabetes and heart disease are considered among the secondary effects of being overweight/obese. Pre-diabetes is defined as a fasting blood sugar level between 100 and 126mg/dl, whereas diabetes is defined as a fasting blood sugar level at 126mg/dl or higher.//www.diabetes.org/diabetes-basics/prevention/pre-diabetes/pre-diabetes-faqs.html. Accessed April 23, 2011.
It has been estimated that the sector of weight-loss or control products and services generates $33 billion per year. Amazingly enough, the pharmaceutical giant GlaxoSmithKline (GSK) has announced plans to stop selling its Alli weight-loss pharmaceutical by the end of 2011.//www.medcitynews.com/2011/04/gsk-to-shed-weight-loss-drug-alli-and-18-other-otcs-sale-expected-by-years-end/ Accessed April 23, 2011. This spells opportunity in this sector for dietary supplements with the following potential ingredients or products for weight and blood-sugar control.
Garcinol is powered by a polyisoprenylated benzophenone active isolated from Garcinia cambogia and Garcinia indica, fruiting evergreen shrubs native to Southeast Asia. It is believed that Garcinol (as in, GarCitrin) enhances the absorption of the biological actives from alpha-hydroxy citric acid (1,2-dyhydroxypropane-1,2,3-tricarboxylic acid). The (-) isomer of hydroxycitric acid has been shown to be a competitive inhibitor of adenosine triphosphate citrate lyase, while also being involved in increasing energy expenditure.Sullivan AC, Singh M, Srere PA, Glusker JP. Reactivity and inhibitor potential of hydroxycitrate isomers with citrate synthase, citrate lyase and ATP citrate lyase. J Biol Chem1977;252(21):7583-7590Vasselli JR, Shane E, Boozer CN, Heymsfield SB. Garcinia cambogia extract inhibits body weight gain via increased energy expenditure in rats. FASEB J1998;12(part 1):A506.
In short, this means that inhibiting citrate lyase results in the body having less to no ability to synthesize fat or make new fat (lipogenesis). When energy expenditure is enhanced, the result is that extra calories are burned, making weight control that much easier.
Garcinol is a fruit antioxidant with other health-related qualities. More recently, garcinol has been combined with (-) hydroxycitric acid in animal trials, showing a protective effect against body-weight gain.Tanaka T., et al. Prevention of colonic crypt foci by dietary feeding of garcinol in male F3444 rats. Carcinogenesis 2000;21(6):1183-1189.Sang S, Pan MH, Cheng X, Bai N, Stark RE, Rosen RT, Lin-Shiau SY, Lin JK, Ho CT: Chemical studies on antioxidant mechanism of garcinol: analysis of radical reaction products of garcinol and their antitumor activities. Tetrahedron 2001, 57:9931-9938.Padhye S, et al. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs. Journal of Hematology & Oncology2009,2:38. doi:10.1186/1756-8722-2-38.
A recent study in 46 overweight women demonstrated that over a 12-week period, more subjects in the group taking the active product lost weight. They lost more weight than the control group and the product seemed to help with appetite control. More studies are needed however; the combination of garcinol with hydroxycitric acid as a weight control product seems promising - much more promising than standard hydroxycitric acid alone.
7-Keto DHEA (3-acetyl-7-oxo-dehydrepiandrosterone, or 3-acetyl-7-oxo-DHEA) is actually 3 beta-acetoxyandrost-5-ene-7, 17-dione; however, the trade and popular name of this naturally occurring ingredient is 7-Keto. (7-Keto has been approved by the Food and Drug Administration as a New Dietary Ingredient.) 7-Keto has undergone multiple clinical research studies that have been published in the peer-reviewed scientific literature. From pharmacokinetic to outcome-based weight-loss trials, 7-Keto has been shown to be safe, well tolerated and effective for aiding in weight loss.Davidson M, Marwah A, Sawchuk RJ et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydrepiandrosterone in healthy male volunteers. Clin Invest med 2000;23(5):300-310.Kalman DS, Colker CM, Swain MA, et al. A randomized double blind, placebo-controlled study of 3-acetyl-7-oxo-dehydrepiandrosterone in healthy overweight adults. Curr Ther Res Clin Exp 2000;61:435-442.Zenk JL, Helmer TR, Kassen LJ, Kuskowski MA. The effect of 7-Keto Naturalean™ on weight loss: a randomized, double-blind, placebo controlled trial. Curr Ther Res 2002;63(4):263-272.Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of Thermogenic compounds, and 3-acetyl-7-oxo-dehydrepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem2007;18:629-634.
For example, 7-Keto, when combined with a sensible diet (in the study, sensible equaled ~1800 calories per day) and 180 minutes of cumulative exercise per week (60 minutes of cross training three times per week), resulted in about two to three times the weight loss of dieting and exercise alone. Subjects taking the 7-Keto also lost a significant amount of body fat as compared to those on placebo.Kalman DS, Colker CM, Swain MA, et al. A randomized double blind, placebo-controlled study of 3-acetyl-7-oxo-dehydrepiandrosterone in healthy overweight adults. Curr Ther Res Clin Exp 2000;61:435-442.
In a follow-up study by different researchers, the same weight-loss effects were observed - almost three times the amount of weight loss for the group receiving 7-Keto than the placebo group.Zenk JL, Helmer TR, Kassen LJ, Kuskowski MA. The effect of 7-Keto Naturalean™ on weight loss: a randomized, double-blind, placebo controlled trial. Curr Ther Res 2002;63(4):263-272. Thus, two studies by separate and different researchers found that the ingredient, when dosed at 200mg/day and combined with a realistic diet (1,800 calories is far from starving), significantly aided in weight loss.
It is believed that 7-Keto does this by enhancing futile metabolic cycling (calories are expended, but are not used for energy; also known as proton slipping).
A third study aimed to determine if 7-Keto could decrease the known metabolic fall (slowing of metabolic rate when an overweight or obese person loses weight) associated with weight loss. It has been demonstrated that when people go on extremely low-calorie diets, the body fights back (part of the set-point theory) by slowing metabolism. One way to offset this is to stimulate metabolic rate during caloric restriction. A recent study found that dieting plus placebo resulted in a decreased metabolic rate of ~3.9 percent, whereas dieting plus 7-Keto significantly increased the metabolic rateby 1.4 percent. This difference alone was about 100 calories per day, which over a year's time, if all else remains the same, would equate to a 10-pound weight loss difference.Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of Thermogenic compounds, and 3-acetyl-7-oxo-dehydrepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem 2007;18:629-634.
Polyphenol-rich seaweed extracts (Ascophyllum nodosum and Fucus vesiculosus) are used as a source of naturally occurring starch and sugar blockers. These are extracts from brown seaweed and work by affecting alpha-amylase (an enzyme used to degrade starches) as well as alpha-glucosidase (an enzyme used for sugar metabolism).Apostolidis E, Lee CM. In vitro potential of Ascophyllum nodosum phenolic antioxidant-mediated alpha-glucosidase and alpha-amylase inhibition. J Food Sci. 2010;75(3):H97-102.
Prescription alpha-glucosidase inhibitors exist (Precose, made from fermented Actinoplanes utahensis), but they are not popular in the United States.//www.rxlist.com/precose-drug.htm Accessed April 24, 2011.
Preliminary research conducted by the Scottish Crop Research Institute has shown that these polyphenols have a real effect.//www.scri.ac.uk/webfm_send/600 Accessed April 27, 2011. The product InSea2, made by innoVactiv, also has human data demonstrating that the laboratory-observed effect occurs in humans, approximating a 48 percent lower post-meal blood sugar, a 12 percent reduction in insulin and an approximate 8 percent improvement in insulin sensitivity.Personal communication. Scott Steil, innoVactiv data report, November 26, 2010.
Controlling blood sugar by modulating how the body metabolizes sugars and starches from foods can also be used to deal with type 2 diabetes. Therefore, a natural cost-saving approach will likely have a carry-over effect for other healthy habits and results.
Citrus aurantium is the scientific name for the Seville orange, or bitter orange.The bioactives in supplements bearing this name are derived from the Seville orange as well as other citrus fruits and certain strains of potatoes. Not all supplements sold under the Citrus aurantium aegis are the same (“bioequivalent”). The branded Advantra Z appears to be the only Citrus aurantium that has been clinically studied for its potential to be a thermogenic agent that also aids in weight control.
Advantra Z is comprised of para-synephrine along with N-methyltyramine, hordenine, octopamine and tyramine. The para-synephrine is the predominant biogenic amine. These “amines” bind to beta-3-adrenergic receptors in the body aiding in a process known as lipolysis (breakdown of fat), while also having a metabolic rate burning effect.Arch JR and Ainsworth AT. Thermogenic and antiobesity activity of a novel beta-adrenoreceptor agonist (BRL26830A) in mice and rats. Am. J. Clin. Nutr, 1999;38; 549-554.Carpene C, GalitzkyJ, Fontana E, Algie C, Lafontan M, Berlan M. Selective activation of beta3-adrenoreceptors by octopamine: comparative studies in mammalian fat cells. Naunyn Schmiedebergs Arch. Pharmacol. 1999;359; 310-321.Sale C, Harris RC, Delves S, Corbett J. Metabolic and physiological affects of ingesting extracts of bitter orange, green.tea and guarana at rest and during treadmill walking in overweight males. Int. J. Obesity 2006;30; 764-773.Tsujita T and Takaku T. Lipolysis induced by segment wall extract from Satsuma mandarin orange (Citrus unshu Mark). J. Nutr. Sci. Vitaminol. 2007;53; 547-551.Gougeon R, Harrigan K, Tremblay JF, Hedrei P, Lamarche M, Morais JA. Increase in the thermic effect of food in women by adrenergic amines extracted from Citrus aurantium.Obesity Res. 2005;13; 1187-1194.
The studies that have been done for the most part have used this Citrus aurantium as part of a multi-ingredient formula. However, one study added the ingredient to a meal and compared the effect on metabolism in men and women.Gougeon R, Harrigan K, Tremblay JF, Hedrei P, Lamarche M, Morais JA. Increase in the thermic effect of food in women by adrenergic amines extracted from Citrus aurantium. Obesity Res. 2005;13; 1187-1194. Interestingly enough, Citrus aurantium when added to a meal significantly enhanced the amount of calories burned from that meal (thermic effect of feeding) in women. This, when coupled with the previous research, provides a glimpse into potential use of this ingredient along with any of the aforementioned ingredients, or as a stand alone method in females to aid in enhancing caloric expenditure and ultimately, weight loss.
Wrapping Weight, Waist, and Blood-Sugar Control
The purpose of this article is to share published science that could be considered defendable, reproducible or of interest for those who are interested in the science of ingredient selection. It very well may be that these and other ingredients when used in combination have synergy to help the end user obtain his or her goal. We know that caffeine alone often has synergy with other metabolic regulating ingredients. We also know that there is growing research on other starch blockers for blood sugar control and potential for weight loss. Ultimately, weight, waist and blood sugar control are often best approached by lifestyle choices within which these types of products may fit in best while having the most chance at consumer success.
Douglas S. Kalman, Ph.D., is a director in the Nutrition and Endocrinology Division of Miami Research Associates (MRA). MRA conducts contract research for the pharmaceutical, medical device, biotechnology, food, nutrition, dietary supplement industries. He can be reached at [email protected] via Miami Research Associates.