Nutrition in Clinical Practice

3 downloads 0 Views 329KB Size Report
Oct 5, 2011 - lars out of pocket to treat illness or improve health in gen- eral.7,8 In 2007, 25% of U.S. ... nonprescription dietary supplements.12 Worse still is that users and nonusers of ...... Supplement Health and. Education Act of 1994.

Nutrition in Clinical Practice http://ncp.sagepub.com/

Nutraceutical Supplements for Weight Loss : A Systematic Review Kavita Poddar, Sanjivani Kolge, Lena Bezman, Gerard E. Mullin and Lawrence J. Cheskin Nutr Clin Pract 2011 26: 539 DOI: 10.1177/0884533611419859 The online version of this article can be found at: http://ncp.sagepub.com/content/26/5/539

Published by: http://www.sagepublications.com

On behalf of:

The American Society for Parenteral & Enteral Nutrition

Additional services and information for Nutrition in Clinical Practice can be found at: Email Alerts: http://ncp.sagepub.com/cgi/alerts Subscriptions: http://ncp.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav

>> Version of Record - Sep 26, 2011 What is This?

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Invited Review

Nutraceutical Supplements for Weight Loss: A Systematic Review

Nutrition in Clinical Practice Volume 26 Number 5 October 2011 539-552 © 2011 American Society for Parenteral and Enteral Nutrition 10.1177/0884533611419859 http://ncp.sagepub.com hosted at http://online.sagepub.com

Kavita Poddar, PhD, CNS, LDN1; Sanjivani Kolge, MD1; Lena Bezman, MD2; Gerard E. Mullin, MD3; and Lawrence J. Cheskin, MD1,3 Financial disclosure: none reported. among nutraceutical agents promoted for weight loss, as well as advice for incorporating healthy alternatives in the diet. (Nutr Clin Pract. 2011;26:539-552)

Obesity is a global public health issue. Although the etiology of this global epidemic is multifactorial, most sufferers would be delighted to find a relatively effortless way to lose weight. Herbal “weight loss pills” can fit the bill. The authors systematically review the scientific evidence concerning various weight loss agents that are available over the counter or in food stores. The review provides a starting point to make informed choices

Keywords:  weight loss; anti-obesity agents; dietary supplements; obesity

O

besity is now recognized as a pathological condition, one that has a direct effect on morbidity and mortality. One-third of the adult American population is now obese (age-adjusted prevalence of obesity being 33.8% in 2007–2008), and another third is overweight, for a combined prevalence of 68%.1 The epidemic of obesity is expanding worldwide, which makes obesity a global public health problem.2 Although the etiology of this global epidemic is multifactorial,2-5 most individuals afflicted by this condition would be delighted to find a relatively effortless way to lose weight. Alternative medicines have been used worldwide for many years to treat illness or promote health.6 Health services such as massage therapy, acupuncture, chiropractic care, and natural and herbal products can all be defined as alternative therapy. Americans are spending billions of dollars out of pocket to treat illness or improve health in general.7,8 In 2007, 25% of U.S. adults reported using different forms of complementary and alternative medicine (CAM) for health promotion, whereas an additional 17% reported using it for treating an illness.6 Surveys consistently show that nutraceutical supplements (vitamins and herbs) and

unconventional methods are the most common forms of CAM used in the United States.8-10 Although use of complementary therapy and alternative medicine is low in those who are obese,11 recent data on the use of dietary supplements for weight loss suggest that more than 30% of those who have attempted serious weight loss have used nonprescription dietary supplements.12 Worse still is that users and nonusers of dietary supplements assume that these supplements have been evaluated for safety and efficacy.12 In reality, few scientifically rigorous studies have been conducted to assess the efficacy of the various agents touted as useful, and anecdotal stories of efficacy are marred by selection bias, exaggerations, and folklore. The limited clinical trials and case reports are widely scattered in the medical literature, making it difficult to compile them and reach a valid conclusion regarding the effects. The material that follows details what has been published regarding most of the botanically derived agents that have any data to support possible efficacy.

Dietary Fiber Dietary fiber intake is associated with a plethora of health benefits, including reduced risk of developing coronary heart disease, hypertension, stroke, and dyslipidemias.13 In addition, high intake of dietary fiber is associated with improved insulin sensitivity and may aid in weight loss and weight maintenance among obese individuals.13 However, data on dietary fiber intake in Americans indicate that Americans are far from consuming the recommended levels (25 g/d for adult women; 38 g/d for adult

From 1Johns Hopkins Weight Management Center, Department of Health, Behavior & Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 2Kennedy Krieger Institute, Baltimore, Maryland; and 3Department of Medicine, Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland. Address correspondence to: Lawrence J. Cheskin, MD, Johns Hopkins Bloomberg School of Public Health, 550 N Broadway, Suite 1001, Baltimore, MD 21205; e-mail: [email protected]

539

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

540   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

men) of fiber.13 This is likely because American diets lack adequate amounts of whole-grain foods, fruits, vegetables, and legumes,14-16 which are associated with high fiber intake, low energy density, and high nutrient density.17-20 Moreover, high fiber intake has been associated with lower body mass index (BMI) and enhanced weight loss and weight maintenance.19,20,22-24 Thus, dietary fiber supplements may provide adjunctive benefit for weight loss/weight maintenance in those seeking to lose weight. Fibers are also classified as dietary fibers, which consist of intrinsic and intact carbohydrates in plants, and functional fibers, which consist of carbohydrates that have a beneficial physiological effect in humans.25,26 All types of fibers are essentially nondigestible by the human gut, although they may be acted upon by gut microflora.25,26 In simple terms, fibers are classified as soluble or fermentable fibers and insoluble fibers, which can be fermented by gut microflora and provide bulk.25,26 Soluble fibers are natural gel-forming fibers such as pectin, gum, and mucilage, and insoluble fibers are structural fibers such as cellulose, lignin, and some hemicellulose.25,26 Fibers are components of a healthful diet and add bulk,25,26 thereby decreasing the energy density of foods.17-21 Insoluble fiber has been shown to decrease subjective appetite and thereby food intake.27 Soluble fibers exert a hygroscopic effect, by which they slow absorption of energy-dense macronutrients. A fiberrich diet has been shown to provide high satiety compared to a low-fiber diet.28 These effects have been observed both during a meal and between meals.28

Psyllium Psyllium, one of the water-soluble fibers, is derived from blonde psyllium seeds; it ferments slowly, helps build up fecal mass,29 and is commonly available over the counter as a laxative.30 Several studies have shown that psyllium supplementation may lower or improve risk factors that are associated with the development of cardiovascular diseases and diabetes, including obesity.31-37 Psyllium supplementation (up to 3.5 g per meal) may have significant beneficial effects on body composition changes in obese individuals, which include BMI and waist circumference, while causing minimal or no abdominal discomfort.31-33 Some data from randomized clinical trials indicate that psyllium supplementation at doses higher than 3.5 g per meal does not have these effects on body composition in obese individuals, but improvements in metabolic risk factors are still evident.35 However, higher doses of psyllium and overall fiber intake per meal (>3.5 g per meal) are associated with significant abdominal discomfort.34,35 Although some observations support the role of psyllium in treating obesity,31-34 inconsistency in data makes it difficult to draw definitive conclusions.35 Still, we can definitely conclude that psyllium has beneficial effects on risk factors associated with the development of cardiovascular diseases.36-38

Konjac Root Fiber Konjac is a plant local to Asian countries, especially India, Japan, and Korea. It contains glucomannan, which is a fermentable, highly viscous dietary fiber. This fiber has been shown to assist in weight loss and improve lipid profile.39,40 Walsh et al40 reported that glucomannan 1 g 3 times a day produced significant weight loss (~5.5 lbs) in obese individuals without any adverse effects. In contrast, 1 study that used a combination of psyllium (3 g/d) and glucomannan (1 g/d) showed no effect on body weight but found hypolipidemic effects.34 Konjac root fiber may have beneficial effects on improving metabolic parameters41-43 and may produce modest weight loss, but larger clinical trials are needed. Studies that found an effect of glucomannan alone were had small sample sizes (n = 20–30).40-43 No adverse events or abdominal discomfort have been reported with the use of this fiber supplement in amounts ranging from 3–4 g/d.40-43 However, its use in those seeking weight loss is inconclusive, and more research with body weight as a primary end point is warranted.

Chitin Chitin is component of crab, shrimp, and lobster shells and thus abundantly available in nature.44 Like dietary fiber, chitin is a polysaccharide that is indigestible by the human gut. Chitosan is deacetylated chitin. In rats, chitosan has been shown to decrease hepatic cholesterol and increase bile acid and fat excretion.45 In contrast, in humans, a combination of chitosan and glucomannan seems to decrease serum cholesterol (via fecal steroid excretion but not fat excretion).46 The exact mechanism of action is not well understood; however, it has been shown that negatively charged lipid molecules avidly bind to the positively charged tertiary anion group of chitosan polysaccharide, and this decreases absorption.46,47 There are not sufficient human studies to prove a beneficial effect of chitosan for weight loss. One metaanalysis reviewed 14 studies that tested the effect of chitosan on weight loss and concluded that it causes a small net effect of approximately 1.7 kg.48 Furthermore, results from the high-quality clinical trials reviewed were clinically insignificant (–0.6-kg weight loss) compared with those from lower quality studies (–2.3-kg weight loss), further suggesting that chitosan may not be effective for weight loss.48 Overall, human studies have yielded mixed results,48,49 having been conducted on a small scale and over a short duration.50 Moreover, many studies of chitosan show that it is ineffective for weight loss.51-55 Only 1 study was found that reported significant improvements in body composition with chitosan supplementation (3 g/d) in overweight adults.56 In sum, studies suggest that chitin/chitosan probably has some weight reduction and cholesterol-lowering effects, but these effects are not clinically significant at reasonable doses (3–6 g/d).51-55

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Nutraceutical Supplements for Weight Loss / Poddar et al   541

Guar Gum Guar gum is derived from the Indian cluster bean (Cyamopsis tetragonolobus) and is known to exert its action via imparting postprandial fullness and increasing bowel viscosity, which in turn may result in reduced appetite, lower food intake, and improved satiety.57-60 Reduced appetite and higher satiety may have an impact on weight loss in obese individuals via lower energy intake; however, evidence from studies on the effects of guar gum supplementation indicate that it may not help in weight loss.57,61 One meta-analysis of randomized controlled trials concluded that it had no significant effects on weight changes in obese individuals.61 Since the meta-analysis, only 1 study has been identified that tested the effect of guar gum on body weight.59 However, this study did not include weight as a primary measure and concluded that guar gum supplementation had an effect on satiety but did not result in changes in body weight.59 In summary, studies on dietary fiber supplements do not provide strong evidence that they may support weight loss. The purported mechanism via which they may induce weight loss includes increased satiety, reduced appetite, and blockage of dietary fat absorption. Although some gastrointestinal discomfort/bloating may accompany acute increases in extract-based or dietary fiber intake, in general, fiber supplementation does not entail significant adverse effects. Dietary fiber is one alternative medicine that can be obtained from a wisely chosen regular diet. When needed, supplements are readily available in supermarkets and pharmacies over the counter.

Garcinia cambogia (Rind of Brindell Berry) Garcinia cambogia is native to Southeast Asia. It has been proposed that hydroxycitric acid (HCA), the active ingredient in G cambogia, competitively inhibits adenosine triphosphate–citrate lyase, an extra-mitochondrial enzyme that may inhibit de novo lipogenesis and reduce appetite in some in vivo studies.62 However, evidence of a positive effect of G cambogia as a weight loss agent is lacking.63-65 One study evaluated the efficacy of this compound (1500 mg/d) on weight and body fat loss in overweight participants and concluded that it did not produce significant changes in the intervention group beyond that seen in the placebo group.63 Preuss et al66 demonstrated weight loss efficacy of this compound but found that the results were better when it was administered in combination with other active agents. One other study showed that supplementation with HCA did not alter fat oxidation and energy expenditure,67 thus reporting conflicting results in comparison to studies that support the role of HCA in fat oxidation.68 More research is warranted regarding the role of this compound in weight loss. One review evaluated the safety of G cambogia and reported no significant health hazards69 vs

another study that did report adverse events.63 In summary, HCA decreases fatty acid synthesis and reduces appetite, but further data in humans are needed to determine its role in weight loss. Evidence on safety and efficacy of the compound is vague, and at this point, no conclusion can be drawn. One needs to use caution before recommending and/or using it as a weight loss agent.

Conjugated Linoleic Acids Conjugated linoleic acids (CLAs) are positional and geometric isomers of linoleic acid, a polyunsaturated fatty acid. CLAs are available in the trans and, more abundantly, in the cis form in meat and dairy products. Several studies have been conducted using in vivo and in vitro models to assess the effect of CLA in cancer, diabetes mellitus, atherosclerosis, immune modulation, and possibly weight loss.70,71 Although these studies have shown health benefits in the in vivo and in vitro models,70 there is lack of enough evidence to support these health benefits in humans.71 Various mechanisms of action have been proposed via which CLA isomers may exert the effect on weight loss in animal models.72-76 In general, they reduce fat synthesis and increase oxidation. However, human trials with CLA provide weak or no evidence to support the role of this compound in the treatment of obesity with varying conclusions.77-82 These results make it difficult to understand the definitive role of CLA on body composition changes in humans. A meta-analysis performed of 18 human studies reached the conclusion that CLAs do possess a beneficial effect on body composition, which, although modest, may play an important role cumulatively over time.80 Although data from in vitro and in vivo studies provide strong support for the role of CLA in weight loss, evidence from human studies has led to conflicting results, suggesting a need for further research.

Teas (Camellia sinensis) Camellia sinensis, the tea plant, is native to southwest China and is grown on a large scale in various tropical countries.83 The processing of tea leaves leads to 3 different types of teas—namely, green tea (20% is produced worldwide and mainly consumed in Asian countries), black tea (78% is produced worldwide and is consumed by Western countries), and oolong tea (2% is produced worldwide and is consumed in southern China).83 All 3 types of teas are brewed differently and undergo partial fermentation and oxidation processes and possess different percentages of polyphenols called catechins.83 Green tea undergoes minimal oxidation and is steamed soon after harvesting to prevent further oxidation. Oolong tea has oxidation levels between green tea and black tea.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

542   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

Black tea is completely oxidized tea and is very popular in some parts of Asia, such as India, and in Africa.83 Teas are perhaps the most widely used alternative medicinal agents. They are inexpensive, are readily available, and have a large spectrum of positive health effects ranging from antioxidative, anticarcinogenic, antidiabetogenic, and antiobesogenic properties.83 Teas are becoming popular for potential benefits in preventing cardiovascular risk factors and longevity as well.83 Health benefits associated with tea consumption are mainly attributed to the polyphenolic compounds called catechins present in them.83 These health benefits depend on the amount of tea consumed along with the type of tea and the bioavailability of the catechins.83 Although different teas are associated with different health benefits, for the purpose of the current review, the role of green tea in the prevention of weight gain will be discussed.

Green Tea The main active polyphenolic compounds found in green tea preparations are (–)-catechin gallate (CG), (–)-gallocatechin gallate (GCG), (–)-epicatechin gallate (ECG), and (–)-epigallocatechin gallate (EGCG); caffeine; proanthocyanidins; and flavonols (myricetin, caempherol, quercetin).84 Green tea has been evaluated in multiple clinical trials for cancer-protective, cardioprotective, antioxidant, and weight loss effects. Although a detailed discussion of its non-weight-related effects is beyond the scope of this article, green tea has been evaluated for and shown to have convincing anticancer effects85-88 and can help prevent the metabolic syndrome by a cholesterol-lowering effect.89 The results related to weight control benefits are more mixed, although multiple studies have shown that catechin-rich (>500 mg/d) green tea significantly reduces body weight and fat.90-94 Researchers have postulated that the active ingredients in green tea help achieve weight reduction via several possible mechanisms: increase in energy expenditure, fat oxidation, and suppression of the lipogenic enzyme fatty acid synthetase, thereby inhibiting lipogenesis.95 It has also been postulated that caffeine in tea may act synergistically with catechins to increase fat oxidation and energy expenditure. In addition, green tea catechins may upregulate enzymes involved in hepatic fat oxidation.95 A recent meta-analysis of 11 clinical trials concluded that catechin-caffeine mixtures may have a small positive effect on weight maintenance via fat oxidation and thermogenesis.96 The magnitude of the effect may vary based on race and level of habitual tea intake.96 However, at least 2 clinical trials contradict these abovementioned conclusions.97,98 One study suggested that low habitual intake of catechin from green tea and caffeine together (270 mg green tea catechin and 150 mg caffeine per day) may assist in weight maintenance after weight loss.99 Caffeine is another constituent of green tea83,84

that has been evaluated for weight loss and is postulated to increase energy expenditure independently.100 These ingredients may work synergistically to effect weight loss. Two studies have been performed with oolong tea as a long-term adjunct for weight reduction; its effect is likely due to its similar active ingredients and same mechanisms of action as green tea.101,102 There are no known adverse effects of green tea and other teas, and they may serve as an adjunct therapy for weight loss.

Caffeine Caffeine is the main active ingredient of the most commonly consumed beverages in the world—namely, coffee, tea, and caffeine-containing drinks that include sodas and sports and energy drinks.103 Caffeine content varies in all these beverages, with the highest being in teas and coffee, in which it is present naturally.103 Variability in the amount of caffeine present in coffee and tea also is dependent on the environmental conditions, such as how it is grown and brewed. On average, 100 mg of caffeine is present in one 8-oz cup of coffee.103 Caffeine is known to have varied health effects in humans. It is generally known as a central nervous system stimulant. It is known to enhance mood, increase alertness, and improve exercise performance.103 Its use in weight control has been evaluated primarily in combination with the catechins in green tea96,99,104 and with ephedrine.105 One study assessed the effect of caffeine intake on body weight in a 12-year prospective study and concluded that an increase in caffeine intake led to reduced weight gain over a period.106 In contrast, a meta-analysis showed that caffeine and catechins together, and not caffeine alone, produce modestly significant reductions in body weight, waist circumference, and BMI.104 A similar double-blind placebocontrolled study showed that caffeine (200 mg/3 times a day) along with ephedra (20 mg/3 times a day) was effective in reducing body weight.105 One study examined the effect of habitual caffeine intake on body weight of obese individuals and concluded that caffeine intake is associated with modest weight loss via thermogenesis and fat oxidation, and habitual low caffeine consumption is associated with weight maintenance.96 However, most of the studies conducted in humans with caffeine are in combination with teas and/or ephedra, making it difficult to draw the exact conclusion that caffeine consumption may have on weight loss. Various mechanisms have been proposed to explain caffeine-induced weight loss. One of them is thermogenesis. Caffeine consumption has been shown to increase the energy expenditure by about 150 kcal in lean subjects and 79 kcal in obese subjects, thereby playing significant role in weight loss.107 Energy expenditure was found to be elevated for several hours after the caffeine intake (as

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Nutraceutical Supplements for Weight Loss / Poddar et al   543

ground caffeinated coffee),100 whereas decaffeinated coffee did not have any such thermogenic effect.108 Caffeine also causes oxidation of fat, thereby stimulating the metabolic rate, thus making lipolysis a mechanism of weight loss.109 However, greater fat oxidation and lipolysis are evident in normal-weight individuals as compared to obese individuals.109 Caffeine has been shown to increase epinephrine in humans, thereby increasing lipolysis.110 These findings indicate that caffeine, when consumed in a limited amount (300 mg/d), including tremors, insomnia, and dizziness.105 The results from the studies on the effect of coffee on weight loss need to be interpreted cautiously as caffeine alone does not seem to be effective in moderate doses (300 mg/d) intake, which may show beneficial effects on weight loss. However, this adds to calories in the diet, which in turn may negate its effect.103

L-Carnitine L-carnitine is a compound that is involved in fatty acid metabolism and helps to transport fatty acids within the mitochondrial matrix, thus helping in oxidation of fat stores.111 Red meat, fish, poultry, and milk are food sources of L-carnitine, but our body can produce it endogenously as needed in the muscles.111,112 In recent years, a lot of research has focused on its potential use as a dietary supplement to treat obesity, angina, and heart failure.111,112 It is being studied for its potential use in improving exercise performance in athletes and reducing fatigue because it is a component of muscles and aids in fat metabolism.111-113 In normal healthy adults, L-carnitine supplementation (1 g/3 times a day) has shown to significantly increase fatty acid oxidation,114 suggesting it may help in weight loss.115 One animal study showed that indeed fatty acid oxidation reduces diet-induced obesity,116 which has been further corroborated in obese humans.117,118 However, a few animal119-122 and human studies123-125 that examined the effect of L-carnitine supplementation on body composition in obesity have concluded that it has no significant effect on body weight loss. One clinical trial in obese individuals reported an increase in fatty acid oxidation after L-carnitine (3 g/d) supplementation, but no changes in body composition

were present.123 Similarly, 1 study examined the effect of L-carnitine supplementation in overweight/obese individuals and concluded that it did not aid in weight loss.124 However, the study included bipolar individuals who had gained significant weight after a medicine that was administered for its treatment. The L-carnitine doses were at 15 mg/kg/d for 26 weeks.124 Villani et al125 examined the effect of L-carnitine (4 g/d) on weight loss in obese individuals for 8 weeks and concluded that it did not promote fat/weight loss in obese individuals. No adverse effects were reported.125 Only 1 animal study reported a significant effect of L-carnitine on weight loss in obese cats.126 These results do not support the role of L-carnitine in weight loss for obese individuals. It may be useful for athletes to improve exercise performance,113 but to recommend this compound as a potential weight loss supplement needs more research evidence. There is no evidence of any adverse effects of L-carnitine supplementation.112,127 Rubin et al127 examined the safety of supplementing 3 g/d of carnitine in healthy adults and determined that it posed no harm in healthy adults.

Ephedra sinica (Ma Huang) Ma huang is a Chinese folk medicine used for thousands of years for a wide variety of ills and conditions, including hay fever, asthma, and headaches, to name a few. China, India, and Pakistan are some of the suppliers of this herb. Usually, the dried green stems of the plant are boiled in water and served as hot tea, with doses varying from 1.5–9 g of the herb.128 Ephedrine is the major alkaloid found in the herb besides 6 others and ranges from 30%–90%. The active chemicals, ephedrine and pseudoephedrine, act as a sympathomimetic agonist and exert therapeutic effects that include central nervous system and cardiac stimulation in addition to other effects. These effects are purported to aid in weight loss and enhance endurance training.128 In recent years, ephedra has been mainly marketed in the United States as a weight loss adjunct and supplement to improve athlete performance.128 Ephedra exerts short-term as well as long-term effects on the autonomic nervous system, increasing sympathetic activity and impairing parasympathetic responses.129,130 It also promotes release of endogenous catecholamines.130 In animal studies, ephedrine has been shown to activate β-adrenergic receptors and thereby stimulate thermogenesis in brown adipose tissue.130 In humans, in addition to promoting thermogenesis in skeletal muscle,131 ephedrine tends to slow gastric emptying, thereby affecting food intake and satiety132 and acting as a weight loss agent. Certain chemicals have been shown to act synergistically or additively to enhance the weight loss effect of ephedrine. These include methylxanthines such as caffeine105 and aspirin.133 Several studies have

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

544   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

Table 1.   Common Dietary Supplements Classified According to Purported Mechanism of Action, Efficacy, and Adverse Effects Dietary Supplement Psyllium

Konjac root fiber

Chitin

Guar gum

Garcinia cambogia Conjugated linoleic acid Green tea

Caffeine L-carnitine Ephedra sinica

Germander Capsaicin Hoodia gordonii

Cissus quadrangularis

Citrus aurantium

Trigonella foenumgraecum Phaseolus vulgaris Ginseng

Mechanism of Action Improves satiety Lowers appetite Lowers food intake Blockage of dietary fat absorption Improves satiety Lowers appetite Lowers food intake Blockage of dietary fat absorption Improves satiety Lowers appetite Lowers food intake Blockage of dietary fat absorption Improves satiety Lowers appetite Lowers food intake Blockage of dietary fat absorption Inhibits de novo lipogenesis and reduces appetite Reduces fat synthesis Increases fat oxidation Increases energy expenditure and fat oxidation Suppresses lipogenic enzyme fatty acid synthetase Increases fat oxidation and thermogenesis Increases fat oxidation Decreases fat synthesis Sympathomimetic agonist

Not known Increases energy expenditure via thermogenesis Promotes fat oxidation Suppresses appetite Increases adenosine triphosphate production and decreases food intake Blocks dietary fat and carbohydrate uptake by inhibiting lipase and amylase enzyme Reduces oxidative stress Adrenergic agonist Decreases gastric motility and lowers food intake Reduces dietary fat intake Decreases energy intake Inhibits digestive enzyme α-amylase and starch absorption Modulates carbohydrate metabolism Delays fat absorption by inhibiting pancreatic lipase activity

Efficacy

Adverse Effects

Some evidencea

Gastrointestinal discomfort and bloating

Some evidencea

Gastrointestinal discomfort and bloating

No evidenceb

Gastrointestinal discomfort and bloating

No evidenceb

Gastrointestinal discomfort and bloating

Uncertainc

No known adverse effects No known adverse effects No known adverse effects

Uncertainc Some evidencea

Uncertain with caffeine alonec No evidenceb

None proven for caffeine alone No adverse effects

Strong evidenced Bannede Some evidencea

Cardiac and central nervous system stimulation Hepatotoxicity Strongly pungent

No known evidenceb

None known

Some evidencea

None known

Some evidencea No evidenceb

No adverse effects attributable to C aurantium None known

Some evidencea

None known

No known evidenceb

None known

a

Some clinical data suggest that it may have weight loss effects. More data are needed. No evidence suggesting it aids weight loss. c Inconsistent clinical data suggesting it aids weight loss. d Strong evidence but safety issues and thus should be discouraged. e No evidence and safety concerns and thus should be strongly discouraged. b

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Nutraceutical Supplements for Weight Loss / Poddar et al   545

shown positive effects of ephedrine with caffeine on weight loss.105,134-136 However, these effects have been observed in conjunction with reports of several adverse events. One review of 5 randomized clinical trials concluded that the benefits associated with ephedra/caffeine intake outweighed the risks,137 but a meta-analysis on the efficacy and safety of this compound indicated that its use is associated with 2.2- to 3.6-fold increase in adverse events.138 It has been reported that ephedra/ephedrine use is linked with psychiatric, autonomic, and gastrointestinal symptoms along with heart palpitations.105,134-138 The nature of the pharmacological effects of ephedra resulted in the Food and Drug Administration (FDA) banning its use in April 2004.139

Germander (Teucrium) Germanders, plants of the mint family that are found worldwide, traditionally have been used as a weight loss remedy, especially in Europe. They are also used for gout. Unfortunately, multiple care reports and case series have been published describing hepatotoxicity related to this herb.140 France banned germander after an epidemic of hepatitis caused by a germander powder-containing capsule that was marketed as an adjunct for weight loss.140,141 The hepatotoxicity of germander has been reproduced and studied in mice. These studies put an end to recommendations of germander as a weight loss adjunct.142,143

Capsaicin Capsaicin is a compound that is synthesized from the placenta of chili peppers, which are eaten worldwide. It is being widely studied for its potential role as an analgesic, anticancer, antioxidant, and antiobesity agent.144 Some evidence in the literature supports the role of capsaicin from chili peppers in reducing weight/fat mass in obesity.145-148 One double-blind randomized placebocontrolled trial showed that capsaicin supplementation in obese individuals resulted in weight loss, which correlated with decreased abdominal adiposity and high fat oxidation. Weight change and abdominal fat loss were higher in the capsinoid group (weight loss, –0.9 kg; abdominal fat loss, –1.11) vs the placebo group (weight loss, 0.5 kg; abdominal fat loss, –0.18) over 12 weeks of supplementation.145 The study reported that 6 mg/d of capsaicin supplementation when administered orally was safe and well tolerated by individuals.145 Capsinoids, nonpungent analogs of capsaicin, have been shown to increase adrenergic activity, energy expenditure, and fat oxidation at rest, suggesting its usefulness in weight loss.146 In addition, capsinoids have also been shown to increase satiety and reduce energy and fat intake.146,147 A recent study

revealed that ingestion of red chili increased energy expenditure and core body temperature, as well as lowered appetite, although prolonged intake may result in desensitization to this effect.148 Similarly, Belza et al149 reported that capsaicin along with caffeine and catechins had the potential to promote thermogenesis, resulting in body fat loss. Mechanisms involved in the weight loss effect of capsaicin include alteration of proteins involved in lipid metabolism and thermogenesis in the white adipose tissues.150 Overall, these results suggest that capsaicin may have an effect on weight loss via altering fat metabolism and increasing thermogenesis. Also, it is important to note that capsaicin supplementation may be necessary as compared to consuming chili peppers to achieve the benefits that are discussed. However, more studies are needed with this promising compound found in peppers.

Traditional Plants/Herbs Hoodia gordonii Hoodia is a plant indigenous to South Africa and Namibia. It is used locally as an appetite suppressant, famously by male tribesman while on prolonged hunting excursions. P57 is the active steroid glycoside present in Hoodia. P57 is thought to suppress appetite through central nervous system pathways.151 Animal studies indicate that P57 increases the production and/or content of adenosine triphosphate (ATP) in hypothalamic neurons and decreases food intake by 50%–60% for 24 hours after intravenous injection.152 Results from 1 double-blind placebo-controlled unpublished study indicate it may assist in weight loss.153 No published human trials have been conducted so far to evaluate the proposed mechanism of action and use of this agent for weight loss.

Cissus quadrangularis L. Cissus quadrangularis, commonly known as Veldt Grape or Devil’s Backbone, is a succulent vine native to West Africa and Southeast Asia. It has been used in traditional African and Ayurvedic medicine, and its use in the treatment of infections, cardiovascular issues, and nervous system disorders has been studied to some extent.154-156 Recently, its role in reducing body weight has been attracting attention.157-159 Some evidence suggests that C quadrangularis supplementation may help in reducing body weight, fat, and waist circumference along with markers associated with metabolic syndrome.157,158 Oxidative stress is a common feature that is associated with obesity, and this compound may help in reducing oxidative stress, as demonstrated in an in vitro model, along with improving body composition measures while

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

546   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

reducing cardiovascular risk factors.159 Although these results provide some evidence in support of the use of C quadrangularis as a weight loss supplement, the studies were conducted by 1 group alone. Duplication of these results by other groups is needed to provide stronger support in favor of this compound in the use of weight loss. There is no evidence of any adverse events by this compound.

Citrus aurantium L. The unripe fruit of Citrus aurantium (bitter orange) has been used for centuries in traditional Chinese medicine. Recently, extracts have become popular in obesity treatment as an alternative to the banned ephedrine alkaloids.160 C aurantium contains the alkaloid synephrine and various phytochemicals and acts as an adrenergic agonist. It has been used clinically as a decongestant, as a vasopressor during surgical procedures, and for pupil dilations.160 C aurantium has physiological effects that are similar to ephedra, and the purported mechanism of action includes decreased gastric motility and thus early satiety and lower intake of food.160 Limited human studies have been conducted with this compound with conflicting results regarding effectiveness for weight control.161-163 In animal studies, the essential oil of Citrus aurantifolia led to a decrease in body weight and food consumption in mice.164 There are some safety concerns, similar to the concerns with ephedra; bitter orange has been listed by Consumer Reports165 as being possibly unsafe and a dietary supplement “to avoid.”

Trigonella foenum-graecum L. Fenugreek (Trigonella foenum-graecum L.) is an herbaceous annual plant belonging to the Leguminosae family that is cultivated in Mediterranean countries, Africa, and India. Fenugreek seeds have long been traditionally used for treating diabetes mellitus and other metabolic and nutritive conditions. The physiological effects of fenugreek seeds can be attributed to its fiber and high saponin content.166 Fenugreek has been previously reported to significantly reduce fasting blood sugar and improve glucose tolerance,167,168 reduce oxidative stress,169,170 improve the lipid profile, and reduce body weight171 in animal models. It has also shown immunomodulatory effects in animal models.172 In humans, it has been shown to significantly reduce fasting blood sugar and improve the glucose tolerance test in patients with type 1 diabetes mellitus173 and improve the lipid profile, insulin sensitivity, and glucose control in individuals with type 2 diabetes mellitus.174,175 Although no studies in humans have examined the effects of fenugreek seeds on body weight, studies in overweight and healthy individuals indicate that there is a significant decrease in dietary fat consumption and subsequent energy

intake with supplementation of fenugreek seed extract in quantities of >1000 mg/d.176,177 Additional studies in humans are needed to draw conclusions on its effectiveness for weight loss. There is no evidence of any harmful effects in humans.

Phaseolus vulgaris Phaseolus vulgaris, the common bean, is an herbaceous annual plant domesticated independently in ancient Mesoamerica and the Andes and now grown worldwide for its edible bean. Water extract of a common white bean has been shown in vitro to inhibit the digestive enzyme α-amylase and prevent starch absorption, which may lead to weight loss.178 Few clinical trials have shown beneficial effects of this bean on weight loss.179-181 One 4-week double-blind, placebo-controlled trial of 25 adults showed that white bean extract supplementation (2000 mg/d) led to significant decreases in body weight (6.0 lbs) and waist circumference (2.0 in.) compared with placebo, despite the finding that these individuals consumed more carbohydrates than control subjects.179 The same research group conducted another study of 50 obese participants and demonstrated that 3000 mg/d of the same extract led to a trend toward weight loss. Although clinical significance was not reached in this 8-week double-blind, placebo-controlled trial, the intervention group lost 3.79 lbs, whereas the placebo group lost 1.65 lbs.180 Celleno et al181 demonstrated that consumption of a supplement containing 445 mg of P vulgaris extract derived from white kidney beans had the potential to reduce weight, fat mass, and other measures of body composition in overweight individuals. Participants in this study consumed the supplement once a day before the main meal, which was rich in carbohydrate.181 Although these studies support the role of P vulgaris in weight loss with no reported adverse effects, further evidence is needed regarding potential gastrointestinal and other adverse effects.

Ginseng Ginseng has been used in traditional medicine for thousands of years and can be found in a number of plant species. Various ginseng extracts include Chinese or Korean ginseng (Panax ginseng), Siberian ginseng (Eleutherococcus senticosus), American ginseng (Panax quinquefolius), and Japanese ginseng (Panax japonicus). Different ginseng extracts are being studied for the treatment of many medical conditions, including weight control.182-185 Traditionally, the root of P ginseng has been used as a stimulant, and a few animal studies have suggested promise as a weight loss adjunct.182,186 In 1 study, extract from the P ginseng root produced significant weight- and fasting glucose-lowering effects in an obese, insulin-resistant rat model.186 Other species from the

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Nutraceutical Supplements for Weight Loss / Poddar et al   547

Ginseng family have shown similar activity. These actions can probably be attributed to the effect of several saponins as pancreatic lipase inhibitors.187 Saponins isolated from P japonicus rhizomes and fed to mice on a high-fat diet delayed the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.188 One study in patients with type 2 diabetes mellitus showed that ginseng therapy may have an effect on body weight.189 This double blind, placebo-controlled clinical trial showed that 200 mg of ginseng supplementation improved mood, improved fasting blood glucose levels, and reduced body weight among patients with type 2 diabetes mellitus.189 However, the placebo group also lost weight, indicating that ginseng may not be responsible for the effect seen in those from the intervention group.189 However, this study did not use body weight as a primary end point, and no other studies are yet available in humans. There are no documented adverse effects of ginseng.

have resulted in contradictory evidence. These supplements include conjugated linoleic acid, ginseng, glucomannan, green tea, HCA, L-carnitine, and psyllium. Although data on some supplements are encouraging, they may lack sufficient data or have been evaluated in poorly conducted clinical trials. Further studies are needed to evaluate the effectiveness of “herbal medicines” for weight loss and weight maintenance. Given the fact that conventional weight loss methods are not often effective long term, nonprescription dietary supplements have become popular among those seeking quick results. However, given the generally limited evidence of efficacy, even the smallest undesirable side effect of these supplements can shift the risk-benefit ratio to the unfavorable. Thus, in conclusion, based on the available science, recommending nonprescription dietary supplements as an adjunct to weight loss currently cannot be strongly recommended.

Conclusion

References

In summary, there is a dearth of data on the effect of dietary supplements on body weight loss in humans. The published data to date provide inconclusive evidence on the usefulness of different dietary supplements for weight loss. Caution must be exercised before recommending the use of these supplements for weight loss, as there is evidence that some may produce harmful effects. When using any of these alternative therapies as adjuncts for weight control, one must remember that, although derived from natural sources, they may nonetheless exhibit powerful pharmacologic effects and are thus still “medicines.” For example, foxglove, the plant origin of digitalis, has wellknown toxic effects comparable to those seen with pharmacologic digitalis dosing. Therefore, it is extremely important to use these supplements wisely and in limited amounts. In closing, it is fitting to highlight that perhaps the most general and safest alternative/herbal approach to weight control is to substitute low-energy density foods for high-energy density and processed foods, thereby reducing total energy intake.16-18 By taking advantage of the low-energy density and health-promoting effects of plant-based foods, one may be able to achieve weight loss, or at least assist weight maintenance without cutting down on the volume of food consumed or compromising its nutrient value. Because of the lack of quality, safety, and efficacy of many of the supplements discussed in this article, their use should generally be discouraged. Some supplements (eg, guar gum and chitosan) seem to show no efficacy. Ephedra, although quite effective for weight loss, is very well known for its adverse effects, and products containing even traces of this supplement should be discouraged. Many other supplements lack enough clinical evidence to support their role in weight loss, or studies

1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010;303:235-241. 2. Nguyen DM, El-Serag HB. The epidemiology of obesity. Gastroenterol Clin North Am. 2010;39:1-7. 3. Grimm ER, Steinle NI. Genetics of eating behavior: established and emerging concepts. Nutr Rev. 2011;69:52-60. 4. Lake A, Townshend T. Obesogenic environments: exploring the built and food environments. J R Soc Promot Health. 2006;126:262-267. 5. Booth KM, Pinkston MM, Poston WS. Obesity and the built environment. J Am Diet Assoc. 2005;105:S110-S117. 6. Davis MA, West AN, Weeks WB, Sirovich BE. Health behaviors and utilization among users of complementary and alternative medicine for treatment versus health promotion. Health Serv Res. 2011 May 10 [Epub ahead of print]. doi: 10.1111/j.1475-6773. 2011.01270.x. 7. Nahin RL, Barnes PM, Stussman BJ, Bloom B. Costs of complementary and alternative medicine (CAM) and frequency of visits to CAM practitioners: United States, 2007. Natl Health Stat Rep. 2009;18:1-14. 8. Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States: prevalence, costs, and patterns of use. N Engl J Med. 1993;328:246-252. 9. Saper RB, Eisenberg DM, Phillips RS. Common dietary supplements for weight loss. Am Fam Physician. 2004;70:1731-1738. 10. Blanck HM, Serdula MK, Gillespie C, et al. Use of nonprescription dietary supplements for weight loss is common among Americans. J Am Diet Assoc. 2007;107:441-447. 11. Bertisch SM, Wee CC, McCarthy EP. Use of complementary and alternative therapies by overweight and obese adults. Obesity. 2008;16:1610-1615. 12. Pillitteri JL, Shiffman S, Rohay JM, Harkins AM, Burton SL, Wadden TA. Use of dietary supplements for weight loss in the United States: results of a national survey. Obesity. 2008;16:790-796. 13. Slavin JL. Position of the American Dietetic Association: health implications of dietary fiber. J Am Diet Assoc. 2008;108(10):1716-1731. 14. O’Neil CE, Nicklas TA, Zanovec M, Cho S. Whole-grain consumption is associated with diet quality and nutrient intake in adults: the National Health and Nutrition Examination Survey, 19992004. J Am Diet Assoc. 2010;110:1461-1468.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

548   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

15. Blanck HM, Gillespie C, Kimmons JE, Seymour JD, Serdula MK. Trends in fruit and vegetable consumption among U.S. men and women, 1994-2005. Prev Chronic Dis. 2008;5:A35. 16. Nicklas TA, Farris RP, Myers L, Berenson GS. Dietary fiber intake of children and young adults: the Bogalusa Heart Study. J Am Diet Assoc. 1995;95:209-214. 17. Ello-Martin JA, Roe LS, Ledikwe JH, Beach AM, Rolls BJ. Dietary energy density in the treatment of obesity: a year-long trial comparing 2 weight-loss diets. Am J Clin Nutr. 2007;85:1465-1477. 18. Ledikwe JH, Blanck HM, Kettel Khan L, et al. Dietary energy density is associated with energy intake and weight status in US adults. Am J Clin Nutr. 2006;83:1362-1368. 19. Kant AK, Graubard BI. Energy density of diets reported by American adults: association with food group intake, nutrient intake, and body weight. Int J Obes (Lond). 2005;29(8):950-956. 20. Ledikwe JH, Blanck HM, Khan LK, et al. Low-energy-density diets are associated with high diet quality in adults in the United States. J Am Diet Assoc. 2006;106:1172-1180. 21. Liu S, Willett WC, Manson JE, Hu FB, Rosner B, Colditz G. Relation between changes in intakes of dietary fiber and grain products and changes in weight and development of obesity among middle-aged women. Am J Clin Nutr. 2003;78:920-927. 22. Bes-Rastrollo M, Martínez-González MA, Sánchez-Villegas A, de la Fuente Arrillaga C, Martínez JA. Association of fiber intake and fruit/vegetable consumption with weight gain in a Mediterranean population. Nutrition. 2006;22(5):504-511. 23. Vioque J, Weinbrenner T, Castelló A, Asensio L, Garcia de la Hera M. Intake of fruits and vegetables in relation to 10-year weight gain among Spanish adults. Obesity. 2008;16:664-670. 24. Du H, van der A DL, Boshuizen HC, et al. Dietary fiber and subsequent changes in body weight and waist circumference in European men and women. Am J Clin Nutr. 2010;91:329-336. 25. Jones JR, Lineback DM, Levine MJ. Dietary reference intakes: implications for fiber labeling and consumption: a summary of the International Life Sciences Institute North America Fiber Workshop, June 1-2, 2004, Washington, DC. Nutr Rev. 2006;64:31-38. 26. United States Department of Agriculture. National Agricultural Library. In: Dietary, Functional, and Total Fiber. http://www.nal. usda.gov/fnic/DRI//DRI_Energy/339-421.pdf 27. Samra RA, Anderson GH. Insoluble cereal fiber reduces appetite and short-term food intake and glycemic response to food consumed 75 min later by healthy men. Am J Clin Nutr. 2007;86:972-979. 28. Lee YP, Mori TA, Sipsas S, et al. Lupin-enriched bread increases satiety and reduces energy intake acutely. Am J Clin Nutr. 2006;84:975-980. 29. Hunt R, Fedorak R, Frohlich J, McLennan C, Pavilanis A. Therapeutic role of dietary fibre. Can Fam Physician. 1993;39:897900, 903-910. 30. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 2nd ed. New York: John Wiley; 1996. 31. Cicero AF, Derosa G, Manca M, Bove M, Borghi C, Gaddi AV. Different effect of psyllium and guar dietary supplementation on blood pressure control in hypertensive overweight patients: a six-month, randomized clinical trial. Clin Exp Hypertens. 2007;29:383-394. 32. Sartore G, Reitano R, Barison A, et al. The effects of psyllium on lipoproteins in type II diabetic patients. Eur J Clin Nutr. 2009;63:1269-1271. 33. Pal S, Khossousi A, Binns C, Dhaliwal S, Ellis V. The effect of a fibre supplement compared to a healthy diet on body composition, lipids, glucose, insulin and other metabolic syndrome risk factors in overweight and obese individuals. Br J Nutr. 2011;105:90-100. 34. Salas-Salvadó J, Farrés X, Luque X, et al. Fiber in Obesity-Study Group: effect of two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight or obese patients: a randomised trial. Br J Nutr. 2008;99:1380-1387.

35. Rodríguez-Morán M, Guerrero-Romero F, Lazcano-Burciaga G. Lipid- and glucose-lowering efficacy of Plantago psyllium in type II diabetes. J Diabetes Complications. 1998;12:273-278. 36. Giacosa A, Rondanelli M. The right fiber for the right disease: an update on the psyllium seed husk and the metabolic syndrome. J Clin Gastroenterol. 2010;44(suppl 1):S58-S60. 37. Ziai SA, Larijani B, Akhoondzadeh S, et al. Psyllium decreased serum glucose and glycosylated hemoglobin significantly in diabetic outpatients. J Ethnopharmacol. 2005;102:202-207. 38. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999;69: 30-42. 39. Keithley J, Swanson B. Glucomannan and obesity: a critical review. Altern Ther Health Med. 2005;11:30-34. 40. Walsh DE, Yaghoubian V, Behforooz A. Effect of glucomannan on obese patients: a clinical study. Int J Obes. 1984;8:289-293. 41. Wood RJ, Fernandez ML, Sharman MJ, et al. Effects of a carbohydrate-restricted diet with and without supplemental soluble fiber on plasma low-density lipoprotein cholesterol and other clinical markers of cardiovascular risk. Metabolism. 2007;56:58-67. 42. Vuksan V, Sievenpiper JL, Owen R, et al. Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial. Diabetes Care. 2000;23:9-14. 43. Vuksan V, Jenkins DJ, Spadafora P, et al. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes: a randomized controlled metabolic trial. Diabetes Care. 1999;22:913-919. 44. Lenz TL, Hamilton WR. Supplemental products used for weight loss. J Am Pharm Assoc. 2004;44:59-67. 45. Gallaher CM, Munion J, Hesslink R Jr, Wise J, Gallaher DD. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr. 2000;130:2753-2759. 46. Gallaher DD, Gallaher CM, Mahrt GJ, Carr TP, Hollingshead CH, Hesslink R Jr, Wise J. A glucomannan and chitosan fiber supplement decreases plasma cholesterol and increases cholesterol excretion in overweight normocholesterolemic humans. J Am Coll Nutr. 2002;21:428-433. 47. Wydro P, Krajewska B, Hac-Wydro K. Chitosan as a lipid binder: a langmuir monolayer study of chitosan-lipid interactions. Biomacromolecules. 2007;8:2611-2617. 48. Mhurchu CN, Dunshea-Mooij C, Bennett D, Rodgers A. Effect of chitosan on weight loss in overweight and obese individuals: a systematic review of randomized controlled trials. Obes Rev. 2005;6:35-42. 49. Mhurchu CN, Poppitt SD, McGill AT, et al. The effect of the dietary supplement, chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults. Int J Obes Relat Metab Disord. 2004;28:1149-1156. 50. Hernández-González SO, González-Ortiz M, Martínez-Abundis E, Robles-Cervantes JA. Chitosan improves insulin sensitivity as determined by the euglycemic-hyperinsulinemic clamp technique in obese subjects. Nutr Res. 2010;30:392-395. 51. Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr. 1999;53(5):379-381. 52. Ho SC, Tai ES, Eng PH, Tan CE, Fok AC. In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects. Singapore Med J. 2001;42(1):6-10. 53. Jull AB, Ni Mhurchu C, Bennett DA, Dunshea-Mooij CA, Rodgers A. Chitosan for overweight or obesity. Cochrane Database Syst Rev. 2008;(3):CD003892. 54. Wuolijoki E, Hirvelä T, Ylitalo P. Decrease in serum LDL cholesterol with microcrystalline chitosan. Methods Find Exp Clin Pharmacol. 1999;21:357-361.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Nutraceutical Supplements for Weight Loss / Poddar et al   549 55. Schiller RN, Barrager E, Schauss AG, Nichols EJ. A randomized, double-blind, placebo-controlled study examining the effects of a rapidly soluble chitosan dietary supplement on weight loss and body composition in overweight and mildly obese individuals. J Am Nutraceut Assn. 2001;4:42-49. 56. Kaats GR, Michalek JE, Preuss HG. Evaluating efficacy of a chitosan product using a double-blinded, placebo-controlled protocol. J Am Coll Nutr. 2006;25:389-394. 57. Kovacs EM, Westerterp-Plantenga MS, Saris WH, Goossens I, Geurten P, Brouns F. The effect of addition of modified guar gum to a low-energy semisolid meal on appetite and body weight loss. Int J Obes Relat Metab Disord. 2001;25:307-315. 58. Evans E, Miller DS. Bulking agents in the treatment of obesity. Nutr Metab. 1975;18:199-203. 59. Kovacs EM, Westerterp-Plantenga MS, Saris WH, et al. The effect of guar gum addition to a semisolid meal on appetite related to blood glucose, in dieting men. Eur J Clin Nutr. 2002;56:771-778. 60. Lyly M, Liukkonen KH, Salmenkallio-Marttila M, Karhunen L, Poutanen K, Lähteenmäki L. Fibre in beverages can enhance perceived satiety. Eur J Nutr. 2009;48:251-258. 61. Pittler MH, Ernst E. Guar gum for body weight reduction: metaanalysis of randomized trials. Am J Med. 2001;110:724-730. 62. McCarty MF. Promotion of hepatic lipid oxidation and gluconeogenesis as a strategy for appetite control. Med Hypotheses. 1994;42:215-225. 63. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998;280:1596-1600. 64. Vasques CA, Rossetto S, Halmenschlager G, et al. Evaluation of the pharmacotherapeutic efficacy of Garcinia cambogia plus Amorphophallus konjac for the treatment of obesity. Phytother Res. 2008;22:1135-1140. 65. Kovacs EM, Westerterp-Plantenga MS, de Vries M, Brouns F, Saris WH. Effects of 2-week ingestion of (–)-hydroxycitrate and (–)-hydroxycitrate combined with medium-chain triglycerides on satiety and food intake. Physiol Behav. 2001;74:543-549. 66. Preuss HG, Garis RI, Bramble JD, et al. Efficacy of a novel calcium/potassium salt of (–)-hydroxycitric acid in weight control. Int J Clin Pharmacol Res. 2005;25:133-144. 67. Kriketos AD, Thompson HR, Greene H, Hill JO. (–)-Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a post-absorptive state. Int J Obes Relat Metab Disord. 1999;23:867-873. 68. Lim K, Ryu S, Nho HS, et al. (–)-Hydroxycitric acid ingestion increases fat utilization during exercise in untrained women. J Nutr Sci Vitaminol (Tokyo). 2003;49:163-167. 69. Preuss HG, Rao CV, Garis R, et al. An overview of the safety and efficacy of a novel, natural (–)-hydroxycitric acid extract (HCA-SX) for weight management. J Med. 2004;35:33-48. 70. Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem. 2006;17:789-810. 71. Plourde M, Jew S, Cunnane SC, Jones PJ. Conjugated linoleic acids: why the discrepancy between animal and human studies? Nutr Rev. 2008;66:415-421. 72. Kanaya N, Chen S. Conjugated linoleic acid reduces body weight gain in ovariectomized female C57BL/6J mice. Nutr Res. 2010;30:714-721. 73. Joseph SV, Liu X, Wakefield A, et al. Trans-8, cis-10+ cis-9, trans11-conjugated linoleic acid mixture alters body composition in Syrian golden hamsters fed a hypercholesterolaemic diet. Br J Nutr. 2010;104:1443-1449. 74. Wendel AA, Purushotham A, Liu LF, Belury MA. Conjugated linoleic acid induces uncoupling protein 1 in white adipose tissue of ob/ob mice. Lipids. 2009;44:975-982.

75. Parra P, Serra F, Palou A. Moderate doses of conjugated linoleic acid isomers mix contribute to lowering body fat content maintaining insulin sensitivity and a noninflammatory pattern in adipose tissue in mice. J Nutr Biochem. 2010;21:107-115. 76. Halade GV, Rahman MM, Williams PJ, Fernandes G. Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice. J Nutr Biochem. 2011;22:459-469. 77. Larsen TM, Toubro S, Gudmundsen O, Astrup A. Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain. Am J Clin Nutr. 2006;83:606-612. 78. Malpuech-Brugère C, Verboeket-van de Venne WP, Mensink RP, et al. Effects of two conjugated linoleic acid isomers on body fat mass in overweight humans. Obes Res. 2004;12:591-598. 79. Venkatramanan S, Joseph SV, Chouinard PY, Jacques H, Farnworth ER, Jones PJ. Milk enriched with conjugated linoleic acid fails to alter blood lipids or body composition in moderately overweight, borderline hyperlipidemic individuals. J Am Coll Nutr. 2010;29:152-159. 80. Whigham LD, Watras AC, Schoeller DA. Efficacy of conjugated linoleic acid for reducing fat mass: a meta-analysis in humans. Am J Clin Nutr. 2007;85:1203-1211. 81. Gaullier JM, Halse J, Høye K, et al. Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr. 2004;79:1118-1125. 82. Watras AC, Buchholz AC, Close RN, Zhang Z, Schoeller DA. The role of conjugated linoleic acid in reducing body fat and preventing holiday weight gain. Int J Obes (Lond). 2007;31:481-487. 83. Khan N, Mukhtar H. Tea polyphenols for health promotion. Life Sci. 2007;81:519-533. 84. Perva-Uzunalić A, Škerget M, Knez Ž, Weinreich B, Otto F, Grüner S. Extraction of active ingredients from green tea (Camellia sinensis): extraction efficiency of major catechins and caffeine. Food Chem. 2006;96:597-605. 85. Cross SE, Jin YS, Lu QY, Rao J, Gimzewski JK. Green tea extract selectively targets nanomechanics of live metastatic cancer cells. Nanotechnology. 2011;22:215101. 86. Roy AM, Baliga MS, Katiyar SK. Epigallocatechin-3-gallate induces apoptosis in estrogen receptor-negative human breast carcinoma cells via modulation in protein expression of p53 and Bax and caspase-3 activation. Mol Cancer Ther. 2005;4:81-90. 87. Sadava D, Whitlock E, Kane SE. The green tea polyphenol, epigallocatechin-3-gallate inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells. Biochem Biophys Res Commun. 2007;360:233-237. 88. Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG. Epigallocatechin-3gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo. BMC Cancer. 2010;10:276. 89. Ikeda I. Multifunctional effects of green tea catechins on prevention of the metabolic syndrome. Asia Pac J Clin Nutr. 2008;17:273-274. 90. Wang H, Wen Y, Du Y, et al. Effects of catechin enriched green tea on body composition. Obesity. 2010;18:773-779. 91. Nagao T, Meguro S, Hase T, et al. A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes. Obesity. 2009;17:310-317. 92. Nagao T, Hase T, Tokimitsu I. A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity. 2007;15:1473-1483. 93. Maki KC, Reeves MS, Farmer M, et al. Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. J Nutr. 2009;139:264-270. 94. Nagao T, Komine Y, Soga S, et al. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am J Clin Nutr. 2005;81:122-129. 95. Rains TM, Agarwal S, Maki KC. Antiobesity effects of green tea catechins: a mechanistic review. J Nutr Biochem. 2011;22:1-7.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

550   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

  96. Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes. 2009;33:956-961.  97. Diepvens K, Kovacs EM, Vogels N, Westerterp-Plantenga MS. Metabolic effects of green tea and of phases of weight loss. Physiol Behav. 2006;87:185-191.   98. Diepvens K, Kovacs EM, Nijs IM, Vogels N, Westerterp-Plantenga MS. Effect of green tea on resting energy expenditure and substrateoxidation during weight loss in overweight females. Br J Nutr. 2005;94:1026-1034.   99. Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res. 2005;13:1195-1204. 100. Astrup A, Toubro C, Cannon S, Hein P, Breum L, Madsen J. Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. Am J Clin Nutr. 1990;51:759-767. 101. He RR, Chen L, Lin BH, Matsui Y, Yao XS, Kurihara H. Beneficial effects of oolong tea consumption on diet-induced overweight and obese subjects. Chin J Integr Med. 2009;15:34-41. 102. Han LK, Takaku T, Li J, Kimura Y, Okuda H. Anti-obesity action of oolong tea. Int J Obes Relat Metab Disord. 1999;23(1):98-105. 103. Heckman MA, Weil J, Gonzalez de Mejia E. Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci. 2010;75:R77-R87. 104. Phung OJ, Baker WL, Matthews LJ, Lanosa M, Thorne A, Coleman CI. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. Am J Clin Nutr. 2010;91:73-81. 105. Astrup A, Breum L, Toubro S, Hein P, Quaade F. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: a double blind trial. Int J Obes Relat Metab Disord. 1992;16:269-277. 106. Lopez-Garcia E, van Dam RM, Rajpathak S, Willett WC, Manson JE, Hu FB. Changes in caffeine intake and long-term weight change in men and women. Am J Clin Nutr. 2006;83:674-680. 107. Dulloo A, Geissler C, Horton T, Miller D. Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers. Am J Clin Nutr. 1989;49:44-50. 108. Horst K, Willson RJ, Smith RG. The effect of coffee and decaffeinated coffee on oxygen consumption, pulse rate and blood pressure. J Pharmacol Exp Ther. 1936;58:294-304. 109. Acheson KJ, Zahorska-Markiewicz B, Anantharaman K, Jequier E. Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals. Am J Clin Nutr. 1980;33:989-997. 110. Benowitz NL, Jacob P III, Mayan H, Denaro C. Sympathomimetic effects of paraxanthine and caffeine in humans. Clin Pharmacol Ther. 1995;58:684-691. 111. Kraemer WJ, Volek JS, Dunn-Lewis C. L-carnitine supplementation: influence upon physiological function. Curr Sports Med Rep. 2008;7:218-223. 112. Hathcock JN, Shao A. Risk assessment for carnitine. Regul Toxicol Pharmacol. 2006;46:23-28. 113. Karlic H, Lohninger A. Supplementation of L-carnitine in athletes: does it make sense? Nutrition. 2004;20:709-715. 114. Müller DM, Seim H, Kiess W, Löster H, Richter T. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism. 2002;51:1389-1391. 115. Ronnett GV, Kim EK, Landree LE, Tu Y. Fatty acid metabolism as a target for obesity treatment. Physiol Behav. 2005;85:25-35. 116. Ji H, Friedman MI. Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity. Metabolism. 2007;56:1124-1130.

117. Fabris R, Mingrone G, Milan G, et al. Further lowering of muscle lipid oxidative capacity in obese subjects after biliopancreatic diversion. J Clin Endocrinol Metab. 2004;89:1753-1759. 118. Kelley DE, Goodpaster B, Wing RR, Simoneau JA. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol. 1999;277:E1130-E1141. 119. Melton SA, Keenan MJ, Stanciu CE, et al. L-carnitine supplementation does not promote weight loss in ovariectomized rats despite endurance exercise. Int J Vitam Nutr Res. 2005;75(2): 156-160. 120. Saldanha Aoki M, Rodriguez Amaral Almeida AL, Navarro F, Bicudo Pereira Costa-Rosa LF, Pereira Bacurau RF. Carnitine supplementation fails to maximize fat mass loss induced by endurance training in rats. Ann Nutr Metab. 2004;48:90-94. 121. Brandsch C, Eder K. Effect of L-carnitine on weight loss and body composition of rats fed a hypocaloric diet. Ann Nutr Metab. 2002;46:205-210. 122. Hongu N, Sachan DS. Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise. J Nutr. 2000;130:152-157. 123. Wutzke KD, Lorenz H. The effect of L-carnitine on fat oxidation, protein turnover, and body composition in slightly overweight subjects. Metabolism. 2004;53:1002-1006. 124. Elmslie JL, Porter RJ, Joyce PR, Hunt PJ, Mann JI. Carnitine does not improve weight loss outcomes in valproate-treated bipolar patients consuming an energy-restricted, low-fat diet. Bipolar Disord. 2006;8:503-507. 125. Villani RG, Gannon J, Self M, Rich PA. L-carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. Int J Sport Nutr Exerc Metab. 2000;10:199-207. 126. Center SA, Harte J, Watrous D, et al. The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine. J Vet Intern Med. 2000;14:598-608. 127. Rubin MR, Volek JS, Gómez AL, et al. Safety measures of L-carnitine L-tartrate supplementation in healthy men. J Strength Cond Res. 2001;15:486-490. 128. Abourashed EA, El-Alfy AT, Khan IA, Walker L. Ephedra in perspective: a current review. Phytother Res. 2003;17:703-712. 129. Chen WL, Tsai TH, Yang CC, Kuo TB. Effects of ephedra on autonomic nervous modulation in healthy young adults. J Ethnopharmacol. 2010;130:563-568. 130. Andraws R, Chawla P, Brown DL. Cardiovascular effects of ephedra alkaloids: a comprehensive review. Prog Cardiovasc Dis. 2005;47:217-225. 131. Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev. 2001;2:199-211. 132. Jonderko K, Kucio C. Effect of anti-obesity drugs promoting energy expenditure, yohimbine and ephedrine, on gastric emptying in obese patients. Aliment Pharmacol Ther. 1991;5:413-418. 133. Dulloo AG, Miller DS. Aspirin as a promoter of ephedrine-induced thermogenesis: potential use in the treatment of obesity. Am J Clin Nutr. 1987;45:564-569. 134. Breum L, Pedersen JK, Ahlstrøm F, Frimodt-Møller J. Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity: a double-blind multi-centre trial in general practice. Int J Obes Relat Metab Disord. 1994;18:99-103. 135. Coffey CS, Steiner D, Baker BA, Allison DB. A randomized double-blind placebo-controlled clinical trial of a product containing ephedrine, caffeine, and other ingredients from herbal sources for treatment of overweight and obesity in the absence of lifestyle treatment. Int J Obes Relat Metab Disord. 2004;28:1411-1419. 136. Boozer CN, Daly PA, Homel P, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord. 2002;26:593-604.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

Nutraceutical Supplements for Weight Loss / Poddar et al   551 137. Greenway FL. The safety and efficacy of pharmaceutical and herbal caffeine and ephedrine use as a weight loss agent. Obes Rev. 2001;2:199-211. 138. Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA. 2003;289:1537-1545. 139. Seamon MJ, Clauson KA. Ephedra: yesterday, DSHEA, and tomorrow: a ten year perspective on the Dietary Supplement Health and Education Act of 1994. J Herb Pharmacother. 2005;5:67-86. 140. Castot A, Larrey D. Hepatitis observed during a treatment with a drug or tea containing wild germander: evaluation of 26 cases reported to the Regional Centers of Pharmacovigilance [in French]. Gastroenterol Clin Biol. 1992;16:916-922. 141. Larrey D, Vial T, Pauwels A, Castot A, Biour M, David M, Michel H. Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. Ann Intern Med. 1992;117:129-132. 142. Loeper J, Descatoire V, Letteron P, et al. Hepatotoxicity of germander in mice. Gastroenterology. 1994;106:464-447. 143. Lekehal M, Pessayre D, Lereau JM, Moulis C, Fouraste I, Fau D. Hepatotoxicity of the herbal medicine germander: metabolic activation of its furano diterpenoids by cytochrome P450 3A depletes cytoskeleton-associated protein thiols and forms plasma membrane blebs in rat hepatocytes. Hepatology. 1996;24:212-218. 144. Luo XJ, Peng J, Li YJ. Recent advances in the study on capsaicinoids and capsinoids. Eur J Pharmacol. 2011;650:1-7. 145. Snitker S, Fujishima Y, Shen H, et al. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. Am J Clin Nutr. 2009;89:45-50. 146. Josse AR, Sherriffs SS, Holwerda AM, Andrews R, Staples AW, Phillips SM. Effects of capsinoid ingestion on energy expenditure and lipid oxidation at rest and during exercise. Nutr Metab (Lond). 2010;7:65. 147. Westerterp-Plantenga MS, Smeets A, Lejeune MP. Sensory and gastrointestinal satiety effects of capsaicin on food intake. Int J Obes. 2005;29:682-688. 148.Ludy MJ, Mattes RD. The effects of hedonically acceptable red pepper doses on thermogenesis and appetite. Physiol Behav. 2011;102:251-258. 149. Belza A, Frandsen E, Kondrup J. Body fat loss achieved by stimulation of thermogenesis by a combination of bioactive food ingredients: a placebo-controlled, double-blind 8-week intervention in obese subjects. Int J Obes (Lond). 2007;31:121-130. 150. Joo JI, Kim DH, Choi JW, Yun JW. Proteomic analysis for antiobesity potential of capsaicin on white adipose tissue in rats fed with a high fat diet. J Proteome Res. 2010;9:2977-2987. 151. Lee RA, Balick MJ. Indigenous use of Hoodia gordonii and appetite suppression. Explore (NY). 2007;3:404-406. 152. MacLean DB, Luo LG. Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain Res. 2004;1020:1-11. 153. Habeck M. A succulent cure to end obesity. Drug Discov Today. 2002;7:280-281. 154. Oliver-Bever B. Medicinal plants in tropical West Africa, III: antiinfection therapy with higher plants. J Ethnopharmacol. 1983;9:1-83. 155. Oliver-Bever B. Medicinal plants in tropical West Africa, II: plants acting on the nervous system. J Ethnopharmacol. 1983;7:1-93. 156. Oliver-Bever B. Medicinal plants in tropical West Africa, I: plants acting on the cardiovascular system. J Ethnopharmacol. 1982;5:1-72. 157. Oben JE, Ngondi JL, Momo CN, Agbor GA, Sobgui CS. The use of a Cissus quadrangularis/Irvingia gabonensis combination in the management of weight loss: a double-blind placebo-controlled study. Lipids Health Dis. 2008;7:12. 158. Oben J, Kuate D, Agbor G, Momo C, Talla X. The use of a Cissus quadrangularis formulation in the management of weight loss and metabolic syndrome. Lipids Health Dis. 2006;5:24.

159. Oben JE, Enyegue DM, Fomekong GI, Soukontoua YB, Agbor GA. The effect of Cissus quadrangularis (CQR-300) and a Cissus formulation (CORE) on obesity and obesity-induced oxidative stress. Lipids Health Dis. 2007;6:4. 160. Haaz S, Fontaine KR, Cutter G, Limdi N, Perumean-Chaney S, Allison DB. Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obes Rev. 2006;7:79-88. 161. Greenway F, de Jonge-Levitan L, Martin C, Roberts A, Grundy I, Parker C. Dietary herbal supplements with phenylephrine for weight loss. J Med Food. 2006;9:572-578. 162. Preuss HG, DiFerdinando D, Bagchi M, Bagchi D. Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview. J Med. 2002;33:247-264. 163. Colker CM, Kalman DS, Torina GC, Perlis T, Street C. Effects of citrus aurantium extract, caffeine, and St. John’s wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res. 1999;60:145-153. 164. Asnaashari S, Delazar A, Habibi B, et al. Essential oil from Citrus aurantifolia prevents ketotifen-induced weight-gain in mice. Phytother Res. 2010;24:1893-1897. 165. Dangerous supplements: what you don’t know about these 12 ingredients could hurt you. Consum Rep. 2010;75:16-20. 166. Madar Z, Stark AH. New legume sources as therapeutic agents. Br J Nutr. 2002;88:S287-S292. 167. Hannan JM, Ali L, Rokeya B, et al. Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in animal models of type 1 and type 2 diabetes by delaying carbohydrate digestion and absorption, and enhancing insulin action. Br J Nutr. 2007;97:514-521. 168. Xue WL, Li XS, Zhang J, Liu YH, Wang ZL, Zhang RJ. Effect of Trigonella foenum-graecum (fenugreek) extract on blood glucose, blood lipid and hemorheological properties in streptozotocininduced diabetic rats. Asia Pac J Clin Nutr. 2007;16:422-426. 169. Annida B, Stanely Mainzen Prince P. Supplementation of fenugreek leaves reduces oxidative stress in streptozotocin-induced diabetic rats. J Med Food. 2005;8:382-385. 170. Dixit P, Ghaskadbi S, Mohan H, Devasagayam TP. Antioxidant properties of germinated fenugreek seeds. Phytother Res. 2005;19:977-983. 171. Dakam W, Shang J, Agbor G, Oben J. Effects of sodium bicarbonate and albumin on the in vitro water-holding capacity and some physiological properties of Trigonella foenum graecum L. galactomannan in rats. J Med Food. 2007;10(1):169-174. 172. Bin-Hafeez B, Haque R, Parvez S, Pandey S, Sayeed I, Raisuddin S. Immunomodulatory effects of fenugreek (Trigonella foenum graecum L.) extract in mice. Int Immunopharmacol. 2003;3: 257-265. 173. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr. 1990;44:301-306. 174. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001;49:1057-1061. 175. Kassaian N, Azadbakht L, Forghani B, Amini M. Effect of fenugreek seeds on blood glucose and lipid profiles in type 2 diabetic patients. Int J Vitam Nutr Res. 2009;79:34-39. 176. Chevassus H, Gaillard JB, Farret A, et al. A fenugreek seed extract selectively reduces spontaneous fat intake in overweight subjects. Eur J Clin Pharmacol. 2010;66:449-455. 177. Chevassus H, Molinier N, Costa F, Galtier F, Renard E, Petit P. A fenugreek seed extract selectively reduces spontaneous fat consumption in healthy volunteers. Eur J Clin Pharmacol. 2009;65:1175-1178. 178. Barrett ML, Udani JK. A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris): a review of clinical studies on weight loss and glycemic control. Nutr J. 2011;10:24.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012

552   Nutrition in Clinical Practice / Vol. 26, No. 5, October 2011

179. Udani J, Singh BB. Blocking carbohydrate absorption and weight loss: a clinical trial using a proprietary fractionated white bean extract. Altern Ther Health Med. 2007;13:32-37. 180. Udani J, Hardy M, Madsen DC. Blocking carbohydrate absorption and weight loss: a clinical trial using phase 2 brand proprietary fractionated white bean extract. Altern Med Rev. 2004;9:63-69. 181. Celleno L, Tolaini MV, D’Amore A, Perricone NV, Preuss HG. A dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women. Int J Med Sci. 2007;4:45-52. 182. Mollah ML, Kim GS, Moon HK, et al. Antiobesity effects of wild ginseng (Panax ginseng C.A. Meyer) mediated by PPARgamma, GLUT4 and LPL in ob/ob mice. Phytother Res. 2009;23: 220-225. 183. Kim HY, Kang KS, Yamabe N, Nagai R, Yokozawa T. Protective effect of heat-processed American ginseng against diabetic renal damage in rats. J Agric Food Chem. 20077;55(21):8491-8497.

184. Lian XY, Zhang Z, Stringer JL. Protective effects of ginseng components in a rodent model of neurodegeneration. Ann Neurol. 2005;57:642-648. 185. Xie JT, Zhou YP, Dey L, et al. Ginseng berry reduces blood glucose and body weight in db/db mice. Phytomedicine. 2002;9:254-258. 186. Lim S, Yoon JW, Choi SH, et al. Effect of ginsam, a vinegar extract from Panax ginseng, on body weight and glucose homeostasis in an obese insulin-resistant rat model. Metabolism. 2009;58:8-15. 187. Kim JH, Kang SA, Han SM, Shim I. Comparison of the antiobesity effects of the protopanaxadiol- and protopanaxatriol-type saponins of red ginseng. Phytother Res. 2009;23:78-85. 188. Han LK, Zheng YN, Yoshikawa M, Okuda H, Kimura Y. Antiobesity effects of chikusetsusaponins isolated from Panax japonicus rhizomes. BMC Complement Altern Med. 2005;5:9. 189. Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care. 1995;18: 1373-1375.

Downloaded from ncp.sagepub.com at JOHNS HOPKINS UNIV on March 20, 2012