Dietary Supplements for Weight Loss

Fact Sheet for Health Professionals

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Introduction

This fact sheet provides information on weight-loss dietary supplements *, including summaries of research on the safety and efficacy of several of the most commonly used ingredients in these products.
More than two-third of adults and almost one-third of children and adolescents in the United States are overweight or obese [1,2]. Forty-five percent of overweight Americans and 67% of those who are obese are trying to lose weight [3].
Health experts agree that making lifestyle changes—including following a healthy eating pattern, reducing caloric intake, and engaging in physical activity—is the basis for achieving long-term weight loss [4-7]. But because making diet and lifestyle changes can be difficult, many people turn to dietary supplements promoted for weight loss in the hope that these products will help them more easily achieve their weight-loss goals.
Use of weight-loss supplements in the United States is fairly common. Approximately 15% of U.S. adults have used a weight-loss dietary supplement at some point in their lives, with more women reporting use (20.6%) than men (9.7%) [8]. Americans spend about $2 billion a year on weight-loss dietary supplements in pill form (e.g., tablets, capsules, and softgels) [9], and to lose weight is one of the top 20 reasons why people take dietary supplements [10].
Dietary supplements promoted for weight loss encompass a wide variety of products and come in a variety of forms, including capsules, tablets, liquids, powders, and bars [11]. Manufacturers market these products with various claims, including that these products reduce macronutrient absorption, appetite, body fat, and weight and increase metabolism and thermogenesis. The average product contains 10 different ingredients, but some contain as many as 96 [11]. Common ingredients include botanicals (herbs and other plant components), dietary fiber, and minerals.
In its report on dietary supplements for weight loss, the U.S. Government Accountability Office concluded that “little is known about whether weight loss supplements are effective, but some supplements have been associated with the potential for physical harm” [12]. Many weight-loss supplements are costly, and some of these products’ ingredients can interact or interfere with certain medications. So it is important to consider what is known—and not known—about each ingredient in any dietary supplement before using it.
People who are considering using weight-loss supplements should talk with their health care provider to discuss these products’ potential benefits and risks. This is especially important for those who have medical conditions, including high blood pressure, diabetes, or heart disease. Yet according to a large national survey, less than one-third of U.S. adults who use weight-loss dietary supplements discuss this use with a health care professional [8].
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*Dietary supplements are labeled with a Supplement Facts panel and do not include meal replacement shakes or prescription or over-the-counter medications.

Regulation of Weight-Loss Dietary Supplements

The U.S. Food and Drug Administration (FDA) regulates dietary supplements promoted for weight loss in accordance with the Dietary Supplement Health and Education Act of 1994 [13]. Like other dietary supplements, weight-loss supplements differ from over-the-counter or prescription medications in that the FDA does not classify them as drugs. Unlike drugs, dietary supplements do not require premarket review or approval by the FDA. Supplement manufacturers are responsible for determining that their products are safe and their label claims are truthful and not misleading. However, manufacturers are not required to provide that evidence to the FDA before marketing their products. If the FDA finds a supplement to be unsafe, it may remove the product from the market or ask the manufacturer to voluntarily recall the product. The FDA and the Federal Trade Commission (FTC) may also take regulatory actions against manufacturers that make unsubstantiated weight-loss claims about their products. The FDA does not permit dietary supplements to contain pharmaceutical ingredients, and manufacturers may not promote these products to diagnose, treat, cure, or prevent any disease [13].
For more information about dietary supplement regulation, see the ODS publication, Dietary Supplements: What You Need to Know.

Common Ingredients in Weight-Loss Dietary Supplements

Weight-loss dietary supplements contain a wide variety of ingredients. Not surprisingly, the amount of scientific information available on these ingredients varies considerably. In some cases, purported benefits are based on limited theoretical data or animal and laboratory studies rather than human clinical trials. In other cases, studies supporting a given ingredient’s use are small, of short duration, and/or of poor quality, limiting the strength of the findings. In almost all cases, additional research is needed to fully understand the safety and/or efficacy of a particular ingredient [3].
Complicating the interpretation of many study results is the fact that most weight-loss dietary supplements contain multiple ingredients, making it difficult to isolate the effects of each ingredient and predict the effects of the combination. Furthermore, dosages and amounts of active components vary widely among weight-loss supplements, and a product’s composition is not always fully described in published studies [14]. Studies may also use different and sometimes inappropriate assessment techniques to measure the effectiveness of a given treatment. All of these factors can make it difficult to compare the results of one study with another.
Table 1 briefly summarizes the findings discussed in more detail in this fact sheet on the safety and efficacy of the most common ingredients of weight-loss dietary supplements. These ingredients are listed and discussed in the table and in the text in alphabetical order. Dosage information is provided when such information is available. However, because ingredients might not be standardized and many products contain proprietary blends of ingredients, the active compounds and their amounts might not be comparable among products [15].

Table 1: Common Ingredients in Weight-Loss Dietary Supplements*
Ingredient	Proposed Mechanism of Action	Evidence of Efficacy	Evidence of Safety+
Bitter orange (synephrine)	Increases energy expenditure and lipolysis, acts as a mild appetite suppressant	Small clinical trials of poor methodological quality Research findings: Possible effect on resting metabolic rate and energy expenditure; inconclusive effects on weight loss	Some safety concerns reported Reported adverse effects: Chest pain, anxiety, and increased blood pressure and heart rate
Caffeine (as added caffeine or from guarana, kola nut, yerba mate, or other herbs)	Stimulates central nervous system, increases thermogenesis and fat oxidation	Short-term clinical trials of combination products Research findings: Possible modest effect on body weight or decreased weight gain over time	Safety concerns not usually reported at doses less than 400 mg/day for adults, significant safety concerns at higher doses Reported adverse effects: Nervousness, jitteriness, vomiting, and tachycardia
Calcium	Increases lipolysis and fat accumulation, decreases fat absorption	Several large clinical trials Research findings: No effect on body weight, weight loss, or prevention of weight gain based on clinical trials	No safety concerns reported at recommended intakes (1,000–1,200 mg/day for adults) Reported adverse effects: Constipation, kidney stones, and interference with zinc and iron absorption at intakes above 2,000–2,500 mg for adults
Chitosan	Binds dietary fat in the digestive tract	Small clinical trials, mostly of poor methodological quality Research findings: Minimal effect on body weight	Few safety concerns reported, could cause allergic reactions Reported adverse effects: Flatulence, bloating, constipation, indigestion, nausea, and heartburn
Chromium	Increases lean muscle mass; promotes fat loss; and reduces food intake, hunger levels, and fat cravings	Several clinical trials of varying methodological quality Research findings: Minimal effect on body weight and body fat	No safety concerns reported at recommended intakes (25–45 mcg/day for adults) Reported adverse effects: Headache, watery stools, constipation, weakness, vertigo, nausea, vomiting, and urticaria (hives)
Coleus forskohlii (forskolin)	Enhances lipolysis and reduces appetite	Few short-term clinical trials Research findings: No effect on body weight	No safety concerns reported Reported adverse effects: None known
Conjugated linoleic acid	Promotes apoptosis in adipose tissue	Several clinical trials Research findings: Minimal effect on body weight and body fat	Few safety concerns reported Reported adverse effects: Abdominal discomfort and pain, constipation, diarrhea, loose stools, dyspepsia, and (possibly) adverse effects on blood lipid profiles
Ephedra (ma huang, ephedrine)	Stimulates central nervous system, increases thermogenesis, reduces appetite	Several short-term clinical trials of good methodological quality, many of ephedra combined with caffeine Research findings: Modest effect on short-term weight loss	Significant safety concerns reported; banned as a dietary supplement ingredient Reported adverse effects: Anxiety, mood changes, nausea, vomiting, hypertension, palpitation, stroke, seizures, heart attack, and death
Fucoxanthin	Increases energy expenditure and fatty acid oxidation, suppresses adipocyte differentiation and lipid accumulation	Studied only in combination with pomegranate-seed oil in one trial in humans Research findings: Insufficient research to draw firm conclusions	No safety concerns reported but not rigorously studied Reported adverse effects: None known
Garcinia cambogia (hydroxycitric acid)	Inhibits lipogenesis, suppresses food intake	Several short-term clinical trials of varying methodological quality Research findings: Little to no effect on body weight	Few safety concerns reported Reported adverse effects: Headache, nausea, upper respiratory tract symptoms, and gastrointestinal symptoms
Glucomannan	Increases feelings of satiety and fullness, prolongs gastric emptying time	Several clinical trials of varying methodological quality, mostly focused on effects on lipid and blood glucose levels Research findings: Little to no effect on body weight	Significant safety concerns reported with tablet forms, which might cause esophageal obstructions, but few safety concerns with other forms Reported adverse effects: Loose stools, flatulence, diarrhea, constipation, and abdominal discomfort
Green coffee bean extract (Coffea aribica, Coffea canephora, Coffea robusta)	Inhibits fat accumulation, modulates glucose metabolism	Few clinical trials, all of poor methodological quality Research findings: Possible modest effect on body weight	Few safety concerns reported but not rigorously studied; contains caffeine Reported adverse effects: Headache and urinary tract infections
Green tea (Camellia sinensis) and green tea extract	Increases energy expenditure and fat oxidation, reduces lipogenesis and fat absorption	Several clinical trials of good methodological quality on green tea catechins with and without caffeine Research findings: Possible modest effect on body weight	No safety concerns reported when used as a beverage, contains caffeine; some safety concerns reported for green tea extract Reported adverse effects (for green tea extract): Constipation, abdominal discomfort, nausea, increased blood pressure, liver damage
Guar gum	Acts as bulking agent in gut, delays gastric emptying, increases feelings of satiety	Several clinical trials of good methodological quality Research findings: No effect on body weight	Few safety concerns reported with currently available formulations Reported adverse effects: Abdominal pain, flatulence, diarrhea, nausea, and cramps
Hoodia (Hoodia gordonii)	Suppresses appetite, reduces food intake	Very little published research in humans Research findings: No effect on energy intake or body weight based on results from one study	Some safety concerns reported, increases heart rate and blood pressure Reported adverse effects: Headache, dizziness, nausea, and vomiting
Pyruvate	Increases lipolysis and energy expenditure	Few clinical trials of weak methodological quality Research findings: Possible minimal effect on body weight and body fat	Few safety concerns reported Reported adverse effects: Diarrhea, gas, bloating, and (possibly) decreased high-density lipoprotein levels
Raspberry ketone	Alters lipid metabolism	Studied only in combination with other ingredients Research findings: Insufficient research to draw firm conclusions	No safety concerns reported but not rigorously studied Reported adverse effects: None known
White kidney bean (Phaseolus vulgaris)	Interferes with breakdown and absorption of carbohydrates by acting as a “starch blocker”	Several clinical trials of varying methodological quality Research findings: Possible modest effect on body weight and body fat	Few safety concerns reported Reported adverse effects: Headache, soft stools, flatulence, and constipation
Yohimbe (Pausinystalia yohimbe, yohimbine)	Has hyperadrenergic effects	Very little research on yohimbe for weight-loss Research findings: No effect on body weight; insufficient research to draw firm conclusions	Significant safety concerns reported Reported adverse effects: Headache, anxiety, agitation, hypertension, and tachycardia

* References to support statements in Table 1 are provided in subsequent text.
+Listed in order of severity, with the most severe reported side effects listed last.
Bitter orange (synephrine)
Bitter orange is the common name for the botanical Citrus aurantium. This plant is a source of p-synephrine (often referred to simply as synephrine) and other protoalkaloids [16-19]. As alpha-adrenergic agonists, synephrine alkaloids can mimic the action of epinephrine and norepinephrine. However, the extent to which bitter orange and synephrine cause similar cardiovascular and central-nervous-system effects to epinephrine and norepinephrine (e.g., increased heart rate and blood pressure) is not clear [16-18].
Studies suggest that bitter orange increases energy expenditure and lipolysis and that it acts as a mild appetite suppressant [16,20]. After the FDA banned the use of ephedrine alkaloids in dietary supplements in 2004 (see section on ephedra [ma huang]), manufacturers replaced ephedra with bitter orange in many products; thus, bitter orange became known as an “ephedra substitute” [21]. Although synephrine has some structural similarities to ephedrine, it has different pharmacological properties [18,20].
Efficacy: Several small human studies have examined whether bitter orange is effective for weight loss [20]. Interpreting the results of these studies is complicated by the fact that bitter orange is almost always combined with other ingredients in weight-loss supplements.
In one study, 20 healthy overweight adults (body mass index [BMI] >25) took a product containing 975 mg bitter orange extract (6% synephrine alkaloids), 528 mg caffeine, and 900 mg St. John’s wort; a placebo; or nothing (control) each day for 6 weeks [22]. All participants also took part in a circuit-training exercise program and were counseled to follow an 1,800 kcal/day diet. At the end of the study, participants taking the combination bitter orange product had a significantly greater reduction in percent body fat and fat mass and a greater increase in basal metabolic rate than those in the placebo and control groups. Participants in all groups lost weight, but the authors did not report whether the mean reduction in body weight in the treatment group (1.4 kg) was significantly greater than that in the placebo (0.9 kg) or control groups (0.4 kg) [23].
In another study, 8 healthy overweight or obese people (BMI 25–40) received counseling to follow a 1,200–1,500 kcal/day diet and were randomized to take either an herbal supplement containing bitter orange (18 mg synephrine/day) and other ingredients, including guarana extract as a source of caffeine (396 mg caffeine/day), or placebo [24]. The peak rise in resting metabolic rate at baseline was significantly higher in participants taking the herbal supplement than those in the placebo group, but the difference was not significant at the end of the 8-week study. The herbal supplement also produced a significant increase in mean body weight (1.13 kg) compared with placebo (0.09 kg) at the end of the study. However, this increase in body weight did not significantly affect body fat and lean tissue levels or waist circumference. The authors noted that the weight gain might have occurred by chance because the trial was insufficiently powered to detect this small difference.
The authors of a 2012 review of 23 small human clinical studies involving a total of 360 participants concluded that synephrine increases resting metabolic rate and energy expenditure [20]. The authors of an earlier review of animal studies, clinical trials, physiologic studies, and case reports concluded that synephrine alkaloids have a “suggestion of some benefit to weight loss,” but the available data are very limited and cannot be considered conclusive [16]. The authors of both reviews stated that longer-term clinical trials with rigorous designs and large samples are needed to determine the value of bitter orange for weight loss.
Safety: Products containing bitter orange have significant safety concerns. Reported adverse effects include chest pain, anxiety, ventricular fibrillation, ischemic stroke, myocardial infarction, and death [25]. However, many of the products with these effects contained multiple herbal ingredients, and the role of bitter orange in these adverse effects cannot be determined. Some studies indicate that bitter orange and synephrine—as bitter orange extract or pure synephrine–—raise blood pressure and heart rate in humans and rats, but other studies show that they do not have these effects [16-18,22,26-29]. Thus, some researchers have suggested that synephrine might not act directly as a cardiovascular stimulant [18,27,29]. Instead, caffeine, other stimulants in multi-component formulations, other constituents of bitter orange or adulterants, such as m-synephrine (which is not naturally present in bitter orange), might be responsible for its observed effects.
Caffeine, including caffeine from guarana, kola nut, yerba mate, or other herbs
Caffeine (either added to a weight-loss supplement or as an herbal source that naturally contains caffeine, such as guarana (Paullinia cupana), kola (or cola) nut (Cola nitida), and yerba mate (Ilex paraguariensis), is commonly found in dietary supplements promoted for weight loss. Green tea and other forms of tea also contain caffeine (see section on green tea). Some weight-loss supplement labels do not declare the amount of caffeine in the product, only the herbal ingredients. As a result, consumers might not be aware that the presence of certain herbs means that a product contains caffeine and possibly other stimulants [30].
Caffeine is a methylxanthine that stimulates the central nervous system, heart, and skeletal muscles. It also increases gastric and colonic activity and acts as a diuretic [31,32]. Its half-life is about 6 hours. Caffeine increases thermogenesis in a linear, dose-dependent fashion in humans [33]. A 100 mg dose of caffeine, for example, increased energy expenditure by a mean of 9.2 kcal/hr more than placebo in healthy humans. Caffeine might also contribute to weight loss by increasing fat oxidation through sympathetic activation of the central nervous system and by acting as a diuretic [30,33]. Habitual use of caffeine however, may diminish these effects due to the development of caffeine tolerance [30,32].
Efficacy: Clinical trials examining the effects of caffeine on weight loss have all been short term and have used combination products. In one study, 167 overweight or obese participants (BMI 25–40) took a supplement containing ma huang (90 mg/day ephedrine) and kola nut (192 mg/day caffeine) or placebo [34]. Participants were counseled to eat a normal diet except for limiting dietary fat to 30% of calories and to exercise moderately. After 6 months, those in the treatment group lost significantly more weight (mean weight loss 5.3 kg) than those in the placebo group (2.6 kg) and had significantly greater body fat reduction.
In another study, 47 overweight adults (BMI 26–30) were randomized to take a combination product containing 336 mg yerba mate (1-1.5% caffeine), 285 mg guarana (3–6% caffeine), and 108 mg damiana (a botanical extract that contains ethereal oils, resins, and tannins but not caffeine) or placebo 15 minutes before each main meal for 45 days while maintaining their normal eating habits [35]. At the end of the study, participants taking the herbal product lost a mean of 5.1 kg compared to 0.3 kg for those taking the placebo.
Data from a 12-year prospective observational study provide some insight into the long-term association between caffeine intake and body weight [36]. In this study, researchers followed 18,417 healthy men and 39,740 healthy women who were enrolled in either the Nurses’ Health Study or the Health Professionals Follow-Up Study. On average, participants gained some weight during the study, but men who increased their caffeine intake during the 12 years of follow-up gained a mean of 0.43 kg less than those who decreased their caffeine consumption. For women, the corresponding mean difference in weight gain was 0.35 kg less.
Safety: For healthy adults, the FDA states that 400 mg/day caffeine is “not generally associated with dangerous, negative effects” [37]. For comparison, an 8- ounce cup of brewed coffee contains about 85 mg caffeine [38]. The FDA has not set a safe level of intake for children, but the American Academy of Pediatrics discourages children and adolescents from consuming caffeine and other stimulants [37].
Caffeine can cause sleep disturbances and feelings of nervousness, jitteriness, and shakiness. Caffeine can be toxic when used in high doses, causing nausea, vomiting, tachycardia, seizures, and cerebral edema [31]. Toxic effects have been reported with doses of 15 mg/kg (about 1,000 mg for a 150-lb adult) and fatalities with doses above 150 mg/kg (about 10,000 mg for a 150-lb adult). Combining caffeine with other stimulants, such as bitter orange and ephedrine, can potentiate these adverse effects.
Calcium
Calcium is an essential mineral that is stored in the bones and teeth, where it supports their structure and function. Calcium is required for vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion [39]. The Recommended Dietary Allowance (average daily level of intake sufficient to meet the nutrient needs of 97%–98% of healthy individuals) for calcium ranges from 1,000 to 1,300 mg/day for children and adults aged 4 years and older.
Several studies have correlated higher calcium intakes with lower body weight or less weight gain over time [40-43]. Two explanations have been proposed. First, high calcium intakes might reduce calcium concentrations in fat cells by decreasing the production of parathyroid hormone and the active form of vitamin D. Decreased intracellular calcium concentrations, in turn, might increase fat breakdown and discourage fat accumulation in these cells [42]. Second, calcium from food or supplements might bind to small amounts of dietary fat in the digestive tract and prevent absorption of this fat [42,44,45]. Dairy products, in particular, might contain additional components that have even greater effects on body weight than their calcium content alone would suggest [43,46-50].
Efficacy: The results from clinical trials examining the effects of calcium on body weight have been largely negative. For example, supplementation with 1,500 mg/day calcium (from calcium carbonate) was investigated in 340 overweight or obese adults (BMI ≥25) with mean baseline calcium intakes of 878 mg/day (treatment group) and 887 mg/day (placebo group) [51]. Compared to placebo, calcium supplementation for 2 years had no clinically significant effects on weight. Three reviews of published studies on the effects of calcium from supplements or dairy products on weight management produced similar conclusions [52-54]. The authors of a 2006 meta-analysis of 13 randomized controlled trials concluded that neither calcium supplementation nor increased dairy product consumption has a statistically significant effect on weight reduction [54]. A 2009 evidence report from the Agency for Healthcare Research and Quality showed that, overall, clinical trial results do not support an effect of calcium supplementation on weight [52]. Also, a 2012 meta-analysis of 29 randomized controlled trials found no benefit of increased consumption of dairy products on body weight and fat loss in long-term studies [53]. Overall, the results from clinical trials do not support a link between higher calcium intakes and lower body weight, prevention of weight gain, or weight loss.
Safety: The Tolerable Upper Intake Level (UL; maximum daily intake unlikely to cause adverse health effects) for calcium established by the Institute of Medicine of the National Academies is 2,500 mg/day for adults aged 19–50 years and 2,000 mg for adults aged 51 and older [39]. High intakes of calcium can cause constipation and might interfere with the absorption of iron and zinc, although this effect is not well established. High intakes of calcium from supplements, but not foods, have been associated with an increased risk of kidney stones [39,55-57].
Chitosan
Chitosan is a polysaccharide derived from the exoskeletons of crustaceans. It is purported to promote weight loss by binding dietary fat in the digestive tract [30]. However, the amount of fat that chitosan binds is clinically insignificant [58].
Efficacy: In a small study, 12 healthy men and 12 healthy women (BMI 20–36) followed the same diet for 12 days (five meals per day with 38% of energy from fat). Chitosan capsules taken before meals (total of 2.5 g/day) slightly increased fecal fat excretion in the men compared to the control group [58]. However, the amount of fat that the chitosan trapped would result in a loss of only 1 pound of body fat over about 7 months. Chitosan had no significant effect on fecal fat excretion in the women compared to the control group.
One clinical trial randomly assigned 59 overweight or obese women (BMI 27–40) to receive either chitosan (3 g/day divided between the two largest meals) or placebo for 8 weeks while continuing their normal dietary and exercise habits [59]. At the end of the study, those in the treatment group lost a mean of 1 kg body weight compared to a mean weight gain of 1.5 kg in the placebo group. In a 28-day trial, chitosan (2 g/day divided into two equal doses) failed to reduce body weight compared to placebo in 28 overweight women and 6 overweight men who maintained their normal diet during the study [60]. The authors of a Cochrane review that included 13 trials examining the effect of chitosan on body weight found that chitosan, when taken for 4 weeks to 6 months, reduced body weight by a mean of 1.7 kg compared with placebo [61]. They concluded that chitosan appears to be more effective than placebo for short-term weight loss, but most studies have been of poor quality. The authors noted that results from high-quality trials indicate that chitosan has minimal effects on body weight and these effects are probably clinically insignificant.
Safety: The adverse effects of chitosan are minor and primarily affect the gastrointestinal tract. These effects include flatulence, bloating, mild nausea, constipation, indigestion, and heartburn [59-61]. Because chitosan is derived from shellfish, people who are allergic to shellfish could theoretically be allergic to chitosan [62].
Chromium
Chromium in its trivalent form (chromium III) is an essential trace mineral that potentiates the action of insulin. The Institute of Medicine of the National Academies has established an Adequate Intake for chromium of 20–35 mcg/day for non-pregnant, non-lactating adults [63]. Dietary supplements commonly contain chromium in the form of chromium picolinate, which consists of chromium and picolinic acid, although they might also contain other forms, including chromium nicotinate and chromium yeast [64]. Poor chromium status may contribute to impaired glucose tolerance and type 2 diabetes [63]. Researchers have hypothesized that chromium supplements increase lean muscle mass and promote fat loss, but study results have been equivocal [30,65]. Some research indicates that these supplements might also reduce food intake, hunger levels, and fat cravings [66], although data on these effects are sparse.
Efficacy: Several studies have evaluated the effects of chromium supplements, usually in the form of chromium picolinate, on weight loss. A 2013 Cochrane review analyzed the results from 9 randomized controlled trials of chromium picolinate supplements in a total of 622 overweight or obese participants (BMI ≥25) [65]. Trial durations ranged from 8 weeks to 6 months, and doses of chromium picolinate were 200 to 1,000 mcg/day. Six of the trials included resistance or weight training, and three did not. The authors found that chromium picolinate supplementation reduced body weight by 1.1 kg more than placebo, but the amount of weight loss did not correlate with the dose of chromium picolinate. The authors stated that the effect is of “debatable clinical relevance” and the overall quality of the evidence is low.
Also in 2013, a systematic review and meta-analysis of 11 randomized, controlled trials (including most of the trials evaluated in the Cochrane review) examined the effects of chromium supplementation in a total of 866 overweight or obese individuals [64]. The authors concluded that chromium reduces body weight by 0.5 kg and percent body fat by 0.46% when taken at daily doses of 137 to 1,000 mcg for 8 to 26 weeks. Like the authors of the Cochrane review, these authors noted that the effect is small and of “uncertain” clinical relevance. Similar findings were reported from an earlier meta-analysis of 12 trials [67].
Safety: Trivalent chromium appears to be well tolerated. Adverse effects from clinical trials include watery stools, headache, weakness, nausea, vomiting, constipation, vertigo, and urticaria (hives) [64,65]. Chromium does not have an established UL because few serious adverse effects have been linked to high chromium intakes [63]. Hexavalent chromium (chromium IV) is toxic and is not found in food or dietary supplements.
Cola (or kola) nut (see section on caffeine above)
Coleus forskohlii (forskolin)
Forskolin is a compound isolated from the roots of Coleus forskohlii, a plant that grows in subtropical areas, such as India and Thailand. Forskolin is purported to promote weight loss by enhancing lipolysis and reducing appetite [68,69].
Efficacy: Although animal studies indicate that forskolin reduces food intake [68], research in humans is very limited and inconclusive. In a small, randomized, double- blind trial, 19 overweight or obese females (BMI 25–35) aged 18–40 years received either forskolin (250 mg of 10% forskolin extract [ForsLean&supTM;] taken before breakfast and dinner for a total daily dose of 500 mg) or placebo while continuing their usual diet for 12 weeks [70]. Compared to placebo, forskolin had no effect on body weight, appetite, caloric intake, or macronutrient intake. The same forskolin product and dose were evaluated in another 12-week, randomized, double-blind trial involving 30 overweight men (BMI ≥26) [69]. In this study, forskolin did not affect body weight, but it did significantly decrease mean body fat by 4.14% compared with placebo (0.96%).
Safety: No significant adverse events were reported in the two 12-week trials detailed above [69,70], but forskolin has not been evaluated in longer-term trials. Additional research is needed to better understand its safety and side effects for both short- and long-term use.
Conjugated linoleic acid
Conjugated linoleic acid (CLA) is a derivative of linoleic acid that is present mainly in dairy products and beef. CLA exists in several different isomeric forms, including c9t11 -CLA and t10c12-CLA, and is available in dietary supplements as a triacylglycerol or as a free fatty acid [71]. Researchers have suggested that CLA enhances weight loss by promoting apoptosis in adipose tissue [72].
Efficacy: Although CLA appears to reduce body fat mass in animals [72], results from human studies suggest that its effects are small and of questionable clinical relevance [73]. One double-blind, placebo-controlled trial evaluated the effects of CLA supplementation (as a 50:50 mixture of c9t11-CLA and t10c12-CLA) in 180 overweight male and female volunteers (BMI 25–30) consuming an ad libitum diet [71]. Participants received CLA as a free fatty acid (3.6 g CLA isomers), CLA as a triacylglycerol (3.4 g CLA isomers), or placebo daily for 1 year. At the end of the study, supplementation with CLA as a free fatty acid and as a triacylglycerol significantly reduced body fat mass by a mean of 6.9% and 8.7%, respectively, compared with placebo. Supplementation with CLA as a free fatty acid (but not as a triacylglycerol) also increased lean body mass compared with placebo.
In another double-blind crossover trial, daily supplementation with CLA oil (6.4 g CLA isomers—approximately equal amounts of c9t11-CLA and t10c12-CLA) for 16 weeks significantly reduced BMI and total adipose mass compared with safflower oil in 35 obese postmenopausal women (BMI >30) with type 2 diabetes [74].
The authors of a systematic review and meta-analysis of 7 randomized controlled trials concluded that taking CLA for 6–12 months reduces body weight by a mean of 0.7 kg and body fat by a mean of 1.33 kg compared to placebo [73]. However, the authors noted that the “magnitude of these effects is small, and the clinical relevance is uncertain.”
Safety: CLA appears to be well tolerated. Most reported adverse effects are minor, consisting mainly of gastrointestinal disturbances, such as abdominal discomfort and pain, constipation, diarrhea, loose stools, and dyspepsia [3,71,73,75,76].
CLA might adversely affect lipid profiles, although results from studies are inconsistent. Some research indicates that CLA has no major effect on lipid profiles, but other research shows that certain CLA isomers might decrease high-density lipoprotein (HDL) cholesterol and increase lipoprotein(a) levels [71,76-80]. The CLA isomer t10c12-CLA has also been reported to increase insulin resistance and glycemia in obese men with metabolic syndrome [80].
Ephedra (ma huang)
Ephedra (also known as ma huang), a plant native to China, is the common name for three main species: Ephedra sinica, Ephedra equisentina, and Ephedra intermedia [81]. The active compounds, which are in the plant’s stem and account for about 1.32% of the plant’s weight, are the alkaloids ephedrine, pseudoephedrine, norephedrine, and norpseudoephedrine [82,83].
In the 1990s, ephedra—frequently combined with caffeine—was a popular ingredient in dietary supplements sold for weight loss and enhanced athletic performance. The FDA no longer permits the use of ephedra in dietary supplements because of safety concerns that are detailed below, but information is provided here due to continued interest in this ingredient.
Efficacy: Ephedrine acts as a stimulant in the central nervous system [84,85]. It also may increase thermogenesis and act as an appetite suppressant [86]. The authors of a meta-analysis that included 20 clinical trials concluded that ephedrine and ephedra are modestly effective for short-term weight loss (6 months or less), but no studies have assessed their long-term effects [87].
Safety: While ephedra was available as a dietary supplement ingredient in the United States, its use with or without caffeine was associated with numerous reported adverse effects, including nausea, vomiting, psychiatric symptoms (such as anxiety and mood change), hypertension, palpitations, stroke, seizures, heart attack, and death [87,88]. Although these reported adverse effects could not be linked with certainty to the use of ephedra-containing dietary supplements, the FDA deemed the safety concerns serious enough to prohibit the sale of dietary supplements containing ephedrine alkaloids in 2004 [89]. As a result of this ruling, manufacturers are no longer permitted to sell dietary supplements containing ephedrine alkaloids in the United States.
Fucoxanthin
Fucoxanthin is a carotenoid that is found in brown seaweed and other algae. Results from laboratory and animal studies suggest that fucoxanthin might promote weight loss by increasing resting energy expenditure and fatty acid oxidation as well as by suppressing adipocyte differentiation and lipid accumulation [90,91].
Efficacy: Only one human clinical trial has been conducted on the possible weight-loss effects of fucoxanthin. This 16-week trial used Xanthigen®, a dietary supplement containing brown seaweed extract and pomegranate-seed oil [92]. In one arm of this study, 110 obese (BMI >30) premenopausal women, 72 of whom had non-alcoholic fatty liver disease (NAFLD), received either a placebo or Xanthigen® three times a day before meals for a total daily dose of 2.4 mg fucoxanthin and 300 mg pomegranate-seed oil. Participants followed a controlled diet that limited total energy intake to 1,800 kcal/day. Compared to the placebo group, those receiving Xanthigen® lost significantly more body weight by the end of the trial (mean loss of 6.9 kg vs. 1.4 kg for placebo in participants with NAFLD; mean loss of 6.3 kg vs. 1.4 kg for placebo in those without NAFLD). Because this is the only clinical trial on a dietary supplement containing fucoxanthin, additional research is needed to understand its potential effects on body weight.
Safety: The safety of fucoxanthin has not been thoroughly evaluated in humans. Although participants using Xanthigen® in the clinical trial described above reported no adverse effects [92], further investigation of the safety and potential side effects of fucoxanthin at various levels of intake is required.
Garcinia cambogia (hydroxycitric acid)
Garcinia cambogia is a fruit-bearing tree that grows throughout Asia, Africa, and the Polynesian islands [93]. The pulp and rind of its fruit contain high amounts of hydroxycitric acid (HCA), a compound that some researchers believe inhibits lipogenesis, increases hepatic glycogen synthesis, suppresses food intake, and reduces weight gain [6,15,72,93,94].
Efficacy: Studies in rats have found that Garcinia cambogia suppresses food intake and inhibits weight gain [3]. In humans, however, the evidence on whether Garcinia cambogia or HCA is effective for weight loss is conflicting, and any effects it has appear to be small [6,72,93-95].
In one randomized, placebo-controlled trial, 89 mildly overweight women (weighing 10–50 lb more than ideal body weight) received Garcinia cambogia (800 mg, 30–60 minutes before meals for a total daily dose of 2.4 g/day [1.2 g HCA]) or placebo and followed a 1,200 kcal diet for 12 weeks [96]. Women receiving Garcinia cambogia lost significantly more weight (3.7 kg) than those receiving placebo (2.4 kg). However, Garcinia cambogia did not alter appetite, and the study produced no evidence that the supplement affected feelings of satiety. In another double-blind, placebo-controlled trial, 135 overweight men and women (BMI 27–38) received either Garcinia cambogia (1,000 mg, 30 minutes before each meal for a total daily dose of 3,000 mg/day [1,500 mg HCA]) or placebo and followed a high-fiber, low-energy diet for 12 weeks [97]. Participants in both groups lost weight, but the between-group weight-loss differences were not statistically significant. HCA also had no effect on body fat loss.
A 2011 review and meta-analysis of 12 randomized, controlled trials with a total of 706 participants examined the effects of HCA on weight loss [95]. The findings from 9 of the trials (those that had data suitable for statistical pooling) indicate that when taken for 2–12 weeks, HCA reduces body weight in the short term by a mean of 0.88 kg compared to placebo. However, the authors noted that when they considered only rigorously designed trials, the effect was no longer statistically significant. Therefore, the effect of HCA on body weight remains uncertain. The authors of a 2013 review of Garcinia cambogia/HCA reached similar conclusions, noting that whether Garcinia cambogia/HCA is effective for obesity “remains to be proven in larger-scale and longer-term clinical trials” [98].
Safety: The reported adverse effects of Garcinia cambogia and HCA are generally mild and include headache, nausea, upper respiratory tract symptoms, and gastrointestinal symptoms [93,95,97]. Cases of liver toxicity have been reported in people taking products containing Garcinia cambogia, other botanical ingredients, and minerals [32]. However, it is unclear whether this toxicity can be attributed to Garcinia cambogia. Because all clinical trials of Garcinia cambogia and HCA have been short, its long-term safety is unknown.
Glucomannan
Glucomannan is a soluble dietary fiber derived from konjac root (Amorphophallus konjac). Some researchers believe that, like guar gum, glucomannan absorbs water in the gastrointestinal tract, thereby increasing feelings of satiety and fullness and prolonging gastric emptying [99,100].
Efficacy: Glucomannan appears to have beneficial effects on blood lipids and glucose levels [100], but its effects on weight loss are inconsistent. In one study conducted in Italy, 2 g/day glucomannan (in 2 divided doses) in 60 obese children (mean age 11.2 years) for 2 months did not significantly affect weight loss compared to placebo [101]. In a small study conducted in the United States, 20 obese women (weighing ≥20% more than ideal body weight) consumed 3 g/day glucomannan (1 g before each meal) or placebo for 8 weeks [102]. At the end of the study, glucomannan produced significantly greater weight loss (mean loss of 2.5 kg) than placebo (mean gain of 0.7 kg). In another study conducted in the United States, supplementation with glucomannan (3.9 g/day) for 4 weeks in 63 healthy men did not significantly affect body weight compared with placebo [103].
The authors of a 2015 systematic review of six randomized controlled trials with a total of 293 participants concluded that 1.24 to 3.99 g/day glucomannan for up to 12 weeks does not have a significant effect on body weight compared to placebo [104,105]. Similarly, a 2014 meta-analysis of eight trials that included 301 participants found that glucomannan did not significantly affect weight loss compared to placebo [106]. The authors of an older meta-analysis of 14 studies designed primarily to investigate glucomannan’s effect on lipid and blood glucose levels concluded that 1.2 to 15.1 g/day glucomannan reduces body weight by a small but statistically significant amount (mean loss 0.79 kg more than placebo) over about 5 weeks [100].
Safety: Little is known about the long-term safety of glucomannan. Glucomannan appears to be well tolerated for short-term use, with minor adverse effects including loose stools, flatulence, diarrhea, constipation, and abdominal discomfort [100,104,106]. The use of tablet forms of glucomannan was reported to be associated with seven cases of esophageal obstruction in 1984–1985 in Australia [99]. Caution is therefore warranted when these forms of glucomannan are used. Powdered or capsule forms have not been associated with this effect [107].
Green coffee bean extract (Coffea aribica, Coffea canephora, Coffea robusta)
Coffee beans (Coffea aribica, Coffea canephora, Coffea robusta) are green until they are roasted. Compared to roasted beans, green coffee beans have higher levels of chlorogenic acid. Green coffee extract, likely due to its chlorogenic acid content, has been shown in mice and humans to inhibit fat accumulation and modulate glucose metabolism [108], perhaps by reducing the absorption of glucose in the gut [109]. Green coffee beans also contain caffeine (see section on caffeine above) [110].
Efficacy: Only a few clinical trials have examined the effects of green coffee bean on weight loss, and all are of poor methodological quality. Onakpoya and colleagues conducted a meta-analysis of three trials in which overweight participants received either 180 or 200 mg/day green coffee extract for 4 to 12 weeks [109]. The researchers concluded that green coffee extract has a moderate but significant effect on body weight (mean weight loss of 2.47 kg more than placebo), but they noted that the methodological quality of all studies included in the meta-analysis was poor.
Another small clinical trial claimed to show a benefit of green coffee extract for weight loss [111], but it was strongly criticized by the FTC for having several critical flaws in the study design [112,113]. Two of the three study authors subsequently retracted the journal publication.
Safety: Green coffee extract appears to be well tolerated, but its safety has not been rigorously studied. Reported adverse effects include headaches and urinary tract infections [109]. The caffeine in green coffee beans acts as a stimulant and can cause adverse effects, depending on the dose and whether it is combined with other stimulants (see section on caffeine above).
Green tea (Camellia sinensis) and green tea extract
Green tea (Camellia sinensis) is a popular beverage consumed worldwide that has several purported health benefits [114]. Green tea is present in some dietary supplements, frequently in the form of green tea extract. The active components of green tea that are associated with weight loss are caffeine (see section on caffeine above) and catechins, primarily epigallocatechin gallate (EGCG), which is a flavonoid [30,114]. A typical brewed cup of green tea has about 240–320 mg catechins [114] and 45 mg caffeine. Experts have suggested that green tea and its components might reduce body weight by increasing energy expenditure and fat oxidation, reducing lipogenesis, and decreasing fat absorption [30,115,116].
The authors of a meta-analysis of 6 randomized controlled trials with a total of 98 participants found that caffeine alone or in combination with catechins significantly increases energy expenditure in a dose-dependent fashion compared with placebo [115]. This effect might be important for maintaining weight loss by helping to counteract the decrease in metabolic rate that can occur during weight loss. Catechins combined with caffeine also significantly increase fat oxidation, but caffeine alone does not. Other human research indicates that EGCG alone does not increase resting metabolic rate, fat oxidation, or the thermic effect of feeding (the increase in metabolic rate associated with the digestion and absorption of food) [117,118].Taken together, these findings suggest that green tea catechins and caffeine might act synergistically [30,115,116].
Efficacy: Several human studies have examined the effects of green tea catechins on weight loss and weight maintenance. A 2012 Cochrane review analyzed the results from 14 randomized controlled trials of green tea preparations in a total of 1,562 overweight or obese participants [119]. The trials lasted from 12 to 13 weeks, and doses of green tea catechins ranged from 141 to 1,207 mg. Green tea supplementation reduced body weight by a mean of 0.95 kg more than placebo. However, when the authors analyzed the six studies that were conducted outside of Japan (where study methodologies were less heterogeneous than in the Japanese studies), they found no statistically significant difference in weight loss for green tea compared to placebo.
Another systematic review and meta-analysis included 15 randomized controlled trials, 6 of which examined the effects of caffeine (39–83 mg/day) with and without green tea catechins (576–690 mg/day) on anthropometric measurements. The authors reported that green tea catechins combined with caffeine over a median of 12 weeks modestly yet significantly reduced body weight by a mean of 1.38 kg and waist circumference by a mean of 1.93 cm compared with caffeine alone [120]. Only two studies in this meta-analysis examined the effects of green tea catechins alone. Their results suggest that green tea catechins alone do not affect body weight or other anthropometric measurements.
A similar meta-analysis of 11 randomized controlled trials found that people who took EGCG combined with caffeine for 12–13 weeks lost a mean of 1.31 kg more body weight (or gained 1.31 kg less weight) than those in control groups [121]. In 2010, the European Food Safety Authority examined health claims related to green tea and concluded that “a cause and effect relationship has not been established between the consumption of catechins (including EGCG) from green tea…and contribution to the maintenance or achievement of a normal body weight.” [122]. Taken together, the findings of these studies suggest that if green tea is an effective weight-loss aid, any effect it has is small and not likely to be clinically relevant [119,120].
Safety: No adverse effects have been reported from the consumption of green tea as a beverage [114]. For green tea extract, most reported adverse effects are mild to moderate, including nausea, constipation, abdominal discomfort, and increased blood pressure [119]. However, consumption of green tea extract—primarily ethanolic extracts of green tea—has been linked to liver damage in several case reports [32]. These reports prompted the U.S. Pharmacopeia (USP) to systematically review the safety of green tea products in 2008 [123]. Using clinical case report data and animal pharmacological and toxicological information, the USP concluded that the consumption of green tea products “probably” caused 7 cases of liver damage and “possibly” caused another 27 cases. The USP noted that problems are more likely to occur when green tea extract is taken on an empty stomach and therefore, advises taking green tea extracts with food to minimize the possible risk of liver damage. Other research indicates that green tea polyphenols do not elevate liver enzymes or cause liver dysfunction when consumed by healthy men for 3 weeks at a dose of 714 mg/day [124]. Liver damage from green tea extracts could be partly due to contaminants in some products [30], but some researchers advise using dietary supplements containing green tea extract with caution [114].
Guarana (see section on caffeine above)
Guar gum
Guar gum is a soluble dietary fiber derived from the Indian cluster bean Cyamopsis tetragonolobus [125]. Guar gum is present in certain dietary supplements and is an ingredient in some food products, especially gluten-free baked goods, because it helps bind and thicken these products. Like glucomannan, guar gum is purported to promote weight loss by acting as a bulking agent in the gut, delaying gastric emptying, increasing feelings of satiety, and, theoretically, decreasing appetite and food intake [125].
Efficacy: In a meta-analysis of 20 randomized, double-blind, placebo-controlled trials that statistically pooled data from 11 trials, Pittler and colleagues evaluated the effects of guar gum for body weight reduction in a total of 203 adults [125]. Trial participants included people with hypercholesterolemia, hyperlipidemia, or type 1 or type 2 diabetes; menopausal women; and healthy volunteers. Doses of guar gum ranged from 9 to 30 g/day; most participants followed their usual diet, and some received dietary advice. Compared with placebo, guar gum had no significant effect on weight loss. The authors concluded that guar gum is not effective for body weight reduction.
Safety: Reported adverse effects for guar gum are primarily gastrointestinal and include abdominal pain, flatulence, diarrhea, nausea, and cramps [125,126]. Case reports indicate that guar gum can cause severe esophageal and small-bowel obstruction if taken without sufficient fluid [127,128]. However, these reports were about a guar gum product that is no longer available [127]. In their meta-analysis, Pittler and colleagues concluded that given the adverse effects associated with the use of guar gum, the risks of taking it outweigh its benefits [125].
Hoodia (Hoodia gordonii)
Hoodia gordonii is a succulent plant that grows in the Kalahari Desert of southern Africa. The San people have traditionally used hoodia as an appetite suppressant during long hunts. This anecdotal evidence, combined with results of a few animal studies indicating that hoodia reduces food intake [129], led to the widespread marketing of hoodia as a weight-loss supplement in the United States.
Efficacy: Despite its immense popularity as a weight-loss supplement, very little scientific research on hoodia has been conducted in humans [130], and a mechanism of action for its potential weight-loss effects has not been proposed. In a randomized, controlled trial, 49 healthy overweight women (mean BMI 25) aged 18–50 years were randomized to receive Hoodia gordonii purified extract (2,220 mg/day in two divided doses taken 1 hour before breakfast and dinner) or placebo combined with an ad libitum diet for 15 days [131]. Compared to placebo, hoodia extract had no significant effect on energy intake or body weight.
Safety: Hoodia has been reported to cause significant increases in heart rate and blood pressure [131]. It also raises bilirubin and alkaline phosphatase levels (which may indicate impaired liver function), although the clinical significance of these findings is unclear because hoodia has not been reported to affect levels of other liver enzymes. Other side effects include headache, dizziness, nausea, and vomiting.
Various news reports indicate that some hoodia products contain little or no hoodia [132]. According to a report released in 2007, only 30%–60% of hoodia products contain adequate amounts of hoodia, although the authors did not indicate whether “adequate” refers to a therapeutic dose or indicates that the quantity of hoodia matches the label claim [133]; more recent data on hoodia content in supplements are not available.
Mate (see section on caffeine above)
Pyruvate
Pyruvate (a derivative of pyruvic acid) is a three-carbon compound that is generated in the body through glycolysis [134]. Pyruvate is also available as a dietary supplement, frequently in the form of calcium pyruvate. Researchers have suggested that pyruvate enhances exercise performance and reduces body weight and body fat, possibly by increasing lipolysis and energy expenditure [6,135,136].
Efficacy: Only a few studies have examined the effects of pyruvate supplementation in humans. Although some of these studies suggest that pyruvate decreases body weight and body fat, others do not. In a double-blind, placebo-controlled trial, 26 overweight men and women (BMI ≥25) were given 6 g/day pyruvate or placebo for 6 weeks [134]. All participants received counseling to follow a 2,000 kcal/day diet and completed 45–60 minutes of circuit training 3 times per week. At the end of the trial, the pyruvate group had significant decreases in body weight (mean loss of 1.2 kg), body fat, and percent body fat compared to baseline but no significant changes in lean body mass. In the placebo group, these measurements did not change significantly compared to baseline.
Another small study of 14 obese women (BMI 28–53) found that pyruvate produces greater weight loss and fat loss when isoenergetically substituted for a glucose placebo for 21 days as part of a low-energy diet [137]. However, a double-blind, placebo-controlled trial in 23 overweight women (mean BMI 27.4) who followed their normal diets and participated in weight training and 30 minutes of walking 3 times per week had a different outcome [136]. In this trial, supplementation with 5 g/day calcium pyruvate for 30 days did not significantly affect body weight, body fat, percent body fat, or lean body mass compared with placebo. The authors of a systematic review and meta-analysis of 6 randomized controlled trials in a total of 203 participants concluded that pyruvate (when taken for 3–6 weeks) reduces body weight by a mean of 0.72 kg and body fat by a mean of 0.54 kg compared to placebo [135]. However, the authors noted that the methodological quality of all trials is weak, preventing them from drawing firm conclusions.
Safety: The safety of pyruvate has not been rigorously studied. Pyruvate causes gas, bloating, diarrhea, and borborygmus (rumbling noise in intestines resulting from gas) but has no serious adverse effects when it is administered for up to 6 weeks [134,135,137]. Pyruvate might also increase LDL levels and decrease HDL levels [135,136]. Additional research is needed to better understand the safety and possible side effects of this compound.
Raspberry ketone
Raspberry ketone is an aromatic compound found in red raspberries (Rubus idaeus). Its chemical structure has some similarities to those of capsaicin (present in hot red peppers) and synephrine, compounds whose effects on obesity and lipid metabolism have been investigated [138]. Raspberry ketone might help prevent weight gain by altering lipid metabolism. Although it has been touted on the Internet and national television as an effective way to burn fat, little evidence exists to support this claim.
Efficacy: Only one randomized controlled trial has examined the effects of a dietary supplement containing raspberry ketone and other ingredients. In this trial, 70 overweight men and women aged 21–45 (BMI >27) received daily supplementation with either a placebo or a weight-loss product, Prograde Metabolism^TM (METABO) [139]. This product contained 2,000 mg of a proprietary blend of raspberry ketone, caffeine, bitter orange, ginger, garlic, cayenne, L-theanine, and pepper extract along with B- vitamins and chromium. During the 8-week study, participants followed a calorie-restricted diet (approximately 500 calories less per day than estimated needs) and engaged in moderate exercise (60 minutes, 3 days per week). Compared to the placebo group, those receiving METABO lost significantly more body weight (mean loss of 1.9 kg vs. 0.4 kg for placebo) and fat mass. However, 25 of the 70 participants dropped out of the study, and results were reported for only the 45 participants who completed the study (i.e., the authors did not complete an intention-to-treat analysis). Furthermore, the product contained many ingredients in addition to raspberry ketone, making it impossible to determine the effects of raspberry ketone alone.
Safety: Participants in the METABO study described above had no serious adverse effects [139]. However, additional research on raspberry ketone is needed to more thoroughly understand its safety and side effects.
White kidney bean/bean pod (Phaseolus vulgaris)
White kidney bean or bean pod (Phaseolus vulgaris) is a legume that is native to Mexico, Central America, and South America and is cultivated worldwide [140]. Phaseolus vulgaris extract is an ingredient in some weight-loss dietary supplements marketed as carbohydrate- or starch-absorption “blockers.” Laboratory research indicates that Phaseolus vulgaris extract inhibits alpha-amylase activity, so experts have hypothesized that the plant interferes with the breakdown and absorption of carbohydrates in the gastrointestinal tract [140-142]. Phaseolus vulgaris might also act as an appetite suppressant [140].
Efficacy: The effect of Phaseolus vulgaris on weight loss and body fat has been examined in a few clinical trials, with inconsistent results. In a randomized, double-blind, placebo-controlled trial conducted in Italy, 60 overweight women (weighing 11–33 lb more than ideal body weight) aged 20–45 followed a 2,000–2,200- calorie meal plan and took a tablet containing approximately 445 mg dried aqueous extract of Phaseolus vulgaris (Phase 2® Starch Neutralizer IV) or a placebo once daily before eating a carbohydrate-rich meal [143]. After 30 days, those receiving Phaseolus vulgaris extract lost significantly more weight (mean weight loss 2.93 kg) than those receiving placebo (mean weight loss 0.35 kg). Those in the Phaseolus vulgaris group also experienced a significantly greater reduction in fat mass, adipose tissue thickness, and waist–hip–thigh circumference. However, in a similar trial conducted in the United States in 39 overweight adults (mostly women, BMI 30–43) aged 20–69, those who consumed 1,500 mg Phase 2® starch neutralizer twice daily with lunch and dinner (total daily dose 3,000 mg) for 8 weeks with a high-fiber/low-fat diet did not experience significantly greater weight loss than those receiving a placebo [141].
The authors of a 2011 review of 6 trials (including the 2 trials described above) with a total of 247 participants concluded that Phaseolus vulgaris significantly reduces body fat (mean difference 1.86 kg compared to placebo) but does not significantly affect weight loss [140]. However, the authors noted that the quality of the trials included in their review was poor, making it impossible to draw firm conclusions.
After the publication of this review, a 12-week clinical trial in 123 overweight and obese men and women found that Phaseolus vulgaris modestly yet significantly reduced body weight and body fat [144]. Participants consumed either a placebo or 1,000 mg Phaseolus vulgaris (IQP-PV-101; marketed under Phase 2®, Starchlite®, and Phaselite^TM brands) 3 times per day before meals for a total daily dose of 3,000 mg while following a mildly hypocaloric diet (500 kcal/day less than basal energy needs). Compared to placebo, those receiving Phaseolus vulgaris lost significantly more body weight (mean loss of 2.91 kg vs. 0.92 kg for placebo) and body fat (2.23 kg vs. 0.65 kg for placebo).
Safety: Reported adverse effects for Phaseolus vulgaris are fairly minor and include headaches, soft stools, flatulence, and constipation [140]. No serious adverse effects of Phaseolus vulgaris have been reported in clinical trials, but no trials have lasted longer than 13 weeks.
Yerba mate (see section on caffeine above)
Yohimbe (Pausinystalia yohimbe, yohimbine)
Yohimbe (Pausinystalia yohimbe, Pausinystalia johimbe) is a West African evergreen tree. The tree’s bark contains the alkaloid yohimbine, which is the main active constituent of yohimbe [145]. Yohimbine has hyperadrenergic physiological effects because it acts as an alpha-2 receptor antagonist [6,146]. Yohimbe extract is found in some dietary supplements that are promoted for libido enhancement, body building, and weight loss [145], but it is used primarily as a traditional remedy for sexual dysfunction in men. A form of yohimbine—yohimbine hydrochloride—is a prescription drug used to treat erectile dysfunction [145,147].
Efficacy: Very little research has been conducted on the use of yohimbe for weight loss and/or its effect on body mass. In a small clinical trial, yohimbine (5 mg taken 4 times/day) resulted in greater weight loss (mean weight loss 3.55 kg) than placebo (mean weight loss 2.21 kg) in 20 obese females (mean BMI 40 and 43 for placebo and yohimbine groups, respectively) who followed a low-energy diet (1,000 kcal/day) for 3 weeks [148]. However, in another clinical trial in 47 men (weighing >20% more than ideal body weight), high-dose yohimbine (peak dose 43 mg/day) for 6 months had no effect on body weight or body fat compared with placebo [149]. The authors of a 2011 review of yohimbe concluded that no conclusive evidence indicates that yohimbe affects body weight or body mass [146]. The author of a 2010 review of yohimbe reached similar conclusions, noting that results from small human trials of yohimbine for weight loss are contradictory and the evidence base is insufficient to support a weight loss claim for this compound [145].
Safety: Yohimbe can be dangerous. Taking 20 to 40 mg has been reported to increase blood pressure slightly, whereas doses of 200 mg or higher can cause headaches, hypertension, anxiety, agitation, tachycardia, myocardial infarction, cardiac failure, and death [32,126,145,146,150]. Although yohimbe is generally well tolerated at low doses [146], no safe dose has been established for it. Yohimbe should only be used under medical supervision because of its potential to produce serious adverse effects [150].

Safety Considerations

Like all dietary supplements, weight-loss supplements can have side effects and might interact with prescription and over-the-counter medications. In some cases, the active constituents of botanical or other ingredients promoted for weight loss are unknown or uncharacterized [21]. Furthermore, many weight-loss supplements contain multiple ingredients that have not been adequately tested in combination with one another.
Pittler and Ernst note that for ingredients lacking convincing evidence of effectiveness, “even minor adverse events shift the delicate risk-benefits balance against their use” [6]. People need to talk with their health care providers about the use of weight-loss dietary supplements to understand what is known—and not known—about these products.

Fraudulent and adulterated products

The FDA and FTC warn consumers to beware of fraudulent claims about weight-loss dietary supplements [151,152]. Messages like “magic diet pill!,” “melt your fat away! ”, and “lose weight without diet or exercise!” that sound too good to be true usually are. At best, products with claims like these do not live up to them, and even worse, they could be dangerous.
Weight-loss products, marketed as dietary supplements, are sometimes adulterated or tainted with prescription-drug ingredients; controlled substances; or untested/unstudied, pharmaceutically active ingredients that could be harmful [153].
Between January 2004 and December 2012, 237 dietary supplements were subject to a Class I recall by the FDA, meaning there was a reasonable probability that the use of or exposure to these products would cause serious adverse health consequences. Of these products, 27% were weight-loss dietary supplements [154]. In most cases, the recall was due to the presence of undeclared drug ingredients. In 2013, the FDA issued 30 public notifications warning consumers not to purchase specific weight-loss products because they contain a hidden drug ingredient—often sibutramine, a weight-loss medication that was withdrawn from the U.S. market in 2010 because of safety concerns [153]. A product represented as a dietary supplement that contains one or more drug ingredients, whether or not they are declared on the label, is considered an unapproved drug and is therefore subject to enforcement action by the FDA. The FDA maintains a webpage

listing public notifications about tainted weight-loss products.

Interactions with medications

Some ingredients in weight-loss dietary supplements can interact with certain medications. For example, glucomannan and guar gum might decrease the absorption of many drugs that are taken orally [107,128]. Glucomannan has been reported to lower blood glucose levels [100] and, therefore, could interact with diabetes medications [107]. Chitosan might potentiate the anticoagulant effects of warfarin [155]. Green tea could interact with chemotherapy drugs [156,157]. Garcinia cambogia was associated with serotonin toxicity in a patient taking the supplement together with two selective serotonin reuptake inhibitor medications [158]. Other ingredients, such as caffeine and bitter orange, could have an additive effect if taken with other stimulants. Bitter orange has also been shown to inhibit CYP3A4 activity, leading to increased blood levels of certain drugs, such as cyclosporine and saquinavir [32].
These are just a few examples of interactions between ingredients of weight-loss dietary supplements and medications. Individuals taking dietary supplements and medications on a regular basis should discuss their use with their health care provider.

Choosing a Sensible Approach to Weight Loss

As this fact sheet shows, the evidence supporting the use of dietary supplements to reduce body weight and stimulate weight loss is inconclusive and unconvincing, and the cost of these products can be considerable [6,14,21,30]. The best way to lose weight and keep it off is to follow a sensible approach that incorporates a healthy eating plan, reduced caloric intake, and moderate physical activity under the guidance of a heath care provider. For some individuals with a high BMI who have additional health risks, physicians may prescribe adjunctive treatments, including FDA-approved prescription medications or bariatric surgery, in addition to lifestyle modifications [7]. Lifestyle changes that promote weight loss might also improve mood and energy levels and lower the risk of heart disease, diabetes, and some cancers [5].
The Weight-control Information Network

, a service of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, provides several helpful publications on weight control, obesity, physical activity, and related nutritional issues.
The federal government’s 2015-2020 Dietary Guidelines for Americans notes that “Nutritional needs should be met primarily from foods. … Foods in nutrient-dense forms contain essential vitamins and minerals and also dietary fiber and other naturally occurring substances that may have positive health effects. In some cases, fortified foods and dietary supplements may be useful in providing one or more nutrients that otherwise may be consumed in less-than-recommended amounts.”
For more information about building a healthy diet, refer to the Dietary Guidelines for Americans

and the U.S. Department of Agriculture’s MyPlate

.
The Dietary Guidelines for Americans describes a healthy eating pattern as one that: