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 have obesity [1,2]. Forty-five percent of Americans who are overweight and 67% of those with obesity are trying to lose weight [3].
Health experts agree that making lifestyle changesincluding following a healthy dietary pattern, reducing caloric intake, and engaging in physical activityis 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.
Approximately 15% of U.S. adults have used a weight-loss dietary supplement at some point in their lives; more women report use (21%) than men (10%) [8]. Americans spend about $2.1 billion a year on weight-loss dietary supplements in pill form (e.g., tablets, capsules, and softgels) [9], and one of the top 20 reasons why people take dietary supplements is to lose weight [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. Weight-loss products can contain dozens of ingredients, and some contain more than 90 [11]. Common ingredients in these supplements include botanicals (herbs and other plant components), dietary fiber, caffeine, 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 knownand not knownabout each ingredient in any dietary supplement before using it.
People who are considering using weight-loss supplements should talk with their healthcare provider to discuss these products' potential benefits and risks. This is especially important for those who have medical conditions, including high blood pressure, diabetes, and liver 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 healthcare professional [8].
*Dietary supplements are labeled with a Supplement Facts panel and do not include meal replacement shakes or prescription or over-the-counter medications.
The U.S. Food and Drug Administration (FDA) regulates dietary supplements, including those promoted for weight loss [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. If the FDA finds a supplement to be unsafe, it may take enforcement action to remove the product from the market or ask the manufacturer to recall the product. The FDA and the Federal Trade Commission can 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 dietary supplements to diagnose, treat, cure, or prevent any disease [13].
For more information about dietary supplement regulation, see the Office of Dietary Supplements (ODS) publication, Dietary Supplements: What You Need to Know.
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, evidence of their purported benefits consists of limited data from animal and laboratory studies, rather than data from human clinical trials. In other cases, studies supporting a given ingredients 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. Evidence may exist for just one of the ingredients in a finished product, and no evidence may be available for an ingredient when it is combined with other ingredients. Furthermore, dosages and amounts of active components vary widely among weight-loss supplements, and a products composition is not always fully described in published studies [14]. Studies might 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 those of 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 text in alphabetical order. Dosage information is provided when it 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].
Research findings: Possible modest reduction in body weight and waist circumference
Reported adverse effects: Headache, difficulty sleeping, flatulence, and gas
Research findings: No effect on body weight
Reported adverse effects: Flatulence
Research findings: Possible increase in resting metabolic rate and energy expenditure; inconclusive effects on weight loss
Reported adverse effects: Chest pain, anxiety, headache, musculoskeletal complaints, and increased blood pressure and heart rate
Research findings: Possible modest effect on body weight or decreased weight gain over time
Reported adverse effects: Nervousness, jitteriness, vomiting, and tachycardia
Research findings: No effect on body weight, weight loss, or prevention of weight gain based on clinical trials
Reported adverse effects: Constipation, kidney stones, and interference with zinc and iron absorption at intakes above 2,0002,500 mg for adults
Research findings: Might reduce energy intake but no effect on body weight
Reported adverse effects: Gastrointestinal distress, increased insulin levels, and decreased high-density lipoprotein (HDL) levels
Research findings: Possible modest reduction in body weight
Reported adverse effects: Nausea, vomiting, diarrhea, abdominal cramps, and a fishy body odor; might increase trimethylamine N-oxide (TMAO) levels, which are linked to greater cardiovascular disease risk
Research findings: Minimal effect on body weight
Reported adverse effects: Flatulence, bloating, constipation, indigestion, nausea, and heartburn
Research findings: Minimal effect on body weight and body fat
Reported adverse effects: Headache, watery stools, constipation, weakness, vertigo, nausea, vomiting, and urticaria (hives)
Research findings: No effect on body weight
Reported adverse effects: More frequent bowel movements, loose stools
Research findings: Minimal effect on body weight and body fat
Reported adverse effects: Abdominal discomfort and pain, constipation, diarrhea, loose stools, dyspepsia, and (possibly) adverse effects on blood lipids and glucose homeostasis
Research findings: Insufficient research to draw firm conclusions
Reported adverse effects: None known
Research findings: Little to no effect on body weight
Reported adverse effects: Headache, nausea, upper respiratory tract symptoms, gastrointestinal symptoms, mania, and liver damage
Research findings: Little to no effect on body weight
Reported adverse effects: Loose stools, flatulence, diarrhea, constipation, and abdominal discomfort
Research findings: Possible modest effect on body weight
Reported adverse effects: Headache and urinary tract infections
Research findings: Possible modest effect on body weight
Reported adverse effects (for green tea extract): Constipation, abdominal discomfort, nausea, increased blood pressure, and liver damage
Research findings: No effect on body weight
Reported adverse effects: Abdominal pain, flatulence, diarrhea, nausea, and cramps
Research findings: No effect on energy intake or body weight based on one study
Reported adverse effects: Headache, dizziness, nausea, and vomiting
Research findings: Inconsistent effects on body fat, waist and hip circumference, and body weight
Reported adverse effects: Gastrointestinal symptoms, such as gas
Research findings: Possible minimal effect on body weight and body fat
Reported adverse effects: Diarrhea, gas, bloating, and (possibly) decreased HDL levels
Research findings: Insufficient research to draw firm conclusions
Reported adverse effects: None known
Research findings: No effect on body weight
Reported adverse effects: Anorexia, weight loss, polyuria, heart arrhythmias, and increased calcium levels leading to vascular and tissue calcification
Research findings: Possible modest effect on body weight and body fat
Reported adverse effects: Headache, soft stools, flatulence, and constipation
Research findings: No effect on body weight; insufficient research to draw firm conclusions
Reported adverse effects: Headache, anxiety, agitation, hypertension, and tachycardia, myocardial infarction, cardiac failure, and death
African Mango [Irvingia gabonensis (Aubry-Lecomte ex ORorke) Baill.]
African mango, or Irvingia gabonensis, is a fruit-bearing tree that is native to western and central Africa [16]. Irvingia gabonensis seed kernel extract has been proposed to promote weight loss by inhibiting adipogenesis, as demonstrated in vitro [17]. In addition, a proprietary extract of Irvingia gabonensis, IGOB131, reduces serum levels of leptin [18], a hormone that is positively correlated with body weight and percentage body fat [19]. IGOB131 might also reduce total cholesterol and low-density lipoprotein (LDL) levels [18].
Efficacy: Studies have examined the effects of Irvingia gabonensis on weight loss to only a limited extent in humans. A clinical trial conducted in Cameroon randomized 102 adults with overweight or obesity (body mass index [BMI] >25) to receive either 150 mg IGOB131 or placebo 3060 minutes before lunch and dinner (300 mg total daily dose) for 10 weeks [18]. Participants who received the extract had significantly lower body weight, body fat, and waist circumference at the end of the trial than those taking a placebo. This trial, along with two others, was included in a 2013 systematic review whose authors reported that Irvingia gabonensis extract causes statistically significant reductions in body weight and waist circumference [19]. The authors noted, however, that the trials included in the review used different study methodologies, small samples, short intervention periods, and varying daily doses of Irvingia gabonensis extract (300 mg to 3,150 mg); in addition, the trials were all conducted by the same authors. Additional trials with larger samples and diverse populations are needed to determine whether Irvingia gabonensis extract is effective for weight loss [19].
Safety: Irvingia gabonensis extract appears to be well tolerated. No adverse effects have been found in rats at doses up to 2,500 mg/kg body weight per day [20], but its safety has not been rigorously studied in humans. Most reported adverse effects are mild, including headache, difficulty sleeping, flatulence and gas [19]. However, Irvingia gabonensis has been associated with renal failure in a patient with chronic kidney disease [21].
Beta-Glucans
Beta-glucans are glucose polysaccharides found in bacteria, yeasts, fungi, and cereal grains (such as oats and barley). As soluble dietary fibers, beta-glucans are proposed to increase satiety and gastrointestinal transit time and to slow glucose absorption [16]. Consumption of beta-glucans from barley has been shown to reduce energy intake and appetite in humans [22].
Efficacy: Several studies have investigated the effects of beta-glucans on blood lipids, blood pressure, and insulin resistance, with weight loss as a secondary outcome. In one of these studies, 66 women who were overweight followed a low-calorie diet (designed to produce a 0.5 kg/week weight loss) for 3 months that was supplemented with 56 g/day beta-glucan (from oat bran), 89 g/day beta-glucan, or no beta-glucan (control) [23]. At the end of the trial, all groups lost weight and had a smaller waist circumference, but there were no significant differences between groups. Similarly, other trials have found that 310 g/day beta-glucans for 412 weeks does not have a significant effect on weight loss [16].
Safety: Beta-glucans appear to be well tolerated. Reported adverse effects include increased flatulence, but not changes in stool consistency, stool frequency, or bloating [24].
Bitter Orange [(Citrus aurantium L.); zhi qiao]
Bitter orange is the common name for the botanical Citrus aurantium. The fruit of this plant is a source of p-synephrine (often referred to simply as synephrine) and other protoalkaloids [25- 28]. 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 [25-27].
Studies suggest that bitter orange increases energy expenditure and lipolysis and that it acts as a mild appetite suppressant [25,27]. After the FDA banned the use of ephedrine alkaloids in dietary supplements in 2004 [see section on ephedra (m hung)], manufacturers replaced ephedra with bitter orange in many products; thus, bitter orange became known as an ephedra substitute [29]. Although synephrine has some structural similarities to ephedrine, it has different pharmacological properties [27,30].
Efficacy: Several small human studies have examined whether bitter orange is effective for weight loss [30]. 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 adults who were overweight (BMI >25) took a product containing 975 mg bitter orange extract (6% synephrine alkaloids), 528 mg caffeine, and 900 mg St. Johns wort; a placebo; or nothing (control) each day for 6 weeks [31]. All participants also took part in a circuit-training exercise program and were counseled to consume 1,800 kcal/day. 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 group (0.9 kg) or control group (0.4 kg) [32].
In another study, 8 healthy people with overweight or obesity (BMI 2540) received counseling to follow a 1,2001,500 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 [33]. 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. Participants taking the herbal supplement had a significant increase in mean body weight (1.13 kg) compared with those taking a 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 [30]. 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 [25]. Similarly, a 2011 systematic review of four weight loss trials (including the two described above) concluded that the evidence of efficacy for bitter orange/synephrine is contradictory and weak [34]. According to all of these reviews, 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 may have significant safety concerns. Reported adverse effects include chest pain, headache, anxiety, elevated heart rate, musculoskeletal complaints, ventricular fibrillation, ischemic stroke, myocardial infarction, and death [34,35]. However, many of the products with these effects contain multiple herbal ingredients, and the role of bitter orange in these adverse effects cannot be isolated. Some studies indicate that bitter orange and synephrineas bitter orange extract or pure synephrineraise blood pressure and heart rate, but other studies show that they do not have these effects [25-27,31,36-39]. For example, a single dose of 900 mg bitter orange standardized to 6% (54 mg) synephrine significantly increased heart rate as well as systolic and diastolic blood pressure for up to 5 hours compared to placebo in 15 healthy men and women [38]. However, in an 8-week clinical trial in 80 healthy, resistance-trained adult men, a dietary supplement containing bitter orange extract (providing 20 mg synephrine/day), 284 mg caffeine, and other ingredients did not increase resting heart rate, systolic or diastolic blood pressure, or reported side effects at 4 and 8 weeks compared to placebo or the same supplement formulation without synephrine [40]. Some researchers have suggested that synephrine might not act directly as a cardiovascular stimulant [27,37,39]. Instead, caffeine, other stimulants in multicomponent formulations, and 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 Mat, or Other Herbs
Many dietary supplements promoted for weight loss contain added caffeine or an herbal sourcesuch as guarana (Paullinia cupana), kola (or cola) nut (Cola nitida), and yerba mat (Ilex paraguariensis)that naturally contains caffeine. 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 and only list 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 [41].
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 [42,43]. Caffeine has a half-life of about 6 hours; blood levels increase within 1545 minutes of consumption, and they peak at around 60 minutes [44]. Caffeine increases thermogenesis in a linear, dose-dependent fashion in humans [45]. 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, and this effect lasted for three hours or more. Caffeine might also contribute to weight loss by increasing fat oxidation through sympathetic activation of the central nervous system and by increasing fluid loss [41,45]. Habitual use of caffeine however, leads to caffeine tolerance and a diminishment of these effects [41,43].
Efficacy: Caffeine increases energy expenditure and fat oxidation [44]. However, the extent to which these effects affect weight loss is less clear, partly because clinical trials examining the effects of caffeine on weight loss have all been short and have used combination products. In one study, 167 participants with overweight or obesity (BMI 2540) took a supplement containing kola nut (192 mg/day caffeine) and ma huang (90 mg/day ephedrine) or placebo [46]. 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. A product containing caffeine plus glucosyl hesperidin (G-hesperidin, a flavonone glycoside found mainly in citrus fruits) reduced abdominal fat and BMI in a clinical trial in Japan [47]. In this study, 75 healthy men and women who were overweight (BMI 2430) received one of five treatments daily for 12 weeks while maintaining their regular lifestyle and eating habits. The five treatments were placebo and four formulations of 0, 25, 50, or 75 mg caffeine plus 500 mg G-hesperidin. The 75 mg caffeine plus G-hesperidin significantly reduced BMI by a mean of 0.56 vs. 0.02 for placebo. The 50 or 75 mg caffeine plus G-hesperidin also significantly reduced abdominal fat compared to placebo, whereas the G-hesperidin alone or with only 25 mg caffeine did not significantly affect BMI or abdominal fat. These findings indicate that the higher doses of caffeine might be responsible for the observed effects.
In another study, 47 adults who were overweight (BMI 2630) were randomized to take a combination product containing 336 mg yerba mat (11.5% caffeine), 285 mg guarana (36% caffeine), and 108 mg damiana (a botanical extract that contains essential oils, resins, and tannins but not caffeine) or placebo 15 minutes before each main meal for 45 days while maintaining their normal eating habits [48]. 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 [49]. In this study, researchers followed 18,417 healthy men and 39,740 healthy women 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. In a cross-sectional study, German adults who had lost weight and maintained the weight loss (n = 494) reported significantly higher consumption of coffee and other caffeinated beverages (mean intake 3.83 cups/day) than the general population (n = 2,129, mean intake 3.35 cups/day), suggesting that caffeine might help with weight loss maintenance [50]. However, further research is needed to confirm this finding.
Safety: For healthy adults, the FDA and the European Food Safety Authority (EFSA) state that up to 400 mg/day caffeine does not pose safety concerns [51,52], whereas the American Medical Association recommends a limit of 500 mg/day [53]. For comparison, an 8-ounce cup of brewed coffee contains about 85100 mg caffeine . The FDA and EFSA have not set a safe level of intake for children, but the American Medical Association recommends that adolescents consume no more than 100 mg/day, and the American Academy of Pediatrics discourages children and adolescents from consuming caffeine and other stimulants [51-54].
Caffeine can cause sleep disturbances and feelings of nervousness, jitteriness, and shakiness. Caffeine can be toxic at doses of 15 mg/kg (about 1,000 mg for a 150-lb adult), causing nausea, vomiting, tachycardia, seizures, and cerebral edema [42]. Doses above 150 mg/kg (about 10,000 mg for a 150-lb adult) can be fatal. Combining caffeine with other stimulants, such as bitter orange and ephedrine, can potentiate these adverse effects. According to an analysis, 47% of calls to the California Poison Control System in 2006 reporting adverse effects or toxicities potentially caused by dietary supplements involved products containing caffeine [55]
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 [56]. The Recommended Dietary Allowance (average daily level of intake sufficient to meet the nutrient needs of 9798% 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 [57-61]. 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 [59]. Second, calcium from food or supplements might bind to small amounts of dietary fat in the digestive tract and prevent absorption of this fat [59,62,63]. Dairy products, in particular, might contain additional components that have even greater effects on body weight than their calcium content alone would suggest [60,64-67]. For example, protein and other components of dairy products might modulate appetite-regulating hormones [61].
Efficacy: A 2014 randomized crossover trial in 15 healthy young men found that diets high in milk or cheese (supplying a total of 1,700 mg/day calcium) significantly increased fecal fat excretion compared to a control diet that supplied 500 mg calcium/day [68]. However, 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 adults with overweight or obesity (BMI 25) with mean baseline calcium intakes of 878 mg/day (treatment group) and 887 mg/day (placebo group) [69]. Compared to placebo, calcium supplementation for 2 years had no clinically significant effects on weight.
The authors of four reviews of published studies on the effects of calcium from supplements or dairy products on weight management reached similar conclusions [70-73]. These reviews include a 2009 evidence report from the Agency for Healthcare Research and Quality whose authors concluded that, overall, clinical trial results do not support an effect of calcium supplementation on weight [70]. In addition, a 2015 meta-analysis of 41 randomized controlled trials found no benefit of calcium supplementation or increased dairy food consumption for body weight or body fat [73]. A 2016 meta-analysis of 33 randomized trials and longitudinal studies lasting 12 weeks to 6 years found that calcium from foods or supplements had no overall effect on body weight [74]. However, in subgroup analyses, calcium did reduce body weight in some groups, including children, adolescents, adult men, premenopausal women, women older than 60, and people with normal BMI [74]. Overall, the results from clinical trials do not support a clear 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 (now the Academy of Medicine at the National Academies of Sciences, Engineering, and Medicine) is 2,500 mg/day for adults aged 1950 years and 2,000 mg for adults aged 51 and older [56]. 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 [56,75-77].
Capsaicin and Other Capsaicinoids
Capsaicinoids give chili peppers their characteristic pungent flavor. Capsaicin is the most abundant and well-studied capsaicinoid [78]. Capsaicin and other capsaicinoids have been proposed to have anti-obesity effects via their ability to increase energy expenditure and lipid oxidation, attenuate postprandial insulin response, increase satiety, and reduce appetite and energy intake [78-82]. Other research suggests that capsaicin increases satiety by inducing gastrointestinal distress (e.g., pain, burning sensation, nausea, and bloating, which could all reduce the desire to eat) rather than by releasing satiety hormones [82].
Efficacy: Most research on capsaicin and other capsaicinoids focuses on their effects on energy intake and appetite, rather than body weight. A meta-analysis of eight randomized, placebo-controlled clinical trials evaluated the effects of capsaicinoids on ad libitum energy intake in a total of 191 participants who had a normal body weight or were moderately overweight [78]. Doses of capsaicinoids ranged from 0.2 mg in a single meal to 33 mg/day for 4 weeks (via chili powder, chili-containing foods, or chili capsules). Overall, consuming capsaicinoids significantly reduced energy intake by a mean of 74 kcal per meal; body weight was not assessed, so the impact of this calorie reduction on weight loss cannot be quantified. The authors noted that the results suggest that at least 2 mg capsaicinoids are needed to reduce calorie intake but that the studies were very heterogeneous.
A 2017 clinical trial compared 2 mg/day and 4 mg/day capsaicinoid supplements for 12 weeks in 77 adults who were overweight [83]. At the end of the trial, participants receiving 4 mg/day capsaicinoids reported a mean intake of 252 fewer calories per day than those receiving placebo and a mean of 140 fewer calories per day than those receiving 2 mg/day capsaicinoids. However, the calorie reductions did not significantly affect body weight at either 6 weeks or 12 weeks.
Safety: Supplementation with 4 mg/day capsaicinoids can cause gastrointestinal distress [83]. It might also increase serum insulin and reduce high-density lipoprotein (HDL) cholesterol levels. Otherwise, capsaicin and other capsaicinoids appear to be safe. Research is underway to reduce the pungency and "chili taste" associated with capsaicin while retaining its potential biological effects [81].
Carnitine
Carnitine is the generic term for several compounds, including L-carnitine itself, several acylcarnitines (e.g., acetyl-L-carnitine), and propionyl-L-carnitine. It is composed of the amino acids lysine and methionine [84]. Carnitine is naturally present in animal products such as meat, fish, poultry, and milk and dairy products; small amounts are present in some plant foods. Humans synthesize carnitine from its constituent amino acids, so dietary carnitine intake is not necessary. Almost all cells of the body contain carnitine, which transports fatty acids into the mitochondria and acts as a cofactor for fatty acid beta-oxidation [85]. Because of these effects, carnitine has been proposed as a weight-loss agent.
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