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Strategies for healthy weight loss: from vitamin C to the glycemic response A meta-analysis of randomized controlled trials Excess vitamin intake: An unrecognized risk factor for obesity The effects of caffeine intake on weight loss: a systematic review and dos-response meta-analysis of randomized controlled trials Dietary supplements for weight loss I Office of Dietary Supplements, NIH.
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Stonebridge Saskatoon. This trial, along with two others, was included in a 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 mg to 3, 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 ].
Irvingia gabonensis extract appears to be well tolerated. 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 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 ]. 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. At the end of the trial, all groups lost weight and had a smaller waist circumference, but there were no significant differences between groups.
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 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 [ 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. Studies suggest that bitter orange increases energy expenditure and lipolysis and that it acts as a mild appetite suppressant [ 25 , 27 ].
After FDA banned the use of ephedrine alkaloids in dietary supplements in [see section on ephedra má huáng ], 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 ].
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.
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. 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. 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 review of 23 small human clinical studies involving a total of participants concluded that synephrine increases resting metabolic rate and energy expenditure [ 30 ].
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. 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 synephrine—as bitter orange extract or pure synephrine—raise blood pressure and heart rate, but other studies show that they do not have these effects [ , 31 , ]. 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. Many dietary supplements promoted for weight loss contain added caffeine or an herbal source—such as guarana Paullinia cupana , kola or cola nut Cola nitida , and yerba maté 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 15—45 minutes of consumption, and they peak at around 60 minutes [ 44 ]. Caffeine increases thermogenesis in a linear, dose-dependent fashion in humans [ 45 ].
A mg dose of caffeine, for example, increased energy expenditure by a mean of 9. 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 ]. 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.
After 6 months, those in the treatment group lost significantly more weight mean weight loss 5. 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 24—30 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 mg G-hesperidin. The 75 mg caffeine plus G-hesperidin significantly reduced BMI by a mean of 0.
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.
At the end of the study, participants taking the herbal product lost a mean of 5. Data from a year prospective observational study provide some insight into the long-term association between caffeine intake and body weight [ 49 ].
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. For women, the corresponding mean difference in weight gain was 0.
However, further research is needed to confirm this finding. For comparison, an 8-ounce cup of brewed coffee contains about 85— mg caffeine. Caffeine can cause sleep disturbances and feelings of nervousness, jitteriness, and shakiness.
Combining caffeine with other stimulants, such as bitter orange and ephedrine, can potentiate these adverse effects. 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 ]. Several studies have correlated higher calcium intakes with lower body weight or less weight gain over time [ ].
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 , ].
For example, protein and other components of dairy products might modulate appetite-regulating hormones [ 61 ]. However, the results from clinical trials examining the effects of calcium on body weight have been largely negative. 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 [ ].
These reviews include a 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 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 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. 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 , ]. 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 [ ].
Other research suggests that capsaicin increases satiety by inducing gastrointestinal distress e. 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 participants who had a normal body weight or were moderately overweight [ 78 ].
Doses of capsaicinoids ranged from 0. 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.
However, the calorie reductions did not significantly affect body weight at either 6 weeks or 12 weeks. 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 is the generic term for several compounds, including L-carnitine itself, several acylcarnitines e.
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. A systematic review and meta-analysis combined the results from nine carnitine supplementation clinical trials in adults including the two described above that assessed weight loss [ 85 ].
The trials included a total of participants. In eight trials, the daily carnitine doses ranged from 1. Overall, study participants who received carnitine supplements lost an average of 1.
Additional research on carnitine for weight loss is warranted. Rarer side effects include muscle weakness in patients with uremia and seizures in those with seizure disorders. Some research indicates that intestinal bacteria metabolize carnitine to form trimethylamine N-oxide TMAO , a substance that might increase the risk of cardiovascular disease [ 91 ].
This effect appears to be more pronounced in people who consume meat than in vegans or vegetarians. The implications of this effect are not well understood and require more research.
Chitosan is a manufactured polysaccharide that is commercially prepared from the exoskeletons of crustaceans. It is purported to promote weight loss by binding to some dietary fat in the digestive tract, preventing its absorption [ 16 , 41 ].
Chitosan might also decrease cholesterol absorption [ 16 ]. Chitosan capsules taken before meals total of 2. However, the amount of fat that the chitosan trapped would result in a loss of only 1 lb body fat over about 7 months.
Chitosan had no significant effect on fecal fat excretion in the women compared to the control group. 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. In this study, chitosan treatment reduced body weight mean weight loss about 2.
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.
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 also noted that results from high-quality trials indicate that chitosan has minimal effects on body weight, and these effects are probably clinically insignificant.
The adverse effects of chitosan are minor and primarily involve the gastrointestinal tract. They include flatulence, bloating, mild nausea, constipation, indigestion, and heartburn [ 93 , 95 , 96 ]. Because chitosan is derived from shellfish, people who are allergic to shellfish could theoretically be allergic to chitosan [ 97 ].
The trivalent form of chromium chromium III is an essential trace mineral that potentiates the action of insulin. 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 [ 99 ].
Poor chromium status might contribute to impaired glucose tolerance and type 2 diabetes [ 98 ]. Researchers have hypothesized that chromium supplements increase lean muscle mass and promote fat loss, but study results have been equivocal [ 41 , ]. Some research indicates that these supplements might also reduce food intake, hunger levels, and fat cravings [ ], although data on these effects are sparse.
Several studies have evaluated the effects of chromium supplements, usually in the form of chromium picolinate, on weight loss. Six of the trials included resistance or weight training, and three did not.
Chromium picolinate supplementation reduced body weight by 1. Also in , 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 individuals with overweight or obesity [ 99 ].
The authors concluded that daily doses of to 1, mcg chromium for 8 to 26 weeks reduce body weight by 0. 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 [ ]. Trivalent chromium appears to be well tolerated. Adverse effects from clinical trials include watery stools, headache, weakness, nausea, vomiting, constipation, vertigo, and urticaria hives [ 99 , ].
Chromium does not have an established UL because few serious adverse effects have been linked to high intakes [ 98 ]. Hexavalent chromium chromium VI is toxic and not found in food or dietary supplements.
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 [ , ], possibly by stimulating cyclic adenosine monophosphate cAMP production.
This increased cAMP production, in turn, is thought to activate lipase and promote the release of fatty acids from adipose tissue [ 16 ]. Although animal studies indicate that forskolin reduces food intake [ , ], research in humans is very limited and inconclusive. Compared to placebo, Coleus forskohlii extract had no effect on body weight, appetite, caloric intake, or macronutrient intake.
In a study in mice, Coleus forskohlii extract caused dose-dependent hepatotoxicity, but pure forskolin did not have this effect, suggesting that other component s of Coleus forskohlii extract might be responsible for the hepatotoxicity [ ].
Forskolin has not been evaluated in longer term trials. Additional research is needed to better understand the safety and side effects of both short- and long-term use. Conjugated linoleic acid CLA is a mixture of linoleic acid isomers containing conjugated double bonds that is present mainly in dairy products and beef.
The various isomeric forms of CLA include c9,tCLA and t10,cCLA, and it is available in dietary supplements as a triacylglycerol or as a free fatty acid [ ]. Researchers have suggested that CLA enhances weight loss by increasing lipolysis and fatty acid oxidation in skeletal muscle, reducing lipogenesis, and promoting apoptosis in adipose tissue [ 17 , ].
Although CLA appears to reduce body fat mass in animals [ 17 ], results from human studies suggest that its effects are small and of questionable clinical relevance [ ]. One double-blind, placebo-controlled trial evaluated the effects of CLA supplementation as a mixture of c9,tCLA and t10,cCLA in male and female volunteers who were overweight BMI 25—30 consuming an ad libitum diet [ ].
Participants received CLA as a free fatty acid 3. At the end of the study, body fat mass dropped by significant amounts with both forms of CLA compared with placebo; reductions, on average, were 6.
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. These findings are similar to those from a randomized, double-blind, placebo- controlled trial in 63 adults with overweight or obesity BMI 24—35 that found statistically significant, but small, reductions in mean weight 0.
In contrast, those in the placebo group did not lose a significant amount of body weight 0. However, 3. The authors of a systematic review and meta-analysis of seven randomized controlled trials concluded that taking 2.
However, the authors noted that the "magnitude of these effects is small, and the clinical relevance is uncertain. 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, nausea, vomiting, and dyspepsia [ 3 , , , , , ].
CLA might also increase some markers of oxidative stress and decrease breastmilk fat levels, but additional research is needed to confirm these effects [ ]. CLA has been linked to hepatitis in three case reports [ ].
However, whether CLA caused this toxicity cannot be definitively established because the products were not analyzed to rule out the presence of a contaminant. 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 HDL cholesterol and increase lipoprotein a levels [ , , , ].
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