In a placebo-controlled trial, 360 people with obesity received 1,200 or 1,800 mg of alpha-lipoic acid per day or placebo for 20 weeks. The alpha-lipoic acid group experienced significantly greater weight and fat loss compared to the placebo group: the average weight loss was 6.1 pounds with 1,800 mg per day of alpha-lipoic acid, 3.3 pounds with 1,200 mg per day, and 2.1 pounds with placebo.¹⁵ A similar trial followed 81 participants with overweight and obesity for 24 weeks and found those taking 600 mg of alpha-lipoic acid per day experienced slightly more weight and percent body fat loss compared to those given placebo.¹⁶ Another placebo-controlled trial included 97 women with overweight or obesity who followed a calorie-restricted diet and were given 300 mg of alpha-lipoic acid or placebo daily for 10 weeks. The women who received alpha-lipoic acid lost an average of 3.3 pounds more than women who received a placebo.¹⁷ An eight-week cross-over design trial found 1,200 mg of alpha-lipoic acid daily not only led to mild weight loss but also resulted in reduced waist circumference, suggesting it may reduce the most dangerous type of body fat.¹⁸ Meta-analysis of multiple randomized controlled trials has further added to the evidence that alpha-lipoic acid has a small effect on short-term weight loss.^19,20 Alpha-lipoic acid may even decrease weight gain associated with the use of antipsychotic medications. It is not clear how alpha-lipoic acid works, but some evidence suggests it may reduce inflammatory, appetite, and metabolic signaling.

Amylase inhibitors are also known as starch blockers because they interfere with digestion of dietary starches and other complex carbohydrates, slowing digestion in general, reducing absorption of glucose, and preventing blood glucose spikes.²¹ Phaseolamin is an amylase inhibitor from white kidney beans (Phaseolus vulgaris) and has been widely studied for its potential to support weight loss.^22,21 In a placebo-controlled trial that included 120 participants with obesity, those treated with 2,400 mg per day of white kidney bean extract lost 2.24 kg (4.9 pounds) after 35 days, while those taking placebo lost only 0.29 kg (0.6 pounds.²⁴ In another trial, mildly overweight adults with stable weight for six months or longer took either 445 mg of white kidney bean extract or placebo daily for 30 days; those taking white kidney bean extract lost 2.93 kg (6.4 pounds), while those taking placebo lost 0.35 kg (0.8 pounds). They also lost more body fat and had greater reductions in waist, hip, and thigh circumferences.²⁵ A meta-analysis that included 11 clinical trials (including some unpublished data from supplement manufacturers) with a combined total of 573 participants found white kidney bean extract, at a dose of at least 1,200 mg per day for a minimum of four weeks, can promote weight loss in people with overweight and obesity. A separate meta-analysis in the same publication, which included three trials with a combined total of 110 subjects, found white kidney bean extract also reduces body fat.²⁶

Blue-green algae, or spirulina, is a rich source of protein, vitamins, minerals, and essential fatty acids. It also provides antioxidant and anti-inflammatory phytochemicals, and one constituent from spirulina has been found to inhibit pancreatic lipase, a fat-digesting enzyme.²⁶ In one placebo-controlled trial, 64 people with obesity took 1 gram of spirulina or placebo daily for 12 weeks; those taking spirulina lost 3.5 pounds and reported a significant decrease in appetite, while those taking placebo lost 1.4 pounds and reported increased appetite.²⁷ Another placebo-controlled trial that included 52 subjects with overweight or obesity found 2 grams of spirulina daily taken during a 12-week reduced-calorie diet program reduced appetite and enhanced weight loss, body fat loss, and waist circumference reduction.²⁸ In a multi-phase crossover trial, people with overweight or obesity had more improvement in body weight and fitness during a six-week exercise program if they were given 4.5 grams of spirulina daily compared to placebo, and the synergistic effect of spirulina and exercise was more profound in those with obesity. In addition, spirulina had positive impacts on body weight and some markers of fitness even in the absence of exercise.²⁹ Comprehensive reviews and a meta-analysis of results from five controlled trials add further weight to findings that spirulina can reduce body weight, body fat, waist circumference, and appetite, and may have positive effects on cholesterol and triglyceride levels in people with overweight and obesity.^30,26

Chitosan is a fiber extracted from the shells of crustaceans such as shrimp and crab or the cell walls of fungi. It is sometimes used in the food industry as a thickener and emulsifier. In a placebo-controlled trial, 96 subjects with overweight and obesity took 2.5 grams of chitosan per day or placebo for 90 days. Despite having similar calorie intake, those in the chitosan group lost an average of 3.1 kg (almost 7 pounds) while those in the placebo group had no significant change in body weight. In addition, the chitosan group had decreased body fat, abdominal fat, and waist circumference, had reductions in high HgA1c (a marker of glucose regulation), and reported improved quality of life.³¹ Two meta-analyses, one that included data from 14 randomized controlled trials with a combined total of 1,101 participants and another that included data from 15 trials with 1,130 participants, showed chitosan mildly reduces body weight and body fat in individuals with overweight or obesity.^32,33 Findings from another trial suggest taking 2 grams per day of vitamin C along with 3 grams per day of chitosan may induce greater weight loss than chitosan alone.³⁴ Chitosan has been shown to reduce fat absorption in laboratory animals, but controlled human trials have found chitosan has little to no impact on fat absorption.^35,36,37,38 Although more research is needed to understand how chitosan induces weight loss, one possibility is that, as a prebiotic fiber, it may alter the gut microbiome composition in ways that promote healthy metabolism.³⁹

The mineral chromium plays an essential role in the metabolism of carbohydrates and fats and may improve insulin sensitivity.⁴⁰ Chromium has also been found to enhance weight loss. Three meta-analyses of randomized controlled trials in subjects with overweight and obesity have concluded chromium has a small positive impact on body weight when used in doses of 200–400 micrograms per day for 12–16 weeks.^41,42,43 Some evidence further shows chromium may help in regulating mood and appetite, and one placebo-controlled trial found chromium had positive effects in women with overweight or obesity who also had binge eating disorder: chromium supplementation resulted in reduced frequency of binge eating and greater weight loss compared to placebo, and 1,000 micrograms per day was more effective than 600 micrograms daily.⁴⁴

Active compounds found in green and roasted coffee beans, such as caffeine, chlorogenic acids (antioxidant polyphenols), and prebiotic fibers, may contribute to beneficial effects on metabolism.^45,46,47 A comprehensive review of the research indicates drinking three to four cups of coffee daily has a positive impact on metabolic health and lowers the risk of death from any cause.⁴⁸ Green coffee beans are thought to have greater potential to support weight loss due to their higher chlorogenic acid content compared to roasted coffee beans. Meta-analyses of 15–16 controlled clinical trials indicate green coffee extract has small weight- and waist circumference-reducing effects in people with overweight and obesity.^49,50

Numerous clinical trials have shown supplementing with viscous (gel-forming) soluble fibers such as psyllium, guar gum, pectins, glucomannan, and beta-glucans (found in oat bran, mushrooms, and other sources) results in decreased body weight and waist circumference, even in individuals eating a regular diet.^51,52 In addition, although the effects may be small, fiber supplement-related weight loss is more profound in those with overweight and obesity, type 2 diabetes, and metabolic syndrome.⁵¹ It is thought viscous fibers work in part by promoting a sense of fullness and slowing the absorption of glucose from the intestines.^52,55 In addition, some types of fiber may have beneficial metabolic effects due to their prebiotic properties—their ability to build colonies of health-promoting bacteria in the intestines. Byproducts of fiber fermentation by gut microbes include short chain fatty acids and other compounds that help regulate immune function, appetite, fat burning, energy expenditure, insulin sensitivity, and glucose metabolism, all of which can impact weight loss.⁵⁵

Green tea contains caffeine and polyphenols known as catechins (such as epigallocatechin gallate, or EGCG), which may work synergistically to support weight loss.⁵⁴ Meta-analyses and reviews of multiple randomized controlled trials have found green tea extract has a small positive effect on weight loss and fat loss in people with overweight and obesity.^54,56,57,58 Research shows green tea extracts can inhibit carbohydrate- and fat-digesting enzymes, improve gut microbiome balance, activate normal adipose tissue metabolism, and possibly raise energy expenditure by increasing heat production.^54,60

The amino acid L-carnitine is thought to be potentially helpful for weight loss because of its role in fat metabolism. L-carnitine has been found to reduce fatigue and hunger and improve weight loss effects of fasting.^59,60 Multiple controlled trials and three meta-analyses have shown that supplementing with L-carnitine can lead to small reductions in body weight in people with overweight and obesity.^61,62,63 In a placebo-controlled trial that included 60 overweight women with polycystic ovary syndrome, taking 250 mg of L-carnitine daily for 12 weeks resulted in weight loss, waist circumference reduction, and improved glucose regulation and insulin sensitivity.⁶⁴

Diets that are low in total calories may not contain adequate amounts of various vitamins and minerals. For that reason, taking a multiple vitamin-mineral supplement is advocated by proponents of many types of weight-loss programs, and is essential when calorie intake will be less than 1,100 calories per day.⁶⁵

The synthetic viscous fiber called polyglycoplex, or PGX, has been reported in several studies to improve metabolic health and support weight loss.⁶⁶ In a one-year placebo-controlled trial with 290 participants with overweight or obesity who also had type 2 diabetes, 15–20 grams per day of PGX improved metabolic parameters and led to mild, sustained weight loss and waist circumference reduction.⁶⁷ Another placebo-controlled trial in 118 overweight adults showed PGX, at 5 grams of granules three times per day, reduced calorie intake, waist circumference, and body weight after 12 weeks.⁶⁸ A one-year controlled trial comparing 5 grams of PGX to 5 grams of psyllium husk, taken three times per day with meals, found PGX was more effective for achieving and maintaining weight reduction.⁶⁹ PGX appear to work by suppressing appetite and increasing fullness.⁷⁰ In addition, some evidence suggests it may also have prebiotic properties, improving composition of the gut microbiome.⁶⁷

People with obesity exhibit differences in gut microbiome composition compared to normal-weight individuals. Multiple controlled trials, meta-analyses, and reviews show probiotic supplements containing various Lactobacillus and Bifidobacterium strains can help to reduce body weight, waist circumference, fat mass, and percent body fat, and may improve cholesterol levels and other markers of metabolic health.^{71,72,73,74,75} These effects may be due to the influence of microbes present in the gut on appetite, mood, inflammatory status, nutrient intake and absorption, and metabolism.⁷⁶ One analysis determined the best effects on body weight reduction were associated with the use of two or more strains of probiotic bacteria, doses below 10¹⁰ [ten billion] colony forming units per day, and probiotics in foods (versus capsules and powders).⁷¹

Animal and human studies have suggested that when soy is used as a source of dietary protein, it may have several biological effects on the body that might help with weight loss.⁷⁷ A preliminary study found that people trying to lose weight using a meal-replacement formula containing soy protein lost more weight than a group not using any formula.⁷⁸ However, controlled studies comparing soy protein with other protein sources in weight-loss diets have not found any advantage of soy.^79,80,81 When soy protein is used for other health benefits, typical daily intake is 20 grams per day or more.

People with obesity are more likely to have poor vitamin D status than their normal-weight counterparts, and low vitamin D may contribute to the systemic inflammation, insulin resistance, and metabolic disturbances associated with obesity.^82,83 The value of vitamin D supplementation in weight loss programs is becoming increasingly apparent. In a placebo-controlled trial that included 44 vitamin D-deficient participants with obesity, supplementing a weight loss diet with 50,000 IU of vitamin D per week for 12 weeks restored healthy vitamin D status, decreased levels of a marker of inflammation, and led to greater weight and body fat reduction than diet and placebo.⁸⁴ In a study with 205 overweight or obese participants enrolled in a three-month weight loss program, those with sufficient baseline vitamin D status lost more weight than those with baseline vitamin D insufficiency, and among those with vitamin D insufficiency, those who began taking 2,000 or 4,000 IU of vitamin D per day lost more weight than those who did not take vitamin D.⁸⁵ Interestingly, a placebo-controlled trial in 218 women with overweight or obesity and vitamin D insufficiency who were randomly assigned to take either 2,000 IU of vitamin D daily or placebo for 12 months found only those who became vitamin D-sufficient through supplementation had greater weight loss compared to placebo.⁸⁶

Whey protein, like other supplemental proteins, may aid people on a low-calorie weight-loss diets by suppressing appetite and preserving muscle.⁸⁷ Protein from whey and other sources also increase heat production and energy expenditure.⁸⁸ Furthermore, whey protein has been shown to have positive effects on cardiovascular and metabolic health generally, with effects such as enhancing blood glucose control, lowering blood pressure, and improving lipid levels.⁸⁹ In one clinical trial, 56 participants with type 2 diabetes and overweight or obesity ate similar lunches and dinners along with either a high-protein breakfast with 28 grams of whey protein, a high-protein breakfast with mixed protein, or a high-carbohydrate (control) breakfast for 12 weeks; at the end of the trial, those in the whey protein group lost an average of 7.6 kg (16.7 pounds), those in the mixed protein group lost 6.1 kg (13.4 pounds) and those in control group lost 3.5 kg (7.7 pounds). In addition, whey protein had greater benefits on blood glucose control than mixed protein.⁹⁰ In a meta-analysis that included nine controlled trials in subjects with overweight and obesity, whey protein supplement use was found to slightly reduce body weight and body fat and improve markers of cardiovascular health.⁹¹