Continuing Education Activity

Over 70% of adults in the United States are overweight or obese. This significantly increases the risk of developing several chronic diseases and levies an enormous cost to the healthcare system. While a nutritious diet and active lifestyle are the foundation of optimal weight and good health, the appeal of a quick fix is strong. Approximately one-third of adults in the United States have used dietary weight-loss supplements. While a nutritious diet and active lifestyle are the foundation of optimal weight and health, the appeal of a quick fix is strong. This activity reviews the types, indications, contraindications, actions, and adverse effects of available non-prescription weight-loss supplements and highlights the role of the interprofessional team in managing patients with overweight and obesity.

Objectives:

• Review data on the efficacy of various dietary weight-loss supplements.
• Explain the mechanisms of action for dietary weight-loss supplements.
• Identify contraindications to common dietary weight-loss supplements.
• Summarize the risks associated with dietary weight-loss supplements and key patient counseling points.

Introduction

Over 70% of adults in the United States are overweight or obese.[1] This significantly increases the risk of developing several chronic diseases and levies an enormous cost to the healthcare system. While a nutritious diet and active lifestyle are the foundation of optimal weight and good health, the appeal of a quick fix is strong. About one-third of adults in the United States attempting to lose weight have utilized dietary supplements.[2] Despite promising mechanistic data, evidence that these supplements are safe and effective is lacking, limiting their clinical usefulness.

Function

Beta-Glucans

Beta-glucans are soluble fibers found in bacteria, yeast, fungi, and grains such as oat bran and barley. They are glucose polysaccharides fermented by the gut microbiota.[3] Weight loss effects may be due to increased satiety and decreased food intake. A meta-analysis published in 2019 showed that most trials reported non-significant or no weight loss from beta-glucans administered at a dose of three to ten grams per day for four to twelve weeks.[4] Data does not currently support their use for the treatment of obesity. Adverse effects include increased flatulence.[5]

Camellia Sinensis

Camellia sinensis is the active ingredient found in the green tea plant. This popular plant is thought to aid in weight loss through anti-lipidemic effects.[6] The data for weight loss in humans have been mixed, generally showing a modest effect. In a 2012 Cochrane systematic review, green tea was associated with a slight, statistically non-significant decrease in weight among overweight and obese adults. The mean difference in weight loss ranged from 0.2 kg to 3.5 kg compared with a placebo.[7] A more recent meta-analysis found a statistically significant but modest decrease in body mass index (BMI) with green tea consumption.[8] 

Consumption of green tea as a beverage is generally regarded as safe in moderate amounts, and the extract appears to be well-tolerated when used for prolonged periods.[9] However, green tea extract may inhibit iron absorption and should be used cautiously in iron-deficient patients. Patients with low bone density should be careful about excessive use since large quantities of green tea extract contain high doses of caffeine that can contribute to urinary calcium losses.[10] In addition, caffeinated green tea may worsen symptoms in patients with anxiety, diarrhea, and dysrhythmias and increase intraocular pressure in glaucoma.[11][12] Patients with liver disease should use supplements containing green tea extract with caution, as there have been isolated cases of associated hepatotoxicity.[13]

Chromium Picolinate

Chromium is an essential mineral associated with reduced hunger levels and food intake, likely via its action on insulin-sensitive signaling pathways in the brain.[14] Chromium is often combined with picolinic acid to aid absorption, and the resulting chromium picolinate compound has been marketed as a diet aid. A 2013 Cochrane systematic review and meta-analysis found that it decreased body weight an average of 1.1 kg more than the placebo, a statistically significant finding but of questionable clinical significance.[15] Furthermore, there have been safety concerns, with reports of nephrotoxicity.[16][17][18] Chromium can cause hypoglycemia, so patients taking diabetes medications must monitor their blood glucose. Adverse events, including urticaria, vertigo, nausea, vomiting, fatigue, abdominal cramps, and bloating, are generally mild and self-limited.

Citrus Aurantium 

Citrus aurantium, also known as bitter orange, is derived from a fruit-bearing tree indigenous to Southeast Asia. Due to its sympathomimetic properties, bitter orange gained popularity as a weight-loss supplement after ephedra was banned because of adverse cardiovascular effects.[19] Like ephedra, Citrus aurantium has alpha and beta-adrenergic effects and is purported to increase metabolic rate and lipolysis.[20] Several studies have examined multi-ingredient products containing bitter orange. They have found these products to have beneficial effects on weight loss, but the individual effect of bitter orange itself is difficult to ascertain.[21] When studied alone, bitter orange increases basal metabolic rate in adults.[22] A review of published and unpublished studies concluded that bitter orange extract and p-synephrine increase metabolism and energy expenditure, but there is a need for long-term efficacy studies in humans.[23] 

There are safety considerations regarding this supplement when used for weight loss. In patients taking diabetes medications, concurrent use of bitter orange may have an additive hypoglycemic effect, and blood glucose should be monitored closely. Bitter orange inhibits CYP3A4 metabolism, and patients taking medications that are CYP3A4 substrates should use the supplement with caution.[24] Bitter orange, especially in combination with caffeine, may increase blood pressure and heart rate, and patients with cardiovascular disease or hypertension should avoid its use.[25] CNS stimulant medications and monoamine oxidase inhibitors can increase the hypertensive and cardio-stimulatory effects of bitter orange, and concurrent use should be avoided. However, there is a lack of direct evidence to support this conservative approach, and randomized controlled studies would be helpful.

Coleus Forskohlii

Coleus forskohlii is a member of the mint family and has been used for centuries for its medicinal properties. Forskolin is derived from the roots of the Coleus forskohlii plant and promotes the release of fatty acids from adipose tissue by stimulating cyclic AMP.[26] Cyclic AMP increases the utilization of body fat and regulation of the body’s thermogenic response to food, which is purported to cause an increase in lean tissue and a loss of body fat. Human studies on forskolin extract have shown inconsistent results. One double-blind placebo-controlled study of 15 obese men administered 500 mg a day of 10 percent forskolin extract for twelve weeks showed promising results with decreased body fat and increased lean body mass.[27] A similar study of 19 moderately overweight women assigned to receive 500 mg per day of 10 percent forskolin extract for twelve weeks showed some appetite reduction but no significant changes in food intake or weight.[28] More clinical data and more extensive studies are needed. No significant side effects or adverse events were reported with C. forskohlii supplementation.

Conjugated Linoleic Acid

Conjugated linoleic acid (CLA) is found in dairy and meat products. In supplement form, it is usually synthesized from safflower and sunflower oils. Animal studies suggest that CLA promotes lipolysis, increases apoptosis in adipose tissue, inhibits lipogenesis, and reduces food intake.[29][30][31] In humans, CLA appears to have a minimal to modest weight-reducing effect. A 2007 meta-analysis showed that CLA was associated with a weight loss of 0.09 kg per week. In a 2012 meta-analysis, overweight and obese individuals who took CLA lost an average of 0.7 kg more than those who received a placebo.[32][33] 

Adverse effects are generally mild, such as constipation and diarrhea. There are concerns that CLA may worsen insulin sensitivity and cholesterol levels, which are often already abnormal in overweight and obese individuals.[34] In addition, CLA may reduce platelet aggregation, so care should be taken if used concurrently with anticoagulants or antiplatelet therapies.[35]

Fucoxanthin

Fucoxanthin is a carotenoid found in brown seaweed and other algae. Preclinical data suggest that fucoxanthin might be effective for treating obesity through its anti-lipidemic properties. Only two clinical trials have been conducted using fucoxanthin. In a 16-week double-blind placebo-controlled trial, 151 non-diabetic, obese, pre-menopausal women with and without non-alcoholic fatty liver disease were given a combination of fucoxanthin with pomegranate seed oil (PSO) at different doses (300 mg algae containing 2.4 mg fucoxanthin plus 300 mg PSO versus 200 mg algae containing 1.6 mg fucoxanthin plus 200 mg PSO).[36] The group taking the higher dose of combined fucoxanthin plus PSO had a statistically significant reduction in body weight, waist circumference, and other metabolic parameters. In a double-blind, placebo-controlled trial of 31 obese participants receiving 0.8 mg fucoxanthin plus 100 mg of PSO versus placebo for sixteen weeks, no significant differences in body fat or weight loss were observed. Toxicological assessments of the combined fucoxanthin and PSO extract administered to rats found no teratogenic or toxic effects.[37] Of note, a statistically significant decrease in body weight and food intake occurred in the treated rats. Based on the results of the published data, no recommendations can be made about the efficacy of fucoxanthin for overweight and obesity treatment in humans, but preclinical and clinical data show promise.

Garcinia Cambogia

Garcinia cambogia is a fruit-bearing tree native to Southeast Asia and India. The plant’s active compound, hydroxy citric acid (HCA), has several potential mechanisms for mediating weight loss. HCA is thought to decrease fatty acid synthesis and lipogenesis, suppress appetite by increasing serotonin availability in the brain and increase hepatic glycogen synthesis, thus increasing satiety. In a 2011 meta-analysis, HCA decreased weight by 0.88 kg on average compared to a placebo.[38] While this finding did reach statistical significance, its clinical significance is questionable. Subsequent randomized controlled trials have failed to find a benefit.[39][40] 

Furthermore, safety has been questioned due to reports of associated liver toxicity. While most of these cases occurred in patients taking combination products, three have occurred with Garcinia cambogia alone, and patients with liver disease should be cautioned.[41][42]

Glucomannan

Glucomannan is a soluble fiber commonly derived from the Amorphophallus konjac root. Because human salivary and pancreatic amylase cannot split β-1,4 linkages, glucomannan passes relatively unchanged into the colon, where the gut microbiota ferment it.[43] While it may be an ingredient in weight-loss products, it is more commonly used to treat constipation or elevated glucose and cholesterol. The compound reportedly promotes satiety, slows gastrointestinal transit, and reduces fat and protein absorption through fecal loss. In animal studies, glucomannan suppressed hepatic cholesterol synthesis and increased the fecal excretion of bile acids and cholesterol.[44] In a 2008 systematic review and meta-analysis, glucomannan significantly lowered total cholesterol, low-density lipoprotein cholesterol, triglycerides, body weight, and fasting blood glucose. This led to a statistically significant, albeit unlikely clinically significant, weight loss of 0.79 kg.[45] However, two recent reviews showed no statistically significant change in weight compared to a placebo, contradicting the earlier meta-analysis.

Glucomannan appears to be well tolerated for short-term use. Minor adverse gastrointestinal effects include belching, bloating, frequent loose stools, flatulence, constipation, and abdominal discomfort.[46] There have been reports of esophageal obstruction following the consumption of glucomannan-containing compounds, specifically with the tablet formulation and in patients with esophageal pathology. The capsule form of the supplement has not been associated with this effect.[47]

Green Coffee Extract

Green coffee beans are unroasted mature or immature coffee beans. They are high in polyphenols, which have purported positive biologic effects, including anti-inflammatory activities and anti-diabetic, anti-lipidemic, and anti-hypertensive effects.[48][49] While earlier studies showed inconsistent benefits of green coffee bean extract on weight and body mass, more recent studies have been more promising. A meta-analysis published in 2011 assessing the efficacy of green coffee extract on weight loss analyzed three human studies and found an overall moderate benefit in favor of green coffee extract versus placebo, with a mean weight loss of 2.5 kg after four to twelve weeks.[50] A study published in 2017 examined 64 obese women randomized to receive 400 mg of green coffee extract per day for eight weeks and found significant reductions in body weight, body mass, and fat mass.[48] The safety of green coffee extract is difficult to assess due to the small sample size and duration of published studies. While none reported adverse events, more research is needed to detail a full safety profile. Given these promising early findings, green coffee extract is a topic for more extensive controlled clinical trials.

Guar Gum

Guar Gum is a soluble fiber supplement derived from the Indian bean Cyamopsis tetragonolobus and is generally found in food products as a thickening agent. Guar gum is purported to promote weight loss by acting as a bulking agent in the gut, which results in delayed gastric emptying and increased satiety. Several studies have evaluated the effect of guar gum on weight reduction. A meta-analysis of 11 randomized, double-blind, placebo-controlled clinical trials of guar gum at dosages of nine to thirty grams daily for three weeks to six months found no significant difference in weight loss compared to placebo.[51] More recently, a clinical trial in 44 patients with type 2 diabetes evaluated the effects of ten grams per day of guar gum on metabolic syndrome parameters and found a significant reduction in waist circumference but no effect on weight loss.[52] 

Reported adverse effects include gastrointestinal complaints, such as abdominal pain, flatulence, diarrhea, nausea, and cramps. More research is needed to support the use of guar gum as a weight-loss supplement.

Hoodia Gordonii

Hoodia gordonii is a succulent plant native to Africa. It contains a steroidal glycoside that acts centrally on the hypothalamus to suppress appetite.[53] While this popular supplement has been used for weight loss, the one randomized, double-blind, placebo-controlled study examining H. gordonii found no significant improvement in energy intake, body weight, or fat percentage compared with a placebo.[54] Furthermore, adverse events were more common among those receiving H. gordonii, with altered skin sensation, headache, dizziness, and nausea among the most commonly reported symptoms. [54]

Irvingia Gabonensis

Irvingia gabonensis, also known as African mango, is a fruit native to Africa and commonly consumed in African cuisine.[55] The plant has many advantageous properties, including high fiber content and anti-diabetic and anti-lipidemic effects. Several studies have examined different formulations of I. gabonensis on weight and found beneficial results. A 2013 systematic review of the efficacy of I. gabonensis for weight management reported significant reductions in body weight, waist circumference, and total cholesterol.[56] An article published in 2018 studied the effect of 150 mg (milligrams) of I. gabonensis taken twice a day over 90 days and found improved and statistically significant differences in waist circumference, serum glucose, and triglycerides.[57] While multiple studies have reported beneficial results on metabolic disease markers, small sample sizes and mixed methods make it difficult to extrapolate a true clinical benefit. Overall, I. gabonensis appears to be safe and well-tolerated. The most common side effects include headache, flatulence, and difficulty sleeping.[58][59] Further studies are needed to determine efficacy, dosing, and safety.

Phaseolus Vulgaris/White Kidney Bean

Phaseolus vulgaris is a legume cultivated worldwide and marketed as a weight-loss supplement for its carbohydrate-blocking effects. Studies show that Phaseolus vulgaris inhibits pancreatic amylase, which decreases the gastrointestinal absorption of dietary starches. There have been several published clinical trials and reviews that show mixed results regarding weight loss efficacy.[60][61] The authors of a 2011 systematic review of six trials found that 445 to 1,500 mg per day of P. vulgaris for four to thirteen weeks significantly reduced body fat but not body weight.[62] A 2014 clinical trial of 123 overweight and obese participants consuming 3,000 mg a day of P. vulgaris with a hypocaloric diet over twelve weeks showed a modest yet significant reduction in body fat and body weight. This indicates that P. vulgaris has a possible modest effect on body fat and weight, but more data is needed to confirm this benefit.

Reported adverse effects of P.vulgaris include headaches, soft stools, flatulence, and constipation.[63] No serious adverse effects of P.vulgaris have been reported. The long-term effects are unknown.

Probiotics

Probiotics are bacteria and yeasts that have historically been used to confer a beneficial effect on gastrointestinal health. Since manipulation of the intestinal microbiome has been linked to changes in energy balance and metabolism, probiotics have garnered interest in their potential role in promoting weight loss. The data, however, have been underwhelming. In one systematic review and meta-analysis, probiotics were associated with a significant but small weight loss compared with placebo (weighted mean difference of 0.6 kg). Subsequently, a 2021 systematic review found no significant decrease in body weight with probiotic supplementation.[64] 

Probiotics have a very good safety profile in healthy individuals. However, they should be used cautiously in patients with central venous catheters or immunodeficiency since there have been rare reports of fungemia and pathogenic colonization.[65][66] Similarly, care should be taken in patients with valvular heart disease who plan to undergo dental surgery, endoscopy, or colonoscopy, as rare cases of lactobacillus endocarditis have occurred in patients taking lactobacillus-containing probiotics.[67][68]

Psyllium

Psyllium seed is a soluble fiber supplement derived from the husk of Plantago psyllium. Psyllium is purported to promote weight loss by acting as a bulking agent in the gut, which results in delayed gastric emptying and increased satiety. Fiber-enriched meals decrease the hunger hormone ghrelin and increase the satiety hormone peptide YY.[69] This finding suggests that fiber-rich meals might reduce appetite and increase satiety, although the data are inconsistent. Many human studies show no improvement in body weight and composition after psyllium consumption. One early study of psyllium supplementation showed improved glucose and lipid control compared to placebo in 125 overweight patients with type 2 diabetes, although no weight loss occurred.[70] Recent studies have demonstrated similar results with improved metabolic parameters without statistically significant weight reduction. A study in overweight and obese individuals noted a dose-response relationship with psyllium supplementation, with a dose greater than 30 g of fiber per day leading to the most robust weight loss effect compared to a placebo.[71] A more recent trial in patients with type 2 diabetes supported these positive findings, demonstrating that 10.5 g of psyllium supplementation daily for eight weeks was associated with a significant reduction in body weight, waist circumference, and hip circumference.[72] 

Psyllium is less readily fermented and does not cause as much flatulence and abdominal distension as other fiber supplements. Still, the most commonly reported side effects are gastrointestinal, including flatulence, abdominal pain, diarrhea, constipation, and nausea. Generally, psyllium is well tolerated for short-term use without serious adverse effects.[73]

Raspberry Ketone

Raspberry ketone is the natural aromatic substance found in red raspberries and is used by the food industry for flavoring. Animal studies have found that raspberry ketone down-regulates key genes responsible for adipogenesis while up-regulating genes that regulate fatty acid oxidation.[74][75] In-vitro studies in adipocytes have shown promising results, including an increase in fatty acid oxidation and suppression of lipid accumulation. One randomized controlled trial of 70 participants with a BMI greater than 27 examined the effects of supplementation with a proprietary blend of raspberry ketone, caffeine, bitter orange, ginger, garlic, cayenne, L-theanine, and pepper extract along with B vitamins and chromium versus placebo over eight weeks.[76] Participants also followed a calorie-restricted diet and engaged in moderate physical activity. Compared to the placebo group, those receiving the raspberry ketone supplement lost significantly more weight and fat mass. However, the data are difficult to interpret given that 25 participants dropped out of the study and an intention-to-treat analysis was not performed. Furthermore, the product contained multiple ingredients, rendering the effects of the single raspberry ketone compound impossible to determine. While typical diets only contain a few milligrams of raspberry ketones daily, dietary supplements contain 100 to 1000mg, leading to concerns about possible cardiotoxic and teratogenic effects.[77]

Issues of Concern

Weight-loss dietary supplements are regulated by the U.S. Food and Drug Administration (FDA). Unlike over-the-counter and prescription medications, the FDA does not classify dietary supplements as drugs. Therefore, these supplements do not require FDA approval before marketing, and the manufacturer determines the product's safety and efficacy. However, the FDA does not allow supplements containing pharmaceutical ingredients or those that claim to diagnose, treat, cure, or prevent disease.[78] The FDA has the authority to remove any supplement deemed unsafe from the market and can act against manufacturers if necessary.

When evaluating the evidence for dietary weight-loss supplements, additional data are needed to more clearly understand the efficacy, dosing, and safety of each ingredient. Human studies are limited, and data are often extracted from animal and laboratory research. Most human trials are small and of questionable quality, limiting interpretation. Many supplements marketed for weight loss contain multiple ingredients, making it impossible to isolate each ingredient's effect. Studies often use different formulations, combinations of ingredients, and variable dosages, all of which complicate the analysis of the supplement's safety and efficacy.

Clinical Significance

Americans spend over $2 billion a year on weight-loss dietary supplements. These supplements are costly and can contain dozens of ingredients, including plant components, herbs, dietary fiber, caffeine, and minerals. The proposed mechanisms of action vary for each supplement. These include blocking the absorption of fats and carbohydrates, reducing appetite and increasing satiety, increasing thermogenesis, and changing metabolism to improve body composition. There are concerns over the efficacy, safety, and purity of the compounds in supplements, which are usually marketed without substantiating data. The FDA regulates dietary supplements as foods, not drugs. 

People considering using weight-loss supplements should talk with their healthcare providers to discuss potential benefits and risks. This is especially important for patients with comorbid conditions who are taking prescription medications. Yet fewer than one-third of U.S. adults who use weight-loss dietary supplements discuss this with a clinician.[79] Healthcare providers should inquire about weight-loss supplements to facilitate open discussion.

The evidence supporting the use of weight-loss dietary supplements is limited, inconclusive, and unconvincing.[80][81] The benefits reported are often neither reproducible nor clinically significant. The safest, most effective way to lose weight is by choosing a healthy diet of whole foods and obtaining regular physical activity. Clinicians can consider FDA-approved pharmaceuticals and bariatric procedures for patients requiring additional measures.

Enhancing Healthcare Team Outcomes

Weight-loss dietary supplements are widely used and available worldwide. Patients considering these supplements should talk to their healthcare providers. The entire healthcare team must understand the ingredients, risks, and potential benefits of supplements and assess patients accordingly. 

Healthcare providers must consider what is known and unknown about each ingredient in a product before recommending its use. Manufacturers market supplements with a variety of claims, many of which have not been substantiated. Some preparations contain multiple ingredients that can cause harm by interacting with medications or causing organ dysfunction. Patients with hypertension, diabetes, cardiac, renal, and liver disease should consult their physicians before using any supplement, especially those marketed for weight loss.

Clinicians should complete a thorough history of prescription and over-the-counter medications and dietary supplements at all patient encounters. This list should be updated regularly and documented in the medical record. Patients should be encouraged to lead a healthy lifestyle with nutritious dietary choices and regular exercise to enhance their weight loss efforts. The interprofessional healthcare team should support the patient's weight loss journey to improve clinical outcomes. [Level 2]