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The Skinny on Weight Loss Supplements: Fact or Fantasy?

  • Authors: Darrell T. Hulisz, PharmD; Karen M. Lindberg, PharmD
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Target Audience and Goal Statement

This activity is intended for pharmacists, nurses, physicians, nurse practitioners, and physician assistants.

The goal of this activity is to review available dietary supplements that are marketed for weight loss, describing studies that have examined their efficacy and safety, so that clinicians will be able to counsel patients on this topic.

Upon completion of this activity, participants will be able to:

  1. Identify the most commonly used non-prescription products for weight loss
  2. Discuss studies that have examined the efficacy of each product
  3. Describe safety concerns, possible side effects, and potential drug interactions for each product


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Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


  • Darrell T. Hulisz, PharmD

    Associate Professor, Department of Family Medicine, Case Western Reserve University School of Medicine, University Hospitals, Case Medical Center, Cleveland, Ohio


    Disclosure: Darrell T. Hulisz, PharmD, has disclosed that he has received grants for educational activities from Pfizer, Takeda, and Novartis. Dr. Hulisz has also disclosed that he has served as an advisor or consultant for Pfizer, Takeda, and Novartis.

  • Karen M. Lindberg, PharmD

    Staff Pharmacist, Rite Aid Pharmacy, North Canton, Ohio


    Disclosure: Karen M. Lindberg, PharmD, has disclosed no relevant financial relationships.

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The Skinny on Weight Loss Supplements: Fact or Fantasy?


Guarana, Hoodia, Hydroxycitric Acid, L-Carnitine, Natural Licorice

Guarana (Paullinia cupana)

Guarana is native to Brazil and Venezuela and contains caffeine, tannins, resins, lipids, saponin, starch, and coloring agents. Guarana has been studied mostly as an herbal blend of various natural products, including Ma Huang, which contains ephedra.

One such preparation containing yerbe maté (leaves of Ilex paraguayenis), guarana (seeds of Paullinia cupana), and damiana (leaves of Turnera diffusa) was used in a small pilot study.[32] In this double-blind trial, gastric emptying and weight were measured following consumption of these capsules over 10 days and 45 days, and body weight maintenance was observed over 12 months.[32] The treatment group experienced significant weight loss and gastric emptying after 45 days. Body weight reductions were 0.8 kg after active treatment, compared with 0.3 kg after placebo capsules over 10 days, and 5.1 kg after active treatment, compared with 0.3 kg after placebo over 45 days. Maintenance treatment over 12 months resulted in no further weight loss or regain.

A number of adverse events have been reported with guarana, including irritability, heart palpitations, anxiety, and other central nervous system events.[30]

Take-home message. Few studies have examined the use of guarana extract alone for weight loss. In clinical trials it has often been combined with other ingredients such as ephedra. Additionally, this supplement probably should be avoided due to reports of adverse central nervous system effects.


Hoodia is a genus that comprises 13 species, including Hoodia gordonii, which is touted for having weight-loss properties. Hoodia is a flowering succulent derived from a South African bush and is described as cactiform, appearing similar to the unrelated cactus family. Its proposed mechanism of action is suppression of the appetite center in the hypothalamus. A potential benefit of hoodia is the absence of stimulant properties and resulting increased blood pressure and anxiety.

Unfortunately, the evidence supporting its use is very limited. In a 2004 animal study, injections of P57 (the supposed active anorectic ingredient of Hoodia gordonii) were given to rats and were shown to reduce subsequent 24-hour food intake by 40% to 60%.[33]

In an unpublished, double-blind, randomized, placebo-controlled trial, Phytopharm, a British company developing hoodia weight-loss products, showed that hoodia decreased caloric intake by about 1000 calories per day.[34] In another unpublished investigation, Goldfarb and colleagues conducted a study in 7 patients over a 28-day period. Participants ingested 1000 mg of hoodia capsules per day, ate a balanced breakfast, and took a multivitamin. Exercise and other eating habits remained unchanged. Patients lost a mean of 3.3% of their body weight, with a median weight loss of 10 pounds.[35]

Take-home message. Hoodia is perhaps the most popular natural nonprescription weight loss aid currently marketed. Unfortunately, there is little evidence in the medical literature to support recommending this agent.

Hydroxycitric Acid (Garcinia cambogia)

Makers of hydroxycitric acid supplements describe it as an accelerator of fat burning. It is derived from the rind of Garcinia cambogia, a fruit native to India. In a 12-week randomized, double-blind, placebo-controlled trial, 135 patients were randomized to 1500 mg hydroxycitric acid per day or placebo.[36] Both groups consumed a high-fiber, low-energy diet. Results showed that the patients taking hydroxycitric acid failed to achieve a significant weight loss when compared with placebo.

Hydroxycitric acid was also studied in a double-blind, placebo-controlled trial of 10 males.[37] The subjects consumed either 3 g of the supplement per day or placebo for 3 days. Respiratory quotients, energy expenditures, and blood samples were not significantly different during rest or exercise.

In a 6-week randomized, placebo-controlled, single-blinded, cross-over trial, 12 males and 12 females consumed 300 mg hydroxycitric acid 3 times daily for 2 weeks.[38] Measured outcomes were 24-hour energy intake, appetite profile, hedonics, mood, and possible change in dietary restraint. Hydroxycitric acid significantly reduced 24-hour energy intake and produced weight loss compared with placebo that did not achieve significance. In a review of side effects, few and mild gastrointestinal adverse events were reported.[30]

Take-home message. Hydroxycitric acid appears to be safe, but proof of efficacy for weight loss in humans is lacking. More studies are needed prior to recommending this supplement to obese patients.


In an 8-week trial, 26 moderately overweight premenopausal women were randomly assigned to placebo or L-carnitine 2 g twice daily.[39] All patients walked for 30 minutes 4 days a week. Outcomes measured were total body mass, fat mass, and resting lipid utilization. There was no significant difference in outcomes for the 2 groups at the end of the study. Five patients in the treatment group experienced nausea or diarrhea leading to dropout from the study.

Natural Licorice

Natural black licorice contains a substance known as glycyrrhizic acid, which has been shown to cause sodium retention and hypertension; however, evidence of benefit in weight loss is lacking.

In 1 study, 15 patients consuming 3.5 g of licorice per day were monitored for 2 months.[40] Endpoints included body fat mass and extracellular water. BMI did not change, but extracellular water was significantly increased and body fat mass was decreased after licorice consumption. Because of the adverse effects on sodium and water balance and the risk of raising blood pressure, patients should be discouraged from consuming large amounts of natural licorice. It should not be recommended as a weight loss aid.