This course will cover the major classes of dietary supplements that are marketed for (and used for) weight loss, including digestion inhibitors, appetite suppressants, and thermogenic agents. The course will also cover some common dietary ingredients, such as fruits and fibers, that are also often promoted for weight loss.

Patients taking other medications may need to steer clear of St. John's wort, which can induce multiple cytochrome P450 (CYP) enzymes, including 3A4, 1A2, 2C19, and 2C9. Together, these enzymes are responsible for metabolizing the majority of prescription drugs available on the market. Induction of these enzymes can increase the metabolism of a drug, reducing its effects. In fact, St. John's wort has been reported to cause life-threatening drug interactions in transplant patients taking immunosuppressants [5].

Unfortunately, these studies were very small and had multiple methodological issues. The efficacy of 5-HTP as an appetite suppressant remains unclear. Additionally, there have been multiple reports of gastrointestinal, psychiatric, and neurological adverse effects with the use of 5-HTP. In serious cases, serotonin syndrome could develop. In general, patients should use caution or avoid 5-HTP supplements for weight loss.

Despite anecdotal reports of traditional use of hoodia for this purpose, very little clinical research has been conducted. One small study in overweight females shows that drinking a yogurt drink that contains hoodia purified extract 1,110 mg twice daily for 15 days does not reduce calorie intake or body weight when compared with placebo. This clinical study also found that some patients taking hoodia had increased blood pressure and heart rate, with increases of 4.6–11.5 mmHg and 4.8–12.4 beats per minute, respectively [12].

Considering the lack of any apparent benefit and the potential for cardiovascular adverse effects, patients should steer away from the use of hoodia for weight loss.

Digestion inhibitors are substances that can reduce the absorption of certain macronutrients, such as proteins, fats, or carbohydrates. Typically, these substances block the enzymes that break down the macronutrients protease, lipase, and amylase, respectively. Proponents of digestion inhibitors claim that blocking the breakdown of these macronutrients will reduce their absorption by the body and result in weight loss.

Clinical research in overweight and obese adults shows that taking 1–3 grams of chitosan daily for up to a year may modestly increase weight loss when compared with placebo. However, the average additional weight lost in these trials was only 1 kg [20,21]. Some of the small clinical studies that have been conducted to date suggest that chitosan is only beneficial when combined with a reduced calorie diet; when patients take chitosan without reducing calorie intake, no benefit is seen.

Although these products may be marketed as safe and natural alternatives to OTC laxative options, stimulant laxatives can cause both minor and serious adverse effects. With normal use, these laxatives can cause abdominal pain, discomfort, bloating, cramping, diarrhea, and flatulence. When taken in high doses for long periods of time, they can cause serious fluid loss and electrolyte imbalance [24].

Fiber is an important component of the diet. It is recommended that all adults consume a minimum amount of fiber every day, with recommendations differing depending on age and biological sex. Adult women 19 to 30 years of age should consume at least 28 grams daily; those 31 to 50 years of age should consume 25 grams daily; those 51 or older should consume 22 grams daily. Recommended intake for men is higher, at 34 grams daily for those 19 to 30 years of age, 31 grams daily for those 31 to 50 years of age, and 28 grams daily for those 51 years of age and older [25].

A meta-analysis of clinical studies in overweight and obese adults shows that consuming flaxseed can modestly reduce body weight by an average of 1.8 kg when compared with not consuming flaxseed. It also reduces BMI by an average of 0.6 kg/m2 and waist circumference by 1.2 cm. These results occurred in people consuming at least 30 grams daily for at least a few months [31,32].

In clinical studies, glucomannan has both increased satiety and modestly increased weight loss. Glucomannan is an indigestible soluble fiber that is typically obtained from the roots of the konjac plant (Amorphophallus konjac). Small clinical studies have shown that it can reduce body weight by about 5 kg when taken in combination with a calorie-restricted diet. It may also modestly reduce BMI, fat mass, and waist circumference. These studies used doses of 3–4 grams daily, divided into two to three doses throughout the day [34,35].

Grapefruit extracts are sometimes marketed as "fat burners" due to laboratory studies that suggest that the flavonoids found in grapefruit can cause lipolysis. Three small clinical studies evaluating one specific product, which contains extracts of orange and grapefruit, suggest that taking the extract daily for 12 weeks can reduce body weight and body fat percentage in healthy overweight adults when compared with placebo. Due to the small size of these studies, any outcomes should be interpreted with caution.

Certain fruit juices can alter the absorption or metabolism of many medications. Depending on the juice, this can be due to the inhibition or induction of enzymes that metabolize these medications, such as the CYP enzymes. This can also be due to the inhibition or induction of transporters that carry medications into cells, including the organic anion-transporting polypeptides (OATP).

Grapefruit is an especially significant culprit and can cause major drug interactions with a wide range of medications. Whole grapefruit, grapefruit juice, and grapefruit extracts have been shown to inhibit CYP3A4, which is responsible for the metabolism of a large number of prescription drugs. A sample list of affected drugs includes clopidogrel, amiodarone, atorvastatin, carvedilol, estrogen, and losartan; CYP3A4 is responsible for the metabolism of hundreds of drugs. The effects of grapefruit on CYP3A4 can last for at least 48 hours, so simply separating the consumption of grapefruit from medications will not prevent an interaction. Generally, patients who are taking medications that can interact with grapefruit should avoid grapefruit products altogether.

Thermogenic agents, often referred to as "fat burning" drugs, increase energy expenditure. In the US, there are currently no prescription drugs that are classified as thermogenic agents. However, there are a handful of dietary supplement products that are marketed and used for this purpose.

When used in moderation, caffeine is generally safe. The available clinical research indicates that consuming up to 400 mg of caffeine daily is not associated with an increased risk of major chronic conditions [50]. This quantity of caffeine can be obtained from approximately 4 cups of coffee or 8 cups of green tea.

Higher daily doses of caffeine can increase the risk of adverse effects, including palpitations, anxiety, restlessness, and diarrhea. Also, chronic use of caffeine can result in tolerance and habituation, which can lead to symptoms of withdrawal when caffeine is not consumed [50]. Patients should be counseled on the importance of limiting daily caffeine intake to no more than 400 mg.

There is some concern that certain green tea extracts may cause hepatotoxicity. There have been numerous case reports of hepatotoxicity with green tea extracts; however, the actual rate of occurrence is estimated to be about 1 in 2.7 million patients. It is unclear whether certain factors can increase the risk of liver damage, although there is some indication that higher doses of EGCG, and higher peak plasma concentrations of EGCG, may be associated with an elevated risk [56].

Unfortunately, synephrine can cause many of the same adverse effects as ephedra, including elevated blood pressure and heart rate [61]. It has also been associated with heart attack, seizure, stroke, and serious arrhythmias [64]. Although clinical research on octopamine is lacking, it is chemically similar to synephrine and may be associated with many of the same safety concerns [65].

This ingredient has seen a relatively recent surge in popularity, obtaining the Internet nickname of "nature's Ozempic." Berberine is a yellow-colored alkaloid that is found in the roots and stem bark of multiple plants, including European barberry, Oregon grape, phellodendron, and tree turmeric.

This plant (Gymnema sylvestre) has gained popularity for weight loss due to a very unique mechanism of action—altering the sense of taste. Certain chemicals found in gymnema can inhibit the ability to taste either bitter or sweet flavors. In some small clinical studies, taking gymnema reduced the consumption of sweet foods when compared with taking placebo, suggesting that this supplement may help with weight loss [77,78].

It is very important to recognize that, as a class, dietary supplements for weight loss are at an increased risk for adulteration. This means that many of these products have been found to contain ingredients that are not listed on the label. In fact, the prevalence of adulterated (contaminated) weight loss products is so high that the FDA has launched a targeted initiative related to these products. To answer consumer and healthcare professional questions about the risks associated with these products, the FDA now hosts a Q&A page on the topic [84].

In the vast majority of cases, weight-loss supplements are adulterated with sibutramine, a prescription drugs that was removed from the U.S. market in 2010 due to serious safety concerns. These concerns included heart attack, stroke, and arrhythmia. This drug can also interact with a number of medications and is more likely to cause serious issues in patients with certain conditions, such as hypertension, cardiovascular disease, liver dysfunction, and more.

To ensure that a patient is selecting a high-quality dietary supplement product, it is generally best to look for third-party quality certification stamps, such as those from USP or NSF. Unfortunately, most dietary supplements that are marketed for weight loss do not carry these stamps, increasing the likelihood for quality and contamination issues. When a certified product cannot be identified, it may be best to counsel patients on foregoing use.