The Safety and Effectiveness of Supplements & Nutraceuticals

By Karl Nadolsky, DO, FACE
woman reaching for supplements bottle


Obesity is a complex disease of excess fat tissue accumulation and dysfunction that can predispose to other chronic conditions, like type 2 diabetes and high blood pressure. Obesity also results in a variety of disruptions to energy balance that may differ between individuals. Cutting calories (energy) in the diet and increasing energy expenditure (burning calories) are the key factors in losing fat and treating or preventing complications, such as type 2 diabetes. Dietary components, exercise and other lifestyle factors like sleep are also critical for health and fighting back against fat tissue-related diseases (also known as “adiposity-based chronic disease”). Unfortunately, making diet and other lifestyle changes is challenging as human biology and genetics along with environmental factors (including other medical conditions or medications) fight against those efforts. This is why medications, and even surgery, have been developed to help patients battle the struggles. To learn about some of the new medications that treat type 2 diabetes and help with weight loss, visit With that in mind, many patients are leary of medications or surgery and prefer to try products marketed as “natural,” which are generally labeled as “supplements” or “nutraceuticals.” Overall, most adults use some form of a dietary supplement with a broad variety ranging from multivitamins to those with alleged performance enhancement in sports.


Let’s first define these terms. “Supplement” technically refers to “a nutrient that may be added to the diet to increase the intake of that nutrient. Sometimes used to mean dietary supplement.” “Nutraceutical” is a more recently devised term that simply combines “pharmaceutical” with “nutrition” and applies to products ranging from dietary supplements and herbal products to even foods. These include so-called “herbal remedies”, which applies to products made from plants/herbs used for medicinal purposes. Dietary supplements (vitamins, minerals, herbs, etc) do not require review or approval by the Food & Drug Administration (FDA) before being sold. The manufacturing companies are responsible for safety of their products and labelling claims truthfully without misleading. However, they do not have to be reviewed by the FDA before the product is marketed. Legislation in 1994, coined “Dietary Supplement Health Education Act” had good intentions of freedom but unintentionally opened up expansion and promotion of potentially harmful and often ineffective products, touting unproven health claims that cost consumers significant financial loss and perhaps undermine the development of legitimate weight loss medications.

Natural medications

"Just because something is marketed as “natural” doesn’t make it safe or effective."

Just because something is marketed as “natural” doesn’t make it safe or effective. Any supplement or “nutraceutical” is technically a medicine based upon definition: “compound or preparation used for the treatment or prevention of disease.” By definition, a “drug” is a substance that has a physiological effect when ingested or otherwise introduced into the body - thus any supplement or nutraceutical that actually has any physiologic effect is a drug. Over-the-counter availability does not make something safe, and if not well-studied or regulated, may not have the desired efficacy or benefits. As an example, there was a very popular and reasonably effective supplement called ephedra or Ma Huang. Ephedra comes from a plant that seemed to have some fat burning and appetite suppression effects but ultimately was tied to very serious side effects, including death, which led to its banishment.

Additionally, as supplements and nutraceuticals are technically medicinal and may actually have drug-like effects, they also may have interactions with other medications that may or may not be well known so they must be cautiously considered for use.

Weight loss supplements are big business

Weight loss is one of the primary reasons people may seek out supplements and in the United States, over $2 billion are spent on weight-loss supplements. A plethora of supplements have been developed and marketed for weight loss and diabetes over the years, far more than can be reviewed in a brief article. However, there are some resources to help guide those who are interested. The Cleveland Clinic has published a nice guidance tool for patients considering supplements to help with glucose control and cholesterol levels based on their review of the evidence for benefits versus risks. To dig even deeper, the National Institutes of Health has a very in depth database of many available supplements to help consumers make informed decisions here:

Examples of popular supplements for weight loss and/or diabetes

A significant consideration when looking into using a less regulated medication (over-the-counter supplement) is the lack of data that may be either supporting its benefits or revealing its risks along with trusting the manufacters’ claims of ingredients and dosing instructions. Another caution is that many products marketed have combinations of several ingredients, causing confusion as to what those benefits and risks may actually be along with potential drug interactions.

Orlistat – a lipase inhibitor, meaning it blocks an enzyme that helps with the digestion and absorption of some fats, is marketed over the counter as “Alli.” This is actually a pharmaceutical, but sold over-the-counter, and also comes in a higher dose that is prescription only. It does have fairly reasonable results in trials for weight loss and glycemic control, especially at the higher prescription strength, but must be taken with meals (preferably low fat meals due to expected side effects from not absorbing fat in diet). Additionally, its use is limited by the gastrointestinal side effects (flatulence, oily stool, diarrhea and abdominal cramping). Caution must also be paid to the potential of malabsorbing fat soluble vitamins like A, D, K and E.

Caffeine – a drug that has been utilized for a long time by humans, caffeine does have stimulant effect and some increase in energy expenditure with fat burning. Short-term studies show some benefits for weight loss while long-term trials and observational studies generally support the benefits of coffee and tea (perhaps due to the caffeine) for fat loss or weight gain prevention and diabetes. Acutely, caffeine can cause reduced insulin sensitivity and higher sugars. Safety concerns are generally only with very high doses near 500 mg/day or 5-6 cups of coffee a day.

Chromium – chromium has been promoted for fat loss and improved glucose control as its deficiency may cause reduced response to glucose in the blood and increased risk of diabetes. The studies on supplementation show some minimal benefits or risks as most people should not be deficient in chromium, which is found in coffee, nuts, green beans and broccoli.

Conjugated Linoleic Acid – fatty acid produced in the digestive tract of ruminants such as cattle, goats and buffalo that may favorably influence lipid metabolism and body composition. This supplement had high expectations but results for fat loss and glucose control have been dissapointing and include adverse effects on cholesterol.

Creatine – known for its relatively well-established benefits for strength training (including increasing muscle mass in elderly), creatine monophosphate supplementation may actually modestly improve glycemic control in combination with exercise, with minimal adverse effects.

Green Tea – green tea obviously contains caffeine so it includes that potential benefit, though some studies have looked at green tea without caffeine and show modest benefit on weight. Minimal safety concerns, especially if consumed as a beverage without other calories added.

Green Coffee – green coffee extract has not lived up to hyped expectations in real life studies. It does seem to have some slight benefits for body composition and “cardiometabolic” health (blood pressure, cholesterol, glucose). Some of its effect may be attributed to the caffeine content.

Forskolin – marketed for fat burning and appetite reduction but the few clinical trials show minimal, if any, benefits, though without significant safety concerns.

Garcinia Cambodia (Hyroxycitric acid) – may slightly decrease appetite and increase fat breakdown but results from studies do not show much benefit for weight. There have been safety concerns reported, especially due to it being combined with other ingredients.

Hoodia Gordonii – initial evidence suggests it suppresses appetite by helping with reducing food intake, though the few human studies have been dissappointing. Minimal safety concerns, though there have been a few reports of heart rate and blood pressure increases along with headaches.

Bitter Orange (synephrine) – synephrine may increase energy expenditure and fat burning though overall benefits in the few studies conducted are unclear. There are safety concerns due to cardiac stimulation, which can be worse when combined with other stimulants.

Glucomannan – a type of water-soluble fiber supplement thought to help with satiety (feeling of fullness) but studies have shown dissapointing results for weight loss and body composition. Some studies show slightly improved glucose control but its use is limited by gastrointestinal side effects.

White Kidney Bean – touted as a “starch blocker” by interfering with the breakdown and thus absorption of carbohydrates. Some trials have shown a slight benefit for body fat and possibly glycemic control.

Berberine – a natural plant alkaloid historically used for its antibiotic properties found to have benefits for blood glucose and cholesterol, adopted for these uses in Asia. Several studies have shown slight weight loss but fairly good improvements of blood glucose, blood pressure and cholesterol limited by some gastrintestinal side effects. Larger and longer trials would help understand long-term benefits and risks.

Raspberry Ketone– has only been studied in combination with other ingredients and has been insufficiently studied to suggest benefit. Probably no concerning safety issues beyond the adverse effects on personal finances.

Yohimbe – relatively famous for its aphrodisiac lore, yohimbe has been thought to benefit fat loss due to its hyperadrenergic (adrenaline) effects. Despite some suggestion of improved fat loss in high level athletes, it has not been studied well enough in those with obesity or diabetes and has several safety concerns.

Probiotics – the gut microbiome has been found to be very important for health, including body weight and fat along with cardiometabolic health. Having good gut health is important, so probiotics have been marketed for weight loss but have only shown very slight benefits in the trials thus far. There may be some glycemic benefit in those with type 2 diabetes.


Most supplements developed and marketed for weight loss and diabetes have not been shown to have great benefits and many are plagued by concerning and/or potential side effects, resulting in risks outweighing the benefits. Even though some supplements/nutraceuticals may have shown some marginal benefit and minimal risks, cost remains the primary concern. With that in mind, remember that these over-the-counter remedies act as medicine (drugs) if they have any benefit and may come with adverse effects. The focus should remain in utilizing the well-studied medications that have been FDA-approved due to benefits that generally outweigh risks. The risks and benefits of each supplement/nutraceutical should be carefully considered in order to make informed decisions with your physician. Improving dietary and exercise habits along with other lifestyle factors (like sleep hygiene and stress reduction) are certainly the most important items to focus on and tend to be cheaper than most supplements. Remember that with weight and weight-related complications like type 2 diabetes, the combination of diet, exercise, other lifestyle measures plus medications or supplements is key to improving health.

Disclosure: Dr. Nadolsky has previously invested in development of a product which contains berberine, a bioactive compound mentioned in this article.