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Many people self-initiate nutritional supplements to tackle a health problem or ensure they avoid a nutrient deficiency that might otherwise create one. However, supplementation without medical supervision can create problems if drug-nutrient interactions affect co-administration with medications or other dietary supplements. Despite this fact, supplement usage continues to rise, with supplement usage increasing from 50% (2007) to 56% (2018). As of 2021, 80% of Americans reported using supplements.

To Eat or to Supplement?

Often, it is said that the best way to consume the necessary vitamins, minerals, antioxidants, and other nutrients is from whole foods in the diet. However, what happens when sufficient levels of micronutrients cannot be achieved through the diet? For example, if an individual preferentially excludes foods, has food sensitivities or intolerances, or does not consume a balanced diet, they may turn to supplements, which may provide a more substantial amount of missing nutrients. Additionally, certain medications, diseases, age-related bioavailability decline, and reduced appetite may increase the need for supplements of specific nutrients. A person may also opt for supplements to increase their consumption of intended nutrients, whereas, with food, individuals may not be aware of its nutritional value.

Indeed, a balanced, whole-food dietary pattern that is rich in a variety of animal- and plant-based sources of carbohydrates, proteins, and fats can support health. Whole foods have the reputation of being superior to taking supplements in large part due to food synergy, or the beneficial relationship between food constituents. Specific vitamins and minerals interact with one another, some increasing the other’s effectiveness and others inhibiting it. There are also many phytochemical interactions occurring at the cellular level that affect how micronutrients and macronutrients are absorbed and used in the body.

However, it is important to be aware of how food-based nutrients are affected by cooking, chemicals, and food preparation, which may diminish the nutrient quality of a food or alter the bioavailability of nutrients, thereby decreasing micronutrient content. If nutrient quality is altered, an individual may unknowingly be under-consuming specific nutrients.

Food-Based vs. Synthetic Supplements

When choosing a supplement, consumers have the choice between food-based and synthetic supplements. A food-based supplement is derived from food and tends to contain more than just one active. A synthetic supplement is one that is made from chemicals or through a non-natural process, involving laboratory methods. It may start with a natural compound but the process to get to the final active is more involved chemically. An example of both types of supplements can be seen with vitamin C: a food-based supplement might be one from amla fruit or acerola cherry, and a synthetic one would be ascorbic acid (commonly synthesized from corn).

There are few studies comparing whole-food and synthetic supplements. Food-based supplements have historically been labeled as superior. Of the research available, studies indicate that there is no difference between the options, but that can depend on the nutrient being tested. When comparing animal- versus plant-derived vitamins, in some cases, animal-derived, whole-food supplements may be more bioavailable. One example would be retinol (preformed vitamin A, which is found in animal sources) compared with beta-carotene (plant source of provitamin A, which requires conversion to vitamin A in the body).

In a rat study, researchers aimed to assess the effects of food-based versus synthetic versions of calcium and magnesium on calcium balance and bone status. The magnesium and calcium from seaweed were compared to synthetic versions (calcium carbonate and magnesium oxide). Study results showed similar intestinal absorption of calcium, but the seaweed calcium extract increased the strength and bone mineral density more than the synthetic version.

A systematic review looked at studies comparing synthetic and natural vitamin C from food. Some animal studies did demonstrate a significant increase in absorption of vitamin C with natural vitamin C (containing other actives like bioflavonoids) compared to synthetic versions. However, another study indicated no significant differences in the bioavailability of vitamin C from natural or synthetic versions.

It is important to remember that most supplement brands that start with whole foods also execute a certain amount of processing to increase the amounts of vitamins and minerals they contain and to standardize dosing. Processing may diminish some of the benefits of eating foods in their whole food forms (e.g., a decrease in amounts of nutrients or nutrient potency).

Considering the health benefits of eating whole foods and the potential risks of supplementation, it intuitively feels as though supplements made from whole foods would have greater benefits than synthetic versions. However, there is limited evidence supporting this belief. In some cases, research suggests there is a future potential benefit of combining food-based supplements and natural products with synthetic versions to protect against age-related diseases. It may be that the nutrient in question needs to be examined side-by-side in both forms for both absorption and activity.

Natural Forms or Biologically Active Options

In addition to food-sourced supplements, there is an argument that some vitamins should be taken as a natural form or a biologically active option. A classic example of this is seen with vitamin E. Older studies have elucidated that natural versus synthetic forms of vitamins have a bioavailability ratio of 2:1, meaning that the natural form of vitamin E is more potent. A 2015 study on natural and synthetic forms of vitamin E on concentrations in nursing mothers’ colostrum confirmed this finding. Both versions increased the concentration of vitamin E, but the natural form was more effective, increasing concentrations by 57.6% versus the 39% exhibited by the synthetic version.

Another common vitamin with synthetic versus natural forms is vitamin K. There are two biologically active forms of vitamin K: menaquinone (MK or K2) and phylloquinone (K1). Their bioavailability is largely dependent on the source of vitamin K and transport mechanisms. Vitamin K1 sourced from plant and vegetable foods versus an equivalent dose of K1 as a supplement had lower absorption rates. Alternatively, K2 from natto (a soybean product) was better absorbed than K1 in food and supplements. Further, the transport mechanism and longer half-life of MK/K2 supplements have demonstrated higher accumulation in the body. This could be a potential hazard due to the effects of vitamin K on coagulation.

Inactive Ingredients to Watch For

While it is important to be cautious about micronutrient interactions, there are additional factors to consider when looking for quality supplements. Many people don’t know what to look for when buying a high-quality dietary supplement, but reading the ingredients label can provide helpful information.

Even the highest-quality supplements may undergo processing and include additional ingredients, including fillers, binders, and other excipients. Although the FDA allows these ingredients, it does not always mean they are safe for long-term consumption, especially if a person has a specific health concern or disease.

Inactive ingredients to consider when reading labels:

• Gums (mastic gum, carrageenan, xanthan gum, guar gum, beta-glucan, locust bean gum, gum tragacanth): Dietary gums generally appear in food products and supplements as thickening agents. While some gums have reported benefits (e.g., mastic gum may have anti-inflammation and antioxidant properties; xanthan gum is associated with reduced postprandial blood glucose), they may trigger responses in sensitive individuals. For example, a 2015 study found that some individuals produced antibodies against gums. Nearly 13% of the samples had IgE antibodies against all gums except carrageenan. However, carrageenan has recently become a topic of interest due to its purported connection to health issues, including insulin resistance, glucose intolerance, inflammatory conditions, ulcers, and digestive system damage. What’s more, carrageenan has been linked to inflammatory bowel diseases, such as colitis.
• Emulsifiers: Dietary emulsifiers are added to products to help mix two liquids. Some emulsifiers (e.g., carboxymethylcellulose and polysorbate 80) have been found to cause inflammation in the gut and affect microbiota function and composition. Some studies suggest that metabolic syndrome could arise due to the long-term impacts on gut microbiota. Of note, emulsifiers may increase the risk of developing cardiovascular disease (CVD).
• Parabens, Phthalates, & Plasticizers: These ingredients might be added to dietary supplements, prescription drugs, and over-the-counter drugs as excipients (i.e., preservatives, fillers, coloring agents, binders, flavorings, coatings, lubricants). While the current body of evidence is still growing, there is concern that the known endocrine-disrupting properties of these chemicals may be involved in breast cancer. Chronic exposure to phthalates may contribute to reproductive issues, a higher risk of ADHD, and increased body fat. Keep in mind these ingredients can be found in food, cosmetics, and personal care products, too.
• Maltodextrin: Oftentimes, maltodextrin is added as a flavoring, thickening agent, or preservative. It is a starch derived from corn, wheat, tapioca, or rice. Despite its natural origins, it may cause damage to the gut. In a study on mice, maltodextrin consumption was correlated with intestinal epithelial barrier injury, crypt hyperplasia, decreased goblet cells, and reduced mucus production. More research is needed to understand how maltodextrin affects the human gut microbiota.
• Gluten: As those with celiac disease and non-celiac gluten sensitivity know, gluten needs to be avoided. There can be gluten in dietary supplements either directly or indirectly (as a byproduct). Furthermore, depending on the foods eaten, long-term gluten-free diets may cause a deficiency in several essential vitamins and minerals. As such, individuals may choose to purchase dietary supplements to prevent nutrient deficiencies. However, some products are formulated with gluten, an excipient, or binder. Caution must be taken when reading ingredient labels.
• Added sugars: Gummy supplements are favorable for some as they are chewable and easier to swallow. However, excess sugar consumption has been associated with diabetes, cardiovascular disease, obesity, mood issues, and cognition.

Many of the studies available are cell studies, mechanistic, or animal studies, which means the findings that there is a correlation between disease from the ingredients mentioned above cannot be extrapolated to humans. However, if a supplement is taken daily for health, it is wise to assess for any potential health risks, seek advice from your healthcare provider, and continue to monitor the literature to see how it evolves.

How to Choose a High-Quality Dietary Supplement

Taking the time to find high-quality supplements will help maximize the benefits and minimize the risks of supplements.

Here are a few actions to take when choosing supplements:

• Read the labels: Look for the ingredients above and be knowledgeable about the different terms for both beneficial and harmful ingredients.
• Choose organically-certified sources when possible: Reduce toxicant contamination, such as from insecticides, pesticides, and GMOs, by opting for organic certification.
• Check for third-party testing: To verify good manufacturing processes, standardization, and quality ingredients, look for supplements with USP, ConsumerLab, and NSF International According to a 2015 study, only 3.6% of the 753 products reviewed had been tested and verified by a third party. It is important to remember that third-party testing is fee-based and not required by manufacturers. However, looking for third-party labels will ensure safer products.
• Look for certifications: Although many products on the shelves claim to be “gluten-free,” it does not guarantee those products are free from gluten. Look for NSF’s gluten-free mark to ensure the product does not contain gluten and is processed in a facility that prevents cross-contamination.
• Contact the manufacturer: Take any questions about the ingredients and quality of the supplements directly to the source and ask the manufacturer.
• Additional cautions: Individuals who are susceptible to kidney stones may wish to avoid supplements containing high doses of vitamin C or supplemental forms of oxalate-containing foods, such as leafy greens, turmeric, ginger, green cardamom, and cinnamon.

Final Word

A savvy consumer is a safe consumer. Education about what makes a quality supplement is one step toward ensuring safe supplementation. As always, talk with your doctor, nutritionist, or another member of your healthcare team before starting any supplementation. Note that some supplements may affect the metabolism of medications, so consult with your pharmacist if taking prescription drugs.