Dietary supplements are part of the American way of life. Given that supplements are ingested directly into the body, safety takes precedence. After safety comes benefit. These products should offer consumers a fair chance at improving their health. Well-made, high-quality supplements do just that.
I’ve designed supplements and educated the public about them for more than 30 years. In my role as INM’s Quality Matters Program Advisor, I’ll help inform consumers and practitioners about supplement quality, active ingredients, additives, manufacturing, health claims, and legal requirements.
Supplement science keeps getting better. More of the world’s most competent researchers are investigating all categories of supplement ingredients. As they produce increasingly better data, these experts are further confirming that many supplement ingredients remarkably improve health and quality of life.
Let’s first clear up the confusion about “nutraceuticals” and dietary supplements. In the United States, nutraceuticals are dietary supplements (there is no legal distinction). Declaring a product or ingredient as a nutraceutical doesn’t necessarily make it better. What’s important is the data establishing its safety and benefits for human health.
The Multiple: Nutritional Health Insurance
Ample evidence suggests that almost everyone should consider taking supplements as a form of nutritional health insurance. Our diets often fall short in providing the essential nutrients we need. Supplements can help bridge these nutritional gaps, and a high-quality “multiple” is particularly effective for this purpose.1Freedman MR, Fulgoni VL, Lieberman HR. Temporal changes in micronutrient intake among United States Adults, NHANES 2003 through 2018: A cross-sectional study. Am J Clin Nutr. 2024 May;119(5):1309-1320. https://doi.org/10.1016/j.ajcnut.2024.02.007. Epub 2024 Feb 17. PMID: 38373695.
Population surveys show many people don’t get enough of one or more essential nutrients from their daily diets. Deficiencies can result in serious health problems and even death. A good multiple ensures we get vitamins, minerals, and other nutrients absolutely necessary for survival. These nutrients are the nuts and bolts of healthy bodily function, vital for the enzyme systems that build and maintain our DNA, generate energy, keep our tissues functioning, and—most important—sustain life. Multiples supply these nutrients in their most bioavailable forms.
At minimum, a high-quality multiple should contain these essential nutrients:
- Vitamins: A, B1 (thiamin), B2, B3, B5 (pantothenic acid), B6, B12, folate, biotin, C, D3, E, K
- Minerals: Magnesium, calcium, zinc, copper, chromium, iodine, selenium, manganese, molybdenum, boron, silicon
- Other vitamin-like nutrients: choline, lutein, zeaxanthin
Excluded Ingredients
Two essential minerals—iron and potassium—are often left out of multiples. Iron should only be routinely taken when blood tests indicate a deficiency. Potassium is usually omitted because the recommended amount for optimal health is so high that it would overwhelm the space in a capsule or tablet.
Supplements don’t need to contain non-essential minerals that have no specific roles in our enzyme systems. Natural doesn’t always mean safe. Many naturally occurring minerals can be toxic to humans.
A good multiple provides nutrients that are sorely lacking in our diets. The ongoing NHANES (National Health and Nutrition Examination Survey) shows that most American adults likely don’t get enough vitamin D, E, or magnesium from food. At least one in ten people lacks vitamins A, B6, C, K, potassium, calcium, and zinc. These deficiencies are only becoming more of a problem.1Freedman MR, Fulgoni VL, Lieberman HR. Temporal changes in micronutrient intake among United States Adults, NHANES 2003 through 2018: A cross-sectional study. Am J Clin Nutr. 2024 May;119(5):1309-1320. https://doi.org/10.1016/j.ajcnut.2024.02.007. Epub 2024 Feb 17. PMID: 38373695.
Nutrient insufficiency from foods, U.S. adults:
- At least 94% lack vitamin D
- At least 68% lack vitamin E
- At least 51% lack magnesium
- At least 47% lack vitamin C
- At least 43% lack vitamin K
- At least 39% lack vitamin A
- At least 29% lack potassium
- At least 28% lack calcium
- At least 20% lack zinc
- At least 11% lack vitamin B6
Some of the reasons for these shortfalls are well established. Today’s foods tend to have lower levels of essential nutrients, partly due to agricultural practices that deplete the soil. Industrial food processing further strips away valuable nutrients.
Numerous drugs can deplete essential vitamins and minerals. Over-the-counter H2 blockers, proton pump inhibitors, and antihistamines are common culprits. Many prescription medications, including antibiotics, also sap vital nutrients. Recreational drug use impairs the body’s ability to absorb vitamins, minerals, and crucial nutrients.
Air pollution and other toxic exposures (cigarette smoking and alcohol consumption), digestive trouble, kidney problems, age, and poor food choices also diminish nutrients. For example, low magnesium can stem from soil depletion and food processing, as well as from consuming too few green vegetables, beans, peas, and nuts.
Supplement Quality Issues
Most U.S. adults already take a multiple, and good multiples can help fill nutrition gaps. However, uncertainty about supplement quality, safety, and regulation continues to grow.
In a 2024 survey conducted by the Industry Transparency Center, more than four of five respondents expressed concerns about the quality, safety, and regulation of dietary supplements. This recent data confirms that supplement quality is a pervasive issue.
There are two major quality challenges with multiples: poorly absorbed mineral oxides and artificial folic acid.
Mineral Oxides and Absorption
Magnesium Oxide
A large portion of multivitamins contain minerals in the form of oxides, such as magnesium oxide (mag oxide). Our bodies need mag to make the energy that sustains us. Magnesium is necessary for brain, heart, and circulatory health, as all our organs depend on it. However, mag oxide is poorly absorbed. Multiples can offer better magnesium ingredients.2Blancquaert L, Vervaet C, Derave W. Predicting and Testing Bioavailability of Magnesium Supplements. Nutrients. 2019; 11(7):1663. https://doi.org/10.3390/nu11071663
I’ve heard that mag oxide is used in multivitamins because it’s more affordable than other magnesium ingredients and requires less space in the capsule. Yet, the mag oxide in multivitamins deprives consumers of authentic magnesium despite surveys consistently showing that at least half of us don’t get enough from diet alone.1Freedman MR, Fulgoni VL, Lieberman HR. Temporal changes in micronutrient intake among United States Adults, NHANES 2003 through 2018: A cross-sectional study. Am J Clin Nutr. 2024 May;119(5):1309-1320. https://doi.org/10.1016/j.ajcnut.2024.02.007. Epub 2024 Feb 17. PMID: 38373695.
Zinc Oxide
Zinc is essential for at least 10 percent of our bodies’ proteins to function properly and has key roles in DNA stability, gene expression, and antioxidant and anti-inflammatory defenses. The mineral supports immunity, insulin and blood sugar stability, positive mood, mental sharpness, healthy skin, and even reproductive health. In children, zinc is crucial for growth.
The reasons for using zinc oxide in supplements likely mirror those for mag oxide use. Like mag oxide, zinc oxide isn’t effectively absorbed. While dietary zinc deficiency isn’t as prevalent as magnesium deficiency, getting zinc from a multiple could still benefit overall health, regardless of age or gender.3Prasad AS. Lessons Learned from Experimental Human Model of Zinc Deficiency. J Immunol Res. 2020;2020:9207279. Published 2020 Jan 9. https://doi.org/10.1155/2020/9207279 9207279
Adding minerals as oxides to supplements is unjustified, unnecessary, and unsupported by science. There are plenty of more effective and cost-efficient alternative ingredients. Multiples should deliver essential minerals in forms that ensure optimal absorption.
Folic Acid Is Lab-Made Folate
Folic acid (FA) is an artificial substance incorrectly linked to the vitamin folate. Folate is so important for metabolism that many foods are fortified with FA to ensure the population is well supplied. Yet FA is not active folate—the body has to process the synthetic form.
Although folic acid is well absorbed, it must first be converted to methylfolate (technically 5–methyltetrahydrofolate or 5–MTHF). All three of the enzymes needed to complete this process are susceptible to functional impairment, most often due to DNA changes called polymorphisms.
Among the trio of folate-converting enzymes, MTHF reductase (MTHFR) is the most studied. MTHFR has numerous polymorphisms; consequently, impaired FA processing is a problem for approximately 89 percent of white individuals, 86 percent of Latina/o/x individuals, and 53 percent of Black individuals.4Graydon JS, Claudio K, Baker S, et al. Ethnogeographic prevalence and implications of the 677C>T and 1298A>C MTHFR polymorphisms in US primary care populations. Biomark Med. 2019;13(8):649-661. https://doi.org/10.2217/bmm-2018-0392
Polymorphisms in the other two enzymes involved in FA conversion further expand the population that cannot effectively benefit from folic acid.
Several studies have confirmed that most of the folic acid (FA) consumed by people is not converted into methylfolate,5Patanwala I, King MJ, Barrett DA, et al. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr. 2014;100(2):593-599. https://doi.org/10.3945/ajcn.113.080507 and there is significant variation in the ability to make this conversion. Since many multivitamins provide FA as the only source of folate, most people taking them aren’t getting the optimal form of folate.
Authentic methylfolate continues to be readily available as a supplement ingredient. With methylfolate, the issue isn’t unoccupied space in the capsule or tablet as with mineral oxides, since the amount of folate required per serving equates to micrograms (millionths of a gram).
When pregnant women lack folate, the risk of birth defects in babies increases. This is why many governments permit or promote FA–fortified foods. Conventional testing shows blood folate levels have increased in the United States due to FA food fortification. But this may be a hollow victory.
Although lab tests may indicate higher blood folate levels than those before food fortification, much of it may be useless, unconverted FA. Serum and plasma testing doesn’t distinguish folic acid from other active folates (such as methylfolate). Consequently, pregnant women may be lulled into a false sense of security.
A recent clinical trial found a high level of unconverted folic acid in a group of breastfeeding women taking FA but very little in a comparison group taking methylfolate.6Cochrane KM, Bone JN, Karakochuk CD, Bode L. Human milk oligosaccharide composition following supplementation with folic acid vs (6S)-5-methyltetrahydrofolic acid during pregnancy and mediation by human milk folate forms. Eur J Clin Nutr. 2024;78(4):351-355. https://doi.org/10.1038/s41430-023-01376-7 Women who took the FA produced breast milk with lower amounts of oligosaccharides, which are important for infant development.
In a 2015 study by the Centers for Disease Control and Prevention and National Institutes of Health’s Office of Dietary Supplements, over 95 percent of a representative sample of the U.S. population had unmetabolized folic acid in their bloodstream.7Pfeiffer CM, Sternberg MR, Fazili Z, et al. Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. J Nutr. 2015;145(3):520-531. https://doi.org/10.3945/jn.114.201210
Clinical research is now probing potential connections of unconverted FA with autism, cancer, immune dysfunction, sickle cell disease, and other health problems.8Fardous AM, Heydari AR. Uncovering the hidden dangers and molecular mechanisms of excess folate: a narrative review. Nutrients. 2023;15(21):4699. Published 2023 Nov 6. https://doi.org/10.3390/nu15214699 Evidence suggests unconverted FA can block methylfolate’s entry from the blood into the brain and eye, causing folate deficiency in these organs. Lack of functional methylfolate can result in a build-up of homocysteine, which increases the risk of stroke.
Given the essential role of methylfolate and other active folate compounds in DNA synthesis and repair, maintaining gene and chromosome integrity, supporting healthy cell growth, and sustaining specialized organ functions, incorporating an ingredient in foods and supplements that blocks folate’s vitamin actions seems like a really bad idea.
Based on a significant body of evidence, I’m convinced folic acid poses a health risk. It baffles me why FA continues to be used in supplements and added to the food supply when it doesn’t occur naturally in the body, the body struggles to activate it, and pre-activated folate is readily available.
Footnotes
- 1Freedman MR, Fulgoni VL, Lieberman HR. Temporal changes in micronutrient intake among United States Adults, NHANES 2003 through 2018: A cross-sectional study. Am J Clin Nutr. 2024 May;119(5):1309-1320. https://doi.org/10.1016/j.ajcnut.2024.02.007. Epub 2024 Feb 17. PMID: 38373695.
- 2Blancquaert L, Vervaet C, Derave W. Predicting and Testing Bioavailability of Magnesium Supplements. Nutrients. 2019; 11(7):1663. https://doi.org/10.3390/nu11071663
- 3Prasad AS. Lessons Learned from Experimental Human Model of Zinc Deficiency. J Immunol Res. 2020;2020:9207279. Published 2020 Jan 9. https://doi.org/10.1155/2020/9207279 9207279
- 4Graydon JS, Claudio K, Baker S, et al. Ethnogeographic prevalence and implications of the 677C>T and 1298A>C MTHFR polymorphisms in US primary care populations. Biomark Med. 2019;13(8):649-661. https://doi.org/10.2217/bmm-2018-0392
- 5Patanwala I, King MJ, Barrett DA, et al. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr. 2014;100(2):593-599. https://doi.org/10.3945/ajcn.113.080507
- 6Cochrane KM, Bone JN, Karakochuk CD, Bode L. Human milk oligosaccharide composition following supplementation with folic acid vs (6S)-5-methyltetrahydrofolic acid during pregnancy and mediation by human milk folate forms. Eur J Clin Nutr. 2024;78(4):351-355. https://doi.org/10.1038/s41430-023-01376-7
- 7Pfeiffer CM, Sternberg MR, Fazili Z, et al. Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. J Nutr. 2015;145(3):520-531. https://doi.org/10.3945/jn.114.201210
- 8Fardous AM, Heydari AR. Uncovering the hidden dangers and molecular mechanisms of excess folate: a narrative review. Nutrients. 2023;15(21):4699. Published 2023 Nov 6. https://doi.org/10.3390/nu15214699