Dietary Supplements – Best Taken With a Grain of Salt
Dietary supplementation is theoretically adjunctive, but has become part of the daily regimen for many. Some spend hundreds of dollars a year online and fill entire cabinets with dietary supplements (DS), while others are loyal to one generic multivitamin from the grocery store, but the inherent issues are the same for all consumers. Many of my patients, family, friends, and myself regularly use DSs, which is what spurred my interest in writing this article. My personal view is that while DSs can play a helpful role in augmenting one’s overall health, they should be approached with a dose of healthy skepticism. This article does not contain dramatic implications of conspiracy theories or provide you with the next “fountain of youth” pill. What it does contain is information to help you navigate this complex market, so that you will be empowered to supplement in a more safe and effective way. Due to the broad array of ingredients available, we cannot delve into the intricacies of each, but I will provide you with some concepts and resources that will hopefully enable you to make the best choice for you.
Definition of a Supplement
According to the U.S. Food & Drug Administration (FDA), a dietary ingredient is defined as a “vitamin, mineral, herb, botanical, or amino acid; dietary substance…to supplement the diet; a concentrate, metabolite, constituent, extract; or combination of the preceding substances.” DSs should not be utilized to “treat, diagnose, prevent, or cure diseases”, as you may have read on the labels of some of these products.1 This is an important clarification, given that many individuals taking them are doing so for this very reason. Over the past decade, estimates of the percentage of the adult U.S. population regularly taking supplements range from around 50% to as high as 76%, with approximately 32 billion dollars spent annually on these products. 2-5
Regulation of the Industry
It is a common misconception that the FDA does not regulate DSs. They do, but with limitations. The FD&C Act of 1938 was first established to “safeguard and protect” the public from a wide array of products, with a focus on the prohibition of “adulteration and misbranding.”6 Several other pieces of legislation followed. First the Dietary Supplementation Health and Education Act (DSHEA) in 1994 established policies specific to DSs;7 the Dietary Supplement and Nonprescription Drug Consumer Protection Act in 2006 required manufacturers to report serious adverse events to the FDA;8 in 2007, the Current Good Manufacturing Practice (CGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for DSs delineated parameters to ensure DS quality;7 finally in 2016, the FDA issued a revised draft for guidelines regarding obligatory notification procedures for “new ingredients.”9
However, several deficiencies remain. Manufacturers are not required to routinely show proof of any research supporting the efficacy or safety of a product prior to or after it enters the market (with the exception of “new” ingredients, but even this is based on the “honor system”). Even when a problem comes to light through report by medical providers, consumers, or third party labs, the U.S. must bear the burden of proof.10 So in essence, manufacturers are presumed innocent until proven guilty. There is also a protocol for manufacturers to claim exemption from performing their own pre-market testing under some circumstances.7 Additionally, the FDA has no independent legal authority, and must coordinate with the Department of Justice to pursue any criminal or civil action.6
Before we condemn the FDA, let’s be fair. Given the ever-blossoming market, 100% monitoring of compliance would be challenging to say the least. To its credit, the administration appears to be proactive in its efforts, working with the National Center for Complimentary and Integrative Health and the Office of DSs (NIH entities), and the Federal Trade Commission. Current FDA policy does assert the authority to perform both field and sample examinations;11 between 2004 and 2012, there were hundreds of products recalled, and their online database attests to an additional multitude of more recent recalls.12 Additionally, the FDA facilitates continued public feedback through an online reporting system.13
Questions to Consider Before Supplementing
If, and this is a big if, we are eating in a nutritious manner, our diet should provide most of us with all of the necessary ingredients for healthy living. However, most of us, myself included, don’t eat as we should and may benefit from supplementation. There are also those who are undergoing unusual stressors or activities, such as intensive exercise or strenuous working conditions, or special health conditions such as pregnancy. Additionally, there are those who have been diagnosed with an actual deficiency by their medical provider and may benefit from targeted supplementation. Attempting to prevent illness through bolstering the immune system is yet another motivator. Finally, there are those who just want to optimize their baseline condition of health.
There are many ingredients that have been shown to have positive health effects. However, even with the crucial vitamins (A, B, C, etc.) and minerals (calcium, iron, etc.), there is still inconsistent evidence about optimal levels in disease prevention. One reason is because studies often do not factor in each person’s unique biological profile and/or the baseline level of the nutrient being studied.14
What am I taking the DS for exactly?
Be careful not to fall victim to advertisements such as “metabolism enhancing” or “energy boosting”. These are vague terms and should be interpreted as so. Determine your objective and if that supplement is designed to help you meet that specific objective. Take Vitamin C, a vital nutrient, often touted as a way to ward off the common cold. While there is substantial evidence showing that it may reduce length and severity of illness, there is little showing any effect on preventing contraction of the virus in the average adult. The misconception that it reliably prevents colds came from studies that were performed only in select populations under abnormally strenuous conditions.15-16
Is more always better?
Not necessarily. First of all, the body can only utilize so much supplementation, so the excess is wasted through the process of urination. Secondly, some excess supplementation may actually cause harm. Take high protein diets, for example. Protein is seemingly innocuous, crucial for sustained normal bodily function, and thought to contribute to weight loss under some circumstances,17 but there is concern for adverse health effects when taken inexcessive amounts over long periods of time. And ultimately, enough excess protein will be stored as, you guessed it, fat.18 Even the everyday vitamins and minerals we discussed above can lead to other nutrient imbalances and become toxic in extreme amounts.14
Does it matter what type of an ingredient I choose?
Yes, in many circumstances. Different forms tend to have varying degrees of strength, mechanisms of action, and bioavailability. For example, calcium comes in the following forms, all with different profiles: calcium carbonate, calcium citrate, calcium gluconate, calcium lactate, calcium phosphate, calcium malate, calcium orotate, and oyster shell calcium.19 With herbs/botanicals, you need to determine what part of the plant the DS is from – root, bark, flower, etc. If there is a “standardized to %” amount, this will tell you about the concentration of that ingredient.20 And don’t forget the serving size, or you may end up taking more or less than your intended amount.
Do I have to worry about other drug interactions, if it is just over the counter?
YES. Just because something is available OTC does not mean it is cannot have significant interactions with other medications. St. John’s wort, an herb used for anxiety, depression, insomnia, etc., can interfere with the metabolism of other drugs, including birth control, the anticoagulant warfarin, and the cardiac medication digoxin; it may also be dangerous if taken with serotonin-modulating antidepressants. Ginkgo biloba, used for anxiety, depression, poor concentration, etc. may also interact with anticoagulants like warfarin, as well as OTC medications like NSAIDs (ibuprofen, naproxen, and aspirin).21
How can I know if the product contains what is supposed to and is effective?
Some degree of variability is expected, but studies have shown that concentrations of ingredients in a product can vary greatly. One study found gross mislabeling of caffeine levels in DSs, one of which did not list caffeine as an ingredient at all.22 In a research project undertaken by a team at the U.S. Department of Agriculture, they examined ingredients in vitamins, comparing the labeled amount to analytical values in a sample of many commercially available supplements; their results showed significant variability for several key nutrients across product lines.3
There have also been serious findings of dangerous and/or “adulterated” (impure) products. Do not confuse the terms “natural” or “organic” with safety.23 To put things in perspective, cyanide is naturally-occurring as well, but we all know how dangerous that is. Some of us may remember the banning of ephedra alkaloids in 2004 due to concerns over an increasing number of adverse reactions, notably of a cardiovascular nature.24 A more recent example involved a thermogenic product by a popular manufacturer, determined to have resulted in 50 cases of documented acute liver injury, presumably from a synthetic form of aegeline.25 Other studies of everyday OTC supplements have resulted in rather alarming findings as well, including variable levels of melatonin and the presence of serotonin in sleep aids,26 controlled steroids in work-out supplements,27 and thyroid hormone (T3) in a product marketed for “adrenal aid.”28
The harsh truth is that you will never have a 100% guarantee, unless you conduct your own randomized controlled trials, and then grow, prepare, and package the product yourself. For the other 99.9% of us, the alternative is to take steps to be as well-informed as possible. In addition to verifying products through the aforementioned companies (USP, NSF, etc.), I highly recommend doing a little research of your own. Below are some free research options:
Google Scholar is an online database where you can view abstracts and full-text from peer-viewed scientific journal articles. This is your best bet for viewing actual research and not just someone’s interpretation of it. https://scholar.google.com/
Examine.com is another option which provides summarized research on specific supplements based on research, which is usually referenced directly. This site does a nice job of explaining the mechanism of action of supplements and breaking down some of the complexities of the research, but again, may be skewed by the author’s personal interpretation. https://examine.com/
The Mayo Clinic, a nonprofit organization, has a website which also provides supplement-specific information, although for the most part, actual citations from articles aren’t included. https://www.mayoclinic.org/drugs-supplements
The FDA and National Institutes of Health websites offer a wealth of information, including databases with listings of specific nutrients. https://www.fda.gov/Food/DietarySupplements/default.htm; https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-Consumer/#h4; https://ods.od.nih.gov/HealthInformation/DS_WhatYouNeedToKnow.aspx; https://ods.od.nih.gov/factsheets/list-all/; https://nccih.nih.gov/health/supplements/wiseuse.htm
Remember, you will likely find research for and against almost anything, so look at both sides, not just what you want to read. Also look at the population that was studied – a study conducted with high school football players may not be applicable to, say, a woman going through menopause. Similarly, was the study performed on cells in a lab (“in vitro”) or in people (“in vivo”)? Sometimes things that happen in a petri dish don’t translate to real life. Note the date of the study–the field of research changes quickly, so try to stick to studies within the past decade if possible. Lastly, did the study look at outcomes at one point in time, or did it assess the effects on participants months or years later? Some studies focus only on short-term effects, and this does not translate to safety or efficacy of long-term use.
What if the label says it is from “an approved FDA facility” or “follows Good Manufacturing Practices?”
The FDA does not officially endorse products, and there is no official FDA seal; if you see a misleading label masquerading as one, do not give it much credence.29Now there are many other independent companies/laboratories whose stated objective is to monitor and evaluate DSs for quality and purity, in exchange for providing their own seal of approval. Some of the more reputable entities are U.S. Pharmacopeia (U.S.P.) (https://www.quality-supplements.org/verified-products) Banned Substances Control Group (BSCG) (https://www.bscg.org/), National Sanitation Foundation (NSF) (http://www.nsf.org/services/by-industry/nutritional-products/supplement -safety), Informed-Choice (https://www.informed-choice.org/), and Informed-Sport (https://www.informed-sport.com/). Please keep in mind that each of these bodies is independent, not a governmental institution, typically accredited through a 3rd party. Each is also, first and foremost, a business. However, their endorsement of a product may convey at least a degree of assurance, so I would recommend cross-referencing products with these sites.
Whom can I consult personally?
Your medical provider is one person whom you should always consult, as they not only have the knowledge base, but are familiar with your history, current medications, etc., and can help monitor your health state once you begin supplementation. A less utilized but very valuable resource is your pharmacist (since most of us don’t have a dedicated pharmacist, you can consult one at your local pharmacy). Terence Chau, Pharm.D., practices in the emergency department at a major Houston-based hospital system and sees many patients on routine supplementation. As he explains,“although many supplements are available over the counter, it doesn’t mean these supplements are always safe. Side effects may occur, as well as drug interactions between herbal supplements and prescription medications. The patient’s pharmacist can play a role in assisting…the patient should also update their home medication list to include both prescription and non-prescription medications and supplements. This comprehensive list should be reviewed with their healthcare provider at each visit.”30
Clear as mud now, right? All of this can basically be summed up by saying that there are very probable benefits to dietary supplementation, but there are also serious risks, not to mention potentially wasted money. So before beginning a regimen, do your research. In the interest of transparency and full disclosure, I myself will continue to take occasional DSs, but only with a grain of salt.
Please feel free to contact me with any questions/comments/concerns.
1. FDA (2018, September 21). DS products and ingredients. Retrieved from https://www.fda.gov
2. Cohen, P. A. (2014) Hazards of hindsight — monitoring the safety of nutritional supplements. New England Journal of Medicine, 370(14), 1277–1280. Retrieved from https://dash.harvard.edu/bitstream/handle/1/34854268/nejmp1315559-2.pdf?sequence=1
3. Andrews, K.W., Gusev, P.A., Dang, P., Savaraia, S., Oh, L., Atkinson, R., & McNeal, M. (2017). Adult Multivitamin/mineral (AMVM-2017) DS study. USDA DS Ingredient Database Release 4.0 (DSID-4). Retrieved from https://dietarysupplementdatabase.usda.nih.gov/dsid_database/Res%20Summ%20DSID%204%20Adult%20MVM-8-2-17%20final.pdf
4. Kantor, E. D., Rehm, C. D., Du, M., White, E., & Giovannucci, E. L. (2016). Trends in DS use among US adults from 1999–2012. JAMA, 316(14), 1464–1474. http://doi.org/10.1001/jama.2016.14403
5. Council for Responsible Nutrition (2017, October 19). DS usage increase, says new survey. Retrieved from https://www.crnusa.org/newsroom/dietary-supplement-usag-increases-says-new-survey
6. Armstrong, K., & Staman, J. (2018). Enforcement of the food, drug, and cosmetic act: Select legal issues. Congressional Research Service. Retrieved from https://fas.org/sgp/crs/misc/R43609.pdf
7. FDA (2007, December 27). Backgrounder on the final rule for current good manufacturing practices (CGMPs) for DSs. Retrieved from https://www.fda.gov/Food/GuidanceRegulation/CGMP/ucm110863.htm
8. Porter, D. (2007). DS and nonprescription drug consumer protection act (P.L.109-462). Congressional Research Service. Retrieved from https://www.everycrsreport.com/files/20070123_RS22480_7fe2015fd82d1cb1fccae81cce54add6c2e292fd.pdf
9. FDA (2018, August 14). New dietary ingredients in DSs – background for industry. Retrieved from https://www.fda.gov/Food/DietarySupplements/NewDietaryIngredientsNotificationProcess/ucm109764.htm
10. Senate and House of Representatives of the United States of America in Congress (1994, October 25). DS health and education act of 1994, 21 U.S.C § 402. Retrieved from https://ods.od.nih.gov/About/DHSE Wording.aspx#sec4
11. FDA (2018, September 10). Examination & sample collection. Retrieved from https://www.fda.gov/ForIndustry/ImportProgram/ActionsEnforcement/ucm459475.htm
12. Harel, Z., Harel, S., Wald, R. Mamdani, M., & Bell, C. (2013). The frequency and characteristics of DS recalls in the United States. JAMA Internal Medicine, 173(10), 929-930. Retrieved from https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1678813
13. FDA (2018, September 25). Recalls, market withdrawals, & safety alerts. Retrieved from https://www.fda.gov/Safety/Recalls/default.htm
14. Fairfield, K. (2017). Vitamin supplementation in disease prevention. In D. Seres & J. Melin (Eds.), UpToDate. Retrieved September 25, 2018 from https://www.uptodate.com/contents/vitamin-supplementation-in-disease-prevention?source=history_widget
15. Can vitamin C prevent a cold? (2017, January). Harvard Health Letter. Retrieved from https://www.health.harvard.edu/cold-and-flu/can-vitamin-c-prevent-a-cold
16. Haider, A.M. (2017). Prevention and treatment of influenza, influenza-like illness, and common cold by herbal, complementary, and natural therapies. Journal of Evidence-Based Complimentary & Alternative Medicine, 22(1), 166-174. Retrieved from http://journals.sagepub.com/doi/pdf/10.1177/2156587216641831
17. Pesta, D. H., & Samuel, V. T. (2014). A high-protein diet for reducing body fat: mechanisms and possible caveats. Nutrition & Metabolism, 11(53). Retrieved from http://doi.org/10.1186/1743-7075-11-53
18. Delimaris, I. (2013). Adverse effects associated with protein intake above the recommended dietary allowance for adults. ISRN Nutrition, 2013. http://doi.org/10.5402/2013/126929
19. Group, E. (2015, December 17). Understanding calcium: The best forms of calcium supplements. Global Healing Center. Retrieved from https://www.globalhealingcenter.com/natural-health/types-of-calcium-supplements/
20. ConsumerLab.com (2017, August 3). With herbal supplements, what is the difference between root powder and root extract? Retrieved from https://www.consumerlab.com/answers/is-there-a-difference-between-root-powder-and-root-extract/powder_vs_extract/
21. Saper, R. (2018). Overview of herbal medicine &DSs. In J. Elmore & J. Melin (Eds.), UpToDate. Retrieved September 25, 2018 from https://www.uptodate.com/contents/overeview-ofherbal-medicine-and-dietary-supplements?search=herbal%20medicine&source=search_result&selectedTitle=1~150usage_type=default&display_rank=1
22. Cohen, P.A., Attipoe, S., Travis, J., Stephens, M., & Deuster, P. (2013). Caffeine content of DSs consumed on military bases. JAMA Internal Medicine, 173(7), 592-594. Retrieved from https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1555822
23. National Center for Complementary and Integrative Health (NCCIH) (2014, June). Using DSs wisely. Retrieved from https://nccih.nih.gov/health/supplements/wiseuse.htm
24. National Center for Complementary and Integrative Health (NCCIH) (2016, September). Ephedra. Retrieved from https://nccih.nih.gov/health/ephedra
25. National Institutes of Health (NIH). (2016, May). Overview – OxyELITE pro. LiverTox – Clinical & Research Information on Drug-Induced Liver Injury. Retrieved from https://livertox.nih.gov/OxyELITEPro.htm
26. Erland, L.A. & Saxena, P.K. (2017). Melatonin natural health products and supplements: Presence of serotonin and significant variability of melatonin content. Journal of Clinical Sleep Medicine., 13(2), 275-281. Retrieved from http://jcsm.aasm.org/viewabstract.aspx?pid=30950
27. Green, G. A., Catlin, D.H., &Starcevic, B. (2001). Analysis of over-the-counter DSs. Clinical Journal of Sport Medicine, 11(4), 254-259. Retrieved from https://journals.lww.com/cjsportsmed/Abstract/2001/10000/Analysis_of_Over_the_Counter_Dietary_Supplements.8.aspx
28. Akturk, H.K., Chindris, A.M., Hines, J.M., Singh, R.J., & Bernet, V.J. (2018). Over-the-counter “adrenal support” supplements contain thyroid and steroid-based adrenal hormones. Mayo Clinic Proceedings, 93(3), 284-290. Retrieved from https://www.sciencedirect.com/science/article/pii/S0025619617308352
29. Does a CGMP or GMP seal or certification mean a DS product is safe or approved? (2018, June 25). Operation Supplement Safety. Retrieved from https://www.opss.org/faqs/does-cgmp-or-gmp-seal-or-certification-mean-dietary-supplement-product-safe-or-approved
30. Chau, T. (2018, September 13). Personal interview.