Dietary Supplements

It is estimated that over 50% of U.S. citizens use a daily supplement, whether an herbal, plant-based, amino acid, or a vitamin.  Many PD patients take one or more of these compounds.  My experience is that there is often an assumption that these products are natural, and therefore good for you, and the supply in stores is safe because the FDA will protect us from harmful substances.  These points should be taken separately.

 Are supplements good for you?

The issue is complex.  Some might be, and some are not.  Consider vitamins, for example. Vitamins are by definition required for health, but for the vast majority of us vitamin supplements are not necessary because we get the very small amounts we need from foods in a healthy diet.  Most of the time, if a person does not have a documented vitamin deficiency, taking over the counter vitamins does not improve health at all.  In fact, many well-designed studies involving hundreds of thousands of people have found no evidence that vitamins prevent heart disease, dementia, or cancers (1-3).  Experts in medicine have called for patients to stop taking unnecessary vitamins (4).  Thus, taking a vitamin to “make sure” you have enough in your system is not recommended.  Complicating matters, there are studies indicating PD patients may be deficient of vitamins B6, B12, and D.  And, there is marketing all around telling consumers to take vitamins.   The best approach is, if indicated, for a qualified doctor to check a level and advise you on whether or not you should take a vitamin.  If taking a vitamin for a specific medical reason, stick to the dose directed by the doctor.  There are certain medical conditions that may call for a period of taking a higher than normal dose of a vitamin. However, in general, taking a “more is better” approach may lead to serious health problems, especially when one takes megadoses (doses many times larger than usual or recommended).  Some vitamins may actually be toxic in high doses commonly available in stores. Vitamin B6 toxicity can cause neuropathy or dermatitis.   Acute vitamin D toxicity may cause confusion, excess urination, excess thirst, loss of appetite, vomiting, and muscle weakness. Chronically high levels of vitamin D may result in kidney stones, loss of bone mineralization, and pain. Vitamin E supplementation was found to be unhelpful for PD in the DATATOP trial of the 1990s, and is also known to be associated with health risks.  A meta-analysis (a review of multiple studies) including nearly 136,000 people showed that use of vitamin E in doses at or above 400IU daily may increase all causes of death (5). The bottom line: take vitamins only if directed by a doctor familiar with the guidelines.

And vitamins are not the only supplements.    The use of CoQ10 is widespread, though in a large, multi-center trial by the Parkinson Study Group, the supplement showed no clinical benefit (6).  In other words, it did not help symptoms or improve scores on PD rating scales. CoQ10 also did not slow down disease, as had been hoped. Similar negative results have been shown in trials of CoQ10 for several other neurologic diseases.

Plants hold a vast potential for medicine. Plant-based supplements however, are not always effective, and some may interact with or block the effect of prescription medications.  Some plant or herb supplements may cause harm. Nature is potent, and produces trees that can be used to make chemotherapy, bark that can be made into aspirin, and clover that is used to make the blood thinner warfarin, to name just a few.  Doctors know that these products are potentially as dangerous as they are helpful.  For example, the molecules used to make warfarin are also used as a poison found in pesticides.  When used as a medicine warfarin has to be adjusted very carefully.  The same care should be taken with any ingested compound, especially if there is the potential for danger. Simply designating a supplement safe because it comes from a plant is a dangerous and irrational position.   For example, the supplement kava (extracted from the pepper plant Piper methysticum), may actually worsen PD symptoms, and if combined with the drug alprazolam, may result in a coma-like state (7). There are many other examples.   Plants have had millions of years to evolve defenses against animals, some of which are very complex.  Plants are potent for good and bad, and that is about as natural as you can get.   This is one very important reason why it is important to make sure the compounds you take are safe.

Does the FDA protect us from harmful substances getting into supplements?

The FDA does not necessarily protect us from the potential dangers of supplements.  By federal law, they are actually quite limited in this regard.  To be clear, it was Congress which defined vitamins and other supplements as “dietary supplements” in 1994 (8), restricted the FDA, and created a law in which the supplement industry was to police itself.   To quote the FDA (9):

“The U.S. Food and Drug Administration (FDA) does not have the authority to review dietary supplement products for safety and effectiveness before they are marketed.  The manufacturers and distributors of dietary supplements are responsible for making sure their products are safe before they go to market.”

Why is there a law preventing the FDA from regulating supplements?

In 1993, Dr. David Kessler, then commissioner of the FDA, attempted to regulate supplements.  He was quoted in the June 15, 1993 edition of the New York Times to say, “The dietary supplement industry is pushing hard for deregulation of their products…There are no assurances that these products are appropriately manufactured, that what’s on the label is actually in the bottle, that they bear adequate directions for use to insure safety or that basic safety data has been collected and reviewed” (10).  This was in the face of numerous cases of injury or death resulting from the use of supplements.  However, according to Dr. Kessler on the program Frontline, January 2016 (11), “What happened was the dietary supplement industry recognized that the standard that we set — significant scientific agreement — would require it, before it could make a claim, to have a scientific basis.  And they just couldn’t make any claim.  And they saw, literally, billions of dollars at stake, and they unleashed a lobbying campaign that was second to none.”  This included a national television commercial (12) presenting the FDA in a fictitious middle-of-the-night, special ops-style raid on the home of actor Mel Gibson because he had a bottle of vitamin C.  The commercial included dark lighting, ominous sound effects, and a voice over with Mel urging, “If you don’t want to lose your vitamins, make the FDA stop.  Call the U.S. Senate and tell them you want to take your vitamins in peace.” The commercial ended with a written instruction to “Protect your right to use vitamins and other supplements. Write Congress Now.”  Several other actors spoke out publically, making similar straw man arguments, and Americans seemed to side with them, rather than the federal agency staffed with scientists and doctors, which had been established to protect them.   The call to action by those with no medical or scientific training, along with organized efforts in health food stores around the country, resulted in massive letter writing.  Per Frontline, Congress received over two million letters on this topic. In 1994, Congress passed the Dietary Supplements Health and Education Act (DSHEA), which limited then, and continues to limit now, the FDA as above.  The key author was Senator Orin Hatch of Utah.  According to author Dan Hurley in his 2006 book Natural Causes (13), supplements were the focus of Utah’s third leading industry, Hatch owned over 35,000 shares of stock in a company that manufactured supplements, and Hatch’s son was a lobbyist for the supplement industry.  Hatch was further noted to be the recipient of large campaign contributions from the supplement industry dating back to the 1980s.

 Is anyone evaluating supplements?

Federal laws restricting the FDA have not stopped independent investigators from analyzing supplements to see if they truly contain what their labels state.   Multiple studies have shown outright substitution of herbal supplements in which the product contains something other than the stated substance (14,15), and whatever is actually in the supplement is not listed. Other studies have demonstrated that traditional supplements manufactured overseas may contain contaminants including toxic heavy metals such as lead, mercury, and arsenic (16-22).  The U.S. manufacture of supplements containing these toxins has also been demonstrated (23).  Per the World Health Organization (24) “It is well known that there are many contaminants and residues that may cause harm to the consumers of herbal medicines.”  There are many reports in which prescription drugs have been added to supplements without reporting this on the label.  Thus, it is of the utmost importance to make sure that the product one is using is safe.  How that will happen is unclear.   Experts call for reform and proper oversight of the supplement industry (25).  Writers in lay press point to the lack of oversight and the politics behind the DSHEA law in less flattering terms (26, 27).   Consumer Reports (CR) dedicated its September 16, 2016 issue to supplements and safety.  The article “Supplements, a complete guide to safety,” notes, “Pills and capsules make promises they can’t keep in a marketplace with a profound lack of oversight.”  The article notes that since DSHEA became law, supplement products have grown in number from about 4,000 in 1994 to over 90,000 today.  CR cites an industry currently generating $40 billion a year.

But this is a safe supplement, right?

Finally, many patients tell me that they believe some supplement is superior because a healthcare provider sold it to them directly in the office.   The American Medical Association (AMA) Code of Physician Conduct (28) notes that the sale of health-related products by physicians raises ethical concerns about financial conflict of interest, undue pressure on the patient, erosion of trust, undermining of the primary obligation of physicians to serve the interests of their patients before their own, and such sales “demean the profession of medicine.”  The Maine Board of Licensure in Medicine also reflects this language.

References   (URLS accessed in August and early September, 2016)

1. Fortmann, et al. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:824-34.
2.  Grodstein, et al. Long-term multivitamin supplementation and cognitive function in men. A randomized trial. Ann Intern Med. 2013; 159:806-14.
3.  Lin, et al. Screening for cognitive impairment in older adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 159:601-12.
4. Guallar, et al. Enough Is Enough: Stop Wasting Money on Vitamin and Mineral Supplements. Ann Intern Med. 2013;159:850-851   http://annals.org/article.aspx?articleid=1789253 .
5. Miller, et al.  Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med.  2005;142(1):37-46.
6. Beal, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014;71(5):543-52.
7. Izzo A, Ernst E.  Interactions between herbal medicines and prescribed drugs: a systematic review.  Drugs. 2001;61(15):2163-75.
8. http://www.fda.gov/food/dietarysupplements/usingdietarysupplements/ucm480069.htm#
9.  http://www.fda.gov/Food/DietarySupplements/UsingDietarySupplements/ucm109760.htm
10. http://www.nytimes.com/1993/06/15/us/fda-is-again-proposing-to-regulate-vitamins-and-supplements.html
11. http://www.pbs.org/wgbh/frontline/film/supplements-and-safety/transcript/       The segment Supplements and Safety may be watched at  http://www.pbs.org/wgbh/frontline/film/supplements-and-safety/
12. https://www.youtube.com/watch?v=IV2olDA0w8U
13. Hurley, Dan. p76.  Natural Causes.  2006, Broadway Books, New York, New York.   A thorough and well-referenced history of the history of the interaction between the FDA and the supplement industry, including the passage of the DSHEA law.
14. de Boer, et al. DNA Barcoding and Pharmacovigilance of Herbal Medicines.  Drug Saf. 2015;38(7):611-20.
15. Parvathy, et al.  Detection of plant-based adulterants in turmeric powder using DNA barcoding.  Pharm Biol. 2015;53(12):1774-9.
16. Saper, et al.  Heavy Metal Content of Ayurvedic Herbal Medicine Products. Jama 2004;292(23):2868-2873.
17. Gair. Heavy Metal Poisoning  from Ayurvedic Medicines. BCMJ. 2008;50(2):105
18. Gogtay, et al. The use and safety of non-allopathic Indian medicines. Drug Safety 2002;25:1005-1019.
19. Lynch, et al. A review of the clinical and toxicological aspects of ‘traditional’ (herbal) medicines adulterated with heavy metals. Expert Opin Drug Saf 2005;4:769-778.
20.  Kumar, et al. Unique Ayurvedic metallic-herbal preparations, chemical characterization. Biol Trace Elem Res 2006;109:231-254.
21. Centers for Disease Control and Prevention (CDC). Lead poisoning associated with Ayurvedic medications—five states, 2000–2003. MMWR. 2004;53:582-584.
22.  Breeher et al. A cluster of lead poisoning among consumers of Ayurvedic medicine International Journal of Occupational 304 and Environmental Health2015;21(4):304-7.
23. Saper et al.  Lead, Mercury, and Arsenic in US- and Indian-Manufactured Ayurvedic Medicines Sold via the Internet JAMA. 2008;300(8): 915–923.
24. WHO Guidelines for assessing quality of herbal medicines with reference to contaminants and residues.  2007  http://apps.who.int/medicinedocs/documents/s14878e/s14878e.pdf
25. Starr R. Should states and local governments regulate dietary supplements? Drug Test Anal. 2016;8(3-4):402-6.
26.  http://www.nytimes.com/2015/02/06/opinion/the-politics-of-fraudulent-dietary-supplements.html?_r=0
27. http://www.nytimes.com/2013/11/05/science/herbal-supplements-are-often-not-what-they-seem.html?pagewanted=all&_r=0
28. AMA Code of Medical Ethics