TOWNSEND LETTER

The Examiner of Alternative MedicineSaturday, February 6, 202

by Ross Pelton, RPh, PhD

This is Part 1 in a two-part series on drug-induced nutrient depletions. In Part 1, I will discuss the history and importance of the topic and summarize the nutrients that are depleted by several classes of commonly prescribed drugs. In Part 2, I will discuss microbiome-disrupting drugs, which is a new category I developed in recognition of the overwhelming importance the microbiome plays in regulating all aspects of health.

       These articles will introduce readers to drug-induced nutrient depletions, but I cannot cover this entire topic in one or two articles. Instead, in Part 1, I will discuss several classes of drugs that enable me to explain factors related to the cause, frequency, and potential seriousness of drug-induced nutrient depletions (I sometimes use the acronym DIND to refer to drug-induced nutrient depletions). In Part 2, I will explain how specific classes of drugs disrupt the microbiome and offer suggestions on how to correct or minimize the problem.

       My overall goal for these two articles is to increase your awareness and knowledge of this topic, and I hope you will be better able to offer advice to your patients. At the end of this article, I will provide directions on how you can obtain a complete drug-induced nutrient-depletions chart. 

      My “journey” into the topic of drug-induced nutrient depletions began in 1997, when I found a book titled Drug-Induced Nutritional Deficiencies, written by Daphne Roe, MD, who was a professor in the department of nutritional sciences at Cornell University.1 I was immediately attracted to this topic because in addition to being a pharmacist, I am also a certified clinical nutritionist (CCN) with extensive knowledge in nutritional biochemistry.2 Dr. Roe’s book, which was published in 1976, only addresses four classes of drugs. I quickly realized that this topic needed to be expanded and updated.

       When I began my research, I discovered that most classes of drugs deplete nutrients and that drug-induced nutrient depletions probably cause or contribute to many health problems. I also began to realize that even though hundreds of studies on drug-induced nutrient depletions exist in the medical literature, this information was not being publicized to healthcare professionals or the general public. Consequently, I made a commitment to update this topic. This project took me two years and thousands of hours of research. In 1999, The Drug-Induced Nutrient Depletion Handbook was finally published,3which is a reference book for pharmacists, physicians, and other healthcare professionals.

       One year later, my business partner, Jim LaValle, and I wrote The Nutritional Cost of Drugs,4 which presents drug-induced nutrient depletions to the general public. These books have now been out-of-print for a number of years, so I am happy to have the opportunity to present this material to healthcare professionals who subscribe to and/or read the Townsend Letter.

       I hope that one day, government authorities and/or politicians will recognize the importance and seriousness ofnthis topic and mandate that part of the FDA’s new drug approval (NDA) process would require/demand that drug companies research and report on the drug-induced nutrient depletions that their drug causes. However, due to the well-known cozy relationship between drug companies and the FDA, I doubt that this will happen in my lifetime.

       I want to begin by addressing some questions I am frequently asked when I give presentations on drug-induced nutrient depletions.

       “Why doesn’t my doctor know about this?” or “Why didn’t my doctor tell me aboutbthis?”  I have located over 500 studies reporting drug-induced nutrient depletions, which have been published in nearly one hundred different medical journals over the past 50 years. Although these studies get published, they seldom get publicized to physicians; and most physicians don’t have the time to dig through the scientific literature to locate these studies. Also, although I organized all this information into one central reference book, most physicians do not have a copy of the Drug-Induced Nutrient Depletion Handbook and many are not aware, or only minimally aware of this body of knowledge.

       “Many of the studies you cite are really old, aren’t there any newer studies?” Some of the studies I cite were published in the 1970s, 80s and 90s. However, this doesn’t negate the value of these older studies. Studies on DINDs are difficult to get funded. Pharmaceutical companies have enormous financial resources, but they are not interested in spending their money to fund a study that will announce to the world that their new drug is causing nutrient depletions.

       What frequently happens is that an alert physician becomes aware of the fact that a number of patients who are taking a specific drug are experiencing the same side effect. Subsequently, they run blood tests on a number of these patients and compare the results to a number of patients who are not on the drug in question. If, for example, they find that the patients taking the drug have lower levels of one or several nutrients compared to age-matched controls who are not taking the drug, they submit this result to a journal for publication. These small observational studies usually do not get published in the big prestigious medical journals, but the information is still important.

       “Why isn’t there any information about drug-induced nutrient depletions on the drug I’m taking?” Drugs are often on the market for a number of years before side effects, especially those caused by drug-induced nutrient depletions, begin to surface and get reported. Hence, there is frequently a time lag before DIND side effects begin to develop. Also, as mentioned previously, drug companies are not motivated to fund studies that tell you and me that their drug is responsible for nutrient depletion-related side effects. Consequently, many drugs on the market have not been studied for DINDs.

       What is the mechanism of drug-induced nutrient depletions? There are numerous possible causes. For example, a drug can inhibit absorption, synthesis, storage, metabolism, or excretion of a nutrient. In some cases, drugs bind with receptor sites, transport proteins, or enzymes. However, many studies reporting DINDs are observational studies, in which a clinician reports that people taking a specific drug have lower levels of a certain nutrients compared to non-users; but the mechanism of how or why the depletion occurs is not researched or reported.

       “How will I know if I am developing a drug-induced nutrient depletion?” When a person develops a side effect from a new drug, the problem is easy to identify because nausea, vomiting, a headache, itching or a rash usually develops within the first 24-48 hours. Side effects due to drug-induced nutrient depletions are more difficult to identify because they develop gradually over time.

       Consider the following scenario: a woman who has been taking oral contraceptives for eight years, seemingly without any problems. However, over the past six months, she has been increasingly complaining to her husband that she is tired all the time. She has trouble getting up in the morning, or by mid-afternoon, she feels so exhausted, she can hardly function. Oral contraceptives deplete folic acid, vitamin B12, coenzyme Q10, and magnesium. Each of these nutrients is critically important for energy production. A depletion of any one of these nutrients can cause tiredness, weakness, lethargy and/or anemia over time. However, this woman probably doesn’t realize that the medication she has been taking for years has been causing nutrient depletions that are now causing health problems.

       I think similar scenarios happen all too often. People take a medication and gradually a nutrient depletion develops, which begins to cause a problem. People then go to their doctor reporting a symptom(s)…and they are given another prescription drug rather than realizing that appropriate nutritional supplements could prevent or correct these symptoms.

       What dose do I need to take to correct a drug-induced nutrient depletion? This is difficult to answer because there are so many variables related to genetics, diet, nutritional status, personal health, etc. However, I think dosage levels should usually be greater than the government-recommended RDA. The RDAs were originally developed to provide an adequate amount of a nutrient that ensures that most people would not develop an outright nutritional deficiency disease. For example, the RDA for vitamin C is 65 mg/day, which is sufficient to prevent scurvy in most people. The RDAs were set decades ago. Nutrient content in foods has continued to decline, environmental pollution levels have escalated, reliance on nutrient-deficient processed foods and fast foods has increased, and people are taking more medications than ever. The RDAs were never intended to provide optimal levels of nutrition. I think clinicians need to assess the health and nutritional status of patients on an individual basis and make appropriate recommendations.

       The following study illustrates this point: “Therapy of side effects of oral contraceptive agents with vitamin B6.”5 The author states that oral contraceptives deplete vitamin B6, which results in lower levels of tryptophan. When these OC-users develop low tryptophan, symptoms that develop include depression, anxiety, decreased libido, and impaired glucose tolerance. When 40 mg of vitamin B6/day was administered (RDA is 1.2 to 1.3 mg/day), biochemical values were restored, and clinical symptoms were relieved. Hence, doses above RDA levels may be appropriate and/or required.

       In addition to individual pharmaceutical drugs, other factors contributing to nutrient depletions include the following:

       Factory Farming: Numerous studies document the fact that there has been a continual decline in the nutritional content of the commercially available food supply in the United States over the past 70 years. There are multiple contributing factors. During the 1950s, farmers began switching from organic manure to nitrogen-based chemical fertilizers; mono-cropping replaced crop rotation; hybrid seeds were developed which increased yields, but weakened the immune system of the plants; and chemical companies convinced farmers that they needed to use pesticides, insecticides, and herbicides that ultimately kill soil bacteria, which decrease the uptake of nutrients into plants.

       Fast Foods/Processed Foods: Many people regularly consume highly processed foods, fast-foods, and “junk” foods that are calorie dense but nutritionally deficient.

       Environmental Toxins: Biochemical detoxification processes in the body utilize nutrients. Increased exposure to toxins depletes specific nutrients that are utilized in detoxification processes, especially in the liver; and of course, the environment is more toxic now than at any time in history. According to the EPA, over 85,000 chemicals are approved for use in the United States, and the vast majority have not been tested for toxicity.6

       Polypharmacy: A study just released in April 2019 titled “Medication Overload: America’s Other Drug Problem” reported that over 40% of older adults take five or more medications. When OTC (over-the-counter) drugs are included, nearly 20% of older people take 10 or more drugs and it is not unusual for some older people to be taking more than two dozen different medications.7 I find that many people are taking two, three, or more drugs that deplete the same nutrient.This substantially increases the likelihood that drug-induced nutrient depletion health problems will develop.

Common Drug-Induced Nutrient Depletions

      Virtually all major classes of drugs, which include both prescription medications and OTC drugs, cause nutrient depletions. It is beyond the scope of this article to present or list the nutrients that are depleted by all medications, since there are nearly 1,500 FDA-approved drugs on the market in the US.8 In this article, I will present several examples that will express the extent and potential health risks associated with DINDs. I will discuss several classes of medications that cause serious health problems due to their DINDs, and I will also discuss a couple nutrients that are depleted by multiple classes of drugs to show how polypharmacy can multiply the seriousness of drug-induced nutrient depletions.

       Oral Contraceptives: When I wrote The Drug-Induced Nutrient Depletion Handbook, I was astounded to learn that oral contraceptives deplete more nutrients than any other class of medications. This alarmed me so much that I wrote a book titled The Pill Problem, which teaches women how to avoid the side effects from birth control pills.9 Results of a survey (2011-2013) reported that 25.9% or 9.7 million women between ages 15-44 use “the pill,” which makes oral contraceptives the most commonly used form of contraception.10

       Studies document the fact that more women than men suffer from health problems such as depression and insomnia. For example, a survey conducted by the National Sleep Foundation reported more women than men (63% vs 54%) suffer from insomnia several nights weekly.11

       A literature review from 1966-1999 reported that women experience depression twice as often as men.12 Another study, sponsored by the World Health Organization (WHO), reported that depressive disorders occur from 1.5 to 3 times more frequently in women than men.13 Furthermore, a meta-analysis of 9 clinical trials reported that rates of depression ranged from 16-56% in women using oral contraceptives.14

       I am convinced that oral contraceptive-induced nutrient depletions help explain why women have higher rates of depression and sleep problems than men. This is due to the fact that OCs deplete vitamin B615 and tyrosine, which are precursors for the synthesis of the key neurotransmitters serotonin, dopamine, and norepinephrine. Thus, OCs deplete nutrients that cause neurotransmitter imbalances, which increase the likelihood of developing depression.

       I previously mentioned a study of oral contraceptive users developing B6 deficiency, which resulted in women having increased incidence of depression, anxiety, decreased libido, and impaired glucose tolerance. The clinician then prescribed 40 mg of vitamin B6 daily and reported that this dosage restored the biochemical values and relieved the clinical symptoms in these women.5 I want to emphasize that the B6 RDA for women is from 1.2 to 1.3 mg/day. A dose of 40.0 mg/day is substantially higher than the RDA. This highlights that fact that people who have developed drug-induced nutrient depletions may require doses of nutrients that are higher than the RDA to correct the nutrient depletion-associated problems.

       Here is a complete list of the nutrients depleted by oral contraceptives: Vitamins B1, B2, B3, B6, B12, folic acid, vitamin C, vitamin E, magnesium, selenium, zinc, tyrosine, DHEA, and coenzyme Q10.16 Fourteen nutrients depleted by a class of drugs that is taken by millions of women. Throughout this article, I will not discuss the health problems associated with specific nutrient depletions. In addition to not having the space, I also assume that most readers of the Townsend Letter are knowledgeable about the health problems associated with deficiencies of essential nutrients.

       Acid-Suppressing Medications. It is a well-established fact that level of acidity in the stomach and throughout the intestinal tract is a critical factor that regulates digestion of food and absorption of nutrients. Acid-suppressing drugs such as PPIs, H-2 blockers, and OTC antacids all either suppress or neutralize acid. This creates a more alkaline pH, which hinders the normal processes of digestion and nutrient absorption. H-2 blockers such as cimetidine, ranitidine, and others have been shown to deplete vitamins B12, D, folate, and the minerals calcium, iron, and zinc.16  There are fewer nutrient depletions recorded for PPIs and antacids, but this is probably due to the fact that no studies have been conducted on these other nutrients with these drugs.

Multiple Drugs Depleting the Same Nutrient

       Coenzyme Q10. Now I want to approach things from a different angle. Instead of listing all of the nutrients that are depleted by a drug, or a class of drugs, I want to list all of the classes of drugs that deplete a specific nutrient, coenzyme Q10. This will highlight the fact that many people are taking multiple drugs that deplete the same nutrient, which increases the likelihood that a depletion of the nutrient will develop into one or more health problems.

       Drugs that deplete coenzyme Q10 include the following: oral contraceptives, hormone replacement therapy (HRT), biguanides (metformin), sulfonylureas, hydralazine (a vasodilator), thiazide diuretics, alpha-2 adrenergic receptor agonists (clonidine & others), beta-blockers, statins, gemfibrozil, tricyclic antidepressants, and major tranquilizers (such as Thorazine & Mellaril). Fourteen different drugs or classes of drugs can deplete coenzyme Q10!

       Many people are probably taking two or three drugs that deplete CoQ10. I’m especially concerned about the widespread use of statins, which I think is one of the most successful and immoral marketing jobs in the history of the world. CoQ10 is essential for mitochondrial function and protection of mitochondrial DNA (mDNA). The mitochondrial theory of aging tells us that mitochondrial dysfunction is at the core of the aging process. Statins and other drugs that cause CoQ10 depletion will accelerate free radical mDNA damage and mitochondrial dysfunction in cells throughout the body. In ten years, I expect to see studies reporting that people taking statins have accelerated aging. In general, low CoQ10 levels are associated with increased risk for atherosclerosis, elevated blood pressure, low energy, kidney dysfunction, neurological problems, sore muscles, and weak heart. 

       Folate is another important nutrient that is depleted by numerous drugs. The list of folate-depleting drugs includes oral contraceptives, antibiotics, anti-convulsant meds, biguanides (metformin), potassium-sparing diuretics, many chemotherapy drugs, corticosteroids, NSAIDs, bile acid sequestrants, and H-2 acid blockers. So again, you can see that many people could be taking two or more drugs that deplete folate. Folate deficiency increases risks of birth defects, low energy, anemia, and elevated homocysteine. I wonder how many women who give birth to an infant who is born with birth defects were taking two or three medications that deplete folate.

Conclusion

       As I mentioned previously, time and space limitations do not permit me to discuss all of the drugs that deplete nutrients and list the multiple nutrients that are depleted by these drugs.

References

1.     Roe DA. Drug-Induced Nutritional Deficiencies, Westport, CT, Avi Publishing, 1976.

2.     In 1994 I passed an exam administered by the Clinical Nutrition Certification Board (CNCB) and become a Certified Clinical Nutritionist (CCN).

3.     Pelton R, et al. The Drug-Induced Nutrient Depletion Handbook, Hudson, OH, Lexi-Comp, 1999. In addition to myself and Jim LaValle, Ernest Hawkins, and Daniel Krinsky are also listed as co-authors. Hawkins was employed at Natural Health Resources and helped with some of the research, editing and proofreading. Krinsky was employed at Lexi-Comp and supplied the monographs of drugs and nutrients for Lexi-Comp’s medical databases.

4.     Pelton R, LaValle J. The Nutritional Cost of Drugs. Hudson, OH, Lexi-Comp, 2000.

5.     Bermond P. Therapy of side effects of oral contraceptive agents with vitamin B6. Acta Vitaminol Enzymol. 1982;4(102):45-54.

6.     National Resources Defense Council (NRDC): TOXIC CHEMICALS. https://www.nrdc.org/issues/toxic-chemicals

7.     LOWN Institute: Medication Overload: How the drive to prescribe is harming older Americans.  https://lowninstitute.org/medication-overload-how-the-drive-to-prescribe-is-harming-older-americans/

8.     Kinch MS, et al. An overview of FDA-approved new molecular entities: 1827-2013. Drug Discovery Today. 2014 Aug;19(8):1033-1039.

9.     Pelton R. The Pill Problem. Available from: http://www.lulu.com/shop/ross-pelton/the-pill-problem/paperback/product-20716933.html.

10.   Daniels K, et al. Current contraceptive use and variation by selected characteristics among women aged 15–44: United States, 2011–2013. National health statistics reports; no 86. Hyattsville, MD: National Center for Health Statistics. 2015.

11.   2002 “Sleep in America” poll. National Sleep Foundation. https://www.sleepfoundation.org/sites/default/files/inline-files/2002SleepInAmericaPoll.pdf

12.   Okiishi CG, et al. Gender differences in depression associated with neurologic illness. J Gender Specific Medicine. 2001;4(2):65-72.

13.   Ustun TB. Cross-national epidemiology of depression and gender. J Gender Specific Medicine. 2000 Mar-Apr;3(2):54-8.

14.   GB Slap, Oral contraceptives and depression: impact, prevalence and cause.                      J Adolescent Health Care. 1981 Sept;2(1):53-64

15.   Doberenz AR, et al. Vitamin B6 Depletion in Women Using Oral Contraceptives as Determined by Erythrocyte Glutamic-Pyruvic Transaminase Activities. Experimental Biology and Medicine. July 1, 1971;137(3):1100-1103.

16.   Pelton R. References are listed in The Drug-Induced Nutrient Depletion Handbook. Lexi-Comp, 2001.