A Practical Guide to Avoiding Drug-Induced Nutrient Depletion

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By Hyla Cass, M.D.

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A little known, but potentially life-saving fact is that common medications deplete your body of a host of vital nutrients essential to your health. In this practical guide I’ll show you how to avoid drug-induced nutrient depletion and discuss options for replacing nutrient-robbing medications with natural supplements.

America has been called a pill-popping society, and the statistics bear this out. Nearly 50 percent of all American adults regularly take at least one prescription drug, and 20 percent take three or more.(1) Our increasing reliance on prescription medications has contributed to the growing problem with nutrient depletion. The truth is that every medication, including over-the-counter drugs, depletes your body of specific, vital nutrients. This is especially concerning when you consider that most Americans are already suffering from nutrient depletion.

Additionally, many of the conditions physicians see in their everyday practice may actually be related to nutrient depletion. The good news is that, armed with information and the right supplements, you can avoid the side effects of nutrient depletion, and even better, you may be able to control and prevent chronic diseases, such as diabetes, cardiovascular disease and osteoporosis.

A Common Scenario

I have seen case after case of patients who have experienced nutrient loss from taking prescribed medications. Too often, neither the patients nor their doctors are aware that the medications are the real cause of their symptoms.

For example, Kathy, a 57-year-old retired schoolteacher, was being treated by her internist with three medications: the thiazide diuretic, Diuril, for high blood pressure; Fosamax for osteoporosis; and the beta-blocker, Tenormin, for heart palpitations.

Kathy was referred to me because she suffered from fatigue, anxiety, depression and insomnia. I couldn’t find an obvious psychological explanation for these symptoms, except perhaps for the stress of her physical illnesses. The likeliest cause of her symptoms was the drugs themselves. So, rather than adding an antidepressant, an anti-anxiety pill or sleeping agent, I investigated the known nutrient depletions associated with these medications.

Any one of her three medications could be depleting her potassium and magnesium levels, resulting in arrhythmias, hypertension, fatigue and depression. Additionally I discovered that the diuretic she was taking could be depleting her zinc levels. Follow-up lab tests confirmed that Kathy was deficient in three essential minerals: magnesium, potassium and zinc.

Based on the lab results, Kathy’s internist agreed to oversee her medications while I supervised her nutritional regimen. Daily doses of magnesium, zinc and potassium, in addition to a high-potency multivitamin, resolved Kathy’s “psychiatric” symptoms. Once her mineral levels were restored, Kathy’s energy and mood were back to normal. Best of all, not only was she spared the burden of taking additional medications, she was able to lower the doses of the three she was already taking.

Drug-Induced Nutrient Depletion is Widespread

I see cases similar to Kathy’s more frequently than I’d like. Physicians often tell their patients that symptoms arising from nutrient depletion are simply “part of the illness” or just signs that they’re “getting older.” To make matters worse, physicians frequently try to address the symptoms arising from drug-induced nutrient depletion by prescribing even more drugs, further compounding the problem.

To understand the role various medications play in causing nutrient depletion, we must first look at the variety of nutrient-depleting mechanisms in pharmacy.

Many drugs, such as the stimulants Ritalin (methylphenidate) and Adderall, are prescribed for attention deficit disorder. These can reduce appetite. This, in turn, decreases the intake of beneficial nutrients. Some antidepressants also tend to have this appetite-reducing effect.

On the flip side, some drugs can deplete nutritional status by increasing the desire for unhealthy foods, such as refined carbohydrates. Many of the neuroleptics (anti-psychotic drugs) and some antidepressants cause insulin resistance or metabolic syndrome, with results in blood sugar swings. Patients then crave simple carbohydrates, such as sugar, bread and pasta. Steroid drugs, including those given by an inhaler, can create similar issues as well.

Certain medications reduce the absorption of specific nutrients in the gastrointestinal tract by binding to them before they’re absorbed into the bloodstream. The antibiotic, tetracycline, for example, can block absorption by binding with minerals, such as calcium, magnesium, iron and zinc in the GI tract.(2)

Weight loss drugs and cholesterol-lowering medicines similarly bind to fats, preventing them from being absorbed. Drugs that treat acid reflux or heartburn raise the pH environment of the upper GI tract, which reduces absorption of needed vitamins and minerals. This is especially problematic among the elderly, who often are already low in stomach acid.

Nutrients are essential to the metabolic activities of every cell in the body. They’re used up in the process and need to be replaced by new nutrients in food or supplements. Some drugs deplete nutrients by speeding up this metabolic rate. These drugs include antibiotics (including penicillin and gentamicin) and steroids, such as prednisone, and the gout medication, colchicine.

Other drugs block the nutrient’s effects or production at the cellular level. In addition to the intended effect on enzymes or receptors, medications can influence enzymes or receptors that help process essential nutrients. For example, widely prescribed statin drugs block the activity of HMG-CoA, an enzyme that’s required to manufacture cholesterol in the body. This action also depletes the body of coenzyme Q10 (CoQ10), which requires HMG-CoA for its production. This has a serious negative impact on muscle and heart health.

Drugs also can increase the loss of nutrients through the urinary system. Any drug that does this can drain the body’s levels of water-soluble nutrients, including B vitamins and minerals, such as magnesium and potassium. The major offenders are medications to treat hypertension, particularly the diuretics that reduce blood pressure by increasing the volume of water flushed out of the body.

Common Nutrient Robbers

The bottom line here is, we need to be aware of drugs that are nutrient robbers. The following provides some of the major drug categories:

Anti-Hypertensives

The ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) (2) concluded that thiazide-type diuretics are better than ACE inhibitors and calcium-channel blockers at preventing heart attacks in high-risk people. Physicians often prescribe potassium to offset the well-known potassium depletion associated with this prescription.

However, these diuretics are also known to deplete other minerals, such as magnesium, sodium, potassium and zinc, which are seldom specifically supplemented. One study found hypokalemia (low potassium) in 8.5 percent of people treated with thiazide diuretics and hyponatremia (low sodium) in 13.7 percent in the same patient population.(2,3) This indicates the importance of testing levels, and not simply restricting sodium.(2,3)

Thiazide diuretics also decrease magnesium in approximately 20 percent of patients(4) and can significantly decrease serum zinc.(5) Loop diuretics deplete potassium, magnesium, calcium, zinc, pyridoxine, thiamine and ascorbic acid.

One study showed that thiamine deficiency was found in 98 percent of patients with congestive heart failure who took 80 mg of furosemide daily, and in 57 percent of patients who took just 40 mg daily. This shows a dose relationship. Furosemide also increases excretion of ascorbic acid and pyridoxine.(6)

For these patients, consider the following daily supplements: calcium (1,000 mg), magnesium (250 mg to 500 mg), potassium (100 mg), vitamins C (1,000 mg), B1 (320 mg), B6 (10 mg to 25 mg) and zinc (25 mg).

Beta Blockers

Beta blockers are among the oldest classes of antihypertensive drugs. They lower blood pressure by reducing the effects of catecholamines, thereby reducing the force and speed of the heartbeat. Beta-adrenergic blockers deplete CoQ10 by interfering with the production of this essential enzyme for energy production.(7) This lack of CoQ10 is particularly dangerous, considering that the target condition is cardiovascular disease. Since the heart is particularly rich in CoQ10-hungry mitochondria, the energy factory of the cell, the end result can be heart failure. To offset this negative side effect you can take CoQ10, 100 mg to 300 mg daily with fat-containing food for best absorption.

These drugs also reduce production of melatonin (N-acetyl-5-methoxytryptamine). Produced from serotonin at night in the pineal gland by stimulating adrenergic beta1- and alpha1-receptors, this neuro-hormone regulates circadian rhythm and promotes sound sleep. By blocking beta receptors, these drugs may inhibit the release of the enzyme serotonin-N-acetyltransferase, which is necessary for the synthesis of melatonin, resulting in sleep disturbance.(8) Take melatonin (3 mg) at bedtime to counter this effect.

Cholesterol-Lowering Drugs

Statin drugs are the most widely prescribed medicines for lowering cholesterol. In fact, Lipitor(atorvastatin) is the best-selling drug on the planet. However, physicians need to address a serious risk. Statins deplete the body of CoQ10 with the following potential side effects: heart failure, muscle pain and weakness, irritability, mood swings, depression and impotence.(9-11) The last few side effects may also be due to lack of cholesterol, which is needed for brain cell and hormone production.

Therefore, people on statins should take 100 mg to 200 mg of CoQ10 daily to counter this potentially fatal depletion.

While no specific recommendations from the pharmaceutical industry exist, one pharmaceutical statin manufacturer observed the depletion effect in early research. This manufacturer holds a patent on a combination statin and CoQ10. Sadly, the patents have never been activated, nor have any warnings been provided by the U.S. pharmaceutical industry.

Health Canada, on the other hand, which is the federal department responsible for helping Canadians maintain and improve their health, requires that manufacturers of statin drugs include warnings on patient safety information sheets about the potential for myopathies and impaired cardiac function.

Acid Blockers

Antacids, histamine-2 receptor antagonists (H2 blockers) and proton-pump inhibitors (PPIs) are commonly prescribed for treating heartburn, gastro-esophageal reflux disease (GERD) and peptic ulcers. Numerous studies indicate that these drugs cause several nutrient deficiencies.

For example, aluminum antacids (Maalox, Mylanta and Gaviscon) and calcium carbonate (Caltrate, Dicarbosil, Rolaids, Titralac and Tums) act by buffering or neutralizing the acid pH of the stomach. Unfortunately, this reduction of stomach acid impairs the breakdown of the ingested food into its component nutrients.

Both PPI and H2 blockers significantly increase the risk of vitamin B12 deficiency in elderly patients. B12 requires adequate gastric acid for absorption. This population is already prone to deficiency in intrinsic factor, necessary for B12 absorption.(12) This lack of stomach acid also decreases the absorption of folic acid, iron and zinc.(13,14) H2 blockers (Tagamet, Pepcid, Axid and Zantac) decrease acid secretion by blocking histamine.

Proton pump inhibitors (PPIs, Prilosec, HK-20), the most potent of acid-reducing medications, are increasingly popular. They reduce stomach acid production by up to 99 percent by decreasing the action of proton pumps, which are part of the stomach lining’s acid-making machinery. This, however, can strongly interfere with nutrient absorption.

One study showed that high doses of PPIs, used for a year or more, could make people 2.5 more times susceptible to hip fracture than control subjects. Lower doses decreased the risk factor to 1.5 times that of nonusers. The longer these drugs are used, the higher the fracture risk. This heightened risk of osteoporosis is probably due to the drastic drop in calcium and vitamin D absorption that occurs with these drugs. Some experts believe the drugs themselves may hamper the body’s ability to build new bone.(15)

For anyone taking acid-reducing medication, I recommend daily intake of vitamin D3 (2,000 IU or more based on lab testing), B12 (200 mcg), folic acid (800 mcg), calcium (1,000 mg), chromium (500 mcg), iron (15 mg), zinc (25 mg to 50 mg) and phosphorus (700 mg).

Oral Hypoglycemics

Metformin (Glucophage, Glucophage XR and Glucovance) enhances the action of insulin in cases of insulin resistance, allowing glucose to enter the cells. This reduces elevated blood sugar. A study published in the Archives of Internal Medicine showed that diabetics on metformin had B12 levels that were less than half those of control subjects. The longer the drug had been used and the higher the dose, the greater the drop in B12.(16)

In people with Type 2 diabetes who take metformin therapy, serum folic acid levels decrease 7 percent and vitamin B12 levels decrease by 14 percent. (17) B12 and folic acid depletion also increases homocysteine levels. In addition, metformin may deplete CoQ10, thereby increasing heart disease risk. To reduce these effects, patients should take vitamin B12 (800 mcg), folic acid (400 mcg) and CoQ10 (100 mg daily).

Psychotropic Medications

For antidepressants to work optimally, an ongoing supply of the B vitamins must be available as co-factors to help manufacture the needed neurotransmitters, such as serotonin and dopamine.(18,19) So, while these drugs may not directly deplete B vitamins, patients on these medications should ensure they get enough of these vitamins. In addition, be aware that lithium carbonate, used for treating bipolar illness, depletes folic acid (take 800 mcg) and inositol (take 500 mg bid).

Hormone Replacement Therapy

Many baby boomers are on hormone replacement therapy (HRT), which can deplete vitamins B6 and B12, folic acid and magnesium. These nutrients are critical for heart health, as well as for mood. Rather than an antidepressant prescription, these women should be given the appropriate supplements to restore balance. I have seen many women do well once these nutrient depletions were addressed. This applies to younger women on oral contraceptives as well.

For women on standard HRT (estrogen and progesterone, orally, including as an oral contraceptive, or as a transdermal skin cream) I may also recommend calcium (1,000 mg to 1,200 mg daily), folic acid (400 mcg to 800 mcg), magnesium (500 mg), vitamin B2 (25 mg), vitamin B6 (50 mg), vitamin B12 (500 mcg to 1,000 mcg), vitamin C (500 mg to 1000 mg) and zinc (25 mg to 50 mg).

Antibiotics

Antibiotics deplete biotin, inositol, vitamins B1, B2, B3, B5, B6, B12 and vitamin K. Additionally, fluoroquinolones and all floxacins (including ciprofloxacin or “Cipro”) deplete calcium and iron. Tetracyclines (suffix, -cycline) deplete calcium and magnesium. Trimethoprim-containing antibiotics (brand names Trimpex, Proloprim or Primsol) deplete folic acid. Penicillins (suffix, -cillin) deplete potassium. Aminoglycosides, such as gentamicin, cause imbalances of magnesium, calcium and potassium.(20) In fact, one study showed that gentamicin causes increased excretion of calcium by 5 percent and magnesium by 8.4 percent.(21)

When you take antibiotics, consider a B vitamin complex along with it. Or take a multivitamin that contains 25 mg of B1 (thiamine), 25 mg of B2 (riboflavin), 50 mg of B3 (niacin), 50 mg of B6 (pyridoxine), 400 mcg to 800 mcg of folic acid, 10 mcg of B12, and 50 mg each of biotin and B5 (pantothenic acid).

Inositol is part of the B vitamin complex, and is likely to be included in a B vitamin or multivitamin formulation. Otherwise, take 500 mg of inositol. (The RDA is 100 mg per day.) In addition, either take a multivitamin that includes magnesium (500 mg), calcium (1,000 mg) and potassium (100 mg), or take them separately.

Antibiotics can disrupt the natural bacteria flora in the digestive system, killing “good” bacteria, including Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium bifidum (B. bifidum). These are probiotics or bacteria that normally live in and on the human body, concentrated mostly in the digestive and genital/urinary systems. Choose a supplement that contains at least 1 billion live organisms per daily dose.

You also may consider 50 mcg daily of vitamin K, which is normally made by friendly intestinal bacteria. Vitamin K is required for proper blood clotting. Deficiency is rare, but when it occurs, life-threatening bleeding can occur from the smallest injury. Vitamin K also plays a part in osteoporosis prevention.

Summary

Drug-induced nutrient depletion is far more common than has been acknowledged. In evaluating patients’ symptoms, doctors must assess whether symptoms are due to the illness, to the side effects of the drugs, or to drug-induced nutrient depletion. Considering the inadequate nutritional status of the majority of the population, we must remember that the illness itself may be due, in part, to nutrient deficiency. For insurance, it is easiest to provide baseline coverage: a daily high potency multivitamin mineral formula, CoQ10 (200 mg), omega-3 fatty acids (2 grams) and additional vitamin D and probiotics.

The bottom line: Physicians must look more deeply and determine underlying causes to determine whether drugs are harming patients – and what we can do to reverse these effects. As a consumer, be aware of these drug-nutrient depletions, and do what you can to avoid taking medications whenever you can, using natural products instead.

For more information, see my book, Supplement Your Prescription: What Your Doctor Doesn’t Know About Nutrition [http://www.cassmd.com/SuppYourPrescrpBk/SupYourPrescp_bk.html] available at my website, www.cassmd.com.

References
1. Centers for Disease Control and Statistics. Health United States 2006. www.cdc.gov/nchs/data/hus/hus06.pdf#093.
2. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. JAMA 2002;288:2998-3007.
3. Clayton JA, Rodgers S, Blakey J. Thiazide diuretic prescription and electrolyte abnormalities in primary care. Br J Clin Pharmacol 2006 Jan;61:87-95.
4. Pak CY. Correction of thiazide-induced hypomagnesemia by potassium-magnesium citrate from review of prior trials. Clin Nephrol 2000;54:271-275.
5. Khedun SM, Naicker T, Maharaj B. Zinc, hydrochlorothiazide and sexual dysfunction. Cent Afr J Med 1995;41:312-315.
6. Zenuk C, Healey J, Donnelly J, et al. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol 2003;10:184-188.
7. Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV: Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. Res Commun Chem Pathol Pharmacol 1977;17:157-164,
8. Stoschitzky K, Sakotnik A, Lercher P et al Influence of Beta-blockers on Melatonin Release. Eur J Clin Pharmacol. Apr1999;55(2):111-15.
9. Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10: A review of animal and human publications. Biofactors 2003;18(1-4):101-111.
10 Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr 2001;20:591-598.
11. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A 1990;87:8931-8934.
12. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol 2004;57:422-428.
13. Russell RM, Golner BB, Krasinski SD. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med 1988;112:458-463.
14. Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr 1991;10:372-375.
15. Yang, YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 296 (24): 2947-53
16. Zhao-Wei Ting R, C Chun Szeto, M Ho-Ming Chan, et al. “Risk factors of vitamin B12 deficiency in patients receiving metformin.” Archives of Internal Medicine Oct 9, 2006: 1975-1979.
17. Wulffele MG, Kooy A, Lehert P, et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: A randomized, placebo-controlled trial. J Intern Med 2003;254:455-463.
18. Bottiglieri T. “Folate, vitamin B12 and neuropsychiatric disorders.” Nutrition Review Dec 1996; 54(12): 382-390.,
19. Bottiglieri T, M Laundy, R Crellin, et al. “Homocysteine, folate, methylation, and monoamine metabolism in depression.” Journal of Neurology, Neurosurgery & Psychiatry Mar 2001; 70(3): 419.
20. Landau D, Kher KK. Gentamicin-induced Bartter-like syndrome. Pediatr Nephrol 1997;11:737-740.
21. Elliott C, Newman N, Madan A. Gentamicin effects on urinary electrolyte excretion in healthy subjects. Clin Pharmacol Ther 2000;67:16-21.

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