Natural Supplements
Nutritional Depletion Caused by Prescription Medications

Thomas M. Bozzuto, D.O.

During pharmacology class, and in most of our experiences, we have been taught important drug-drug interactions, as well as contraindications, adverse reactions, etc. Nowhere do I remember being taught the importance of drug-nutrient interactions. The storing and utilization of essential nutrients in our bodies are regulated by a host of complex mechanisms. Any condition or pharmacological agent that interferes with one or more of those mechanisms has the potential of causing depletion of a given nutrient. For patients with multiple medical problems, depletion of some nutrients may exacerbate their condition or cause new symptoms. Non-steroidal anti-inflammatories (NSAIDS) are some of the most prescribed medications in the United States today. Many are also available over the counter. This article will address nutritional depletion caused by NSAIDS. Subsequent articles will discuss cardiac, cholesterol, GI, contraceptives, and psychotropic medications.

IRON: NSAIDs can damage the stomach as well as the small and large intestines, causing ulceration, chronic bleeding, and eventually iron deficiency.1-3 Significance of Depletion :Iron deficiency may be associated with oxidative DNA damage.4 In children, iron deficiency leads to cognitive dysfunction. Other pathologies associated with depleted levels of iron include anemia and compromised immune function. Symptoms include dizziness, fatigue, shortness of breath, pallor, and tachycardia.5 Therapeutic doses for replacement therapy for adults range from 100 to 200 mg/day (2 to 3 mg/kg/day) of elemental iron, usually in 3 divided doses. Iron levels should be monitored carefully; excess levels could also be associated with oxidative DNA damage as well as increased risk of cancer and heart.4 The oral lethal dose of elemental iron is estimated to be 200 to 250 mg/kg with symptoms presenting after ingestion of 30 to 60 mg/kg. Iron supplements can cause GI irritation; administering the supplement with food will prevent GI upset and bleeding .6

MELATONIN: Plasma levels of melatonin were significantly reduced after administration of both ibuprofen (400 mg) and indomethacin (75 mg) compared to controls, perhaps through interference with prostaglandin synthesis.7 Significance of Depletion: Alterations in melatonin levels have been associated with disturbances in the sleep-wake cycle and jet lag.8 Optimal doses for melatonin therapy have not been established. Commonly available doses range from 0.3 to 5 mg. Physiological blood levels are achieved with doses of 0.3 mg; higher doses (1 mg) result in supraphysiological levels of melatonin in the blood. The efficacy of melatonin supplementation is dependent upon the time of administration, as effects are related to circadian rhythms.

FOLATE: Non-steroidal anti-inflammatory drugs (NSAID'S), such as ibuprofen, have antifolate activity.9 It is not known if chronic ibuprofen treatment will cause a folate deficiency. Significance of Depletion : Low levels of folate have been linked to colon cancer, heart disease, cognitive deficits, and birth defects, specifically neural tube defects.4, 5 Deficiency increases chromosome breakage and elevates serum homocysteine.10 Vitamin B9 deficiency may also lead to megaloblastic anemia. The recommended dietary allowance (RDA) for adults is 300 to 600 mcg/day. However, recommendations of doses of folic acid as high as 2000 mcg/day have been reported in the literature. For replacement therapy, doses should be based upon the patient's individual needs, considering the clinical presentation, serum folate levels, age, gender, dietary habits, and medication regimen.

ZINC: Administration of naproxen (250 mg tid) in ten healthy volunteers for either 7 or 14 days resulted in a 35% increase in urinary zinc excretion but serum zinc levels remained unchanged.11 However, another report indicates that serum zinc levels were altered by NSAIDS therapy and decreased to 10.47 mmol/L in patients treated with NSAID'S.12 Significance of Depletion : Clinically, signs and symptoms of zinc deficiency include alopecia, dermatitis, diarrhea, growth retardation, increased susceptibility to infection, and loss of appetite or sense of taste.4, 13 Severe zinc deficiency further impacts dermatologic, gastrointestinal, immune, nervous, reproductive, respiratory, and skeletal systems.4, 14 Doses of zinc up to 50 mg/day may be recommended.14 This upper limit includes an adult's total daily intake, which may be higher than anticipated because of the increasing trend to fortify foods with zinc. It is important to be mindful of this limit, even if decisions are deliberately made to temporarily exceed this level for anticipated pharmacological benefits.

References

  1. Bertschinger P, Zala GF, Fried M. [Effect of non-steroidal antirheumatic agents on the gastrointestinal tract: clinical aspects and pathophysiology]. Schweiz Med Wochenschr. 1996;126(37):1566-1568.
  2. Bjarnason I, Macpherson AJ. Intestinal toxicity of non-steroidal anti-inflammatory drugs. Pharmacol Ther. 1994;62(1-2):145-157.
  3. Davies NM. Toxicity of nonsteroidal anti-inflammatory drugs in the large intestine. Dis Colon Rectum. 1995;38(12):1311-1321.
  4. Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci. 2000;889:87-106.
  5. Covington T, ed. Nonprescription Drug Therapy Guiding Patient Self-Care. St Louis, MO: Facts and Comparisons; 1999: 467-545.
  6. Hines Burnham T, et al, eds. Drug Facts and Comparisons. St Louis, MO: Facts and Comparisons; 2000.
  7. Surrall K, Smith JA, Bird H, Okala B, Othman H, Padwick DJ. Effect of ibuprofen and indomethacin on human plasma melatonin. J Pharm Pharmacol. 1987;39(10):840-843.
  8. Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med. 1998;30:122-130.
  9. Baggott JE, Morgan SL, Ha T, et al. Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J. 1992;282(Pt 1):197-202.
  10. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol. 1996;27(3):517-527.
  11. Elling H, Kiilerich S, Sabro J, Elling P. Influence of a non-steroid anti-rheumatic drug on serum and urinary zinc in healthy volunteers. Scand J Rheumatol. 1980;9:161-163.
  12. Balogh Z, El-Ghobarey AF, Fell GS, et al. Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis. Ann Rheum Dis. 1980;39:329-332.
  13. Falchuk KH. Disturbances in Trace Elements. In: Fauci A, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill Companies Health Professional Division; 1998:490-491.
  14. Hambidge M. Human zinc deficiency. J Nutr. 2000;130(5S Suppl):1344S-1349S.
Jacksonville Medicine / June/July, 2002

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