1.0 Introduction to Drug-Induced Nutrient Depletion (DIND)

Drug-Induced Nutrient Depletion (DIND) is a critical and often overlooked clinical concept describing the reduction of essential nutrients in the body caused by prescription and non-prescription medications. Coined in the 1990s by pharmacists James B. LaValle and Ross Pelton, the study of DIND has become increasingly important in modern clinical practice. This is largely due to the high prevalence of polypharmacy in the United States, where multiple medication use is common for managing chronic health conditions. Understanding the biochemical impact of pharmaceuticals is no longer an academic exercise but a clinical necessity for comprehensive patient care.

The scale of prescription drug use in the United States is staggering. Total prescription drug sales are projected to reach $1.7 trillion by 2030, and in 2018, nearly 60-70% of insured Americans were regularly taking prescription drugs for a chronic health issue. Many of these individuals take four or more drugs concurrently. This widespread use creates a significant population-level risk for nutrient depletions that can accumulate over months or years of therapy.

The central thesis of DIND is that the gradual depletion of essential vitamins, minerals, and other cofactors can manifest as the very side effects attributed to a medication. If these depleted nutrients are not replenished, this can lead to the worsening of existing symptoms or the development of new chronic health conditions over time. Problems can range from short-term issues like low energy, muscle cramps, and insomnia to long-term conditions such as chronic inflammation, type 2 diabetes, cardiovascular disease, and cognitive decline. Understanding the underlying pathophysiology by which these depletions occur is the first step toward effective clinical intervention.

2.0 The Pathophysiology and Compounding Factors of DIND

Understanding the mechanisms by which medications deplete nutrients is of paramount clinical significance. Many of the side effects commonly associated with a particular drug are often indistinguishable from the symptoms of the specific nutrient deficiencies it induces. This direct correlation provides a powerful framework for anticipating, identifying, and managing adverse drug events through targeted nutritional support. By recognizing this link, practitioners can move beyond simply adding another prescription to manage a side effect and instead address the underlying biochemical imbalance.

A classic example of this phenomenon is the diuretic hydrochlorothiazide. It is well-documented to deplete several key nutrients, including magnesium, potassium, sodium, Coenzyme Q10 (CoQ10), and zinc. The known side effects of this medication include muscle spasms, headaches, increases in blood sugar, and anxiety. These are precisely the clinical symptoms of a magnesium deficiency. When a patient on hydrochlorothiazide presents with muscle cramps, a practitioner aware of DIND would recognize the high probability of magnesium depletion as the root cause, rather than viewing it as an idiopathic side effect of the drug itself.

A patient’s susceptibility to DIND is not solely determined by their medication regimen. Pre-existing lifestyle and dietary factors can create a state of functional nutritional deficiency, lowering their baseline and making them more vulnerable to the clinical consequences of drug-induced depletions.

• Prevalence of Nutrient Deficiencies: The average American diet often fails to provide adequate nutrition. Studies report that almost 10% of the U.S. population has one or more nutrient deficiencies, creating a suboptimal nutritional foundation before any medication is even prescribed.
• Poor Dietary Habits: A significant portion of the population does not meet basic dietary guidelines. Approximately 75% of Americans do not consume the recommended intake of fruit, and over 80% do not consume the recommended intake of vegetables.
• Chronic Stress: Modern life places significant demands on the body’s nutrient stores. Chronic stress, whether physical, mental, or emotional, increases the metabolic demand for key nutrients such as B vitamins, vitamin C, vitamin D, and magnesium.
• Environmental Toxin Exposure: Exposure to environmental toxins from pollution, pesticides, and heavy metals increases the body’s need for specific nutrients like selenium and the cofactors required to produce glutathione, a critical antioxidant for detoxification.
• Impaired Nutrient Absorption: Many individuals suffer from pre-existing digestive issues that impair nutrient absorption. This can be compounded by the use of certain medications, such as antacids, which alter the gastric environment and further reduce the uptake of essential minerals and vitamins.

These compounding factors establish a low nutritional baseline, meaning many patients are already in a state of subclinical or functional nutrient deficiency. When a medication that further depletes these same nutrients is introduced, the patient is far more likely to experience clinically significant symptoms and adverse effects. This reality makes a baseline nutritional assessment an indispensable component of a responsible prescribing process.

3.0 Analysis of Major Pharmaceutical Classes and Associated Nutrient Depletions

This section provides a systematic review of the most commonly prescribed pharmaceutical categories and their potential to induce specific nutrient depletions. For each drug class, the associated DIND profile will be detailed, outlining the nutrients at risk and the potential clinical ramifications for the patient. Recognizing these patterns allows clinicians to anticipate and mitigate adverse effects through targeted nutritional support.

3.2.1 Gastrointestinal Agents

Gastrointestinal agents, particularly antacids and acid-suppressing medications, are among the most widely used drugs, with antacid sales exceeding 10 billion dollars annually in the U.S. Their mechanism of action, which involves altering gastric pH, directly impacts the absorption of numerous essential nutrients.

3.2.2 Cardiovascular and Renal Agents

Cardiovascular drugs are the most prescribed class of medications in the United States, used to manage conditions like hypertension and hyperlipidemia. Many of these agents, especially diuretics and statins, have well-documented impacts on mineral and coenzyme balance.

3.2.3 Endocrine and Metabolic Agents

Medications that modulate the endocrine system are widely prescribed. According to CDC data from 2015–2017, 12.6% of women aged 15–49 in the United States were using oral contraception, and over 44% of postmenopausal women reported using some form of hormone replacement therapy (HRT). These agents can significantly alter the metabolic pathways of numerous vitamins and minerals.

3.2.4 Anti-inflammatory and Analgesic Agents

This category includes some of the most frequently used over-the-counter (OTC) and prescription drugs for pain and inflammation. For instance, more than 60 million Americans consume acetaminophen weekly, and between 70-90% of people aged 65 and older use NSAIDs at least once a week. Chronic use places a high demand on the body’s nutrient stores for tissue repair and detoxification.

3.2.5 Central Nervous System Agents

Medications targeting the central nervous system have a significant market presence, with antidepressants accounting for over $14 billion in sales in 2017. Their use is widespread; for example, about 31 million adults in the US (1 in 8) reported taking benzodiazepines in the last year. These drugs alter neurochemistry and can interfere with the synthesis and metabolism of nutrient-dependent cofactors.

3.2.6 Antimicrobial Agents

Antibiotics are a cornerstone of modern medicine, with 266.1 million courses dispensed to outpatients in U.S. community pharmacies in 2014 alone. While essential for treating infections, their primary collateral effect is the disruption of the gut microbiome, which is responsible for synthesizing and aiding in the absorption of many key nutrients.

A related and equally important concern is the direct effect of many drugs on the gut microbiome.

4.0 Drug-Induced Microbiome Disruption (DIMD): A Related Clinical Concern

Drug-Induced Microbiome Disruption (DIMD) describes the disturbance of the body’s beneficial microflora caused by certain medications. This concept is strategically linked to DIND because a healthy microbiome is essential for both the synthesis of certain vitamins and the proper absorption of nutrients from the diet. When the microbiome is disrupted, it can exacerbate existing nutrient depletions or create new ones, profoundly impacting a patient’s overall metabolic homeostasis.

The systemic consequences of DIMD are far-reaching, as the gut microbiome plays a central role in regulating numerous physiological processes. A disruption in this delicate ecosystem can affect:

• Nutrient absorption
• Gut-Immune-Brain signaling
• Blood glucose balance and insulin resistance
• Hormonal balance (sex, thyroid, appetite, stress)
• Sleep
• Detoxification
• Inflammatory processes

A surprising number of non-antibiotic drugs have been found to impact the gut microbiome. Practitioners should be aware of the potential for DIMD when prescribing medications from the following classes.

Common Drug Classes Implicated in DIMD

• Antibiotics
• NSAIDs (non-steroidal anti-inflammatory drugs)
• Corticosteroids
• Oral Contraceptives / Hormone Replacement Therapy (OCs/HRT)
• Proton Pump Inhibitors (PPIs) / H2 blockers
• Metformin
• Statins
• Antipsychotics
• Opioids

Understanding the dual risks of DIND and DIMD is essential for modern clinical practice. Identifying these problems, however, is only the first step; the critical next phase is implementing effective strategies to manage and mitigate them.

5.0 Clinical Application: Mitigation and Management Strategies

Knowledge of Drug-Induced Nutrient Depletion (DIND) and Drug-Induced Microbiome Disruption (DIMD) becomes clinically valuable only when it is translated into proactive patient care. An awareness of these phenomena provides practitioners with a framework to anticipate and protect patients from the potential downstream consequences of long-term medication use. This section outlines a direct and logical approach to mitigation.

The primary strategy for managing DIND is straightforward: identify which essential nutrients are likely to be depleted by a patient’s specific medication regimen and then implement a plan to replenish those nutrients through diet and targeted supplementation. This proactive approach can help prevent the onset of deficiency symptoms, reduce the incidence of side effects, and support the body’s overall biochemical resilience.

Implementing this strategy requires a personalized assessment of a patient’s medications. Below are specific, actionable examples based on common prescribing scenarios:

• For patients on Proton Pump Inhibitors (PPIs) or other acid-blocking drugs: These medications are known to impair the absorption of multiple nutrients. Recommending a quality multiple vitamin/mineral supplement is a crucial first step. The supplement should contain key nutrients at risk, including vitamin B12, folic acid, calcium, vitamin D, iron, and zinc.
• For patients on statins or beta-blockers: These cardiovascular drugs are well-documented to deplete Coenzyme Q10 and interfere with melatonin production. Supplementation with Coenzyme Q10 (100-300mg daily) can support cardiovascular and muscle health, while Melatonin (3-15mg at bedtime) can help mitigate potential sleep disturbances.
• For patients taking antibiotics or other microbiome-disrupting drugs: To counter the effects of DIMD, the use of a probiotic supplement is a logical intervention. While some protocols recommend starting probiotics after the course of antibiotics is complete to avoid immediate destruction of the probiotic bacteria, many clinicians advocate for co-administration, advising the patient to take the probiotic at least 2-3 hours apart from the antibiotic dose to support the microbiome throughout treatment.

By proactively managing nutrient status, clinicians can enhance a medication’s therapeutic efficacy and safety profile, ensuring the treatment solves a problem without creating a new one.

6.0 Conclusion

Drug-Induced Nutrient Depletion (DIND) is a common, clinically significant, and frequently overlooked consequence of long-term medication use. The high prevalence of polypharmacy ensures that a substantial portion of the patient population is at risk. As this paper has detailed, the biochemical disruptions caused by DIND are not trivial; they can lead to a wide array of symptoms, worsen existing conditions, and contribute to the development of new chronic diseases over time.

A key takeaway for the practicing clinician is the direct correlation between many reported drug side effects and the classic symptoms of the nutrient deficiencies that these same drugs induce. This recognition transforms the clinical paradigm from one of reactive symptom management—often with additional prescriptions—to a proactive strategy of addressing the underlying nutritional imbalance.

Ultimately, this understanding calls for a more integrative clinical approach. Healthcare professionals who actively anticipate and manage medication side effects by supporting the body’s biochemistry with appropriate dietary and supplemental interventions are better positioned to improve patient outcomes. This proactive management can enhance medication tolerance, improve quality of life, and potentially reduce the cascade of polypharmacy that often begins when a side effect is mistaken for a new, unrelated medical condition.

7.0 References

1. Statista. Total revenue of the pharmaceutical market worldwide from 2001 to 2021, with a forecast for 2024. Available at: www.statista.com. Accessed April 2020.
2. Rapaport L. The danger in taking prescribed medications. U.S. News & World Report. September 27, 2016. Available at: https://health.usnews.com/health-news/patient-advice/articles/2016-09-27/the-danger-in-taking-prescribed-medications. Accessed April 2020.
3. Centers for Disease Control and Prevention (CDC). Therapeutic Drug Use. NCHS Data Brief No. 334, February 2019. Available at: www.cdc.gov. Accessed April 2020.
4. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200-1205.
5. Coleman JJ. Adverse drug reactions. Clin Med (Lond). 2016;16(5):481-485.
6. Centers for Disease Control and Prevention (CDC). Drug Overdose Deaths. Available at: www.cdc.gov. Accessed April 2020.
7. Centers for Disease Control and Prevention (CDC). National Poison Data System. Available at: www.cdc.gov. Accessed April 2020.
8. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Available at: https://health.gov/dietaryguidelines/2015/. Accessed April 2020.
9. Bastard JP, Ceperuelo-Mallafré V, Clément K, et al. Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications. Aliment Pharmacol Ther. 2018;47(3):332-345.
10. Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555:623-628.
11. Centers for Disease Control and Prevention (CDC). Outpatient Antibiotic Prescriptions — United States, 2014. Available at: www.cdc.gov. Accessed May 2020.
12. Centers for Disease Control and Prevention (CDC). Antibiotic Use in the United States, 2017: Progress and Opportunities. Available at: www.cdc.gov. Accessed May 2020.
13. Vilhelmsson A, Svensson T, Meeuwisse A, et al. Reports on psychiatric adverse drug reactions with antidepressant medications. BMC Clin Pharmacol. 2011;11:16.
14. American Psychiatric Association. Benzodiazepine Use and Misuse. Available at: www.psychiatry.org. Accessed May 2020.
15. Greenblatt DJ. Benzodiazepine hypnotics: sorting the pharmacodynamic facts. J Clin Psychiatry. 1991;52(9, suppl):4–10.
16. American Psychiatric Association. APA Poll on Benzodiazepine Use. Available at: www.psychiatry.org. Accessed May 2020.
17. Erviti J, Gorricho J, Salvo F, et al. Oral bisphosphonates may not decrease hip fracture risk in elderly Spanish women: a nested case-control study. BMJ Open. 2013;3(2):e002084.
18. Centers for Disease Control and Prevention (CDC). National Diabetes Statistics Report, 2020. Available at: www.cdc.gov. Accessed May 2020.
19. Nichols GA, Hillier TA, Brown JB. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis. Am J Med. 2008;121(6):519-524.
20. Statista. Number of metformin prescriptions in the U.S. from 2004 to 2019. Available at: www.statista.com. Accessed April 2020.
21. Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.
22. Centers for Disease Control (CDC). NCHS Data Brief, Number 328, January 2019. Available at: www.cdc.gov. Accessed March 2019.
23. UC Berkeley School of Public Health. Don’t Go Overboard With Ibuprofen. Health & Wellness Alerts. Available at: https://www.healthandwellnessalerts.berkeley.edu/topics/dont-go-overboard-with-ibuprofen/. Accessed May 2020.
24. Centers for Disease Control and Prevention (CDC). Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants — United States, 2015–2016. MMWR 2018;67:349–358. Accessed May 2020.
25. Centers for Disease Control and Prevention. Vital Signs: Changes in Opioid Prescribing in the United States, 2006–2015. MMWR. 2017; 66(26):697-704.
26. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318(10):927-938.
27. Mahabaleshwarkar RK, Yang Y, Datar MV, et al. Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients. Curr Med Res Opin. 2013;29(4):315-323.
28. MacKenzie JF, Russell RI. The effect of pH on folic acid absorption in man. Clin Sci Mol Med. 1976;51(4):363-368.
29. O’Neil-Cutting MA, Crosby WH. The effect of antacids on the absorption of simultaneously ingested iron. JAMA. 1986;255(11):1468-1470.
30. Bell RG. Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K-epoxide cycle. Fed Proc. 1978;37(12):2599-2604.
31. Brion M, Lambs L, Berthon G. Metal ion-tetracycline interactions in biological fluids. Part 5. Formation of zinc complexes with tetracycline and some of its derivatives and assessment of their biological significance. Agents Actions. 1985;17(2):229-242.
32. Brodie MJ, Boobis AR, Hillyard CJ, et al. Rifampicin and vitamin D metabolism. Clin Pharmacol Ther. 1980;27(6):810-814.
33. Cummings JH, Macfarlane GT. Role of intestinal bacteria in nutrient metabolism. JPEN J Parenter Enteral Nutr. 1997;21(6):357-365.
34. Jacobson ED, Faloon WW. Malabsorptive effects of neomycin in commonly used doses. JAMA. 1961;175:187-190.
35. Kahn SB, Fein S, Brodsky I, et al. Effects of trimethoprim on folate metabolism in man. Clin Pharmacol Ther. 1968;9(5):550-560.
36. Robinson C, Weigley E. Basic Nutrition and Diet Therapy. New York, NY: MacMillan; 1984:46-54.
37. Solecki TJ, Aviv A, Bogden JD. Effect of a chelating drug on balance and tissue distribution of four essential metals. Toxicology. 1984;31(3-4):207-216.
38. Toppet M, Van-Laethem Y, Clumeck N, et al. Sequential development of vitamin D metabolites under isoniazid and rifampicin therapy. Arch Fr Pediatr. 1988;45(2):145-148.
39. Zietse R, Zoutendijk R, Hoorn EJ. Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol. 2009;5(4):193-202.
40. Bell IR, Edman JS, Morrow FD, et al. Brief communication: Vitamin B1, B2, and B6 augmentation of tricyclic antidepressant treatment in geriatric depression with cognitive dysfunction. J Am Coll Nutr. 1992;11(2):159-163.
41. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007;167(12):1240-1245.
42. Edelbroek PM, Linssen AC, Zitman FG. Amitriptyline metabolism in relation to antidepressive effect. Clin Pharmacol Ther. 1984;35(4):467-473.
43. Haney EM, Chan BK, Diem SJ, et al. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007;167(12):1246-1251.
44. Richards JB, Papaioannou A, Adachi JD, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188-194.
45. Tinguely D, Sener A, Lejeune F, et al. Determination of compliance with riboflavin in an antidepressive therapy. Arzneimittelforschung. 1985;35(2):536-538.
46. Adams JF, Clark JS, Ireland JT, et al. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia. 1983;24(1):16-18.
47. de Groot-Kamphuis DM, van Dijk PR, Groenier KH, et al. Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin. Neth J Med. 2013;71(7):386-390.
48. Kishi T, Kishi H, Watanabe T, Folkers K. Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus. J Med. 1976;7(3-4):307-321.
49. al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis. 1994;24(5):737-752.
50. Brady JA, Rock CL, Horneffer MR. Thiamin status, diuretic medications, and the management of congestive heart failure. J Am Diet Assoc. 1995;95(5):541-544.
51. Golik A, Zaidenstein R, Dishi V, et al. Zinc metabolism in patients treated with captopril versus enalapril. Metabolism. 1990;39(7):665-667.
52. Hanze S, Satter H. Studies of the effect of the diuretics furosemide, ethacrynic acid and triamterene on renal magnesium and calcium excretion. Klin Wochenschr. 1967;45(6):313-314.
53. Kishi H, Kishi T, Williams RH, Folkers K. Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q-enzymes by clinically used anti-hypertensive drugs. Res Commun Chem Pathol Pharmacol. 1975;12(3):533-540.
54. Kishi H, Kishi T, Folkers K. Bioenergetics in clinical medicine. III. Inhibition of coenzyme Q10-enzymes by clinically used anti-hypertensive drugs. Res Commun Chem Pathol Pharmacol. 1975;12(3):533-540.
55. 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(1):157-164.
56. Kupfer S, Kosovsky JD. Effects of cardiac glycosides on renal tubular transport of calcium, magnesium, inorganic phosphate and glucose in the dog. J Clin Invest. 1965;44:1132-1143.
57. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs. 1985;30(2):145-155.
58. Lindeman RD. Hypokalemia: causes, consequences and correction. Am J Med Sci. 1976;272(1):5-17.
59. Mydlik M, Derzsiova K, Zemberova E. Metabolism of vitamin B6 and its requirement in chronic renal failure. Kidney Int Suppl. 1997;62:S56-S59.
60. Palva IP, Salokannel SJ, Timonen T, et al. Drug-induced malabsorption of vitamin B12. IV. Malabsorption and deficiency of B12 during treatment with slow-release potassium chloride. Acta Med Scand. 1972;191(4):355-357.
61. Reyes AJ. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J. 1983;64(24):936-941.
62. Rosen RC, Kostis JB, Jekelis AW. Beta-blocker effects on sexual function in normal males. Arch Sex Behav. 1988;17(3):241-255.
63. Schwinger RH, Böhm M, Erdmann E. Heart failure and electrolyte disturbances. Methods Find Exp Clin Pharmacol. 1992;14(4):315-325.
64. Seligmann H, Halkin H, Rauchfleisch S, et al. Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med. 1991;91(2):151-155.
65. Vidrio H. Interaction with pyridoxal as a possible mechanism of hydralazine hypotension. J Cardiovasc Pharmacol. 1990;15(1):150-156.
66. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand. 1980;208(3):209-212.
67. Colquhoun DM, Jackson R, Walters M, et al. Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. Eur J Clin Invest. 2005;35(4):251-258.
68. Harris JI, Hibbeln JR, Mackey RH, et al. Statin treatment alters serum n-3 and n-6 fatty acids in hypercholesterolemic patients. Prostaglandins Leukot Essent Fatty Acids. 2004;71(4):263-269.
69. Ghayour-Mobarhan M, Lamb DJ, Taylor A, et al. Effect of statin therapy on serum trace element status in dyslipidemic subjects. J Trace Elem Med Biol. 2005;19(1):61-67.
70. Beltowski J, Wójcicka G, Jamroz-Wiśniewska A. Adverse effects of statins – mechanisms and consequences. Curr Drug Saf. 2009;4(3):209-228.
71. Mossmann B, Behl C. Selenoprotein synthesis and side-effects of statins. Lancet. 2004;363(9412):892-894.
72. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA. 1990;87(22):8931-8934.
73. Delgado-López F, Bautista-Lorite J, Villamil-Fernández F. [Worsening for using statin in carnitine palmityl transferase deficiency myopathy]. Rev Neurol. 2004;38(11):1095.
74. Bhuiyan J, Seccombe DW, Bhagavan N. The effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition on tissue levels of carnitine and carnitine acyltransferase activity in the rabbit. Lipids. 1996;31(8):867-870.
75. Folkers K. Basic chemical research on coenzyme Q-10 and integrated clinical research on therapy of diseases. In: Lenaz G, ed. Coenzyme Q. John Wiley & Sons; 1985.
76. Ghirlanda G, Oradei A, Manto A, et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol. 1993;33(3):226-229.
77. Lamperti C, Naini AB, Lucchini V, et al. Muscle coenzyme Q10 level in statin-related myopathy. Arch Neurol. 2005;62(11):1709-1712.
78. Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med. 1997;18(Suppl):S137-S144.
79. Roe DA. Drug-Induced Nutritional Deficiencies. 2nd ed. Westport, CT: Avi Publishing; 1985:158-159.
80. Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. BMC Med. 2013;11:57.
81. Šulcová J, Štulc T, Hill M, et al. Decrease in dehydroepiandosterone level after fibrate treatment in males with hyperlipidemia. Physiol Res. 2005;54(2):151-157.
82. Ahmed F, Bamji MS, Iyengar L. Effect of oral contraceptive agents on vitamin nutrition status. Am J Clin Nutr. 1975;28(6):606-615.
83. Bhagavan HN, Brin M. Drug-vitamin B6 interaction. Curr Concepts Nutr. 1983;12:1-12.
84. Blum M, Kitai E, Ariel Y, et al. Oral contraceptive lowers serum magnesium. Harefuah. 1991;121(10):363-364.
85. Butterworth CE Jr, Hatch KD, Gore H, et al. Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. Am J Clin Nutr. 1982;35(1):73-82.
86. Dorea JG, Ferraz E, de Queiroz EF. Effects of anovulatory steroids on serum levels of zinc and copper. Arch Latinoam Nutr. 1982;32(1):101-110.
87. Haspels AA, Coelingh Bennink HJ, van Keep PA. Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women. Maturitas. 1978;1(1):15-20.
88. Miller LT. Do oral contraceptive agents affect nutrient requirements–vitamin B-6? J Nutr. 1986;116(7):1344-1345.
89. Nash AL, Cornish EJ, Hain R, et al. Metabolic effects of oral contraceptives containing 30 micrograms and 50 micrograms of oestrogen. Med J Aust. 1979;2(6):277-281.
90. Prasad AS, Lei KY, Oberleas D, et al. Effect of oral contraceptives on nutrients. III. Vitamins B6, B12, and folic acid. Am J Obstet Gynecol. 1976;125(8):1063-1069.
91. Rivers JM. Oral contraceptives and ascorbic acid. Am J Clin Nutr. 1975;28(5):550-554.
92. Shaarawy M, Fayad M, Nagui AR, et al. Serotonin metabolism and depression in oral contraceptive users. Contraception. 1982;26(2):193-204.
93. Shojania AM. Oral contraceptives: effect of folate and vitamin B12 metabolism. Can Med Assoc J. 1982;126(3):244-247.
94. Matsui MS, Rozovski SJ. Drug-nutrient interaction. Clin Ther. 1982;4(6):423-440.
95. Thorp VJ. Effect of oral contraceptive agents on vitamin and mineral requirements. J Am Diet Assoc. 1980;76(6):581-584.
96. Webb JL. Nutritional effects of oral contraceptive use: a review. J Reprod Med. 1980;25(4):150-156.
97. Becker GL. The case against mineral oil. Am J Dig Dis. 1952;19:344.
98. Faloon WW. Drug production on intestinal malabsorption. N Y State J Med. 1970;70:2189.
99. Gaginella TS. Drug-induced malabsorption. Drug Therapy. 1985;Dec:88.
100. Ritsema GH, Eilers G. Potassium supplements prevent serious hypokalaemia in colon cleansing. Clin Radiol. 1994;49(12):874-876.
101. Jara A, Lee E, Stauber D, et al. Phosphate depletion in the rat: effect of bisphosphonates and the calcemic response to PTH. Kidney Int. 1999;55(4):1434-1443.
102. Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc. 2009;84(7):632-637.
103. Simmons C, Amir E, Dranitsaris G, et al. Altered calcium metabolism in patients on long-term bisphosphonate therapy for metastatic breast cancer. Anticancer Res. 2009;29(7):2707-2711.
104. Kalyan S, Huebbe P, Esatbeyoglu T, et al. Nitrogen-bisphosphonate therapy is linked to compromised coenzyme Q10 and vitamin E status in postmenopausal women. J Clin Endocrinol Metab. 2014;99(4):1307-1313.
105. Aloisi AM, Buonocore M, Merlo L, et al. Chronic pain therapy and hypothalamic-pituitary-adrenal axis impairment. Psychoneuroendocrinology. 2011;36(7):1032-1039.
106. Bawor M, Bami H, Dennis BB, et al. Testosterone suppression in opioid users: a systematic review and meta-analysis. Drug Alcohol Depend. 2015;150:1-9.
107. Beam J, Gupta R, Stewart D, et al. Sulphatoxymelatonin excretion during opiate withdrawal: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(4):877-881.
108. Leedman PJ, Stein AR, Chin WW, Rogers JT. Thyroid hormone modulates the interaction between iron regulatory proteins and the ferritin mRNA iron-responsive element. J Biol Chem. 1996;271(20):12017-12023.
109. Adachi Y, Shiota T, Tsukamoto Y, et al. Bone mineral density in patients taking H2-receptor antagonist. Calcif Tissue Int. 1998;62(4):283-285.
110. Akrivos F, Hadjipetrou L, Laussac JP. An assessment of the physiological significance of cimetidine interactions with copper and zinc in biofluids as based on the computer-simulated distribution of the involved complexes at therapeutic levels of the drug. Agents Actions. 1984;15(5-6):649-659.
111. Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H2-receptor antagonists. Med Toxicol Adverse Drug Exp. 1988;3(6):430-448.
112. Belaiche J, Cattan D, Zittoun J, et al. [Effect of ranitidine on secretion of gastric intrinsic factor and absorption of vitamin B12]. Gastroenterol Clin Biol. 1983;7(4):381-384.
113. Bellou A, Aimone-Gastin I, De Korwin JD, et al. Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy. J Intern Med. 1996;240(3):161-164.
114. Bengoa JM, Bolt MJ, Rosenberg IH. Hepatic vitamin D 25-hydroxylase inhibition by cimetidine and isoniazid. J Lab Clin Med. 1984;104(4):546-552.
115. Bo-Linn GW, Davis GR, Buddrus DJ, et al. An evaluation of the importance of gastric acid secretion in the absorption of dietary calcium. J Clin Invest. 1984;73(3):640-647.
116. Campbell NR, Kara M, Hasinoff BB, et al. Ferrous sulfate reduces cimetidine absorption. Dig Dis Sci. 1993;38(5):950-954.
117. Caron P, Cales P, D’Amour P, et al. [Cimetidine treatment of primary hyperparathyroidism]. Biomed Pharmacother. 1987;41(3):143-146.
118. Fashner J, Gitu AC. Common gastrointestinal symptoms: risks of long-term proton pump inhibitor therapy. FP Essent. 2013;413:29-39.
119. Festen HP. Intrinsic factor secretion and cobalamin absorption. Physiology and pathophysiology in the gastrointestinal tract. Scand J Gastroenterol Suppl. 1991;188:1-7.
120. Force RW, Nahata MC. Effect of histamine H2-receptor antagonists on vitamin B12 absorption. Ann Pharmacother. 1992;26(10):1283-1286.
121. Geller JL, Adams JS. Proton pump inhibitor therapy and hip fracture risk. JAMA. 2007;297(13):1429.
122. Ghishan FK, Walker F, Meneely R, et al. Intestinal calcium transport: effect of cimetidine. J Nutr. 1981;111(12):2157-2161.
123. Gluszek J, Kwasniewska M, Wysocki M, et al. [Effect of intravenous administration of cimetidine on renal excretion of calcium, phosphates, magnesium and adenosine cyclic monophosphate]. Pol Tyg Lek. 1990;45(40-41):817-819.
124. Håkanson R, Böttcher G, Ekblad E, et al. Elevated serum gastrin after food intake or acid blockade evokes hypocalcemia. Regul Pept. 1990;28(2):131-136.
125. Johnson GJ, Esser KA, Krawitt EL. Long-term treatment of systemic mastocytosis with histamine H2 receptor antagonists. Am J Gastroenterol. 1980;74(6):485-489.
126. Joshaghani H, Amirani T, Vaghari G, et al. Effects of omeprazole consumption on serum levels of trace elements. J Trace Elem Med Biol. 2012;26(4):234-237.
127. Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton-pump inhibitors–a review. Neth J Med. 2009;67(5):169-172.
128. Line D, Bourgeay-Causse M, Thomas M, et al. [Primary hyperparathyroidism. Lack of effect of cimetidine on plasma levels of parathyroid hormone and calcium]. Presse Med. 1984;13(12):727-730.
129. Broeren MA, Geerdink EA, Vader HL, van den Wall Bake AW. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med. 2009;151(10):755-756.
130. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med. 1994;120(3):211-215.
131. Merenich JA, Klements UH, Shaker JL, et al. Failure of cimetidine to reduce postoperative hypocalcemia in patients with primary hyperparathyroidism undergoing neck exploratory operation. Surgery. 1993;113(6):619-623.
132. Odes HS. Effect of cimetidine on hepatic vitamin D metabolism in humans. Digestion. 1990;46(2):61-64.
133. Partlow ES, Campbell NR, Chan SC, et al. Ferrous sulfate does not reduce serum levels of famotidine or cimetidine after concurrent ingestion. Clin Pharmacol Ther. 1996;59(4):389-393.
134. Pinelli A, Trivulzio S, Scarpati P, et al. Antiprostatic effect associated with zinc depletion in cimetidine-treated rats. Pharmacol Res Commun. 1988;20(4):329-335.
135. Russell RM, Dutta SK, Golner B, et al. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med. 1988;112(4):458-463.
136. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B12. Scand J Gastroenterol. 1982;17(1):129-131.
137. Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr. 1994;13(6):584-591.
138. Schenk BE, Festen HP, Kuipers EJ, et al. Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin. Aliment Pharmacol Ther. 1996;10(4):541-545.
139. Skikne BS, Lynch SR, Cook JD. Role of gastric acid in food iron absorption. Gastroenterology. 1981;81(6):1068-1071.
140. Steinberg WM, King CE, Toskes PP. Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. Dig Dis Sci. 1980;25(3):188-191.
141. Stewart CA, Termanini B, Sutliff VE, et al. Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. Aliment Pharmacol Ther. 1998;12(1):83-98.
142. Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr. 1991;10(4):372-375.
143. Termanini B, Gibril F, Sutliff VE, et al. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med. 1998;104(5):422-430.
144. 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(4):422-428.
145. Walan A, Ström M, Bodemar G. Metabolic consequences of reduced gastric acidity. Scand J Gastroenterol Suppl. 1985;111:24-30.
146. Wyatt CL, Jensen LS, Rowland GN 3rd. Effect of cimetidine on eggshell quality and plasma 25-hydroxycholecalciferol in laying hens. Poult Sci. 1990;69(11):1892-1899.
147. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-2953.