Rx Side Effects: Unmasking Vitamin Deficiencies Caused by Common Meds

Rx Side Effects: Unmasking Vitamin Deficiencies Caused by Common Meds

Common Meds and Vitamin Deficiencies or Labs to Monitor: 

When it comes to managing your medicines, there’s more than meets the eye! While our various therapies have transformed our lives for the better, allowing us to live healthier and longer lives, these therapies have their side effects. Before you pick up that statin medication, review this article. We’re here to share a few vitamin or nutrient deficiencies that can come up with certain commonly seen medications.

Note that this is a very high-level overview and is not intended to be a comprehensive list for any of these deficiencies. This is also not intended to be specific medical advice – always consult with your provider before starting or stopping a medication or supplement.

Vitamin B12 Deficiency

• Metformin:
  • Long-term use of metformin can lead to vitamin B12 deficiency, which can cause you to feel tired, fatigued, and out of breath. This is especially true for people who have taken this medicine for 4 years or longer, or for people who also have peripheral nerve pain or anemia (not enough red blood cells).
• Acid-lowering agents (i.e. omeprazole, famotidine)
  • Since acid-lowering drugs make the digestive region less acidic, these meds can decrease the absorption of vitamin B12 found in foods. Although an exact timeframe is unclear, one study from JAMA reports this deficiency in patients taking this drug for at least 2 years. This decrease depends on the dose – higher doses of the drugs are associated with less vitamin B12 absorption. Proton pump inhibitors like Prilosec may have a higher association with this deficiency compared to drugs like Pepcid (famotidine) or Tagamet (cimetidine), which work quicker and do not lower acid levels as intensely.
• Oral Contraceptives (i.e. Junel, Ortho Tri-Cyclen)
  • Oral Contraceptives (birth control) have an association with reduced vitamin B12, vitamin B6, and possibly folate levels. A study enrolling over 200 women observed that vitamins B6 and B12 were significantly lower in women taking oral contraceptives compared to the women not taking oral contraceptives.

Vitamin D Deficiency

• Laxatives (i.e. mineral oil)
  • We all might come across the need for the occasional extra “push,” but the regular use of laxatives can decrease the body’s stores of mineral electrolytes and vitamins, including vitamin D. This could lead to issues with joint pain, muscle weakness, and loss of hearing. The tricky part about this issue is that chronic functional constipation is strongly connected to vitamin D deficiency, meaning the real reason you might be reaching for that laxative is to treat a vitamin D problem! 
• Seizure-preventing medications (i.e. carbamazepine, phenytoin)
  • Anti-seizure medications can substantially alter the body’s levels of minerals and electrolytes. Drugs like carbamazepine, phenytoin, and phenobarbital impact the liver’s cytochrome P450 enzyme system, a system crucial towards breaking down products.. This system, amplified to move quicker by these medications, breaks down active vitamin D into more inactive forms – as a result, vitamin D deficiency could occur.
• Steroids (i.e. dexamethasone, prednisone)
  • Steroid hormones impact pretty much everything in your body, from controlling metabolism and development to helping your body fight infections – there’s a lot that can occur. From a vitamin D perspective, there is an association between steroid use and vitamin D deficiency. The exact cause is unknown – steroids can decrease bone formation and calcium absorption from the intestines, which may help reduce vitamin D levels. Similar to anti-seizure meds, steroids may also increase the levels of an enzyme that inactivates vitamin D. 
• Orlistat (weight-loss drug):
  • This popular weight loss drug can reduce a lot more than your BMI. This drug works by blocking the action of lipase, an intestinal enzyme that breaks down fat. This reduces the body’s absorption of fat from foods, but
    “no good deed goes unpunished” – it also prevents the absorption of fat-soluble vitamins like A, E, K, and D. 

Calcium

• Anti-seizure medications
  • While the reasons vary based on the medication, there is a strong association between anticonvulsant drug levels.and decreased calcium in the body. Since vitamin D is needed to absorb calcium, vitamin D deficiencies from these medications further lessens calcium absorption. 
• Steroids 
  • Steroids decrease calcium absorption from the intestine and increase calcium excretion from the body.
• Acid-Lowering Therapies
  • In suppressing acid production, these meds are associated with reducing calcium absorption. This can lead to decreased bone density.

Coenzyme Q10 (CoQ10)

• Beta-blockers (i.e. metoprolol, propranolol)
  • Coenzyme Q10 is an antioxidant found in almost every cell and is needed for producing energy in the body. Beta-blockers have been shown to inhibit CoQ10-dependent enzymes, but little data is available on the severity of this impact.
• Statins (i.e. atorvastatin, pravastatin) and Fibric Acid Derivatives (i.e. gemfibrozil)
  • Statins inhibit the enzyme called HMG-CoA reductase. This enzyme is required to synthesize both cholesterol and CoQ10, resulting in decreased levels of CoQ10, especially with higher statin doses. Decreased CoQ10 levels in the blood are associated with statin-induced muscle pain. However, supplementing CoQ10 does not always improve this pain. Lopid (gemfibrozil), though not inhibiting the same enzyme as statins, has also demonstrated the ability to reduce CoQ10 in a small study.
• Certain diabetes meds (i.e. metformin, glipizide)

Folic Acid (Vitamin B9) Deficiency

• Methotrexate 
  • This medication interferes with your body’s ability to break down folate. While not always the case, standard doses of methotrexate often require folic acid supplementation. Symptoms of folate acid deficiency include paleness, forgetfulness, and palpitations.
• Bactrim (sulfamethoxazole and trimethoprim)
  • Sulfamethoxazole prevents the formation of folic acid, while trimethoprim may lower current levels of folic acid in the body. 
• Oral Contraceptives
  • As mentioned before, folate deficiency has been observed in various studies, although not as conclusively as vitamin B12 or vitamin B6 deficiencies. Some oral contraceptives now include folate to reduce the risk of neural tube defects in pregnancies conceived shortly after discontinuing oral contraceptives, where the drugs still have some activity.

Magnesium Deficiency

• Thiazide (i.e. hydrochlorothiazide, chlorthalidone) and loop diuretics (i.e. bumetanide, furosemide) can result in serious adverse events including muscle spasms, irregular heartbeat, and convulsions.
• Proton Pump Inhibitors (i.e. omeprazole)
  • While the mechanism for this deficiency is not known, proton pump inhibitors might be affecting the magnesium gradient by altering gastric pH, resulting in larger magnesium loss. This is a class effect, but does not seem to occur greatly with drugs like famotidine or cimetidine (histamine blockers). 

Vitamin K Deficiency

Most of the time, we only worry about vitamin K deficiencies in newborns. 

• Some antibiotics (i.e. cephalosporin)
  • This is especially true with use for over 10 days, as these antibiotics may kill helpful bacteria that make vitamin K. Caution should be taken with long-term cephalosporins given to newborns.

Additional Note about Warfarin

• Warfarin
  • Warfarin works by blocking a vitamin K-dependent step in forming clotting factors. Thus, it works against Vitamin K, but does not directly inhibit the vitamin. It’s very important that patients on warfarin continue to take in about the same amount of vitamin K every day, as changes to vitamin K can  impact warfarin and increase the risk of dangerous blood clots..

Skippack Pharmacy carries supplements for all of the vitamins and minerals mentioned in this article, along with many more! If you are searching for a specific supplement, call or visit us for additional information and guidance.

References and Further Reading: 

1. https://www.uspharmacist.com/article/druginduced-nutrient-depletions-what-pharmacists-need-to-know
2. Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Medicine (Baltimore). 2019;98(46):e17918. doi:10.1097/MD.0000000000017918
3. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. doi:10.1001/jama.2013.280490
4. Panarese A, Pesce F, Porcelli P, et al. Chronic functional constipation is strongly linked to vitamin D deficiency. World J Gastroenterol. 2019;25(14):1729-1740. doi:10.3748/wjg.v25.i14.1729
5. Saket S, Varasteh N, Halimi Asl AA, Saneifard H. How Antiepileptics May Change the Serum Level of Vitamin D, Calcium, and Phosphorus in Children with Epilepsy. Iran J Child Neurol. 2021;15(1):19-27. doi:10.22037/ijcn.v15i1.25952
6. Davidson ZE, Walker KZ, Truby H. Clinical review: Do glucocorticosteroids alter vitamin D status? A systematic review with meta-analyses of observational studies. J Clin Endocrinol Metab. 2012;97(3):738-744. doi:10.1210/jc.2011-2757
7. McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy. 2002;22(7):814-822. doi:10.1592/phco.22.11.814.33627
8. Garrido-Maraver J, Cordero MD, Oropesa-Ávila M, et al. Coenzyme q10 therapy. Mol Syndromol. 2014;5(3-4):187-197. doi:10.1159/000360101
9. Florentin M, Elisaf MS. Proton pump inhibitor-induced hypomagnesemia: A new challenge. World J Nephrol. 2012;1(6):151-154. doi:10.5527/wjn.v1.i6.151