Expert insights on latest evidence and effects of vitamin D3 drug interactions

By: DSM Pharma Solutions Editors

The current vitamin D landscape 

The current pandemic has highlighted the importance of vitamin D3 (or cholecalciferol) for immune health. Evidence shows that people with underlying chronic medical conditions are at increased risk of COVID-19 infection. They are also often using multiple medication and several of these drugs are known to interfere with vitamin D metabolism. 

DSM recently hosted a webinar detailing the consequences of vitamin D3 drug interactions and how the administration of vitamin D3 can improve the pharmacological action of some drugs. The event reflected on a number of relevant topics such as the importance of healthcare professionals’ awareness and knowledge regarding which drug treatments would benefit from vitamin D supplementation. The webinar was held by renowned expert Dr Diane L. McKey, Director of Tufts University’s Friedman Online Graduate Certificate Programs, and Assistant Professor in the Friedman School of Nutrition Science and Policy, at the Tufts School of Medicine.

Why adequate vitamin D status is important

Vitamin D can be obtained either from the diet or through UV-activated synthesis in the skin. It is involved in the regulation of blood calcium and phosphate levels, bone growth and maintenance, cell differentiation, and gene expression1. Causes of vitamin D deficiency include reduced sun exposure, skin pigmentation, genetic polymorphisms, and/ or inadequate intake. Vitamin D deficiency is prevalent worldwide and concerns a considerable number of people. Using a definition of <20 ng/mL, up to a third of the world’s population is deficient, while severe vitamin D deficiency, defined as <12 ng/mL, is seen in approximately 7% of the population worldwide2.

Epidemiological studies have found an association between autoimmune diseases and insufficient vitamin D levels3. Although differences may be due to genetic and lifestyle factors other than vitamin D levels, data link lower vitamin D serum levels, increasing latitude, and decreased sunlight exposure with a higher prevalence of autoimmune inflammatory diseases. Age-related systemic inflammation, so-called “inflammaging”, is another condition associated with depleted vitamin D4. These correlations between inflammation and vitamin D levels suggest a promising role for vitamin D supplementation. 

Download our new whitepaper for onward reading on the potential of vitamin D3 as an important and safe adjuvant therapy.

Critical vitamin D3-drug interactions 

Several commonly prescribed medications have a negative impact on vitamin D status. Medications most likely to affect the status or actions of vitamin D3 include those used to manage hyperlipidemia, arthritis, diabetes, depression, asthma, and COPD5. Statin therapy in hyperlipidemics is central to cholesterol management and risk reduction for coronary heart disease and related mortality. Unfortunately, statin-induced muscle symptoms (SAMS) occur in up to 10% of patients and are one of the most common causes of statin noncompliance and discontinuation. The prevalence of SAMS is associated with low vitamin D status6. Randomized controlled trials are necessary to establish whether vitamin D3 supplementation reduces the risk of statin-associated myalgia.

Thiazolidinedione antidiabetics are associated with fractures and low bone mineral density (BMD), especially in women. Dietary intake of nutrients critical for bone health, including vitamin D, is reported to be insufficient in T2DM patients on antidiabetics. Combined treatment of vitamin D3 and pioglitazone may be more effective in improving BMD and bone metabolism than vitamin D or pioglitazone alone in type 2 diabetic nephropathy patients (of note, patients with nephrotic syndrome are predisposed to bone disease, which results from imbalances of calcium and vitamin D metabolism)7. Bone health has also been shown to be compromised in patients who use selective serotonin reuptake inhibitors8.

Corticosteroids are commonly used to treat arthritis, asthma, allergies, and other inflammatory conditions. Evidence indicates that exposure to glucocorticoids (a class of corticosteroids) increases the risk of bone loss and fractures, and corticosteroids are the leading cause of secondary osteoporosis. Supplementation with calcium and vitamin D3 has a significant effect on reducing the risk of hip and nonvertebral fractures9, consistent with guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis10. Reduced serum vitamin D levels are associated with impaired lung function, increased airway hypersensitivity response, and reduced corticosteroid response. Some studies of patients with asthma suggest that vitamin D supplementation may improve asthma severity and treatment response11

Recommended dose for vitamin D3 supplementation

Vitamin D supplementation may play an important role in reducing the likelihood of adverse effects in patients who require long-term treatment for the above-mentioned chronic diseases. Despite the many potentially beneficial applications for vitamin D supplementation, there is currently no international consensus on the recommended dosage for vitamin D3 intake, and dietary reference values in healthy individuals vary per country and per age group12. Individual differences exist in the resulting increase in vitamin D levels depending on baseline serum level and sun exposure, treatment duration, and genetic background. To raise the blood level of vitamin D consistently above the sufficient level of 75 nmoL/L may require an intake of at least 2000 IU/day in patients at risk of vitamin D deficiency according to the Endocrine Society13. Higher doses of 10,000 to 50,000 IU/day may be necessary to replenish vitamin D in severely deficient patients, which needs to be done under careful monitoring in a clinical setting14.

Including vitamin D3 supplementation into standard of care

Vitamin D3 is an important nutrient of concern to public health worldwide that affects a considerable proportion of the population. Deficient or insufficient levels of circulating vitamin D are not only due to low dietary intake or lack of sun exposure; long-term or chronic use of medications prescribed for highly prevalent chronic conditions is an important but underappreciated and under-recognized contributing factor, especially in the context of an aging population. High quality intervention trials are needed to better understand the clinical relevance and clinical importance of these drug-nutrient interactions, as are appropriate guidelines for clinicians. 

In the opinion of Dr McKay, the next steps for integrating vitamin D3 into certain therapies should be to promote awareness among healthcare professionals and to adequately train medical students on the nutritional needs of patients. Moreover, guidelines for the care of chronic diseases requiring long-term use of medications that interfere with vitamin D3 metabolism, particularly statins and corticosteroids, should recommend vitamin D3 supplementation. Elderly adults in nursing homes or assisted living facilities are a prime opportunity for vitamin D3 supplementation interventions. Healthcare practitioners should be more aware of which patients might be susceptible to vitamin D deficiency and could monitor those who are on supplements in order to guide appropriate dosing and avoid adverse effects.

There are many innovation opportunities for vitamin D3 supplementation to ameliorate the effects of drugs, improve treatment outcomes, and meet evolved market needs. With more than 70 years of experience in producing and securing the supply of active pharmaceutical ingredients, DSM has become a trusted partner in the development of life-changing therapies that safely and efficiently improve people’s lives - today and tomorrow. 

Partner with us, to grow and win in the fast-evolving vitamin D market.

Published on

07 April 2021

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References

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  2. Giustina, A. et al. Controversies in Vitamin D: A Statement From the Third International Conference. JBMR Plus 4, e10417 (2020).
  3. Illescas-Montes, R., Melguizo-Rodríguez, L., Ruiz, C. & Costela-Ruiz, V. J. Vitamin D and autoimmune diseases. Life Sci 233, 116744 (2019).
  4. Gonçalves de Carvalho, C. M. & Ribeiro, S. M. Aging, low-grade systemic inflammation and vitamin D: a mini-review. Eur J Clin Nutr 71, 434-440 (2017).
  5. CDC/NCHS National Ambulatory Medical Care Survey, 2012.
  6. Michalska-Kasiczak, M. et al. Analysis of vitamin D levels in patients with and without statin-associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol 178, 111-116 (2015).
  7. Wang, L. X. et al. Effects of vitamin D combined with pioglitazone hydrochloride on bone mineral density and bone metabolism in Type 2 diabetic nephropathy. Biosci Rep 37 (2017).
  8. Gorgas, M. Q. et al. Effects of selective serotonin reuptake inhibitors and other antidepressant drugs on the risk of hip fracture: a case-control study in an elderly Mediterranean population. Eur J Hosp Pharm 28, 28-32 (2021).
  9. Chen, L.-R., Wen, Y.-T., Kuo, C.-L. & Chen, K.-H. Calcium and Vitamin D Supplementation on Bone Health: Current Evidence and Recommendations. International Journal of Gerontology 8, 183-188 (2014).
  10. Buckley, L. et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken) 69, 1095-1110 (2017).
  11. Sutherland, E. R., Goleva, E., Jackson, L. P., Stevens, A. D. & Leung, D. Y. Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med 181, 699-704 (2010).
  12. Bouillon, R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol 13, 466-479 (2017).
  13. Holick, M. F. et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96, 1911-1930 (2011).
  14. Charoenngam, N. & Holick, M. F. Immunologic Effects of Vitamin D on Human Health and Disease. Nutrients 12 (2020).