Vitamin D supplementation: a comprehensive review on supplementation for tuberculosis prophylaxis

Abstract

Vitamin D plays a large role in the innate immune response against Mycobacterium tuberculosis (MTB) infection, activation and progression. Likewise, vitamin D deficiency is shown by evidence presented here to be a known risk factor for developing both MTB infection and active tuberculosis (TB). This comprehensive review discusses the evidence and remaining questions regarding vitamin D supplementation as a prophylactic measure in those who are at high risk of MTB infection and active TB. Vitamin D supplementation is routinely prescribed for osteoporosis prevention; yet, guidelines are lacking for its prescription for TB prevention, despite the adverse effects being rare. Policymakers are urged here to review the literature and provide urgent guidelines on vitamin D supplementation for TB prophylaxis.

Keywords:

• Mycobacterium tuberculosis
• prophylaxis
• supplementation
• tuberculosis
• vitamin D

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilised in the production of this manuscript.

Key issues

• A sufficient physiological level of vitamin D, through intracellular vitamin D receptor activation, enhances innate immunity and stimulates cathelicidin production, creating an antimicrobial effect via bacterial cell membrane disruption and monocyte autophagy.

• Low vitamin D levels appear to be a risk factor for developing both Mycobacterium tuberculosis (MTB) infection and active tuberculosis (TB).

• Higher serum vitamin D levels are significantly associated with a lower probability of acquiring both MTB infection and active TB.

• One prospective study found 800 IU of vitamin D supplementation/day for 6 months caused a 59% reduction in MTB infection (p = 0.06).

• No prospective randomised controlled trial (RCT) has been completed to assess whether supplementation would decrease the risk of developing active TB, though two studies are in preparation stage.

• Classification of vitamin D deficiency or insufficiency varies widely, with no internationally agreed or standardised definitions, complicating supplementation studies and policymaking.

• Various genetic polymorphisms associated with different populations may mean individual patients require differing doses of vitamin D supplementation in order to reach sufficient prophylactic levels.

• A systematic review of vitamin D supplementation RCTs found very few serious adverse effects, even at high loading doses.

• There are no current guidelines on a recommended supplementation dosage.

• Daily recommended intakes for vitamin D supplementation are required that could on balance ensure major deficiencies are corrected for within a more normal range.

Notes