# A Systematic Review of Evidence, Misinterpretations, and the Urgent Need for Population-Specific Reference Standards Related to Vitamin D Deficiency in India: A Global Myth Imposed Locally?

## TL;DR

This paper reviews vitamin D deficiency in India and argues that global thresholds may be misrepresenting the true health situation there.

## Contribution

The study emphasizes the need for population-specific vitamin D deficiency thresholds in India, based on local physiological and environmental factors.

## Key findings

- High-quality RCTs show no benefit of vitamin D supplementation for non-skeletal outcomes.
- Indian PTH-calcium studies suggest 12 ng/mL is sufficient for normocalcemia, challenging global thresholds.
- Current global vitamin D deficiency thresholds may be inflating the reported burden in India.

## Abstract

India reports very high biochemical vitamin D deficiency when global cut-offs are applied, yet the corresponding disease burden appears low. Whether current thresholds are appropriate for Indian populations, therefore, remains uncertain. In this review, we aimed to systematically analyze the literature on vitamin D and non-skeletal outcomes and critically evaluate whether current deficiency thresholds are appropriate for India. We searched PubMed, Scopus, and the Cochrane databases (Jan 1, 2010, to Feb 29, 2024), focusing on randomized trials (RCTs), meta-analyses, and observational studies addressing vitamin D and disease outcomes. Indian-specific modifiers, including sunlight, skin pigmentation, calcium intake, and parathyroid hormone (PTH) sensitivity, were analyzed. Two reviewers independently screened records, assessed risk of bias (Cochrane Risk of Bias 2.0 (RoB 2.0) for RCTs and Newcastle-Ottawa Scale (NOS) for observational studies), and performed a narrative synthesis, with prespecified quantitative pooling conducted when studies were homogeneous.

Out of 22,435 records, 78 studies were included. High-quality RCTs (VITAL, D-Health) consistently showed no benefit from supplementation for non-skeletal outcomes. Indian prevalence data, using a <20 ng/mL threshold, revealed high “deficiency” rates but minimal clinical disease. PTH-calcium studies from India indicated that 25(OH)D levels >12 ng/mL are sufficient to maintain normocalcemia and suppress secondary hyperparathyroidism, thereby questioning the validity of global thresholds. Global cut-offs have therefore created an inflated burden of vitamin D deficiency in India. Thresholds must be recalibrated using Indian outcome-linked data, not extrapolated norms. Evidence suggests that a threshold of 12 ng/mL is more physiologically valid for Indian populations. Mass screening and supplementation in asymptomatic populations should therefore be discouraged.