Vitamin D and Multiple Sclerosis
Multiple sclerosis (MS) has one of the strongest and most consistent latitude gradients in medicine — prevalence rises sharply above 40°N and below 40°S. Vitamin D status is a leading explanation for the pattern, and it is one of the few modifiable risk factors identified for the disease.
The latitude gradient
MS prevalence is ~2–3× higher in Scotland (57°N) than in the Mediterranean, and higher in Tasmania than in Queensland. Migration studies suggest the risk is largely fixed before puberty — people who move from a low- to high-latitude country in childhood acquire the higher risk of their new home; those who move as adults keep their original risk.
Genetic evidence — Mendelian randomisation
Studies using genetic variants that lower 25(OH)D as instruments (Mendelian randomisation) find genetically low vitamin D is associated with higher MS risk. This design is less confounded than conventional observational studies, and it supports the deficiency-causes-MS hypothesis rather than reverse causation.
Supplementation trials
- SOLAR (2018) — cholecalciferol 14,000 IU/day for 48 weeks in relapsing-remitting MS on interferon-β; no reduction in new MRI lesion primary endpoint.
- CHOLINE (2019) — 100,000 IU every 2 weeks; reduced new T2 lesions but not annualised relapse rate.
- PrevANZ / D-Lay MS — ongoing prevention trials in high-risk relatives.
Overall: supplementation may reduce inflammatory MRI activity but the disease-modifying effect is smaller than expected from observational data. Vitamin D adjunctive therapy is reasonable in deficient MS patients; it does not replace disease-modifying drugs.
Target 25(OH)D in MS
Most MS neurology consensus statements suggest maintaining 25(OH)D between 40–60 ng/mL (100–150 nmol/L) in people with MS, using cholecalciferol 2,000–5,000 IU/day titrated to serum level. Doses above the 4,000 IU/day IOM upper limit are commonly used under specialist supervision.