Annals of Neurology August 2012; Vol. 72; No. 2; pp. 234 – 240 Ellen M. Mowry, MD, Emmanuelle Waubant, MD, PhD, Charles E. McCulloch, PhD,Darin T. Okuda, MD, Alan A. Evangelista, BA, Robin R. Lincoln, BS, Pierre-AntoineGourraud, PhD, Don Brenneman, BA, Mary C. Owen, NP, Pamela Qualley, MA,Monica Bucci, MD, Stephen L. Hauser, MD, Daniel Pelletier, MD Primarily from the Multiple Sclerosis Center, Department of Neurology, University ofCalifornia at San Francisco KEY POINTS FROM THIS STUDY: 1) These authors sought to determine whether vitamin D status is associatedwith developing new T2 lesions or contrast-enhancing lesions on brain magneticresonance imaging (MRI) in relapsing multiple sclerosis (MS). 2) EPIC is a 5-year longitudinal MS cohort study at the University of California atSan Francisco. Participants had clinical evaluations, brain MRI, and blood drawsannually. The authors adjusted for age, sex, ethnicity, smoking, and MStreatments, annual 25-hydroxyvitamin D levels and subsequent new T2-weighted and gadolinium-enhancing T1-weighted lesions on brain MRI, clinical relapses, anddisability levels (Expanded Disability Status Scale [EDSS]). 3) Each 10 ng/ml higher 25-hydroxyvitamin D level was associated with a 15%lower risk of a new T2 lesion and a 32% lower risk of a gadolinium-enhancinglesion. 4) Each 10 ng/ml higher vitamin D level was associated with lower subsequentdisability [by 53%]. 5) Higher vitamin D levels were associated with lower MS relapse risk. 6) Interpretation: Vitamin D levels are inversely associated with MS activity onbrain MRI. 7) Multiple sclerosis (MS) is an autoimmune disorder occurring in those whopossess or are exposed to a combination of genetic and environmental risk factors. 8) Known MS environmental risk factors include: * cigarette smoking * infection with Epstein – Barr virus * lower vitamin D levels 9) The brain MRI scans were acquired on a 3T unit. 10) Standard vitamin D levels are presented in nanograms per milliliter (ng/ml). 11) The average vitamin D level by year 4 was 5.3 ng/ml higher than atbaseline. Those who reported using vitamin D supplements within the past 12months had an 8.7ng/ ml higher vitamin D level than those who did not. 12) For each 10 ng/ml higher vitamin D level was associated with a 15% lowerrisk of later developing new T2 lesions. 13) Even after adjusting for baseline vitamin D, each 10ng/ml within-personincrease in vitamin D was associated with a much lower risk of developing a new T2lesion [by 33%] 14) Each 10 ng/ml higher vitamin D level was associated with nearly a 1/3reduction in the risk of a subsequent contrast-enhancing lesion. 15) After adjusting for baseline vitamin D, each 10 ng/ml within-person increasein vitamin D was associated with a substantially lower risk of gadolinium-enhancinglesions [by 47%] 16) Higher vitamin D levels were also associated with lower risk of relapse. 17) Each 10 ng/ml higher vitamin D level was associated with a lower disabilityscore. 18) Individuals with higher vitamin D levels are at much lower risk of thesubsequent development of new lesions and of gadolinium-enhancing lesions onbrain MRI, even after accounting for potential confounding factors. Particularlyimportant is that the within-person effect of vitamin D, which is less subject toconfounding at the individual level, is even stronger. 19) Vitamin D levels did appear to be inversely associated with subsequentdisability. 20) Those who were active smokers at entry in the study were at substantiallygreater risk of developing new T2 lesions and clinical relapses throughout the study.Smoking is a relatively well-established risk factor for MS. 21) Our findings provide further support for the role of vitamin D in MSinflammatory activity and for a randomized trial of vitamin D supplementation. COMMENT FROM DAN MURPHY The studies on the benefits of vitamin D just keep coming. Again, we target 50ng/ml for our patients.