Chirag M Vyas, Beth L Ostaszewski, Amirah K Anderson, Nancy R Cook, Jae H Kang, David Mischoulon, Charles F Reynolds, Grace Chang, Jennifer R Gatchel, JoAnn E Manson, Dennis J Selkoe, Olivia I Okereke
The sample mean (SD) age was 65.0 (6.6) years; 49.2% were female, and 8.2% were Black adults. Neither vitamin D3 nor omega-3s, compared to placebo, significantly reduced ADRD biomarkers over 4 years. Pre-specified subgroup analyses suggested potential interactions by sex and race. Vitamin D3 supplementation resulted in a reduction in NT1 among males (-2.7%) but not females (p-interaction = 0.08). Among Black participants, vitamin D3 supplementation resulted in a 16.2% reduction in NfL levels [95% CI: -30.5% to 1.1%; p-interaction = 0.06], while omega-3 supplementation showed a 12.4% reduction in GFAP levels [95% CI: -21.5% to -2.2%; p-interaction = 0.049].
INTRODUCTION: Vitamin D3 and omega-3 supplementation may slow outcomes related to Alzheimer's disease and related dementias (ADRD), with variation by sex or race, but their effects on ADRD-associated biomarkers are unknown.
METHODS: In this secondary analysis of a randomized clinical trial (RCT), we included 929 participants from the in-clinic subcohort of the VITamin D and OmegA-3 TriaL - a completed, placebo-controlled, 2×2 factorial trial testing vitamin D3 (2000 IU/day) and omega-3s (1 g/day) for cardiovascular disease and cancer prevention. Plasma ADRD biomarkers were assayed at baseline and 2- and/or 4-year follow-up. Study outcomes were longitudinal change in four ADRD biomarkers: N-terminal tau fragment (NT1), amyloid beta (Aβ)40:42, neurofilament-light (NfL), and glial fibrillary acidic protein (GFAP). Repeated-measures models were used, with sex and race were pre-specified effect modifiers.
RESULTS: The sample mean (SD) age was 65.0 (6.6) years; 49.2% were female, and 8.2% were Black adults. Neither vitamin D3 nor omega-3s, compared to placebo, significantly reduced ADRD biomarkers over 4 years. Pre-specified subgroup analyses suggested potential interactions by sex and race. Vitamin D3 supplementation resulted in a reduction in NT1 among males (-2.7%) but not females (p-interaction = 0.08). Among Black participants, vitamin D3 supplementation resulted in a 16.2% reduction in NfL levels [95% CI: -30.5% to 1.1%; p-interaction = 0.06], while omega-3 supplementation showed a 12.4% reduction in GFAP levels [95% CI: -21.5% to -2.2%; p-interaction = 0.049].
DISCUSSION: In this secondary analysis of a RCT, neither vitamin D3 nor omega-3s significantly reduced selected plasma ADRD biomarkers over 4 years. Potential differences were observed by sex and race in reductions of ADRD biomarkers in response to these supplements; however, these analyses were uncorrected for multiple hypothesis testing and should be interpreted cautiously as hypothesis-generating signals requiring replication.
TRIAL REGISTRATION: ClinicalTrials.gov identifiers: c (VITAL); NCT01696435 (VITAL-DEP).