Associations among dietary intakes, blood biomarkers, and postmortem brain tissue vitamin D and K concentrations in older adults

Authors: SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RUTT, JOSH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; AGARWAL, PUJA - Rush University Medical Center; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/17/2026
Publication Date: 4/1/2026
Citation: Shea, K., Rutt, J., Dawson-Hughes, B., Agarwal, P., Fu, X., Booth, S.L. 2026. Associations among dietary intakes, blood biomarkers, and postmortem brain tissue vitamin D and K concentrations in older adults. Journal of Nutrition. 156(4). https://doi.org/10.1016/j.tjnut.2026.101428.
DOI: https://doi.org/10.1016/j.tjnut.2026.101428

Interpretive Summary: The overall goal of this research was to clarify how blood-based biomarkers and dietary intakes reflect actual nutrient levels in human brain tissue for vitamins D and K - two nutrients which have been implicated in brain health. To achieve this, we used data from approximately 300 older adults who had participated in a long-term study on cognitive decline and aging. Participants completed diet questionnaires over several years, and their blood-based biomarkers of vitamin D and K were measured a few years before death. Brain tissue samples collected at autopsy were analyzed for vitamins D and K. We found plasma 25(OH)D, the biomarker of vitamin D status, reflected both vitamin D intake and brain vitamin D stores. For vitamin K, however, the associations among plasma biomarkers, dietary intakes, and brain concentrations were not as straightforward. More research is needed to determine how well current blood-based biomarkers capture brain vitamin K status and what that means for cognitive health.

Technical Abstract: Background: Circulating biomarkers are often used to infer nutrient intakes and overall nutrient status but may not accurately reflect nutrient concentrations in specific tissues. Since direct measurement of human tissue nutrient levels is rarely feasible, researchers rely on biomarkers as proxies. Studies linking diet, circulating biomarkers, and tissue nutrient concentrations are needed to enhance biomarker interpretability. Objective: We sought to evaluate the inter-relationships among dietary intakes, circulating biomarkers, and human brain tissue stores of vitamins D and K - two nutrients implicated in cognitive health. Methods: Brain 25-hydroxyvitamin D3 (25(OH)D3) and menaquinone-4 (MK4), metabolites of vitamins D and K, were measured in 288 and 322 deceased participants, respectively, of the Rush Memory and Aging Project. Plasma 25(OH)D3, phylloquinone (vitamin K1) and uncarboxylated matrix gla protein (ucMGP, a functional biomarker vitamin K status), were measured from samples collected ~3.4 yrs before death. Food frequency questionnaires were completed biannually for up to 14 years before death, and dietary intakes of vitamins D and K were averaged over that period. Results: Total vitamin D intake was positively associated with plasma 25(OH)D3 and brain 25(OH)D3 concentrations (p<=0.033). Phylloquinone intake was positively associated with plasma phylloquinone and inversely associated with plasma ucMGP (p<=0.006). Plasma ucMGP was inversely associated with brain MK4 (p<=0.006); however, phylloquinone intake was not associated with brain MK4 concentrations (p=0.567). Conclusion: These findings indicate key assumptions underlying the inter-relationships among nutrient intakes, circulating biomarkers, and brain tissue stores were generally satisfied for vitamin D, and support the use of circulating 25(OH)D3 as an indicator of overall vitamin D intake and brain 25(OH)D3 concentrations. However, for vitamin K the inter-relationship among dietary intakes, circulating biomarkers, and brain tissue stores was not as straightforward, highlighting a need for further research to clarify the use of vitamin K biomarkers in cognitive health.