Do Omega-3, Vitamin D3, and Vitamin K2 Work Together for Heart, Brain, and Bone?

This review pulls together research on three fat-soluble nutrients — long-chain omega-3s (EPA/DHA), vitamin D3, and vitamin K2 (MK-7) — and how they might interact with aging processes that affect the heart, brain, and bones at the same time. The authors describe a proposed “Heart-Brain-Bone axis,” a conceptual framework built from separate lines of evidence rather than a confirmed biological system.

Mechanistically, vitamin K2 helps activate proteins that direct calcium toward bone and away from artery walls, which may help explain why vitamin D alone can sometimes raise blood calcium without clear cardiovascular benefit. Omega-3 fatty acids are involved in resolving inflammation in blood vessels and nerve tissue, and several bone- and vessel-derived signals appear to link all three organ systems together.

However, human trial results are mixed. Omega-3 heart trials show conflicting outcomes depending on formulation and baseline risk (positive in REDUCE-IT, null in VITAL/STRENGTH/ASCEND). Brain/cognition trials were mostly null or only showed effects in specific subgroups. Vitamin K2 improved some bone and artery-calcification markers in one trial but not others, and combining it with vitamin D3 didn’t consistently outperform either nutrient alone. The review also flags safety considerations, including a dose-related increase in atrial fibrillation risk with high-dose omega-3 and interactions between vitamin K2 and blood-thinning medications.