Nutritional Synergy: A Complex Symphony of Well-Being
Scientific research into nutrition is on the rise, due to the growing understanding that good nutrition is vital for the prevention of disease. Most nutritional research focusses on the effects of individual nutrients; however nutrients rarely act in isolation within the body. In fact, nutrients interact with each other chemically and biologically, in a variety of complex ways, which can have synergistic or antagonistic effects. Understanding these nutritional interactions is vital in order to get the most benefit from nutritional supplementation.1
Vitamin D and Vitamin K have a clear synergistic effect in the body, primarily via the regulation of calcium. In short, vitamin D increases levels of calcium in the blood, while vitamin K binds calcium in various tissues. Vitamin D plays a vital role in the regulation of blood calcium levels. When serum calcium levels drop, the parathyroid gland releases parathyroid hormone (PTH), which increases the production of active vitamin D (calcitriol) in the kidney. Calcitriol then acts to increase blood calcium levels by: 1,2
1. Increasing intestinal absorption of calcium
2. Reducing renal excretion of calcium
3. Releasing calcium from bone
It also inhibits further release of PTH, thereby returning the body to homeostasis. As well as liberating calcium from the bone when blood calcium is low, vitamin D also indirectly increases calcium deposition in the bone, via its effects on vitamin K-dependant proteins. Vitamin D promotes the synthesis of the protein osteocalcin, which is then activated by vitamin K via carboxylation of glutamic acid residues. Once activated by vitamin K, osteocalcin binds calcium from the bloodstream and delivers it to the bone for mineralisation. Osteocalcin is required for the growth and maturation of calcium hydroxyapatite crystals.3,4 In this way, vitamin D and vitamin K work synergistically to increase bone mineralisation and bone density. Meta analysis data shows that supplementation with vitamin D and vitamin K together significantly increases bone mineral density, with a pooled effect size of 0.316, indicating a moderate effect size (p=0.03). Subgroup analysis demonstrated that benefits were greater when vitamin K2 was used, rather than vitamin K1.5 Further meta analyses have found similar effects when vitamin K is given alongside calcium,6 and in combination with vitamin D, calcium and/or bisphosphonates.7
Vitamin D and vitamin K also work synergistically to regulate calcium homeostasis in other tissues. Research is particularly highlighting their synergistic effects in maintaining cardiovascular health.3 Vitamin D promotes the synthesis of another protein, called matrix Gla protein (MGP), which is then carboxylated and activated by vitamin K.3 Activated MGP binds calcium in soft tissues, most notably in blood vessels, and prevents calcification of these tissues. Vitamin K also activates growth arrest-specific gene 6 protein (Gas6), which regulates platelet activation and vascular homeostasis. Vitamin D and Vitamin K thereby ultimately reduce the risk of coronary heart disease, atherosclerosis and clot formation.3,4
Figure 1: Overview of synergy between vitamins D and K on bone and cardiovascular health