https://examine.com/supplements/vitamin-k/research/#safety-and-toxicology_general
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Vitamin D and Vitamin K are thought to be highly synergistic as they both interact with proteins involved in bone and tissue calcification (namely osteocalcin, where vitamin D creates the protein and vitamin K carboxylates/activates it). One study has noted that supplemental vitamin K was able to elevate parathyroid hormone (PTH) concentrations as well, which (due to PTH being inversely related to vitamin D) a suppression of vitamin D concentrations and a higher need to supplement if superloading (45mg) the variant of vitamin K known as MK-4.
The most important interaction between the two is in bone health, where the addition of vitamin K (usually MK-4) to bone cells is able to augment a vitamin D induced osteocalcin production and due to MK-4 localizing osteocalcin to the extracellular matrix to promote mineralization they appear synergistic in osteoblasts (dependent on the vitamin K cycle). In osteoclasts (negative regulators of bone mass), vitamin K (MK-4 only, phylloquinone inactive) suppresses the proliferative effects of vitamin D; this can also indirectly support bone mass and is independent of the vitamin K cycle, but may only apply to pharmacological doses of MK-4 (45mg or so).
Vitamin D and Vitamin K (vitamin A as well to a degree, but is not the topic here) are vitamins that appear to work together in the function of some vitamin K dependent enzymes. Additionally, vitamin K appears to promote the beneficial effects of vitamin D on osteoblasts while higher doses of MK-4 are able to suppress the negative effects of vitamin D on osteoclast formation
In studies that compare a vitamin K only group against a vitamin K group also given vitamin D, the combination therapy groups tend to experience greater benefits to bone health as assessed by bone mineral density.
Some trials on bone health either use vitamin D regardless (keeping the only difference between groups the vitamin K) or they compare vitamin K against combined therapy with vitamin D and vitamin K; it appears that combination therapy routinely outperforms vitamin K alone
Toxicity of Vitamin D is hypothesized to be related to an imbalance with Vitamin K, as the former vitamin can increase a protein known as matrix Gla protein (MGP) while Vitamin K activates it via carboxylation; if MGP is not carboxylated then it can independently promote arterial calcification. This hypothesis is supported by how Vitamin D toxicity and Vitamin K deficiency are phenotypically similar, and how Warfarin can augment the toxicity of Vitamin D while having a similar toxicity profile and both Vitamin D and Warfarin toxicity being protected against by a common drug (ibandronate).
Vitamin D toxicity is thought to be secondary to either vitamin K depletion (excessive levels of vitamin K dependent proteins depleting the bodily reserves) or secondary to an accumulation of unactivated proteins due to a relatively higher vitamin D intake to vitamin K
