Vitamin D gets a lot of attention these days, not only for its roll in bone health, but also due to the multiple health benefits associated with robust levels of circulating vitamin D, specially in kidney disease. However, the role of vitamin K working in tandem with vitamin D often gets overlooked. This blog will focus on the importance of vitamin K in kidney health.

Vitamin K in Vascular, Kidney and bone Health

Nutrients don’t work solo, they function as part of a symphony with other nutrients to help our body perform at its best and prevent disease, including kidney damage and chronic kidney disease (CKD). 

Vitamin D Background

Vitamin D3, also known as cholecalciferol, is a fat-soluble vitamin that plays a role as a pro-hormone. It Is naturally found in some foods like fish, egg yolks, and beef liver, but humans rely on making it through a process in the skin that requires sunlight exposure. For a full review of vitamin D visit our previous blog

Vitamin D play a role in multiple aspects of health including bone mineral balance, neuromuscular function, immunity and autoimmune disease, cognitive health, and insulin regulation. Maintaining adequate vitamin D levels can be beneficial when managing or treating many conditions, including:

  • Back or musculoskeletal pain
  • Osteoporosis
  • Frequent colds or flu
  • Cardiovascular disease
  • Diabetes
  • Fatigue
  • Seasonal Affective Disorder (depression)

Vitamin D interaction with other nutrients

Calcium and Phosphorous 

Vitamin D is necessary for absorption of calcium and phosphorous from food sources in the intestines into the blood as well as regulating the amount of those minerals in circulation. This is a delicate balance, these two minerals are essential for bone remineralization and remodeling (bone building), skeletal muscle contractility, as well as kidney and cardiovascular health.

Vitamin K: K1 vs K2

Vitamin K is a general term for a group of compounds that function as part of the coagulation (blood clotting) pathways that help us regulate blood thinning and prevent risk of bleeding from cuts or injuries. Vitamin K is typically thought of for bleeding disorders, but proper balance may also be useful in the management and treatment of the following conditions:

  • Atherosclerosis and ischemic heart disease 
  • Cirrhosis, hepatitis, and liver disease
  • Osteoporosis ad bone loss 
  • Cancer

Vitamin K naming and structure is one of the most misunderstood topics in nutritional medicine, so let’s spend a few minutes understanding these foundations. Vitamin K is the general term used to describe a group of compounds that share a common ring structure. There are 2 subcategories to keep in mind, K1 and K2.

K1, also known as phylloquinone or phytonadione, is the primary form found in plants. Leafy vegetables are the main source of vitamin K1. This is the form that is utilized in the liver and involved in clotting. This is also the form that interacts with blood thinners like warfarin and why patients on blood thinners are told to carefully monitor their intake of leafy greens.  

K2, referred to menaquinones, describes a group of varying chemical structures that are used outside the liver (in the bone and vascular wall). The number of isoprenyl units determine the name of the structure. So, a K2 with 4-isoprenyl units is MK4, and MK7 means there are 7 isoprenyl units. This is the form that is involved in bone health and the focus of kidney-relevant associations of this vitamin. 

Vitamin K2 can be found in the diet in multiple forms (for example MK4, MK7, MK8, and MK9) in egg yolks, meats, cheese and other dairy products, natto (fermented soybeans), and seems to be much more readily bioavailable than K1 sources. In addition, menaquinones are synthesized by bacteria in the colon. 

Considering what we already know about the impact of the microbiome of kidney health and risk factors, menaquinone might play a larger role in the gut-kidney connection than we’ve been giving it credit for. Though there are multiple factors that contribute to the circulating level of vitamin K in the body, there is speculation that dysbiosis (imbalance of healthy gut bacteria in the gut) may be a significant contributing factor to inadequate circulating levels of K2 contributing to cardiovascular, kidney and bone disease. 

Supplementing Vitamin K2

Supplements containing vitamin K are available commercially as K1, MK4, and MK7. However, it’s important to note that safety and efficacy of each form is not equal and has contributed to significant confusion and inaccurate recommendations. 

There’s little evidence supporting the supplementation of phylloquinone, or K1. This may be due to poor bioavailability and low rate of conversion to active forms. K2 on the other hand seems to be the superior form, with more recent data supporting the use of MK7. 

In older studies, MK4 form seemed to be established as the most efficacious form when it comes to certain conditions like osteoporosis and hepatocellular carcinoma. However, MK7 seems to be more bioavailable and have a steadier blood concentration when compared to MK4 (and K1), meaning more stable blood concentrations and requiring lower doses. Additionally, the added benefit of MK7, particularly in osteoporosis, may in part be related to MK7 inhibition of NF-kB, an inflammatory mediator known to increase disease progression. 

Like Vitamin D3, K2 helps to manage calcium deposition. Adequate levels of Vitamin K2 are required to deposit calcium into the bone and to prevent calcium deposition into soft tissue like cardiovascular arteries and the kidneys. So, you see, depletion of K2 along with vitamin D3 can be a risk factor for bone loss, cardiovascular and kidney disease and supplementation of the two combined might yield the best health outcomes.

Manufacturers and companies selling vitamin K supplements often do not reveal whether contains MK-4 or MK-7. Therefore, it’s important to use formulations with full transparency and quality control. This is important for ensuring the highest efficacy, but also for safety concerns surrounding vitamin K supplements and that they may interfere with the stability of anticoagulant medications such as warfarin. This is also why it’s very important to work with your nutritionist or doctor to choose the correct product and dose. If you’re on a blood thinner, never make changes to your diet or supplements without consulting with the healthcare provider monitoring your medication and INR (test for bleeding tendencies). 

Studies that examine the benefit of MK-7 supplementation showed a positive effect on cardiovascular calcification. Although MK-7 did not prevent CKD-associated hypertension and hypertrophy, it did demonstrate prevention of calcification of blood vessels. The recommended dose of MK-7 is typically 45μg/d, though doses of 100μg/d have been suggested likely based on studies of the less potent form of MK-4 which, as explained above, is not equivalent.

Although further studies are still underway, it’s safe to say that considering the low risk and cost, it’s worth optimizing vitamin D3 and K2 (MK7) levels in patients with associated risk factors for or diagnosed with CKD. Work with your nutritionist and nephrologist to personalize your intake and optimize your nutrient levels safely and effectively.