Why Vitamin K Is the Next Vitamin D

Photo: Gayvoronskaya_Yana/Shutterstock.com

Over the past few years, vitamin D has been touted as a major player in overall health and wellness. Researchers have connected low vitamin D status to several chronic illnesses, including autoimmune disorders, cardiovascular disease, diabetes, cognitive disorders, cancer, obesity, and more. Due to a variety of factors, including increased time spent indoors and more sunscreen use, the natural synthesis of vitamin D is reduced for most people, leading to a higher risk of deficiency or insufficiency. With such compelling research continually presented, the medical community quickly jumped on board, making it more common to screen for vitamin D status as part of preventative health measures and advising patients to supplement with vitamin D. From what I have been reading, the next vitamin to receive similar attention will be vitamin K.

Vitamin K plays some key roles in general health and well-being. It is best known as an important cofactor in blood clotting, but recent research demonstrates it does so much more. The most common source of vitamin K in the diet is phylloquinone, or K-1, which is abundant in leafy greens but is also found in other foods such as cashews, avocado, blueberries, blackberries, and lentils. However, you can also get vitamin K from fermented foods, including cheese, chicken liver, meat, and eggs, which is in the form of menaquinone, or K-2. The gut microbiome also produces a small amount of vitamin K-2. However, many people still do not get sufficient levels of vitamin K from their diets, which could lead to health problems.

Vitamin K Insufficiency 

A recent study reviewing data from the NHANES study 2011 – 2012, which looked at 2,092 men and 2,214 women over the age of 20, determined a large portion of the population is not getting adequate vitamin K from their diets. According to the results of this study, only 43 percent of men met the adequate intake for vitamin K, which is 120 ug per day. More women (62.5 percent) met the adequate intake levels of 90 ug per day. Men over the age of 51 had the lowest self-reported intakes of this important vitamin. These numbers were not any lower compared to the levels of the past 15 years. Vegetables remained the highest source of the vitamin, with 36.1 percent of the low-vegetable intake group and 60 percent of those in the high-vegetable-intake group receiving their phylloquinone from vegetables, while mixed dishes contributed to 16 and 28 percent respectively.

To make matters worse, secondary vitamin K insufficiency and deficiency can exist due to vitamin K antagonists such as warfarin, which are very popular medications to treat heart disease. Thus, even more people might have low levels of vitamin K than what is revealed by reviewing dietary habits.

So why does it matter that so many people are not getting sufficient levels of vitamin K in their diets? Well, vitamin K deficiency is associated with several chronic illnesses. Additionally, consuming adequate amounts might just hold a key to health and wellness, since there is an inverse relationship between higher dietary intake and all-cause mortality, as well as death from cancer and cardiovascular disease.

Cardiovascular Health 

One of the functions of vitamin K in the body is to assist in the formation of proteins that have the ability to bind ions of calcium. A vitamin-K dependent protein known as Matrix Gla-protein (MGP) exists in atherosclerosis plaque and acts to prevent the precipitation of calcium in a similar manner to vitamin K’s actions on bone. Without vitamin K, the body cannot synthesize this protein, which could lead to calcification of arteries. A study on mice found those without MGP exhibited signs of massive aortic and coronary calcification, even while very young. This finding points to the important role of MGP in preventing the calcification of arteries and the associated cardiovascular problems.

This association is seen in humans as well. Researchers reviewed data from the longitudinal Rotterdam study data and found increased intake of K-2 but not K-1 had an inverse relationship with aortic calcification and all-cause mortality. This suggests that dietary K-2 might have a protective effect for cardiovascular disease. To further point to the role of vitamin K in heart health, these findings are not associated with what most people would think of as healthy lifestyles, since K-2 is found in meat, cheese, and eggs rather than vegetables. Another cross-sectional study of postmenopausal women based on a subset group from the PROSPECT study supported these findings. Intake of K-1 had a relative risk of 1.17 (95% CI; 0.96-1.42) for coronary calcification, while intake of K-2 had a relative risk of 0.80 (95% CI: 0.65-0.98). This further demonstrates the positive impact that K-2 has on reducing coronary calcification.

A significant number of studies have looked specifically at the connection between vitamin K deficiency, chronic kidney disease, and the development of calcified arteries. Those with chronic kidney disease are at a high risk of developing aortic and coronary calcification. In this population, when calcification develops, it is rapid with a poor prognosis. This result might be due to the kidney disease contributing to vitamin K deficiency, which in turn increases the risk of arterial calcification.

Diabetes and Metabolic Syndrome 

Recent studies have pointed to vitamin K’s role in regulating glucose metabolism and insulin sensitivity, which might mean that deficiency or insufficiency of this vitamin plays a role in the development of diabetes and metabolic syndrome. One study found higher levels of K-2 were associated with lower occurrences of metabolic syndrome. The study looked at participants for their consumption of both K-1 and K-2 through a food frequency questionnaire and serum levels of desphospho-uncarboxylated matrix-Gla protein level to see if there was a relationship with the development of metabolic syndrome. Then, they looked at the participants 10 years later. At the start, metabolic syndrome had a prevalence ratio of 0.74 (95% CI, 0.54-1.03) in those with high consumption of K-2. At the 10-year follow-up, the highest tertiles of K-2 intake and vitamin K status had lower rates of metabolic syndrome, with a prevalence ratio of 0.62 and 0.57 respectively.

In another study using data from the PREDIMED study, which looked at individuals with cardiovascular disease to determine the preventative impact of the Mediterranean diet on those with a high risk of developing it, there was a lower association with the occurrence of type 2 diabetes in the participants who consumed higher levels of K-1. In those who developed type-2 diabetes during the time of the study, the dietary intake of K-1 was lower at the baseline of the study. For each additional intake of 100 ug of K-1, there was a 17 percent lower risk of incident, although there was no association with lowered glucose levels. Subjects who increased their consumption of vitamin K had a 51 percent reduced risk of developing diabetes compared to those who did not change their intake levels or decreased them. These studies show that both K-1 and K-2 might play a role in preventing diabetes and metabolic syndrome.

Cognitive Impairment 

Vitamin K also plays a role in the brain, although the exact mechanisms are not yet identified. Therefore, a deficiency might contribute to cognitive impairment. One study looked at 67 patients with a mean age of 83.4 for their cognitive status and use of vitamin K antagonists. The researchers found the participants with cognitive impairment based on the results of the Mini State Examination frequently used vitamin K antagonists. There was a 15 percent higher risk of cognitive impairment in those using vitamin K antagonists, and there was an independent association with a fully adjusted odds ratio of 17.4. Although this study did not look specifically at vitamin K status, it does show those who are more likely deficient due to their medication did have an association with their cognitive abilities.

In another study, researchers reviewed a sample of 320 men and women between the ages of 70 and 85 from the Quebec Longitudinal study to see if there was a relationship between vitamin K and cognitive function. The participants had no diagnosed cognitive impairment at the onset of the study. The participants underwent different tests, and the researchers found there was an association between higher serum concentrations of K-1 and better performances on verbal episodic memory tests. To further support this idea, a study on rats found that older rats that had lived on a low vitamin K diet their whole lives had cognitive deficits at 20 months of age. These rats were fine at the 6 and 12 months of age, demonstrating an age-related cognitive decline due to a lifelong inadequate diet of vitamin K.

These studies point to an important area of interest. Cognitive decline is common in the elderly, and so is the use of vitamin K antagonists like warfarin. With a potential association between vitamin K deficiency and cognitive dysfunction, it becomes even more important to recognize the potential long-term effects of this medication to be able to better develop a risk analysis for patients and ways to mitigate this potential effect.

Bone Health 

Vitamin K’s role in bone health is well known. The stimulation of gamma-carboxylation of osteocalcin leads to increased formation of bone through facilitating the development of functional osteocalcin (noncollagenous protein that is abundant in bone). This effect might help make bone strong, even if it is not very dense. A study on postmenopausal women with osteopenia found that supplementing with 5 mg of vitamin K1 had no effect on bone mineral density, but it did lead to a decrease of fractures.

It is not just bones that benefit from vitamin K; joints might also require vitamin K, thanks to its regulation of cartilage mineralization, which is also affected by the Gla proteins. In a longitudinal study reviewing knee osteoarthritis, the researchers found that those with subclinical vitamin K deficiency at the onset of the study, 14.5 percent were identified at the 30-month follow-up visit as having developed incident radiographic osteoarthritis despite being free of the disease at the onset of the study. Those with a subclinical vitamin K deficiency had a risk ratio of 1.56 (95% CI; 1.08 – 2.25) compared to those who had sufficient levels of the vitamin. There was also an association with cartilage lesions but not for osteophytes.

Vitamin K and SNPs

The role of vitamin K in health and disease processes can be influenced by a person’s genetics. Many studies on vitamin K and genetic single nucleotide polymorphisms (SNPs) have been conducted with regards to medications such as warfarin. These medications are known for having a wide variability of therapeutic doses and screening for particular genetic polymorphisms related to vitamin K metabolism. For instance, VKORC1 and CYP2C9 can help doctors make more accurate prescription recommendations. People with a particular genotype may be more sensitive to changes in dietary vitamin K intake and vitamin K supplementation due to a greater activation of clotting factors. Genotype would also impact medication dose adjustments.

Studies have looked at the correlation between particular SNPs and some of the conditions discussed above. A study on 97 young, healthy Japanese adults analyzed the relationship between vitamin K intake, vitamin K-dependent proteins found in the bones, and a gene that codes for γ-glutamyl carboxylase (GGCX), the enzyme that modifies those proteins. Researchers found a significant positive correlation between dietary vitamin K intake and serum levels of vitamin K in study participants, but there were genotype-specific differences in osteocalcin within the bone. This finding may have implications for bone mineral density across the lifespan.

In a separate study, researchers used 7,159 DNA samples from the NHANES III 1988-1994 study to analyze the effects of six VKORC1 SNPs on bone density and osteoporosis risk. The overall effect was small as there are many genes that are involved in bone health and metabolism. However, they did find one SNP was associated with osteoporosis in white males in unadjusted and adjusted models while there were no significant associations in any of the females of the study, regardless of race. One SNP was associated with decreased bone mineral density in white males in an unadjusted model and two SNPs were associated with increased bone mineral density in black males.

Several SNPs related to vitamin K levels have been found to be positively associated with coronary artery disease. In a study on patients with chronic kidney disease, some polymorphisms of the VKORC1 gene were found to be positively associated with vascular calcification while others were associated with a lower odds ratio of vascular calcification.

Summary

There is much still to learn about the importance of vitamin K in the body. Some studies have also pointed to anti-inflammatory properties of the vitamin, in addition to its blood-clotting and calcification regulatory roles. Although the importance of vitamin K can be likened to that of vitamin D, screening for and prescribing vitamin K is not as straightforward. As of now, there is no simple, single biomarker to measure vitamin K levels. However, I predict that moving forward, there will be changes as more and more research points to such an important impact of vitamin K on health.

As discussed, it is important for people to ensure they get adequate vitamin K from their diets to prevent some of the health conditions associated with deficiency and insufficiency. The best way to add vitamin K to your diet is to consume more green vegetables, cheese, and fermented foods. Keeping your gut bacteria healthy can also help to provide some vitamin K, although the levels are small. The body needs both K-1 and K-2, as these studies demonstrate. Therefore, it is best to find ways to consume both varieties to boost your overall health and wellbeing and help prevent some of these chronic illnesses. For those on blood thinners and other medication, discuss the interaction of vitamin K and these medications with a doctor prior to increasing the levels of vitamin K in your diet to reduce the chance of any adverse effects.

 

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2 Comments

  1. Tom Sult

    Dr. Minich. Great article. Thank you for highlighting the importance of Vit K. Like you I have been pushing for greater understanding of the braided role of Vik metabolism.

    Reply
    • dminich

      Dear Dr. Sult, thank you so much for your advocacy for vitamin K.

      Reply

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