It Takes K2 to Tango

‍

For years, various dietary interventions and supplements have been investigated for their ability to reduce the risk of heart disease and heart attacks. 

‍

One supplement that has gotten some attention is Vitamin K2. Can it help reduce heart attacks?

‍

 “Hardening of the arteries” or atherosclerosis is a process that starts with cholesterol deposition in the walls of the arteries. This is caused by high cholesterol levels, high levels of inflammation, and some other contributing factors. After the cholesterol and inflammatory compounds have been deposited in the walls, a calcification process regulated by “matrix Gla protein” follows over time. Historically, we tried to interrupt or prevent this process of plaque development by targeting the cholesterol. Lately, we have also begun to target the inflammation portion of the process. And all along, researchers have been trying to understand the “hardening” or calcification part of the process.

‍

A growing body of evidence suggests that vitamin K2 plays a significant role in protection against vascular calcification. This is because it stimulates and activates something called Matrix GIa Protein (MGP), which is considered to be the strongest inhibitor of the calcification or “hardening” processes in the blood vessel wall. Many research studies have demonstrated a strong association between low MGP activity and risk of heart attack and dying.

‍

Vitamin K2 is found naturally in fermented foods, like Kimchi, Sauerkraut and Japanese natto. In fact, intake of natto has been shown to be associated with a 25% lower risk of cardiovascular mortality in a large Japanese cohort study of ~30,000 men and women, followed over 16 years. 

‍

So does eating a diet high in Vitamin K2 improve health? In 2009, Gast and colleagues observed that high levels of dietary K2 intake reduced risk of heart disease by 9% per 10 micrograms/day of vitamin K2 intake. And in 2008, Beulens found that K2 intake was associated with 20% decreased risk of coronary calcification. The Rotterdam study recruited 4807 subjects with dietary data and no history of myocardial infarction between 1990 and 1993, and followed patients until January 2020. These authors found that participants who had the highest dietary intakes of vitamin K2 (but not K1) had 57% reduced cardiovascular and 26% lower all-cause mortality. These findings persisted after adjusting for traditional risk factors and dietary factors

‍

But because it is found mostly in fermented foods, K2 is in low abundance in Western diets. So if we aren’t getting enough of it in our diets, would supplementation help?

‍

Supplementation with K2 has indeed been shown to improve arterial stiffness in studies of healthy adults, postmenopausal women, patients with CAD and renal transplant recipients. But does it do more than just that?

‍

A recently published study sheds a little more light on the subject. 

‍

In this recent randomized study, 304 participants were divided between two groups: half received vitamin K2 (720 micrograms/day) and Vitamin D (25 micrograms/day) and the other half received a placebo. They were followed for 2 years. Both groups experienced an increase in mean calcium scores from baseline to 24-month follow-up, and while progression slowed in the Vitamin K2 group, it didn’t reach statistical significance. Therefore the improvement could have been due to chance. So this was officially a negative result for the study.

‍

But in patients with Calcium Scores ≥400, progression WAS significantly lower in the Vitamin K2 group. And patients who were also taking statins had a significant effect from Vitamin K2 as well. 

‍

And while it was not statistically significant, 8.0% of participants in the placebo group experienced a worsening of coronary obstructions, while the number was only 4.5% in the vitamin K2 and D group. And there were fewer heart attacks, deaths and stents/surgery in the Vitamin K2 subjects (1.9% vs 6.7%), which just missed statistical significance. Regarding the volume/size of “soft plaque”, the analysis showed a progression of 46 μL in the placebo group while it was −6 in the intervention group, but again not statistically significant between the groups. While we can’t make any conclusions about these findings, they certainly suggest a theoretical benefit and that a larger/longer study should be performed.

‍

Two ongoing Danish studies will hopefully contribute to more knowledge about the effect of vitamin K2 supplementation. The newly started InterVitaminK trial (NCT05259046) is a randomized controlled trial aiming to investigate if supplementation with 333 micrograms of vitamin K2 can reduce coronary calcium progression in a population with baseline CAC score ≥10 over a 3-year follow-up. Another new randomized controlled study, DANCODE (DANish COronary DEcalcification) trial will enroll high-risk men and women with CAC score ≥400 ( NCT05500443) and look at the effect of Vitamin K2 in these participants.

‍

So while we’ll have to wait for the results of these trials to know more definitively if there is benefit to taking Vitamin K2, there seems to be little harm in taking it until we know for sure.

‍

‍

‍

References:

‍

Hasific S et al. JACC Adv. 2023 Nov, 2 (9) 100643

‍

Hariri E et al. Open Heart 2021;8:e001715

‍

Gast G et al. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10

‍

Beulens JWJ et al. Atherosclerosis 203(2):489-932

‍

Nagata C et al. Am J Clin Nutr2017;105:426–31