AHA News: Despite Hopes, Vitamin K2 Supplements Fail to Slow Calcium Buildup in Heart Valve

MONDAY, April 25, 2022 (American Heart Association News) -- The progressive narrowing of the aortic heart valve in a group of older men could not be slowed during a recent clinical trial using vitamin K2 supplements, dampening hopes of finding a medical treatment for this common but serious condition.

The research, published Monday in the American Heart Association journal Circulation, built upon earlier studies suggesting vitamin K2 supplements could slow the progression of aortic stenosis, a narrowing of the valve that controls blood flow from the heart to the rest of the body. But this randomized, double-blind, placebo-controlled trial – considered the gold standard of epidemiological studies – found vitamin K2 and vitamin D supplements did not slow the progression of calcium deposits on the aortic valves of older men once the process had begun.

"As previous animal studies, epidemiological studies and an open-label study did suggest a beneficial effect, we hoped for a positive trial," said lead study author Dr. Axel Diederichsen, a professor in the department of cardiology at Odense University Hospital in Denmark. "Thus, we were surely disappointed."

Aortic stenosis is the most common heart valve disease in high-income countries, according to the study, which estimates it affects about 2% to 5% of people older than 65. The number of people in the United States and Europe with aortic stenosis is expected to more than double by the year 2050, according to American Heart Association statistics that estimate 12.4% of people over 75 have the condition.

Symptoms may include chest pain, a fluttering heartbeat, trouble breathing, lightheadedness, fatigue, swollen ankles or feet and difficulty sleeping. There are no treatments when detected early, other than trying to control risk factors such as high blood pressure, high cholesterol, obesity, diabetes and gum disease. In the later stages, it is treated by replacing the heart valve. If not treated, aortic stenosis can progress and lead to heart failure and death.

"We haven't had any medical therapies that slow the progression of stenosis," said Dr. Brian Lindman, medical director of the Structural Heart and Valve Center and an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. "We anticipate when we see it in the earlier stages that it will eventually become severe, and you'll have to have your valve replaced."

Lindman, who was not involved in the research, said he was disappointed by the results because prior research suggested "this might be an effective intervention. I very much want to identify an effective medical therapy for these patients, so there's an emotional component to it."

In the study, 365 men with aortic stenosis from four Danish hospitals were randomly assigned to receive placebo or 720 micrograms of vitamin K2 and 25 micrograms of vitamin D for two years. All were 65 to 74 years old with aortic valve calcification scores of 300 AU or higher, a measure obtained with CT scans showing calcification had begun. The scores were measured again at the end of one year and at the end of the study. They also measured calcification levels in participants' coronary arteries, which supply blood to the heart.

Researchers found no significant differences in valve calcification progression between the two groups, leading them to conclude the supplements were ineffective in slowing disease progression. However, there was some suggestion the group taking them experienced slower progression of calcification in their coronary arteries. Diederichsen said this needs to be explored in future studies. Researchers also said because the study only included men, the findings do not apply to women.

Research has suggested eating a diet high in vitamin K can benefit heart health. Vitamin K comes in two forms and is primarily found in leafy vegetables such as kale and spinach. Vitamin K2 is the less common form and is found in fermented foods, such as cheese. A study published last August in the Journal of the American Heart Association found eating a diet rich in vitamin K was associated with a lower risk for hospitalizations from cardiovascular disease related to plaque buildup in the arteries.

But Diederichsen said most foods contain insufficient levels of vitamin K2 to make an impact on heart health – with one exception. Natto, a traditional Japanese food made from fermented soybeans, is high in vitamin K2.

While vitamin K2 supplements showed no promise for treating aortic stenosis, Lindman remains hopeful researchers will find another way to slow the progression of the disease. "There are a number of potential drugs and pathways that still need to be tested."

American Heart Association News covers heart and brain health. Not all views expressed in this story reflect the official position of the American Heart Association. Copyright is owned or held by the American Heart Association, Inc., and all rights are reserved. If you have questions or comments about this story, please email editor@heart.org.

By Laura Williamson, American Heart Association News