Ask the Doctors: Studies needed to assess vitamin K, bone health

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Q: My 83-year-old mother has advanced osteoporosis. She and I recently read several articles touting the benefits of vitamin K2. Does it help strengthen bones? If so, what is the recommended daily dose? Are there side effects?

A: Vitamin K is necessary for the coagulation of blood. There are two main forms, appropriately named vitamin K1 (phylloquinone) and K2 (menaquinone). The major source of K1 is green vegetables, while K2 is produced by the bacteria in the intestine. K2 also can be obtained from fermented soy, cheese and curds.

Vitamin K helps the hormone osteocalcin create more structurally sound bone in a process called carboxylation. When vitamin K levels are low, the carboxylate form of osteocalcin is also low, leading to more fragile bone. Vitamin K also increases the activity of cells involved in bone formation and decreases the activity of cells involved in bone destruction.

Low vitamin K consumption and decreased blood levels of vitamin K are each associated with an increased risk of hip fractures in men and women, so one could assume that taking supplements would naturally help decrease the rate of hip fractures. The evidence, however, isn't completely convincing.

A 2006 analysis of seven Japanese studies looked at the K2 supplement menaquinone-4. Six of the trials assessed the impact of 45 milligrams of menaquinone-4 in women over the age of 55. The trials lasted 12 to 24 months. The supplement led to a decrease in overall hip fractures by 6 percent, spinal fractures by 13 percent and all other fractures by 9 percent. The authors also showed improvement in bone density with the use of either vitamin K1 or K2.

A 2015 combined analysis of 19 randomized controlled trials similarly analyzed the impact of K2 supplements. Ten of the studies focused on people with osteoporosis, and the researchers found, as expected, an increase in the carboxylate form of osteocalcin among those taking K2. In women without osteoporosis, there was no difference in bone density among those who took K2. Women with osteoporosis showed an improvement of spinal bone density, but no change in hip bone density. (Note that, although this was a combined analysis, two-thirds of the patients came from one study in Japan.) Lastly, a 2016 Japanese study found improvement in bone density when vitamin K2 was combined with a bisphosphonate medication.

Few studies outside of Japan have assessed the impact of K2 supplements, so it's difficult to say whether supplementation might have the same impact for Americans. The typical Japanese diet is very different from the typical American diet, so factors other than K supplementation may play a role in fracture risk and bone density -- or vitamin K may be more necessary in a Japanese diet.

A 2009 study in the United States enrolled 381 postmenopausal women with low bone density to take either vitamin K1 (1 milligram), vitamin K2 (menaquinone-4 at 45 milligrams) or a placebo for 1 year. The authors found no difference in bone density or bone markers between the three groups, except that the carboxylate osteocalcin was higher in the groups that took either form of vitamin K.

That said, vitamin K2 supplements have been linked to greater amounts of nausea and abdominal pain compared with placebo. Of special note, vitamin K should not be taken with the blood thinner warfarin because it counters the effect of the drug.

Although the devastating impact of hip fractures underscores the need for improved bone-strengthening options, we need randomized trials in the U.S. and Europe evaluating K2 supplements before we can make broader conclusions about their benefit.

Robert Ashley, M.D., is an internist and assistant professor of medicine at the University of California, Los Angeles. Send your questions to askthedoctors@mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095. Owing to the volume of mail, personal replies cannot be provided.

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