Vitamin K appears to be a relatively under-appreciated nutrient. Many articles on nutrition seem to focus on Vitamins C and E, well-known vitamin antioxidants. I, too, could probably benefit from understanding Vitamin K better than I do. So here, I report on my scan of the scientific literature about Vitamin K, including it’s vitamers, dietary sources, suggested intake, toxicity, and relationship to disease or its prevention.
A friend, knowing that I’m at least somewhat well-read when it comes to the science literature on nutrition and supplementation, recently asked me what I thought of Vitamin K. I replied that it seems like an important vitamin, one that is difficult to get enough by diet alone. I also read in Life Extension Magazine (they did an interesting review of it here) that there seems to be substantial evidence that adequate Vitamin K levels will prevent or reverse arterial calcification. I encourage all readers who want to learn more about vitamin K to read that LEF article.
But my answer to my friend was unsatisfactory to me; I really didn’t feel like I knew well enough to be describing it at much length.
So, in this article, I do a quick scan of the recent scientific literature, focusing on free-access, full-text scientific papers (so I can freely share their contents in this article). In the process, I hope to learn a bit more about the biochemistry and health benefits of Vitamin K, as well as inform you, Dear Reader.
What is Vitamin K?
Vitamin K actually refers to two structurally-similar, fat-soluble vitamins, K1 (also called “phylloquinone”) and K2 (called “menaquinones”, of which there are multiple forms). They play a prominent role in calcium metabolism and blood clotting.
There is apparently something that is called ‘Vitamin K3’ (a.k.a. “menadione”), but it seems to be a precursor to the other forms of Vitamin K, so some refer to it as a “pro-vitamin”. However, “K3” may also be a precursor of K2, in the body’s conversion of K1 to K2.
Why care about Vitamin K? Arterial calcification, cardiovascular disease, “mortality”, insulin sensitivity, and bone fractures
There is evidence that higher vitamin K intake is associated with less arterial calcification, and this calcification has been independently linked to cardiovascular disease and death (“mortality”). So, it looks like there’s a good chance that having sufficient vitamin K intake will help prevent cardiovascular disease (and death from it).
Here are some quotes from a review on this topic by Shea and Holden:
Vascular calcification occurs when calcium accumulates in the intima (associated with atherosclerosis) and/or media layers of the vessel wall. Coronary artery calcification (CAC) reflects the calcium burden within the intima and media of the coronary arteries. In population-based studies, CAC independently predicts cardiovascular disease (CVD) and mortality…..Phylloquinone [one form of vitamin K] is the primary dietary form of vitamin K and available supplementation trials, albeit limited, suggest phylloquinone supplementation is relevant to CAC. Yet observational studies have found higher dietary menaquinone [a second form of vitamin K], but not phylloquinone, to be associated with less calcification…..
Vitamin K and insulin resistance (Type 2 Diabetes)
There has been at least one study showing that vitamin K supplementation improved insulin sensitivity in young, healthy men. This might be interpreted in a few different ways; perhaps this supplementation reversed a modest vitamin K deficiency in these men. Or perhaps extra vitamin K, above and beyond its normal function, has this effect of enhanced insulin sensitivity. In any case, enhanced insulin sensitivity is probably a good thing, with nearly 10% of the U.S. population having Type 2 diabetes (a disease of insulin resistance) as of 2012.
But my excitement about this one study showing vitamin K supplementation to improve insulin sensitivity in men needs to be tempered just a bit. I found a different study showing no change in insulin sensitivity with vitamin K supplementation in postmenopausal women. This study, published in 2010, said:
Twenty-one community-dwelling postmenopausal women received 1 mg phylloquinone daily for 12 mo (experimental group), and 21 subjects were treated with a placebo during the same period (control group)…..In postmenopausal women, phylloquinone administration is not associated with changes in insulin secretion and action despite reductions in ucOC concentrations. Changes in ucOC concentrations do not alter glucose metabolism in women.
So again, possible causes of these different results could be:
- A noteworthy difference between men and women
- A noteworthy difference between pre- and post-menopausal women (perhaps in pre-menopausal women, a positive effect on insulin sensitivity would have been observed)
- Perhaps the form or dose of vitamin K makes a difference
- Or something else I’m not thinking of
At any rate: it’s a bit promising to me, since the positive result in the previous study was in a male cohort (spoiler alert: I’m male).
Vitamin K and bone health
Because vitamin K apparently affects calcium metabolism, and calcium is a very important part of bone health, I wonder if vitamin K has any effect on bone health or bone mineral density (also known as “BMD”). I scanned the scientific literature on this topic. I remind readers (as I often will) that scientific results between studies are rarely consistent. One can’t confidently conclude a hypothesis is “true” or “false” by the result of a single study. For myself, I think of each study as a certain amount of “weight” toward supporting or denying a given hypothesis (such as the hypothesis “vitamin K supplementation improves bone health). Keep this in mind as I report what I found during a quick scan of the scientific literature on bone mineral density.
I found one study on vitamin K supplementation on bone loss in elderly people published in 2008. From the abstract of the study (emphases mine):
Design, Participants, and Intervention: In this 3-yr, double-blind, controlled trial, 452 men and women (60–80 yr) were randomized equally to receive a multivitamin that contained either 500 μg/d or no phylloquinone plus a daily calcium (600 mg elemental calcium) and vitamin D (400 IU) supplement.
Main Outcome Measures: Measurements of the femoral neck, spine (L2–L4), and total-body BMD, bone turnover, and vitamins K and D status were measured every 6–12 months. Intent-to-treat analysis was used to compare change in measures in 401 participants who completed the trial.
Results: There were no differences in changes in BMD measurements at any of the anatomical sites measured between the two groups. The group that received the phylloquinone supplement had significantly higher phylloquinone and significantly lower percent undercarboxylated osteocalcin concentrations compared with the group that did not receive phylloquinone. No other biochemical measures differed between the two groups.
Conclusions: Phylloquinone supplementation in a dose attainable in the diet does not confer any additional benefit for bone health at the spine or hip when taken with recommended amounts of calcium and vitamin D.
My summary: it looks like they tried to control for calcium deficiency by supplementing with vitamin D and calcium, which seems wise (calcium deficiency could have made the result negative, regardless of whether vitamin K was good for BMD). The study went pretty long (as long as 36 months). Even after controlling for vitamin D and calcium, there was no reported change in BMD. Possible reasons:
- The type of vitamin K supplemented was not helpful for bone mineral density (BMD) they used phylloquinone; I discuss at the end of this article that K2 “menaquinones” might be much more helpful.
- Many patients have other, serious problems which negatively affect BMD or calcium metabolism
- Vitamin K actually doesn’t help at all for improving BMD
In a different study published in 2009 (a literature review, which are often a good place to start when studying any topic), the authors evaluated vitamin K and a different bone-health-related outcome measure than BMD: fracture risk. The authors of this study report (from the abstract; emphases mine):
Although systematic review and meta-analysis of randomized controlled trials (RCTs) have concluded that vitamin K is effective in preventing fractures, the effect of vitamin K on the skeleton remains a matter of controversy. The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women…..The results of these [randomized controlled trials] showed that vitamin K1 and vitamin K2 supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K1 and vitamin K2 supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. The review of the reliable literature confirmed the effect of vitamin K1 and vitamin K2 supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.
I’m inclined to feel more confident about the conclusions from a literature review, than I am from a single experimental study. It turns out this literature review found, too, that studies on vitamin K in relation to bone health tended to not show a change in BMD, even though fracture risk was reduced with higher vitamin K status or intake.
Vitamin K supplementation and osteoporotic fractures
More specifically addressing the question of bone fractures in the context of osteoporosis, one review article published in 2012 wrote in its abstract:
Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women.
So, it appears that this benefit might be confined to postmenopausal women only (since that’s all the review article concentrated on).
Absorption of Vitamin K
So, if you’re considering getting some more vitamin K, what should you learn next? One thing to consider is that vitamin K is fat-soluble.
“The intestinal absorption of vitamin K follows a well-established pathway that applies to most dietary lipids, which includes bile salt- and pancreatic-dependent solubilization, uptake of mixed micelles into the enterocytes, the packaging of dietary lipids into CM” [Maximus: chylomicrons, I presume), “and their exocytosis into the lymphatic system
This is why Vitamin K is considered to be a “fat-soluble” vitamin; it’s absorbed just like other dietary fats, needing solubilization by bile acids. If one has any chemistry background, one might guess this from the picture of Vitamin K1 above. The fairly large molecule has very few oxygen (“O”) atoms given the number of carbon atoms, suggesting it is not very soluble in water.
In short: take Vitamin K with fat to help ensure it’s absorbed.
It also turns out that this solubilization is very important in Vitamin K absorption. Gijsbers et al. (1998) report that compared to a detergent-solubilized Vitamin K supplement, only 4% of Vitamin K from spinach alone (with no fat) was absorbed in humans. So, if you’re not eating fat with it, and have a well-functioning gall bladder, your absorption of Vitamin K may be impaired.
About supplemental Vitamin K: from scanning the scientific literature, it looks like this can quickly get complicated. One study by Sato et al. (2012) observed that the Vitamin K type called MK-4 was not absorbed with a meal, but the type MK-7 was. So, there appears to be some variability with regard to which types are absorbed (more on this below).
Sources of Vitamin K
Spinach is a good source of certain forms of vitamin K
I have been occasionally visiting the World’s Healthiest Foods website for around 7 years now. Their front page is getting too cluttered for me, so here is their page of what they consider the “world’s healthiest foods”. They have a pretty good summary of foods that contain the most Vitamin K (and for any vitamin and mineral – that’s helpful), as well as a thorough description of the biochemistry and health effects of Vitamin K. I’m a little concerned that these dietary sources from the World’s Healthiest Foods website doesn’t make a distinction between K1 and K2, which might be very important for getting vitamin K’s health benefits (K2 appears to be better – see the next section for more about that).
The form of Vitamin K seems to matter (K2 “menaquinones”> K1 “phylloquinone”)
Finally, I want to comment briefly on the different forms of vitamin K. It appears that the form of vitamin K supplemented might matter considerably when trying to preserve or improve one’s health. That LEF article on vitamin K I mentioned at the beginning of this article references studies done comparing vitamin K1 (“phylloquinone”) and K2 (menaquinones, which include “MK-4” and “MK-7”). Apparently, vitamin K2 is superior for both raising blood levels of vitamin K, as well as health outcomes with supplementation.
That LEF article reports (emphases mine):
In a fascinating study, rats given vitamin K1 plus warfarin were not protected against arterial calcification. The scientists fed rats a diet containing warfarin plus vitamin K1, vitamin K2 (MK-4), or both vitamin K1 and K2 (MK-4). None (0%) of the rats that received vitamin K2 developed arterial calcification, while 100% of the rats that received vitamin K1 without vitamin K2 displayed calcification in the aorta and carotid arteries! A more recent study showed that higher-dose vitamin K decreased arterial calcium content by 50% in rats. What makes this finding so remarkable is that most people over age 30–40 already have some degree of arterial calcification and up until now have had no means to reverse it.
One of the most convincing studies showing the cardioprotective benefits of K2 can be seen in a large-scale, well-controlled trial called the Rotterdam Heart Study—a Dutch trial that tracked 4,800 participants for seven years.
The Rotterdam Heart Study revealed that participants who ingested the greatest quantities of vitamin K2 in their diet experienced a 57% reduction in death from heart disease compared with people who ingested the least. The same relationship did not hold for vitamin K1.
“Fascinating” indeed. And exciting.
Personally, I just supplement with LEF’s Super K. It’s cheap (about $7/month with an LEF membership, and I take it every other day, so it costs me more like $3.50/month), and it has both MK-4 and MK-7, as well as K1.
Kale has quite a lot of vitamin K in it, but may not have much of the optimal forms.
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