I’m taking another break from vitamin K2 to report on a study that a reader passed on regarding methylcobalamin (1).
There has been very little testing of methylcobalamin and so I normally recommend taking cyanocobalamin because it is a more stable form of vitamin B12 and there are anecdotal reports of people needing large doses of methylcobalamin to achieve results.
A 2011 clinical trial from Korea sheds some light on this issue. The study was done with people who had their stomachs removed (gastrectomy) due to cancer. Patients who have had a gastrectomy can no longer produce intrinsic factor, a molecule required for efficient B12 absorption, and they are typically given B12 injections.
In this trial, patients took 1,500 µg of methylcobalamin each day.
At baseline, their B12 levels were an average of 170 pg/ml and 24 out of 30 had tingling in their hands and feet, the traditional sign of vitamin B12 deficiency. Many had other indicators as well, including elevated homocysteine (an average of 17.5 µg/l). Over the course of the 3 month trial, vitamin B12 levels steadily increased to an average of 810 pg/ml, homocysteine steadily decreased to 11.4 µg/l, 28 patients experienced symptom relief, and 16 patients were free of all symptoms.
A drawback to this trial is that it did not have a placebo group; all the patients knew they were receiving vitamin B12. But these results are, in my opinion, too impressive to be due simply to placebo and based on the homocysteine and symptom improvement, it appears safe to say that 1,500 µg per day of methylcobalamin should be enough for just about anyone.
1. Kim HI, Hyung WJ, Song KJ, Choi SH, Kim CB, Noh SH. Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Ann Surg Oncol. 2011 Dec;18(13):3711-7. | link
In Vitamin K2: Part One and Vitamin K2: Part Two, I reported some weak associations suggesting that vitamin K2 (found in animals foods), but not vitamin K1 (found in plant foods), might play a role in protecting against heart disease.
Part Three is on yet another study from The Netherlands, this time a component of the The Rotterdam Study published in 2004 (1). Unlike the other other two studies, this one had much stronger results.
The study had a prospective component in which 4,807 men and women aged 55 years and older were followed for an average of 7.2 years. At baseline, all participants were given an ECG to determine if they had heart disease and were excluded if they did.
Vitamin K2 intake was positively associated with the intake of total fat, saturated fat, and calcium, as well as body mass index, and diabetes; it was inversely associated with intake of polyunsaturated fatty acids.
For vitamin K1, the results once again showed it not to be associated with a reduced risk of heart disease (nor mortality).
In model 1, that adjusted for age, gender, and total energy intake, when comparing the group with the highest daily intake (> 33 µg) of vitamin K2 to the lowest (< 22 µg), K2 was associated with a reduced risk of heart disease (.71, .51-1.00), death from heart disease (.59, .35-.99), and overall mortality (.81, .67-.98). These findings are borderline statistically significant.
However, in model 2 that adjusted for factors in model 1 and also body mass index, smoking status and history, diabetes, education, and intake of alcohol, saturated fat, polyunsaturated fat, flavonols (a group of antioxidants), and calcium, the associations became much stronger for heart disease (.59, .40-.86), death from heart disease (.43, .24-.77), and overall mortality (.74, .59-.92).
There was also a cross-sectional component of the study in which 4,473 people were given x-rays at baseline to determine if they had aortic artery calcification. Vitamin K2 intake was inversely associated with severe calcification in model 1 (.56, .39-.80) and model 2 (.48, .32-.71).
As for the possibility of reverse causation (in which people with poor health decided to eat fewer foods high in K2), the authors said, “In contrast to phylloquinone [K1], intake of menaquinone [K2] (mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese), is not related to a healthy lifestyle or diet, which makes it unlikely that the observed reduction in coronary risk is due to confounding. Subjects with a history of MI were excluded from the analysis to avoid bias that may arise from intentional changes in diet.”
They also said, “We hypothesize that menaquinones in cheese (MK-8 and MK-9) could exert a beneficial effect in the cardiovascular system and that the high cheese consumption in France and the Mediterranean countries may possibly account for lower prevalences of [heart disease].”
Although the results from this one study are fairly strong, it takes a lot more than one cohort study to justify recommendations for preventing chronic disease. You could combine these results with those for the studies reviewed in Vitamin K2: Part One and Part Two, but those studies are not nearly as strong. Finally, all of these studies included only older people from The Netherlands; we need data from other regions.
In a relatively quick search of PubMed, I could not find any other studies looking at the association between vitamin K2 and heart disease in humans. In fairness to me, the search was quick because so few results were returned. But I will be looking around some more and also reviewing more studies on vitamin K2 and other diseases in the upcoming days.
At this point in time, I am not going out to get vitamin K2 supplements. However, I’m also not dismissing the idea that in a few weeks from now, I might be.
1. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. | link
In Vitamin K2: Part One, I reported on a study from EPIC that followed 16,000 women for 8 years and found an arguably borderline statistically significant, beneficial association for vitamin K2 and the prevention of heart disease.
The same group of researchers, from The Netherlands, published another study of 564 post-menopausal women, comparing their vitamin K intakes to coronary artery calcification (1).
The theory is that vitamin K activates proteins that sequester calcium. Vitamin K1 is cleared from the bloodstream for use in the liver while vitamin K2 is much more likely to be found in the vessel walls where it can prevent calcium from being deposited in the vessel walls.
As predicted, the results showed that vitamin K1 was not associated with a reduced amount of coronary artery calcification. Vitamin K2, however, was associated with reduced risk in a borderline statistically significant manner.
In comparing the highest one-fourth of intake to the lowest, in the model adjusted only for age, the risk was barely statistically significant at 0.82 (0.68–0.99).
In the model adjusted further for smoking, diabetes, BMI, hypertension, educational attainment, HDL and LDL cholesterol, the risk was 0.85 (0.72–1.02); not statistically significant.
And in the model adjusted even further for alcohol consumption and energy-adjusted intake of protein, calcium and fiber the risk was back to statistically significant at 0.80 (0.65–0.98).
Interestingly, the women in the highest intake of vitamin K2 also had the highest intake of calcium at 1,317 mg per day, and calcium and vitamin K2 intakes were significantly associated with each other. Ditto for protein (but not fiber).
Why would women with the highest calcium intake have the lowest amount of artery calcification? Well, as I have written about before, dietary calcium does not appear to cause calcification of the arteries until calcium intakes reach at least 1,400 mg per day, if at all (see Calcium Supplements – The Final Word?).
MK4 was the only vitamin K2 subtype that showed an individual trend towards less artery calcification.
People should keep in mind that this study was cross-sectional, making it a less reliable form of evidence than a prospective study (other things being equal).
In summary, vitamin K2 intake was weakly associated with a lower risk for artery calcification.
1. Beulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93. | link
Quick detour from vitamin K to report on a new study about the blood type diet.
I have posted a number of times about the blood type diet, as described in the book Eat Right For Your (Blood) Type (1996), by Peter D’Adamo (see posts).
I lived in Atlanta during the late 1990s and it was quite popular there. And why not? Who wouldn’t want to eat right for their blood type?
In my humble opinion, while the diet and book are a stroke of marketing genius, it is a pretty far-fetched piece of science. I’m talking way out there. La la land.
I should probably mention that this humble opinion is shared by every medical doctor, nutrition research scientist, and dietitian I’ve ever heard on the subject.
Most unfortunately, the blood type diet has never been tested with an actual clinical trial. Rather RDs, MDs, PhDs, and even WMDs, dismiss it by saying that there is simply no evidence to support it. And while I’m terribly sympathetic to the idea that there is no evidence to support it, I don’t think this is satisfying to a layperson who reads the book. When the subject comes up, I can almost see them thinking to themselves, “You silly dietitians are just brainwashed by the grain and dairy lobbies,” or whatever they think might be biasing that particular dietitian (such as the desire to promote veganism among people with all blood types).
We now have at least a cross-sectional study that provides more evidence about the (lack of) effectiveness of eating right for your blood type (1).
The participants were 993 women and 462 men, aged 20 to 29 years old, taking part in the Toronto Nutrigenomics and Health study.
Based on the food items listed in Eat Right for Your Type, subjects received a positive point for consuming a serving of a recommended food item for one’s blood type and a negative point for eating a food to avoid. The foods that were not listed either to consume or avoid were ignored.
Here is an idea of what the diets are like:
A – almost vegan (no meat, little dairy)
B – semi-vegetarian (low grains, more dairy)
AB – very similar to B with a little less fruits and vegetables and a little more meat
O – paleo (high-meat, high-vegetables, no grains and little dairy)
The data was analyzed in two different ways.
In the first, the entire population was separated into thirds according to their scores for each diet and regardless of their blood type. To make a long story short, the type A and type AB diets fared the best in terms of disease risk factors (see the abstract linked below for the details).
The second set of analyses had four separate sub-analyses in which everyone was divided according to how close they ate the particular blood type diet being examined. Then the people with that blood type were compared to the rest of the population. According to the authors, “no significant interaction effects were observed between diet adherence and blood group for most of the risk factors, suggesting that effects of following ‘Blood-Type’ diets is independent of an individual’s blood group.”
Note that they said no significant interaction was found for most of the risk factors. Given the number of data points they compared (hundreds), it is not surprising that they found some statistically significant, but still rather weak associations, and, in my opinion, the associations they found were inconsistent enough to be meaningless.
With this study, I think we finally have something that moves beyond “no evidence to support” to “evidence to disprove.” However, it still isn’t going to be very persuasive to a believer, especially given how hard it is to explain.
Clinical trials are expensive and since no researcher actually believes there’s anything behind the blood type diet, it’s no wonder that more money hasn’t been forked out to test it.
The diet seems to have gone out of fashion, but if it experiences a resurgence, it might be time to bite the bullet and spend the money on a clinical trial that, with little doubt, would finally allow us to show people that there is no need to eat according to your blood type.
1. Wang J, García-Bailo B, Nielsen DE, El-Sohemy A. ABO Genotype, ‘Blood-Type’ Diet and Cardiometabolic Risk Factors. PLoS One. January 15, 2014.
DOI: 10.1371/journal.pone.0084749 | link
In the past year and a half, vitamin K2 has been the second most common topic, after oxalate, that I’ve received questions about.
Vitamin K2 is relevant to vegan diets because the only plant food that has an appreciable amount is natto, a fermented soy product that most of us don’t eat and which has a taste many people don’t care for.
Until recently, mainstream science has considered K2 to be unnecessary both because people can get the same benefits from K1 (which is found in leafy greens) and because K2 is made by common intestinal bacteria. But then research came out at the end of the 00′s suggesting that K2 might have benefits.
My plan is to review the studies on K2 more closely to try to figure out to what extent, if any, vegans are setting themselves up for heart disease, osteoporosis, or other diseases by not having an intake of vitamin K2.
A quick refresher on the forms of vitamin K:
– Phylloquinone is vitamin K1 and found primarily in plant foods, especially leafy greens.
– Menaquinone (forms MK4 through MK10) is vitamin K2. It is found in animal tissues and made by bacteria.
More background info can be found in the article vitamin K at VeganHealth.org.
The first study I’ll review is from one of the two Dutch cohorts of the European Prospective Investigation Into Cancer (EPIC). It was published in 2009 (1). They followed over 16,000 women for an average of 8 years.
The researchers did a fairly rigorous job in measuring vitamin K intake which ranged from 1 – 128 µg, with an average of 29 µg.
They found that every 10 µg increase in vitamin K2 intake was associated with an decreased risk of heart disease but the finding was of only borderline statistical significance (.92, .85 – 1.00). Interestingly, even though they divided the group into quartiles of vitamin K2 intake, they did not report on the relative risk between the different quartiles.
In contrast, intake of vitamin K1 was not associated with risk of heart disease.
Unlike Aglaée Jacob, the authors caution against getting vitamin K2 through typical animal foods:
“Thus, although our findings may have important practical implications on [cardiovascular disease] prevention, it is important to mention that in order to increase the intake of vitamin K2, increasing the portion vitamin K2 rich foods in daily life might not be a good idea. Vitamin K2 might be, for instance more relevant in the form of a supplement or in low-fat dairy. More research into this is necessary.”
I’m skeptical that their findings have important practical implications for cardiovascular disease prevention, but I’ll be reviewing other papers in the days ahead to find out more.
1. Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10. | link
“According to the two men’s research, the insects are 69 percent protein by dry weight as compared with 31 percent for chicken breast and 29 percent for sirloin steak; they provide more iron than beef does and nearly as much calcium as milk. They produce one-eightieth the amount of methane that cattle do, and need one-twelfth their feed, based on 100-gram portions of each. And they can reproduce quickly and don’t require acres of grassland to graze.”
A move from people eating mammals and birds to crickets is something I can get behind.
Amy’s has a gluten-free, vegan burrito. More info.
Vitamin D & Bone Pain: A Study of One
I received a nice note from a reader:
“You may want to know that after reading your book and watching your presentation at the Vegetarian Society of Hawaii, I started taking Vitamin D in winter and autumn, which “cured” my muscular pain. Also, your recommendations helped my mother fix her high homocysteine level. Since she is vegetarian and not vegan, I thought she needed just a little B12 (wrong!).”
Food for Thought: Adopting an animal-friendly menu policy
If you are involved with an animal shelter that doesn’t serve vegan food at their functions, check out Animal Place’s Food for Thought campaign which strives to make shelter events friendly to all animals. More info.
Dr. Greger just finished releasing a 4-part video series on nutrition and eyesight that I found very informative. Link.
A study was released a couple weeks ago from Austria – a cross-sectional survey of eating habits and various health outcomes. But it has so many issues that I don’t think it’s worth commenting on except in the interest of being thorough in documenting the research on vegetarians.
Trying to infer dietary effects on health by using cross-sectional studies is always fraught with problems, but this study had even more than usual.
The diet categories included vegan, lacto-ovo-vegetarian, and pesco-vegetarian which was fine; in the final analysis all of these were grouped as “vegetarians.” The remaining diet groups were:
– carnivorous diet rich in fruits and vegetables
– carnivorous diet less rich in meat
– carnivorous diet rich in meat
This is unusual, and they didn’t define them even for the participants when they were asking them which category they belonged to.
For the health outcomes, instead of a list of diseases and incidence rates, they created a number of indicators that I would not have much confidence in. Finally, their p-values made little sense to me.
To sum up their findings, they say, “Both a vegetarian diet and a carnivorous diet rich in fruits and vegetables were related to the best self-rated health and the lowest incidence of chronic conditions. However, the quality of life was better in subjects who consume a carnivorous diet rich in meat. Nevertheless, as diets rich in fruits and vegetables were associated with better health as well as better health-related behavior, these diets should be recommended, and public health programs will be needed to reduce the health risk due to nutritional factors.”
So for what it’s worth, I suppose this is good news.
1. Burkert NT, Freidl W, Großschädel F, Muckenhuber J, Stronegger WJ, Rásky E. Nutrition and health: different forms of diet and their relationship with various health parameters among Austrian adults. Wien Klin Wochenschr. 2013 Dec 17. [Epub ahead of print] | link