I have finally finished researching vitamin K2 and heart disease. I've already published all of the research summaries in this blog, so I will not repeat them again here. However, if you would like to see all of them in one place, check out Vitamin K2 and Cardiovascular Disease at VeganHealth.org.
Here is a summary:
Preliminary evidence suggests that vitamin K2 could reduce the risk of heart disease, but the research is mixed and the positive findings come from only one country. More research is needed. If vitamin K2 reduces the risk of heart disease, it does not mean that eating animal products high in vitamin K2 will also reduce the risk, since animal products often contain other components that may increase the risk of heart disease more than vitamin K2 decreases it. Clinical trials are needed and, luckily, at least one is underway (1).
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I don’t think it is a terrible article – there are nutrients that vegetarians and vegans have to pay attention to in order to achieve optimal health and he hits on most of them. However, he makes it seem like all vegetarians or vegans are going to have problems with all of those nutrients, which is not the case.
Vitamin B12 is one example of his overblown concern. He emphasizes the myriad of problems that can occur from B12 deficiency, which are quite frightening. In fact, if you allow vitamin B12 deficiency to go on long enough, you’ll die – and along the way some pretty bad things are going to happen. But all you need to know is to take a supplement and you’ll likely have a better B12 status than your average omnivore.
I’m not going to go through every nutrient he mentions and point out what I think he got right and wrong – but you can check out any of them at VeganHealth.org.
Kresser asks, “But don’t vegetarians live longer than omnivores?” He answers, “While it’s true that some observational studies suggest that vegetarians and vegans enjoy longer lifespans, these studies were plagued by the ‘healthy user bias’.”
He goes on to explain that people with healthy lifestyle habits choose to be vegetarian and so the lower mortality of vegetarians can be explained simply by other lifestyle factors.
Kresser singles out the Health Food Shoppers (HFS) study as being the one study that has risen above healthy user bias, and points out that it showed vegetarians to be no better off than non-vegetarians.
In fact, the HFS study is one of the weakest study designs of all the cohort studies comparing mortality rates of vegetarians. In the 1996 paper on the HFS that Kresser cites, the authors state:
“Another limitation is that the questionnaire was short and did not include several important food groups (for example, dairy products, fish, alcoholic drinks), did not allow us to estimate energy intake, and did not include other factors known to be associated with health (exercise, socioeconomic status, past smoking habits). We were therefore unable to explore whether the significant associations observed were partly due to confounding by other dietary or non-dietary variables.”
In contrast, the Adventist Health Study-2, which produced the most recently published paper on vegetarian mortality, adjusted for smoking, exercise, income, education, alcohol, geographic region, and sleep. They found that vegans had a 15% lower rate of early death than non-vegetarians (this finding was not statistically significant, though very close).
Additionally, there are good reasons why a vegan diet might lead to lower mortality – much lower LDL cholesterol levels, body mass index, and hypertension. There is very strong evidence to suggest vegans have only a fraction of the risk of type 2 diabetes, partly due to plant iron being harder to absorb (link).
Kresser says, “Still, while it may be possible to obtain adequate nutrition on a vegetarian diet, it is not optimal – as the research above indicates.”
I will agree that meat-eating is the more convenient choice for getting some nutrients – though sometimes it’s an all too convenient way to get too many, such as in the case of iron, saturated fat, and cholesterol.
While we don’t yet know for certain if a vegan diet increases the chance of living longer, when you consider the dearth of studies showing that meat-eaters live longer than vegetarians, it seems like a jump to conclude that meat-eating is the “optimal” choice.
In doing my final search for studies on vitamin K2 and cardiovascular disease (CVD), I came across one on type 2 diabetes (1). Since diabetes can be fairly related to CVD, I decided to review it.
As with most of the studies on vitamin K2, the population was from The Netherlands. And just like the research on stroke, it was using the combined data from the Prospect and MORGEN arms of EPIC. After excluding people with prevalent diabetes at baseline, they had a study population of 38,094 men and women. The average daily intake of vitamin K2 was 49 µg in the highest one-fourth versus 15 µg in the lowest one-fourth.
After a median follow-up of 10.3 years, and adjusting for many variables (2), in comparing the highest intakes to the lowest, there was a trend towards a lower risk of diabetes, although the finding was not statistically significant (.80, .62–1.02). When looking at what effect an increase of 10 µg had on the risk of diabetes over the entire range of intakes, there was a borderline statistically significant beneficial association (.93, .87–1.00; p < .038).
The researchers had a number of guesses as to why vitamin K2 might be protective against diabetes, all of which amounted to an indirect effect on insulin sensitivity. They also pointed out that the fact that vitamin K2 comes from animal products might have hidden the true strength of a beneficial effect on type 2 diabetes.
1. Beulens JW, van der A DL, Grobbee DE, Sluijs I, Spijkerman AM, van der Schouw YT. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care. 2010 Aug;33(8):1699-705. doi: 10.2337/dc09-2302. Epub 2010 Apr 27. | link
2. Variables adjusted for: age, sex, waist circumference, smoking status, physical activity, hypertension, education, alcohol consumption, total energy intake, saturated fat, polyunsaturated fat, monounsaturated fat, protein, fiber, calcium, vitamin C, and vitamin E.
I was getting ready to publish my conclusions regarding vitamin K2 and cardiovascular disease and decided to check PubMed one last time to make sure nothing had come out recently. Sure enough, there was a paper on vitamin K2 and stroke from December!
This study combined the data from the two Dutch cohorts of EPIC, Prospect and MORGEN (1). After excluding people with prevalent stroke or cardiovascular disease at baseline, they had a study population of 35,476 men and women. The average daily intake of vitamin K2 was 49 µg in the highest one-fourth versus 16 µg in the lowest one-fourth.
There was no association found between vitamin K2 and incidence of stroke either with all stroke combined, or with ischemic stroke and hemorrhagic stroke analyzed separately. None of the vitamin K2 sub-types were significantly associated with a reduced risk for stroke.
The researchers considered this finding to be in contrast to some previous population studies that found fermented dairy products to be associated with a lower risk of stroke.
They also pointed out that recent research has suggested that artery calcification (which may be associated with lower intakes of vitamin K2) may not be a cause of stroke as it is for heart disease, and that might explain some of the inverse associations found between vitamin K2 and heart disease whereas none was found for stroke in this study.
This was the only study they, or I, are aware of examining the association between vitamin K2 and stroke.
1. Vissers LE, Dalmeijer GW, Boer JM, Monique Verschuren WM, van der Schouw YT, Beulens JW. Intake of dietary phylloquinone and menaquinones and risk of stroke. J Am Heart Assoc. 2013 Dec 10;2(6):e000455. | link
In 2009, a 4-week clinical trial putting overweight people on a low-carbohydrate vegan diet, known as the Eco-Atkins, was released. I mentioned it in my article Of Oil and Ethics.
It was promising because after 2 weeks, LDL cholesterol levels went from 174 to 134 mg/dl. After 4 weeks, LDL cholesterol levels appeared to be stuck, at an average of 136 mg/dl. Participants also lost weight and had some other improvements, and they reported feeling more satisfied than did the participants in the control diet (a lacto-ovo, semi-low-fat vegetarian diet).
It took the researchers awhile to publish it, but they just released a report on what happened to the participants after 6 months (1). Unfortunately…not much. Their LDL cholesterol levels were back up to 157 mg/dl at the end of 6 months. They had still lost some body weight (15 lbs) and their risk for heart disease had improved over baseline.
The analysis was done on an intention-to-treat basis which means that people who didn’t stick with the diet were included in the final results (or their numbers were estimated). Overall diet compliance was fairly low at only about 34% of the recommended foods.
For those on Eco-Atkins, percentage of fat went up from their normal diet, but only from 34.4 to 36.0% of calories. And when you consider that their calories went down, from 1,840 to 1,388, their total fat intake actually went down, from 70 to 56 g.
The authors suggested that increases in monounsaturated fat (MUFA) could account for some of the improvements in heart disease risk factors, but their MUFA fat intake, while increasing slightly on a percentage basis, actually went down in total, from 27 to 23 g.
When you add in the fact that fiber increased from 12 to 21 g, it seems that all of the improvements could simply be attributed to a lower intake of calories and an increase in fiber.
Still, the Eco-Atkins did better than the 28% fat, lacto-ovo vegetarian diet. However, at baseline, the participants in the lacto-ovo group had an average daily caloric intake of 1,598, which was 242 calories less than the Eco-Atkins dieters. During the study, the lacto-ovo vegetarian dieters ate a very similar amount of calories to the Eco-Atkins dieters (1,347 and 1,388 respectively). As such, the Eco-Atkins dieters had a lot more room for improvement which could possibly explain why they did somewhat better.
In conclusion, this trial provides evidence that fiber is good and calories are bad for lowering cholesterol and losing weight.
1. Jenkins DJ, Wong JM, Kendall CW, Esfahani A, Ng VW, Leong TC, Faulkner DA, Vidgen E, Paul G, Mukherjea R, Krul ES, Singer W. Effect of a 6-month vegan low-carbohydrate (‘Eco-Atkins’) diet on cardiovascular risk factors and body weight in hyperlipidaemic adults: a randomised controlled trial. BMJ Open. 2014 Feb 5;4(2):e003505. | link
The lower absorption from zinc oxide was almost entirely due to three participants who absorbed much lower amounts, with two absorbing almost none.
The authors reviewed other studies which indicated that zinc sulfate and zinc acetate might also be absorbed well.
Interestingly, they noted that none of the study subjects were vegan. They didn’t explain why they pointed this out, but it’s good to know that vegans are on their radar.
1. Wegmüller R, Tay F, Zeder C, Brnic M, Hurrell RF. Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide. J Nutr. 2014 Feb;144(2):132-6. | link
In June of 2013, the Cochrane Collaboration updated their meta-analysis of double-blinded, placebo-controlled randomized controlled trials testing whether zinc is useful in treating or preventing the common cold (1).
Their analysis included 16 trials for treating colds, with a total of 1,387 participants. Intake of zinc was associated with a significant reduction in the duration of the cold, reducing it by about one day. It did not show a benefit in reducing the severity of the symptoms.
Of the 16 trials, 11 showed benefit for zinc, while the others did not. The authors reported that trials showing no benefit have been criticized for using too little zinc or a form that is not bioavailable. (Zinc gluconate is a good choice for bioavailability; more on that in a future post.)
The analysis also included two preventive trials with a total of 394 participants. Both studies found a statistically significant benefit from zinc supplementation with the combined incidence of developing a cold reduced by 36% (0.64, 0.47-0.88).
As for how zinc helps treat or prevent colds, the authors had a few explanations. Zinc ions have an affinity for the receptor sites where the cold virus (rhinovirus) attaches to the nasal passages. It can bind both to the virus and to the nasal passages, thus blocking the ability of the virus to attach. Zinc might also prevent the formation of virus proteins, stabilize cell membranes, prevent histamine release, and inhibit prostaglandin metabolism.
The authors suggest treating a cold with 75 mg of zinc per day. They did not give an amount for preventing colds.
I have written before about the idea that some vegans might benefit from a zinc supplement for immune function and wound healing (see the VeganHealth.org article Zinc). A side benefit of zinc supplementation is that it can prevent cadmium absorption (see the Zinc and Alzheimer’s Disease section of the VeganHealth.org article Cadmium).
Personally, I have taken zinc for a number of years now and I have never had so few colds; those I’ve had have lasted less than a day rather than the usual week. So, whether it is a placebo or a coincidence, I continue to take zinc religiously, in two daily doses of 3.75 mg (as part of a Trader Joe’s calcium, magnesium, and zinc supplement).
1. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013 Jun 18;6:CD001364. | link
It appears that I have exhausted the research on vitamin K2 and heart disease that measures direct outcomes in humans. I will summarize that research soon.
In the meantime, I have just finished reading a 2013 double-blinded, randomized, placebo-controlled trial on the MK-7 version of vitamin K2 conducted in The Netherlands (1).
The study included 244 healthy postmenopausal women who received either 180 µg of MK-7 or a placebo in one daily dose for 3 years. Bone measurements were taken after 1, 2, and 3 years.
There were so many measurements of bone health taken in the study at various parts of the skeleton that it would be tedious to read a list of each of them and what was found. Suffice it to say that there were some statistically significant reductions in bone deterioration in the treatment group that tended not to appear until the 3rd year. There was also a trend towards fewer moderate vertebral fractures in the treatment group, but the numbers were too small to determine statistical significance. To me, the trends seem too strong to be due simply to taking so many measurements that by chance some benefits were found from the treatment.
One caveat is that the trial was funded by Nattopharma, a company that makes an MK-7 supplement.
It should be noted that 180 µg of MK-7 is a much higher dose than you can get from animal products. In the Prospect-EPIC study, MK-7 intake from animal products ranged only from 0 – 2.2 µg (2). In contrast, the fermented soybean product, natto, has much higher amounts of MK-7 (about 775 µg per 100 g (3)).
1. Knapen MH, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013 Sep;24(9):2499-507. | link
2. 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
3. Abstract of: Tsukamoto Y, Ichise H, Kakuda H, Yamaguchi M. Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and gamma-carboxylated osteocalcin concentration in normal individuals. J Bone Miner Metab. 2000;18(4):216-22. | link
A reader pointed out an abstract of a cohort study looking at heart disease and vitamin K2 intake (1), the only one I’ve seen that was not from The Netherlands.
In this case it was the EPIC-Heidelberg cohort from Germany and their findings disagreed with The Netherlands studies depicted in the previous K2 posts.
Vitamin K1 was found to be inversely associated with a fatal heart attack (.49, .25-.94), while vitamin K2 was not associated with incidence (1.21, .81–1.80) or fatal (1.09, .46–2.62) heart disease.
Results were adjusted for smoking, body mass index, waist circumference, hypercholesterolemia, high blood pressure, aspirin use, physical activity, education, and intakes of energy, fat, alcohol, calcium, and folate.
In another short report, a letter to Lancet described a trial in which people on dialysis with osteoporosis were given 45 mg/day of vitamin K2 (2). After six months, their LDL cholesterol had gone from 225 to 195 mg/dl. After treatment was discontinued, cholesterol levels returned to normal.
A couple caveats about this: 45 mg/day of vitamin K2 is about 1,000 times more than a normal intake, and these are very high LDL levels in a rather ill population which might not apply to healthy people.
1. Nimptsch K, Rohrmann S, Linseisen J, Kaaks R. Dietary intake of vitamin K and risk of incident and fatal myocardial infarction in the EPIC-Heidelberg cohort study Gesundheitswesen 2010; 72: V143-DOI: 10.1055/s-0030-1266323 | link
2. Nagasawa Y, Fujii M, Kajimoto Y, Imai E, Hori M. Vitamin K2 and serum cholesterol in patients on continuous ambulatory peritoneal dialysis. Lancet. 1998 Mar 7;351(9104):724. | link