Strokes and Diet: Part 3

Today, it’s Part Three in our four-part series on strokes and diet. 

In our first story, we investigate the drop in stroke risk as the Japanese diet became Westernized.

Stroke was the leading cause of death in Japan, but the mortality rate sharply decreased as they moved away from their traditional diets and started eating more like those in the west; so, maybe there was a protective effect of all the extra meat and dairy they started to eat. After all, their animal fat and animal protein intake were going up at the same time their stroke rates were going down.

“Protection from stroke by eating animal foods? Surely not!” commented a noted Loma Linda cardiology professor. “Many vegetarians, like myself have almost come to expect the data to indicate that they have an advantage, whatever the disease that’s being considered. Thus, it is disquieting to find evidence in a quite different direction for at least one subtype of stroke.”

Can dietary saturated fat, like that found in meat and dairy, be beneficial in the prevention of stroke risk? There appeared to be a protective association, but only in East Asian populations. High dietary saturated fat was found associated with a lower risk of stroke in Japanese but not in non-Japanese. So, what was it about the traditional Japanese diet where the Westernization of their diets made things better when it came to stroke risk? Well, at the same time their meat and dairy was going up, their salt intake was going down.

The traditional Japanese diet was packed with salt—in fact, they had some of the highest salt intakes in the world, like a dozen spoonfuls of salt a day. Before the widespread availability of refrigeration, they ate all sorts of salted, pickled, fermented foods from soy sauce to salted fish. And, in the areas that had twice the salt intake, they had twice the stroke mortality, but when the salt intake dropped do did the stroke death rates, because when the salt came down their blood pressures came down, too. And, high blood pressure is perhaps the single most important modifiable risk factor for stroke. So, it’s no big mystery why the westernization of the Japanese diet led to a drop in stroke risk.

When they abandoned their more traditional diets, their obesity rates went up, their diabetes and coronary artery disease went up, but as they gave up the insanely high salt intake their insanely high stroke rates correspondingly fell. It’s like if you look at their stomach cancer rates, a cancer closely associated with excess salt intake. Their stomach cancer rates came down beautifully as they westernized their diets away from salt-preserved foods, but of course as they started eating more animal foods like dairy, their rates of fatal prostate cancer, for example, shot through the roof. Compared to Japan, not only does the U.S. have seven times more deaths from prostate cancer, but five times more deadly breast cancer, three times more colon cancer and lymphoma mortality, and six to twelve times the death rate from heart disease. Yes, Japanese stroke and stomach cancer rates were higher, but they were also eating about six spoonfuls of salt a day.

That would seem to be the most likely explanation, rather than some protective role of animal fat, as eventually acknowledged by the official Japanese guidelines for the prevention of cardiovascular disease.

Now, one of the Harvard cohorts found a protective association between both saturated fat and trans fat for hemorrhagic strokes, prompting a “sigh of relief throughout the cattle-producing Midwest,” even though the researchers clearly concluded that, of course, we all have to cut down on animal fat and trans fat for the heart disease benefit regardless, but looking at another major Harvard cohort, they found no such protective association for any kind of stroke, and put all the studies together and zero protection across the board.

Observational studies have found that higher LDL cholesterol seems to be associated with lower risk of hemorrhagic stroke, raising the possibility that cholesterol may be a double-edged sword, decreasing the risk of ischemic stroke but increasing the risk of hemorrhagic stroke. But low cholesterol levels in the aged may just be a surrogate for nutrient deficiencies, or a sign of debilitating diseases, or maybe they’re on a combo of cholesterol-lowering drugs and blood thinners, and that’s why we tend to see more brain bleeds in those with low cholesterol? You don’t know, until you: put it to the test. Put together about two dozen randomized controlled trials, and the lower your cholesterol the better when it comes to overall stroke risk, with no significant increase in the risk of hemorrhagic stroke with lower achieved LDL cholesterol levels.

The genetic data appears mixed, with some suggesting a lifetime of elevated LDL would give you a higher hemorrhagic stroke risk, and other data suggesting more of a double-edged sword effect, but any possible excess of bleeding stroke with lower cholesterol is greatly outweighed by the protective effect against the much more common clotting stroke, not to mention heart disease, perhaps on the order of 18 fewer clotting strokes for every one extra bleeding stroke with cholesterol lowering.

If there is some kind of protective factor in animal foods, it is to be hoped that a diet can be found that still protects against killer #1, heart disease, without increasing the risk of killer #5, stroke. But first, we have to figure out what that factor is, a hunt that will continue, next.

Next up, we look at whether animal protein-induced increases in the cancer-promoting growth hormone IGF-1 help promote brain artery function.

In 2014, a study on dietary protein intake and stroke risk found that greater intake was associated with lower stroke risk, and furthermore it was the animal protein that appeared to be particularly protective. Might that help explain why vegetarians were recently found to have a higher stroke rate than meat-eaters?

Animal protein consumption increases the levels of a cancer-promoting growth hormone in the body known as IGF-1, insulin-like growth factor one, which can accelerate the progression of precancerous changes to invasive cancer. High blood concentrations are associated with an increased risk of breast, prostate, colorectal, and lung cancers, potentially explaining the association between dairy milk and prostate cancer risk, for example. But, there are also IGF-1 receptors on blood vessels; so, maybe IGF-1 promotes cancer but also brain artery integrity.

People who have strokes appear to have lower blood levels of IGF-1, but it could just be a consequence of the stroke rather than the cause. There weren’t any prospective studies over time —until 2017, and indeed higher IGF-1 levels were linked to lower risk of stroke, but is it cause and effect? In mice, the answer appears to be yes, and in a petri dish, IGF-1 appears to boost production of elastin, a stretchy protein that helps keep our arteries elastic. Higher levels are associated with less artery stiffness, but acromegaly patients, like Andre the giant, those with excessive levels of growth hormones like IGF-1 do not appear to have lower stroke rates, and a more recent study of dietary protein intake and risk of stroke, looking at a dozen studies of more than a half million people, compared to only 7 studies with a quarter million in the previous analysis, found NO association between dietary protein intake and the risk of stroke. In fact, if anything dietary plant protein intake may actually decrease the risk of stroke.

However, those with high blood pressure who have low IGF-1 levels do appear to be at increased risk of developing atherosclerosis, thickening of the artery walls leading up to the brain, but no such association was found in people with normal blood pressure. So, there may be a cautionary lesson for vegans here. Yes, a whole food plant-based diet to down-regulate IGF-1 activity may slow the human aging process, not to mention reducing the risk of some of the common cancers that plaque the Western world. But, perhaps, the ‘take-home’ message should be that people who undertake to down-regulate IGF-1 activity by cutting down on animal protein intake as a pro-longevity measure should take particular care to control their blood pressure to preserve their cerebrovascular health, the health of their arteries in their brain. In particular, they should keep salt intake relatively low while ensuring an ample intake of potassium to keep their blood pressures down. So, that means avoiding processed foods and avoiding added salt, and in terms of potassium-rich foods, beans, sweet potatoes, and dark green leafy vegetables.

So, might this explain the higher stroke risk found among vegetarians? No. Why? Because dairy and egg whites are animal proteins too. Only vegans have lower IGF-1 levels in both men and women; so, low IGF-1 levels can’t explain why higher rates of stroke were found in vegetarians. So, what is it already? I think the best explanation for the mystery is something called homocysteine, which I’ll cover, next.

Leonardo da Vinci had a stroke. Might his vegetarian diet have been to blame? “His stroke… may have been related to an increase in homocysteine level because of the long duration of his vegetarian diet.” A suboptimal intake of vitamin B12, which is common in those eating plant-based diets unless they take B12 supplements or regularly eat B12-fortified foods, can lead to an increased level of homocysteine in the blood, which is accepted as an important risk factor for stroke. “Accepted” may be overstating it; there’s still controversy surrounding the connection between homocysteine and stroke risk. But, those with higher homocysteine levels do seem to have more atherosclerosis in the carotid arteries that lead up to the brain compared to those with single digit homocysteine levels, and do seem to be at higher risk for clotting strokes in observational studies, and more recently bleeding strokes, as well as increased risk of dying from cardiovascular disease, as well as all causes put together.

Even more convincing is the genetic data. About 10% of the population has a gene that increases homocysteine levels about 2 points, and they do appear to have significantly higher odds of having a stroke. Most convincing would be randomized double-blind placebo-controlled trials to prove homocysteine lowering with B vitamins can lower strokes, and that indeed appears to be the case for clotting strokes, strokes with homocysteine-lowering interventions more than 5 times as likely to reduce stroke compared with placebo.

Ironically, one of the arguments against the role of homocysteine in strokes is that assuming that vegetarians have lower vitamin B12 levels then the incidence of stroke should be increased among vegetarians, but supposedly this wasn’t the case, but it had never been tested, never been studied… until, now, and vegetarians do appear to be at higher risk and no wonder, as about a quarter of the vegetarians and nearly three-quarters of the vegans studied were B12 depleted or deficient, resulting in extraordinarily high homocysteine levels.

Why so much B12 deficiency? Because only a small minority were taking a dedicated B12 supplement. And, unlike the U.S., B12 fortification of organic foods isn’t allowed; so, while U.S. soymilk and other products may be fortified with B12, UK products may not. We don’t see the same problem among U.S. vegans in the Adventist study, presumed to be because of the B12 fortification of commonly eaten foods. It may be no coincidence that the only study I was able to find that showed a significantly lower stroke mortality risk among vegetarians was an Adventist study.

But. start eating strictly plant based without B12 fortified foods or supplements, and B12 deficiency can develop, but that was only for those not eating sufficient foods fortified with B12. Those eating plant-based not being careful about getting a regular reliable source of B12 have lower B12 levels and consequently higher homocysteine levels.

The only way to prove vitamin B12 deficiency is a risk factor for cardiovascular disease in vegetarians is to put it to the test. When researchers measured the amount of atherosclerosis in the carotid arteries, the main arteries supplying the brain, between vegetarians and nonvegetarians, no significant difference was found. They both look just as bad even though vegetarians tend to have better risk factors such as cholesterol and blood pressure. They suggest B12 deficiency is playing a role, but how do they know? Some measures of artery function weren’t any better either. Again, they surmise vitamin B12 deficiency overwhelming the natural plant-based benefits. Yes, the beneficial effects of vegetarian diets on cholesterol and blood sugars need to be advocated, but the necessity to correct vitamin B12 deficiency in vegetarian diets cannot be overstated.

Sometimes vegetarians did even worse. Worse artery wall thickness. Worse artery wall function, raising concern, more than a decade before the new stroke study, about the vascular health of vegetarians. Yes, their B12 was low, yes, their homocysteine was high, suggesting that vitamin B12 deficiency in vegetarians might have adverse effects on their vascular health, but what you’d need is an interventional study, where you give them B12 and see if that fixes it and… Here we go, a double-blind, placebo-controlled, randomized crossover study and the title gives it away: Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. So, that may explain it. Compromised vitamin B12 status among those eating more plant-based diets due to not taking B12 supplements, or regularly eating vitamin B12 fortified foods may explain the higher stroke risk found among vegetarians.

Unfortunately, many vegetarians resist taking vitamin B12 supplements due to misconceptions, like holding on to the old myth that deficiency of this vitamin is rare among plant-based eaters. A common mistake is to think that the presence of dairy products and eggs in the diet, as in a lacto-ovo vegetarian diet can still ensure a proper intake of B12, despite excluding meat.

Now that we may have nailed the cause, maybe future studies should focus on identifying ways of convincing vegetarians to routinely take vitamin B12 supplements in order to prevent a deficiency.