 Welcome to the Nutrition Facts Podcast. I'm your host, Dr. Michael Greger. The coronavirus pandemic has made many of us very aware of the importance of maintaining and improving our health. Make that your silver lining. Because the more positive change we can make to our diet and lifestyle, the better. 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 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, so 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 there'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 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 US have 7 times more deaths from prostate cancer, but 5 times more deadly breast cancer, 3 times more colon cancer, and lymphoma mortality, and 6 to 12 times the death rate from heart disease. Yes, Japanese stroke and stomach cancer rates were higher, but they were also eating up to 6 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 increases in the risk of hemorrhagic stroke risk, 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, you know, 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's some kind of protective factor in animal foods, it is to be hoped that a, you know, diet can be found that still protects against killer number one, heart disease, without increasing the risk of killer number five, stroke. But first, we have to figure out what that factor is, a hunt that we'll continue next. 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 level of a cancer-promoting growth hormone in the body, known as IGF-1, Instantly Growth Factor 1, which can accelerate the progression of precancerous changes to invasive cancer. High blood concentrations are associated with 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. In 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 seven 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 reduce the risk of some most common cancers that plague 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 as a pro-longivity measure should take particular care to control their blood pressure, to preserve their cerebrovascular health, the health of the 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 adding 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, to 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 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 a B12 supplement or eat B12 fortified foods regularly, can lead to an increased level of homocysteine in the blood, which is accepted as an important risk factor for stroke. Excepted 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 crotted arteries that lead up to the brain, compared to those with single-digit homocysteine levels, and do seem to be at higher risk of 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 at about two 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 five times as likely to reduce stroke compared to 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. It's about a quarter of 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. soy milk and other products may be fortified with B12, U.K. products may not. We don't see the same problem among U.S. vegans in the Adventist study, presumably 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 and vegetarians is to put it to the test. And when researchers measured the amount of atherosclerosis in the crotted arteries, the main arteries supplying the brain between vegetarians and non-vegetarians, no significant difference was found. They both looked just as bad, even though vegetarians tend to have better risk factors such as cholesterol and blood pressure. They should just be 12 deficiencies 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 HOMOSysteine was high, suggesting that vitamin B12 deficiency in vegetarians might have adverse effects on their vascular health, but what you would need is an interventional study, where you give them B12 and see if that fixes it. And here we go. Double-blind, placebo-controlled, randomized crossover study, and the title gives it away. Vitamin B12 supplementation improves arterial function of vegetarians with subnormal vitamin B12 status. So that may explain it. Compromised vitamin B12 status among those eating more plant-based 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 proper intake of B12 despite excluding meat. And 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. We would love it if you could share with us your stories about reinventing your health through evidence-based nutrition. Go to nutritionfacts.org slash testimonials. We may share it on our social media to help inspire others. To see any graphs, charts, graphics, images, or studies mentioned here, please go to the nutrition facts podcast landing page. There you'll find all the detailed information you need, plus links to all the sources we cite for each of these topics. For a vital timely text on the pathogens that cause pandemics, you can order the e-book, audio book, or now hard copy of my latest book, How to Survive a Pandemic. For recipes, pre-order my How Not to Diet Cookbook out this December. It's beautifully designed with more than 100 recipes for delicious and nutritious meals, and all proceeds I receive from the sales of my books go to charity. NutritionFacts.org is a non-profit, science-based public service where you can sign up for free daily updates and the latest in nutrition research via bite-sized videos and articles. Everything on the website is free. There's no ads, no corporate sponsorship. It's strictly non-commercial, not sign anything. I just put it up as a public service, as a labor of love as a tribute to my grandmother, whose own life was saved with evidence-based nutrition.