Not taking B12 supplements or regularly eating B12 fortified foods may explain the higher stroke risk found among vegetarians.
Vegetarians and Stroke Risk Factors—Vitamin B12 and Homocysteine?
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
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 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 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.
Please consider volunteering to help out on the site.
- Öztürk Ş, Altieri M, Troisi P. Leonardo Da Vinci and stroke - vegetarian diet as a possible cause. Front Neurol Neurosci. 2010;27:1-10.
- Ozturk S. Leonardo Da Vinci (1452-1519) as a stroke victim: hemiparesis: a result of a vegetarian diet?. J Med Biogr. 2009;17(1):7.
- Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther. 2018;16(8):559-565.
- Spence JD. Carotid plaque burden is associated with higher levels of total homocysteine. Stroke Vasc Neurol. 2017;2(1):40.
- He Y, Li Y, Chen Y, Feng L, Nie Z. Homocysteine level and risk of different stroke types: a meta-analysis of prospective observational studies. Nutr Metab Cardiovasc Dis. 2014;24(11):1158-65.
- Zhou Z, Liang Y, Qu H, et al. Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Sci Rep. 2018;8(1):2568.
- Peng HY, Man CF, Xu J, Fan Y. Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies. J Zhejiang Univ Sci B. 2015;16(1):78-86.
- Hankey GJ, Eikelboom JW. Homocysteine and stroke. Lancet. 2005;365(9455):194-6.
- Martí-carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8:CD006612.
- Finsterer J. Low risk of ischaemic stroke in hyperhomocysteinaemia. Lancet Neurol. 2017;16(9):682-683.
- Tong TYN, Appleby PN, Bradbury KE, et al. Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study. BMJ. 2019;366:l4897.
- A M J Gilsing, F L Crowe, Z Lloyd-Wright, T A B Sanders, P N Appleby, N E Allen, T J Key Serum Concentrations of Vitamin B12 and Folate in British Male Omnivores, Vegetarians and Vegans: Results From a Cross-Sectional Analysis of the EPIC-Oxford Cohort Study. Eur J Clin Nutr . 2010 Sep;64(9):933-9
- Sobiecki JG, Appleby PN, Bradbury KE, Key TJ. High compliance with dietary recommendations in a cohort of meat eaters, fish eaters, vegetarians, and vegans: results from the European Prospective Investigation into Cancer and Nutrition-Oxford study. Nutr Res. 2016;36(5):464-77.
- Bonner G, Warwick H, Bmardo M, Lobstein T. Fortification examined: how added nutrients can undermine good nutrition. The Food Commission (UK) Ltd: London, 1999.
- Mariotti F., editor. Vegetarian and Plant-Based Diets in Health and Disease Prevention. Elsevier; New York, NY, USA: 2017.
- Key TJ, Fraser GE, Thorogood M, et al. Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies. Public Health Nutr. 1998;1(1):33-41.
- Mądry E, Lisowska A, Grebowiec P, Walkowiak J. The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study. Acta Sci Pol Technol Aliment. 2012;11(2):209-12.
- Obersby D, Chappell DC, Dunnett A, Tsiami AA. Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis. Br J Nutr. 2013;109(5):785-94.
- Pawlak R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?. Am J Prev Med. 2015;48(6):e11-26.
- Su TC, Jeng JS, Wang JD, et al. Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores. Atherosclerosis. 2006;184(2):356-62.
- Su TC, Torng PL, Jeng JS, Chen MF, Liau CS. Arterial function of carotid and brachial arteries in postmenopausal vegetarians. Vasc Health Risk Manag. 2011;7:517-23.
- Kwok T, Chook P, Tam L, et al. Vascular dysfunction in Chinese vegetarians: an apparent paradox?. J Am Coll Cardiol. 2005;46(10):1957-8.
- Kwok T, Chook P, Qiao M, et al. Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. J Nutr Health Aging. 2012;16(6):569-73.
- Rizzo G, Laganà AS, Rapisarda AM, et al. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients. 2016;8(12)
Video production by Glass Entertainment
Motion graphics by Avocado Video
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
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 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 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.
Please consider volunteering to help out on the site.
- Öztürk Ş, Altieri M, Troisi P. Leonardo Da Vinci and stroke - vegetarian diet as a possible cause. Front Neurol Neurosci. 2010;27:1-10.
- Ozturk S. Leonardo Da Vinci (1452-1519) as a stroke victim: hemiparesis: a result of a vegetarian diet?. J Med Biogr. 2009;17(1):7.
- Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther. 2018;16(8):559-565.
- Spence JD. Carotid plaque burden is associated with higher levels of total homocysteine. Stroke Vasc Neurol. 2017;2(1):40.
- He Y, Li Y, Chen Y, Feng L, Nie Z. Homocysteine level and risk of different stroke types: a meta-analysis of prospective observational studies. Nutr Metab Cardiovasc Dis. 2014;24(11):1158-65.
- Zhou Z, Liang Y, Qu H, et al. Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Sci Rep. 2018;8(1):2568.
- Peng HY, Man CF, Xu J, Fan Y. Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies. J Zhejiang Univ Sci B. 2015;16(1):78-86.
- Hankey GJ, Eikelboom JW. Homocysteine and stroke. Lancet. 2005;365(9455):194-6.
- Martí-carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8:CD006612.
- Finsterer J. Low risk of ischaemic stroke in hyperhomocysteinaemia. Lancet Neurol. 2017;16(9):682-683.
- Tong TYN, Appleby PN, Bradbury KE, et al. Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study. BMJ. 2019;366:l4897.
- A M J Gilsing, F L Crowe, Z Lloyd-Wright, T A B Sanders, P N Appleby, N E Allen, T J Key Serum Concentrations of Vitamin B12 and Folate in British Male Omnivores, Vegetarians and Vegans: Results From a Cross-Sectional Analysis of the EPIC-Oxford Cohort Study. Eur J Clin Nutr . 2010 Sep;64(9):933-9
- Sobiecki JG, Appleby PN, Bradbury KE, Key TJ. High compliance with dietary recommendations in a cohort of meat eaters, fish eaters, vegetarians, and vegans: results from the European Prospective Investigation into Cancer and Nutrition-Oxford study. Nutr Res. 2016;36(5):464-77.
- Bonner G, Warwick H, Bmardo M, Lobstein T. Fortification examined: how added nutrients can undermine good nutrition. The Food Commission (UK) Ltd: London, 1999.
- Mariotti F., editor. Vegetarian and Plant-Based Diets in Health and Disease Prevention. Elsevier; New York, NY, USA: 2017.
- Key TJ, Fraser GE, Thorogood M, et al. Mortality in vegetarians and non-vegetarians: a collaborative analysis of 8300 deaths among 76,000 men and women in five prospective studies. Public Health Nutr. 1998;1(1):33-41.
- Mądry E, Lisowska A, Grebowiec P, Walkowiak J. The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study. Acta Sci Pol Technol Aliment. 2012;11(2):209-12.
- Obersby D, Chappell DC, Dunnett A, Tsiami AA. Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis. Br J Nutr. 2013;109(5):785-94.
- Pawlak R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?. Am J Prev Med. 2015;48(6):e11-26.
- Su TC, Jeng JS, Wang JD, et al. Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores. Atherosclerosis. 2006;184(2):356-62.
- Su TC, Torng PL, Jeng JS, Chen MF, Liau CS. Arterial function of carotid and brachial arteries in postmenopausal vegetarians. Vasc Health Risk Manag. 2011;7:517-23.
- Kwok T, Chook P, Tam L, et al. Vascular dysfunction in Chinese vegetarians: an apparent paradox?. J Am Coll Cardiol. 2005;46(10):1957-8.
- Kwok T, Chook P, Qiao M, et al. Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. J Nutr Health Aging. 2012;16(6):569-73.
- Rizzo G, Laganà AS, Rapisarda AM, et al. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients. 2016;8(12)
Video production by Glass Entertainment
Motion graphics by Avocado Video
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Vegetarians and Stroke Risk Factors—Vitamin B12 and Homocysteine?
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Content URLDoctor's Note
I have updated my recommendation for B12 supplementation. I now suggest at least 2,000 mcg (µg) cyanocobalamin once each week, ideally as a chewable, sublingual, or liquid supplement taken on an empty stomach, or at least 50 mcg daily of supplemental cyanocobalamin (you needn’t worry about taking too much). You can also do servings of B12-fortified foods three times a day (at each meal), each containing at least 190% of the Daily Value listed on the nutrition facts label (based on the new labeling mandated to start January 1, 2020—the target is 4.5 mcg three times a day). Note that those over age 65 only have basically one option, taking 1000 micrograms a day.
We started this stroke series with what to eat and not eat for stroke prevention, and whether vegetarians really have a higher stroke risk.
The last few videos have looked at specific factors:
- Vegetarians and Stroke Risk Factors—Vitamin D?
- Vegetarians and Stroke Risk Factors—Omega 3s?
- Vegetarians and Stroke Risk Factors—Vegan Junk Food?
- Vegetarians and Stroke Risk Factors—Saturated Fat?
- Vegetarians and Stroke Risk Factors—Animal Protein?
Stay tuned for:
- How to Test for Functional Vitamin B12 Deficiency
- Should Vegetarians Take Creatine to Normalize Homocysteine?
- The Efficacy and Safety of Creatine for High Homocysteine
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