Many doctors mistakenly rely on serum B12 levels in the blood to test for vitamin B12 deficiency.
How to Test for Functional Vitamin B12 Deficiency
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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.
Two cases of young strictly vegetarian individuals with no known vascular risk factors—yet suffering a stroke, or multiple strokes. Why? Most probably because they weren’t taking vitamin B12 supplements, which leads to high homocysteine levels, which can attack your arteries.
So those eating plant-based failing to supplement may increase one’s risk of both heart disease and stroke. Now vegetarians have so much heart disease risk factor benefit that they are still at lower risk overall, but this may help explain why vegetarians were found to have more stroke. Presumably this disparity would disappear with adequate B12 supplementation and this benefit, would grow even larger.
Compared with non-vegetarians, vegetarians enjoy all these other advantages: better cholesterol, blood pressures, blood sugars, and obesity rates. But, like what about that stroke study? And even among studies that show benefits, they’re not as pronounced as one might expect, which may be a result of poor vitamin B12 status. Vitamin B12 deficiency may negate some of the cardiovascular disease prevention benefits of vegetarian diets; so, in order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements.
How can you determine your B12 status? By the time you’re symptomatic with B12 deficiency it’s too late, and initially the symptoms can be so subtle you might even miss them. And well before you develop clinical deficiency, you develop metabolic vitamin B12 deficiency: a missed opportunity to prevent strokes, where you have enough B12 to avoid deficiency symptoms, but not enough to keep your homocysteine in check. Underdiagnosis of the condition results largely from failure to understand that a normal B12 blood level may not reflect an adequate functional B12 status. The levels of B12 in your blood does not always represent the levels of B12 in your cells. You can have a severe functional deficiency of B12 even though your blood levels are normal or even high.
Most physicians tend to assume that if the B12 level in your blood is “normal”, there is no problem. But, within the lower range of normal, 30% of patients could have metabolic B12 deficiency, with high homocysteine levels.
Measuring methylmalonic acid levels or homocysteine directly are a more accurate reflection of vitamin B12 functional status. Methylmalonic acid can be a simple urine test; you’re looking for less than a value of 4 (micrograms per milligram of creatinine). “Elevated MMA is a specific marker of vitamin B12 deficiency while homocysteine rises in [the context of] both vitamin B12 and folate deficiencies”; and so, metabolic B12 deficiency is defined by an elevation in MMA levels or by elevation of homocysteine in people getting enough folate. Even without eating beans and greens, which are packed with folate, folic acid is added to the flour supply by law; and so, high homocysteine levels these days may be mostly a B12 problem. Ideally, you’re looking for a homocysteine level in your blood down in the single digits.
Measured this way, “the prevalence of functional vitamin B12 deficiency is dramatically higher than previously assumed,” like 10%-40% of the general population, and more than 40% in vegetarians, and the majority of vegans who aren’t scrupulous about getting their B12. Some suggest that those on plant-based diets check their vitamin B12 status every year, but you shouldn’t need to if you’re adequately supplementing, and evidently there are rare cases of vitamin B12 deficiency that can’t be picked up on any test; so, better to just make sure you’re getting enough. If you do get your homocysteine tested and it’s still up in the double digits even despite B12 supplementation, I do have a suggestion in the final videos of this series, which we’ll turn to, next.
Please consider volunteering to help out on the site.
- Saadah MA, Thakre MC, Saadah LM, Nazzal ME. Homocystinemia and stroke in vegetarians. Neurosciences (Riyadh). 2006;11(2):107-11.
- Mccarty MF. IGF-I activity may be a key determinant of stroke risk--a cautionary lesson for vegans. Med Hypotheses. 2003;61(3):323-34.
- 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.
- Pawlak R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?. Am J Prev Med. 2015;48(6):e11-26.
- Woo KS, Kwok TC, Celermajer DS. Vegan diet, subnormal vitamin B-12 status and cardiovascular health. Nutrients. 2014;6(8):3259-73.
- Spence JD. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res. 2016;36(2):109-16.
- Hannibal L, Lysne V, Bjørke-monsen AL, et al. Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency. Front Mol Biosci. 2016;3:27.
- Spence JD. Nutrition and Risk of Stroke. Nutrients. 2019;11(3)
- Li J, Ren M, Dong A, et al. A retrospective study of 23 cases with subacute combined degeneration. Int J Neurosci. 2016;126(10):872-7.
- Rizzo G, Laganà AS, Rapisarda AM, et al. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients. 2016;8(12):767.
- Aparicio-ugarriza R, Palacios G, Alder M, González-gross M. A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population. Clin Chem Lab Med. 2015;53(8):1149-59.
- Spence JD, Stampfer MJ. Understanding the complexity of homocysteine lowering with vitamins: the potential role of subgroup analyses. JAMA. 2011;306(23):2610-1.
- Herrmann W, Geisel J. Vegetarian lifestyle and monitoring of vitamin B-12 status. Clin Chim Acta. 2002;326(1-2):47-59.
- Mariotti F., editor. Vegetarian and Plant-Based Diets in Health and Disease Prevention. Elsevier; New York, NY, USA: 2017.
- Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood. 2005;105(3):978-85.
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.
Two cases of young strictly vegetarian individuals with no known vascular risk factors—yet suffering a stroke, or multiple strokes. Why? Most probably because they weren’t taking vitamin B12 supplements, which leads to high homocysteine levels, which can attack your arteries.
So those eating plant-based failing to supplement may increase one’s risk of both heart disease and stroke. Now vegetarians have so much heart disease risk factor benefit that they are still at lower risk overall, but this may help explain why vegetarians were found to have more stroke. Presumably this disparity would disappear with adequate B12 supplementation and this benefit, would grow even larger.
Compared with non-vegetarians, vegetarians enjoy all these other advantages: better cholesterol, blood pressures, blood sugars, and obesity rates. But, like what about that stroke study? And even among studies that show benefits, they’re not as pronounced as one might expect, which may be a result of poor vitamin B12 status. Vitamin B12 deficiency may negate some of the cardiovascular disease prevention benefits of vegetarian diets; so, in order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements.
How can you determine your B12 status? By the time you’re symptomatic with B12 deficiency it’s too late, and initially the symptoms can be so subtle you might even miss them. And well before you develop clinical deficiency, you develop metabolic vitamin B12 deficiency: a missed opportunity to prevent strokes, where you have enough B12 to avoid deficiency symptoms, but not enough to keep your homocysteine in check. Underdiagnosis of the condition results largely from failure to understand that a normal B12 blood level may not reflect an adequate functional B12 status. The levels of B12 in your blood does not always represent the levels of B12 in your cells. You can have a severe functional deficiency of B12 even though your blood levels are normal or even high.
Most physicians tend to assume that if the B12 level in your blood is “normal”, there is no problem. But, within the lower range of normal, 30% of patients could have metabolic B12 deficiency, with high homocysteine levels.
Measuring methylmalonic acid levels or homocysteine directly are a more accurate reflection of vitamin B12 functional status. Methylmalonic acid can be a simple urine test; you’re looking for less than a value of 4 (micrograms per milligram of creatinine). “Elevated MMA is a specific marker of vitamin B12 deficiency while homocysteine rises in [the context of] both vitamin B12 and folate deficiencies”; and so, metabolic B12 deficiency is defined by an elevation in MMA levels or by elevation of homocysteine in people getting enough folate. Even without eating beans and greens, which are packed with folate, folic acid is added to the flour supply by law; and so, high homocysteine levels these days may be mostly a B12 problem. Ideally, you’re looking for a homocysteine level in your blood down in the single digits.
Measured this way, “the prevalence of functional vitamin B12 deficiency is dramatically higher than previously assumed,” like 10%-40% of the general population, and more than 40% in vegetarians, and the majority of vegans who aren’t scrupulous about getting their B12. Some suggest that those on plant-based diets check their vitamin B12 status every year, but you shouldn’t need to if you’re adequately supplementing, and evidently there are rare cases of vitamin B12 deficiency that can’t be picked up on any test; so, better to just make sure you’re getting enough. If you do get your homocysteine tested and it’s still up in the double digits even despite B12 supplementation, I do have a suggestion in the final videos of this series, which we’ll turn to, next.
Please consider volunteering to help out on the site.
- Saadah MA, Thakre MC, Saadah LM, Nazzal ME. Homocystinemia and stroke in vegetarians. Neurosciences (Riyadh). 2006;11(2):107-11.
- Mccarty MF. IGF-I activity may be a key determinant of stroke risk--a cautionary lesson for vegans. Med Hypotheses. 2003;61(3):323-34.
- 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.
- Pawlak R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?. Am J Prev Med. 2015;48(6):e11-26.
- Woo KS, Kwok TC, Celermajer DS. Vegan diet, subnormal vitamin B-12 status and cardiovascular health. Nutrients. 2014;6(8):3259-73.
- Spence JD. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res. 2016;36(2):109-16.
- Hannibal L, Lysne V, Bjørke-monsen AL, et al. Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency. Front Mol Biosci. 2016;3:27.
- Spence JD. Nutrition and Risk of Stroke. Nutrients. 2019;11(3)
- Li J, Ren M, Dong A, et al. A retrospective study of 23 cases with subacute combined degeneration. Int J Neurosci. 2016;126(10):872-7.
- Rizzo G, Laganà AS, Rapisarda AM, et al. Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients. 2016;8(12):767.
- Aparicio-ugarriza R, Palacios G, Alder M, González-gross M. A review of the cut-off points for the diagnosis of vitamin B12 deficiency in the general population. Clin Chem Lab Med. 2015;53(8):1149-59.
- Spence JD, Stampfer MJ. Understanding the complexity of homocysteine lowering with vitamins: the potential role of subgroup analyses. JAMA. 2011;306(23):2610-1.
- Herrmann W, Geisel J. Vegetarian lifestyle and monitoring of vitamin B-12 status. Clin Chim Acta. 2002;326(1-2):47-59.
- Mariotti F., editor. Vegetarian and Plant-Based Diets in Health and Disease Prevention. Elsevier; New York, NY, USA: 2017.
- Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood. 2005;105(3):978-85.
Video production by Glass Entertainment
Motion graphics by Avocado Video
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Title
How to Test for Functional Vitamin B12 Deficiency
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
Now if you do get your homocysteine tested and despite both B12 supplementation and eating beans and greens it’s still too high (meaning double digits), I have a suggestion, as covered in the final two videos in this video series: Should Vegetarians Take Creatine to Normalize Homocysteine? and The Efficacy and Safety of Creatine for High Homocysteine.
How did we end up here? Watch the full series if you haven’t yet:
- What to Eat for Stroke Prevention
- What Not to Eat for Stroke Prevention
- Do Vegetarians Really Have Higher Stroke Risk?
- 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?
- How to Test for Functional Vitamin B12 Deficiency
2023 Update: I recently put out a new video, Update on Vegetarian Stroke Risk.
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