Those on a healthy plant-based diet with elevated homocysteine levels despite taking sufficient vitamin B12 may want to consider taking a gram a day of contaminant-free creatine.
The Efficacy and Safety of Creatine for High Homocysteine
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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.
The average blood levels of homocysteine in men is about one and a half points higher than in women. Maybe that’s one of the reasons why men tend to be at higher risk for cardiovascular disease. Women don’t need to make as much creatine as men since they tend to have less muscle mass, and that may help explain the ‘gender gap’ in homocysteine levels. If you remember from my last video, in the process of making creatine, your body produces homocysteine as a by-product. So maybe for people with stubbornly high homocysteine levels that don’t sufficiently respond to B vitamins, perhaps creatine supplementation may represent a practical strategy to draw homocysteine levels down into the normal range.
It seemed to work in rats but in humans, it worked in one study, this one, but didn’t seem to work in another study, this one, or this one…and in this study homocysteine levels were even driven up. So this whole suggestion that taking creatine supplements would lower homocysteine was called into question. But all those studies were done in non-vegetarians, so they were already effectively supplementing with creatine every day in the form of muscle meat, so they were basically just testing higher vs. lower supplementation. Those eating strictly plant-based make all their creatine from scratch, so may be more sensitive to an added creatine source, but there were never any studies on creatine supplementation in vegans for homocysteine lowering … until, now.
They took a bunch of vegans who were not supplementing their diets with vitamin B12, so some of their homocysteine’s were through the roof, a few as high as 50 when the ideal is more like under 10, but after taking some creatine for a few weeks all of their homocysteine levels normalized before, and… after. Now they didn’t really normalize, which would be under 10, but that’s presumably because they weren’t taking any B12. Give vegetarians and vegans vitamin b12 supplements, either daily dosing or once a week, and their levels really normalize in a matter of months, but the fact that even without any B12, you could bring down homocysteine levels with creatine alone suggests—to me at least—that if your homocysteine is elevated on a plant-based diet, meaning above 10, despite taking B12 supplements (and eating greens and beans to get enough folate), well then it might be worth experimenting with supplementing with a gram of creatine for a few weeks and see if your homocysteine comes down.
Why one gram? That’s approximately how much nonvegetarians are not having to make themselves, that’s how much erased vegetarian discrepancies in blood and muscle, and how much has been shown to be safe in the longer-term.
How safe exactly is it? Well one can take a bit of comfort in the fact that it’s one of the world’s best-selling dietary supplements, with literally billions of servings taken, and the only consistently reported side effect has been weight gain, presumed to be from water retention. The only serious side-effects appear to be among those with pre-existing kidney diseases taking whopping doses of like 20 grams a day. A concern was raised that creatine could potentially form a carcinogen known as form N-nitrososarcosine when it hit the acid bath of the stomach, but when actually put to the test this does not appear to be a problem.
Bottomline, doses of up 3 grams a day are unlikely to pose any risk provided high purity creatine is used, and as we all know dietary supplements are not regulated by the FDA and may contain contaminants or not actually contain what’s on the label, contaminants generated during the industrial production. When researchers look at 33 samples of creatine supplements made in the U.S. and Europe, they all did actually contain creatine, which is nice, but about half exceeded the maximum level recommended by food safety authorities for at least one contaminant. The researchers recommend that consumers give their preference to products obtained by producers that ensure the highest quality control. Easier said than done.
Because of the potential risks I don’t think people should be taking creatine supplements willy-nilly, but the potential benefits may exceed the potential risks if, again, you’re on a healthy plant-based diet, taking B12 and your homocysteine levels are still not under 10 I would suggest giving a gram a day of creatine a try to see if it brings it down.
The reason I did this whole video series all goes back to this study, which found that although the overall cardiovascular risk is lower in vegetarians and vegans combined, they appeared to be at slightly higher stroke risk. I went through a list of potential causes, arrived at elevated homocysteine, and the solution? A regular, reliable source of vitamin B12. The cheapest, easiest method that I personally use is one 2500 mcg chewable tablet of cyanocobalamin, the most stable source of B12, once a week.
And then as I detailed in this video, a back-up plan for those doing that and still having elevated homocysteine is an empirical trial of one gram a day creatine supplementation, which was shown to improve at least capillary blood flow in those who started out with high homocysteine levels.
The bottom line is that plant-based diets appear to markedly reduce our risk of multiple leading killer diseases—heart disease, type 2 diabetes, and many common types of cancer, but an increased risk for stroke may represent an ‘Achilles heel’. Nonetheless, they have the potential to achieve a truly exceptional ‘healthspan’ if they face this problem forthrightly by restricting salt intake and taking other practical measures that promote brain artery healthy health. Nonetheless, these considerations do not justify nutritional nihilism. On balance, even strictly plant-based diets offer such versatile protection to long-term health that they remain highly recommendable. Most likely, the optimal strategy is to eat plant-based, along with going out of your way to eat particularly protective foods as I talked about before, regular aerobic exercise, and most importantly taking your vitamin B12. Oh, and try not to huff whipped cream charging canister gas.
Please consider volunteering to help out on the site.
- Mccarty MF. Supplemental creatine may decrease serum homocysteine and abolish the homocysteine 'gender gap' by suppressing endogenous creatine synthesis. Med Hypotheses. 2001;56(1):5-7.
- Brosnan JT, Da silva RP, Brosnan ME. The metabolic burden of creatine synthesis. Amino Acids. 2011;40(5):1325-31.
- Steenge GR, Verhoef P, Greenhaff PL. The effect of creatine and resistance training on plasma homocysteine concentration in healthy volunteers. Arch Intern Med. 2001;161(11):1455-6.
- Petr M, Navratil T, Heyrovsky M, Kohlikova E. The role of supplemented creatine in human metabolism. Curr Org Chem. 2011;15(17):3029-42.
- Korzun WJ. Oral creatine supplements lower plasma homocysteine concentrations in humans. Clin Lab Sci. 2004;17(2):102-6.
- Steenge GR, Verhoef P, Greenhaff PL. The effect of creatine and resistance training on plasma homocysteine concentration in healthy volunteers. Arch Intern Med. 2001;161(11):1455-6.
- Peters BA, Hall MN, Liu X, et al. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. J Nutr. 2015;145(10):2245-52.
- Jahangir E, Vita JA, Handy D, et al. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vasc Med. 2009;14(3):239-48.
- Wyss M, Schulze A. Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?. Neuroscience. 2002;112(2):243-60.
- Van bavel D, De moraes R, Tibirica E. Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets. Fundam Clin Pharmacol. 2019;33(4):428-440.
- Del Bo' C, Riso P, Gardana C, Brusamolino A, Battezzati A, Ciappellano S. Effect of two different sublingual dosages of vitamin B on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: a randomized controlled trial. Clin Nutr. 2019;38(2):575-583.
- Blancquaert L, Baguet A, Bex T, et al. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial. Br J Nutr. 2018;119(7):759-770.
- Lobo DM, Tritto AC, Da silva LR, et al. Effects of long-term low-dose dietary creatine supplementation in older women. Exp Gerontol. 2015;70:97-104.
- Bizzarini E, De angelis L. Is the use of oral creatine supplementation safe?. J Sports Med Phys Fitness. 2004;44(4):411-6.
- Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18.
- Archer MC. Creatine: a safety concern. Toxicol Lett. 2004;152(3):275.
- Derave W, Vanden eede E, Hespel P, Carmella SG, Hecht SS. Oral creatine supplementation in humans does not elevate urinary excretion of the carcinogen N-nitrososarcosine. Nutrition. 2006;22(3):332-3.
- European Food Safety Authority. Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to creatine monohydrate for use in foods for particular nutritional uses. EFSA J. 2004;2(4):1-6.
- Butts J, Jacobs B, Silvis M. Creatine Use in Sports. Sports Health. 2018;10(1):31-34.
- Moret S, Prevarin A, Tubaro F. Levels of creatine, organic contaminants and heavy metals in creatine dietary supplements. Food Chem. 2011;126(3):1232-8.
- 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.
- 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.
- Antonucci MU. Subacute Combined Degeneration from Recreational Nitrous Oxide Inhalation. J Emerg Med. 2018;54(5):e105-e107.
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.
The average blood levels of homocysteine in men is about one and a half points higher than in women. Maybe that’s one of the reasons why men tend to be at higher risk for cardiovascular disease. Women don’t need to make as much creatine as men since they tend to have less muscle mass, and that may help explain the ‘gender gap’ in homocysteine levels. If you remember from my last video, in the process of making creatine, your body produces homocysteine as a by-product. So maybe for people with stubbornly high homocysteine levels that don’t sufficiently respond to B vitamins, perhaps creatine supplementation may represent a practical strategy to draw homocysteine levels down into the normal range.
It seemed to work in rats but in humans, it worked in one study, this one, but didn’t seem to work in another study, this one, or this one…and in this study homocysteine levels were even driven up. So this whole suggestion that taking creatine supplements would lower homocysteine was called into question. But all those studies were done in non-vegetarians, so they were already effectively supplementing with creatine every day in the form of muscle meat, so they were basically just testing higher vs. lower supplementation. Those eating strictly plant-based make all their creatine from scratch, so may be more sensitive to an added creatine source, but there were never any studies on creatine supplementation in vegans for homocysteine lowering … until, now.
They took a bunch of vegans who were not supplementing their diets with vitamin B12, so some of their homocysteine’s were through the roof, a few as high as 50 when the ideal is more like under 10, but after taking some creatine for a few weeks all of their homocysteine levels normalized before, and… after. Now they didn’t really normalize, which would be under 10, but that’s presumably because they weren’t taking any B12. Give vegetarians and vegans vitamin b12 supplements, either daily dosing or once a week, and their levels really normalize in a matter of months, but the fact that even without any B12, you could bring down homocysteine levels with creatine alone suggests—to me at least—that if your homocysteine is elevated on a plant-based diet, meaning above 10, despite taking B12 supplements (and eating greens and beans to get enough folate), well then it might be worth experimenting with supplementing with a gram of creatine for a few weeks and see if your homocysteine comes down.
Why one gram? That’s approximately how much nonvegetarians are not having to make themselves, that’s how much erased vegetarian discrepancies in blood and muscle, and how much has been shown to be safe in the longer-term.
How safe exactly is it? Well one can take a bit of comfort in the fact that it’s one of the world’s best-selling dietary supplements, with literally billions of servings taken, and the only consistently reported side effect has been weight gain, presumed to be from water retention. The only serious side-effects appear to be among those with pre-existing kidney diseases taking whopping doses of like 20 grams a day. A concern was raised that creatine could potentially form a carcinogen known as form N-nitrososarcosine when it hit the acid bath of the stomach, but when actually put to the test this does not appear to be a problem.
Bottomline, doses of up 3 grams a day are unlikely to pose any risk provided high purity creatine is used, and as we all know dietary supplements are not regulated by the FDA and may contain contaminants or not actually contain what’s on the label, contaminants generated during the industrial production. When researchers look at 33 samples of creatine supplements made in the U.S. and Europe, they all did actually contain creatine, which is nice, but about half exceeded the maximum level recommended by food safety authorities for at least one contaminant. The researchers recommend that consumers give their preference to products obtained by producers that ensure the highest quality control. Easier said than done.
Because of the potential risks I don’t think people should be taking creatine supplements willy-nilly, but the potential benefits may exceed the potential risks if, again, you’re on a healthy plant-based diet, taking B12 and your homocysteine levels are still not under 10 I would suggest giving a gram a day of creatine a try to see if it brings it down.
The reason I did this whole video series all goes back to this study, which found that although the overall cardiovascular risk is lower in vegetarians and vegans combined, they appeared to be at slightly higher stroke risk. I went through a list of potential causes, arrived at elevated homocysteine, and the solution? A regular, reliable source of vitamin B12. The cheapest, easiest method that I personally use is one 2500 mcg chewable tablet of cyanocobalamin, the most stable source of B12, once a week.
And then as I detailed in this video, a back-up plan for those doing that and still having elevated homocysteine is an empirical trial of one gram a day creatine supplementation, which was shown to improve at least capillary blood flow in those who started out with high homocysteine levels.
The bottom line is that plant-based diets appear to markedly reduce our risk of multiple leading killer diseases—heart disease, type 2 diabetes, and many common types of cancer, but an increased risk for stroke may represent an ‘Achilles heel’. Nonetheless, they have the potential to achieve a truly exceptional ‘healthspan’ if they face this problem forthrightly by restricting salt intake and taking other practical measures that promote brain artery healthy health. Nonetheless, these considerations do not justify nutritional nihilism. On balance, even strictly plant-based diets offer such versatile protection to long-term health that they remain highly recommendable. Most likely, the optimal strategy is to eat plant-based, along with going out of your way to eat particularly protective foods as I talked about before, regular aerobic exercise, and most importantly taking your vitamin B12. Oh, and try not to huff whipped cream charging canister gas.
Please consider volunteering to help out on the site.
- Mccarty MF. Supplemental creatine may decrease serum homocysteine and abolish the homocysteine 'gender gap' by suppressing endogenous creatine synthesis. Med Hypotheses. 2001;56(1):5-7.
- Brosnan JT, Da silva RP, Brosnan ME. The metabolic burden of creatine synthesis. Amino Acids. 2011;40(5):1325-31.
- Steenge GR, Verhoef P, Greenhaff PL. The effect of creatine and resistance training on plasma homocysteine concentration in healthy volunteers. Arch Intern Med. 2001;161(11):1455-6.
- Petr M, Navratil T, Heyrovsky M, Kohlikova E. The role of supplemented creatine in human metabolism. Curr Org Chem. 2011;15(17):3029-42.
- Korzun WJ. Oral creatine supplements lower plasma homocysteine concentrations in humans. Clin Lab Sci. 2004;17(2):102-6.
- Steenge GR, Verhoef P, Greenhaff PL. The effect of creatine and resistance training on plasma homocysteine concentration in healthy volunteers. Arch Intern Med. 2001;161(11):1455-6.
- Peters BA, Hall MN, Liu X, et al. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial. J Nutr. 2015;145(10):2245-52.
- Jahangir E, Vita JA, Handy D, et al. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vasc Med. 2009;14(3):239-48.
- Wyss M, Schulze A. Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?. Neuroscience. 2002;112(2):243-60.
- Van bavel D, De moraes R, Tibirica E. Effects of dietary supplementation with creatine on homocysteinemia and systemic microvascular endothelial function in individuals adhering to vegan diets. Fundam Clin Pharmacol. 2019;33(4):428-440.
- Del Bo' C, Riso P, Gardana C, Brusamolino A, Battezzati A, Ciappellano S. Effect of two different sublingual dosages of vitamin B on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: a randomized controlled trial. Clin Nutr. 2019;38(2):575-583.
- Blancquaert L, Baguet A, Bex T, et al. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial. Br J Nutr. 2018;119(7):759-770.
- Lobo DM, Tritto AC, Da silva LR, et al. Effects of long-term low-dose dietary creatine supplementation in older women. Exp Gerontol. 2015;70:97-104.
- Bizzarini E, De angelis L. Is the use of oral creatine supplementation safe?. J Sports Med Phys Fitness. 2004;44(4):411-6.
- Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18.
- Archer MC. Creatine: a safety concern. Toxicol Lett. 2004;152(3):275.
- Derave W, Vanden eede E, Hespel P, Carmella SG, Hecht SS. Oral creatine supplementation in humans does not elevate urinary excretion of the carcinogen N-nitrososarcosine. Nutrition. 2006;22(3):332-3.
- European Food Safety Authority. Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to creatine monohydrate for use in foods for particular nutritional uses. EFSA J. 2004;2(4):1-6.
- Butts J, Jacobs B, Silvis M. Creatine Use in Sports. Sports Health. 2018;10(1):31-34.
- Moret S, Prevarin A, Tubaro F. Levels of creatine, organic contaminants and heavy metals in creatine dietary supplements. Food Chem. 2011;126(3):1232-8.
- 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.
- 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.
- Antonucci MU. Subacute Combined Degeneration from Recreational Nitrous Oxide Inhalation. J Emerg Med. 2018;54(5):e105-e107.
Video production by Glass Entertainment
Motion graphics by Avocado Video
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Title
The Efficacy and Safety of Creatine for High Homocysteine
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
This concludes my series on stroke risk. If you missed any of the videos here they are:
- 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
- Should Vegetarians Take Creatine to Normalize Homocysteine?
Now I’m assuming that nearly everyone who’s taking their B12 will have normal homocysteine levels, so these last two videos are just for the rare person that doesn’t, but those on a healthy plant-based diet with elevated homocysteine levels despite taking sufficient vitamin B12 should consider taking a gram a day of contaminant-free creatine (which would be about a quarter teaspoon).
OK, so where do you get contaminant-free creatine? You can’t rely on supplement manufacturers no matter what they say, since the regulation is so lax, so I would recommend going directly to the chemical suppliers that sell it to laboratories and guarantee a certain purity. Here are some examples from some of the largest companies in alphabetical order where you can get unadulterated creatine:
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