Health Journal Online

Tag: Homocysteine

  • Is Creatine Safe and Efficient for High Homocysteine? 

    Is Creatine Safe and Efficient for High Homocysteine? 

    Those on a healthy plant-based diet who have elevated homocysteine levels despite taking sufficient vitamin B12 may want to consider taking a gram a day of contaminant-free creatine.

    The average blood levels of homocysteine in men are about 1.5 points higher than in women, which may be one of the reasons 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. That may help explain “the ‘gender gap’ in homocysteine levels.” If you remember from my previous video and as seen below and at 0:36 in The Efficacy and Safety of Creatine for High Homocysteine, in the process of making creatine, our body produces homocysteine as a by-product. So, for people with stubbornly high homocysteine levels that don’t respond sufficiently to B vitamins, “creatine supplementation may represent a practical strategy for decreasing plasma homocysteine levels”—that is, lowering the level of homocysteine into the normal range. 

    It seemed to work in rats. What about humans? Well, it worked in one study, but it didn’t seem to work in another. It didn’t work in yet another either. And, in another study, homocysteine levels were even driven up. So, this suggestion that taking creatine supplements would lower homocysteine was called into question. 

    However, all those studies were done with non-vegetarians, so they were already effectively supplementing with creatine every day in the form of muscle meat. In that way, researchers were testing higher versus lower supplementation. Those eating strictly plant-based make all their creatine from scratch, so they may be more sensitive to an added creatine source. There weren’t any studies on creatine supplementation in vegans to lower homocysteine until now. 

    Researchers took vegans who were not supplementing their diets with vitamin B12, so some of their homocysteine levels were through the roof. A few were as high as 50 when the ideal is more like under 10, for example. After taking some creatine for a few weeks, all of their homocysteine levels normalized. You can see the before and after in the graph below and at 2:04 in my video. 

    Now, they didn’t normalize, as that would have been a level under 10, but that’s presumably because they weren’t taking any B12. Give vegetarians and vegans vitamin B12 supplements, either dosing daily or once a week, and their levels normalize in a matter of months, as you can see below and at 2:20 in my video. However, the fact that you could bring down homocysteine levels with creatine alone, even without any B12, suggests—to me at least—that if your homocysteine is elevated (above 10) on a plant-based diet despite taking B12 supplements and eating greens and beans to get enough folate, it might be worth experimenting with supplementing with a gram of creatine a day for a few weeks to see if your homocysteine comes down. 

    Why just a single gram? That’s approximately how much non-vegetarians do not have to make themselves; it’s the amount that erased vegetarian discrepancies in blood and muscle, as you can see in the graph below and at 3:01 in my video, and how much has been shown to be safe in the longer term. 

    How safe is it? We 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 closer to 20 grams a day. A concern was raised that creatine could potentially form a carcinogen known as N-nitrososarcosine when it hit the acid bath of the stomach, but, when it actually put to the test, researchers found this does not appear to be a problem. 

    Bottom line: Doses of supplemental creatine up to 3 grams a day are “unlikely to pose any risk,” provided “high purity creatine” is used. However, as we all know, dietary supplements in the United States “are not regulated by the US Food and Drug Administration and may contain contaminants or variable quantities of the desired supplement” and may not even contain what’s on the label. We’re talking about “contaminants…that may be generated during the industrial production.” When researchers looked at 33 samples of creatine supplements made in the United States and Europe, they found that they all actually contained 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 and certify the maximum amount of contaminants present in their products.” Easier said than done.

    Because of the potential risks, I don’t think people should take creatine supplements willy-nilly, but the potential benefits may exceed the potential risks if, again, you’re on a healthy plant-based diet and taking B12, and your homocysteine levels are still not under 10. In that case, I would suggest giving a gram a day of creatine a trying to see if it brings it down.

    The reason I did this whole video series goes back to “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,” which found that, although the overall cardiovascular risk is lower in vegetarians and vegans combined, they appeared to be at slightly higher stroke risk, as you can see in the graph below and at 5:06 in my video. 

    I went through a list of potential causes, as you can see at 5:11 and below, and arrived at elevated homocysteine. What’s the solution? A regular, reliable source of vitamin B12. The cheapest, easiest method that I personally use is one 2,500 mcg chewable tablet of cyanocobalamin, the most stable source of B12, once a week. (In fact, you can just use 2,000 mcg once a week.) And, again, a backup plan for those doing that but still having elevated homocysteine is an empirical trial of a single gram a day of creatine supplementation, which was shown to improve at least capillary blood flow in those who started out with high homocysteine levels. 

    In sum, plant-based diets appear to “markedly reduce risk” for 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, vegans 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 cerebrovascular [brain artery] health…Nonetheless, these considerations do not justify nutritional nihilism. On balance, low-fat vegan diets offer such versatile protection for long-term health that they remain highly recommendable. Most likely, the optimal strategy is to adopt such a [plant-based] diet, along with additional measures—appropriate food choices, exercising training, judicious supplementation [of vitamin B12]—that will mitigate the associated stroke risk.” And try not to huff whipped cream charging canister gas. Leave the “whippets” alone.

    This concludes my series on stroke risk. If you missed any of the other videos, see the related posts below.

    I’m assuming that nearly everyone taking their B12 will have normal homocysteine levels, so these last two videos are just for the rare person who doesn’t. However, 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 should be about a quarter teaspoon.

    Where do you get contaminant-free creatine? Since regulations are so lax, you can’t rely on supplement manufacturers no matter what they say, so I would recommend going directly to the chemical suppliers that sell it to laboratories and guarantee a certain purity. Here are some examples (in alphabetical order) of some of the largest companies where you can get unadulterated creatine: Alfa Aesar, Fisher Scientific, Sigma-Aldrich, and TCI America.



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  • Creatine to Normalize Homocysteine in Vegetarians? 

    Creatine to Normalize Homocysteine in Vegetarians? 

    What are the consequences of having to make your creatine rather than relying on dietary sources?

    “Almost universally, research findings show a poor vitamin B12 status among vegetarians” because they aren’t taking vitamin B12 supplements like they should, which results in an elevation in homocysteine levels. This may explain why vegetarians were recently found to have higher rates of stroke, as you can see in the graph below and at 0:30 in my video Should Vegetarians Take Creatine to Normalize Homocysteine?.

    Of course, plant-based eating is just one of many ways to become deficient in vitamin B12. Even nitrous oxide (laughing gas) can do it in as little as two days, thanks to the recreational use of whipped cream canister gas. (I just learned about “whippits”!)

    When researchers gave vegetarians and vegans as little as 50 daily micrograms of cyanocobalamin, which is the recommended and most stable form of vitamin B12 supplement, their homocysteine levels, which had started up in the elevated zone, normalized right down into the safe zone under 10 mmol/L within only one to two months. Just 2,000 micrograms of cyanocobalamin once a week gave the same beautiful result, as you can see in the graph below and at 1:15 in my video. 

    Not always, though. In another study, even 500 daily micrograms, taken as either a sublingual chewable or swallowable regular B12 supplement, didn’t normalize homocysteine within a month, as shown below and at 1:24. Now, presumably, if the participants had kept it up, their levels would have continued to fall as they did in the 50-daily-microgram study.

    If you’re plant-based and have been taking your B12, but your homocysteine level is still too high (above 10 mmol/L), is there anything else you can do? Well, inadequate folate intake can also increase homocysteine, but folate comes from the same root as foliage. It’s found in beans and leaves, concentrated in greens. If you’re eating beans and greens, taking your B12, and your homocysteine level is still too high, I’d suggest taking 1 gram of creatine a day as an experiment, then getting your homocysteine levels retested in a month to see if it helped.

    Creatine is a compound formed naturally in the human body that is primarily involved with energy production in our muscles and brain. It’s also formed naturally in the bodies of many other animals. So, when we eat their muscles, we can also take in some of the creatine in their bodies through our diet. We only need about 2 grams of creatine a day, so those who eat meat may get about 1 gram from their diet and their body makes the rest from scratch. There are rare birth defects where you’re born without the ability to make it, in which case, you have to get it from your diet. Otherwise, our bodies can make as much as we need to maintain normal concentrations in our muscles.

    As you can see in the graph below and at 2:54 in my video, when you cut out meat, the amount of creatine floating around in your bloodstream goes down.

    However, the amount in your brain remains the same, as shown in the graph below and at 2:57. This shows that dietary creatine doesn’t influence the levels of brain creatine, because our brain makes all the creatine we need. The level in vegetarian muscles is lower, but that doesn’t seem to affect exercise performance, as both vegetarians and meat eaters respond to creatine supplementation with similar increases in muscle power output. If vegetarian muscle creatine were insufficient, then presumably an even bigger boost would be seen. So, all that seems to happen when we eat meat is that our body doesn’t have to make as much. What does all of this have to do with homocysteine?

    As you can see below and at 3:36 in my video, in the process of making creatine, our body produces homocysteine as a waste product. Now, normally this isn’t a problem because our body has two ways to detoxify it: by using vitamin B6 or a combination of vitamin B12 and folate. Vitamin B6 is found in both plant and animal foods, and it’s rare to be deficient. But, vitamin B12 is mainly found in animal foods, so its level can be too low in those eating plant-based who don’t also supplement or eat B12-fortified foods. And, as I mentioned, folate is concentrated in plant foods, so it can be low in those who don’t regularly eat greens, beans, or folic-acid-fortified grains. Without that escape valve, homocysteine levels can get too high. However, if you’re eating a healthy plant-based diet and taking your B12 supplement, your homocysteine levels should be fine. 

    What if they aren’t? We might predict that if we started taking creatine supplements, our level of homocysteine might go down since we won’t have to make so much of it from scratch, producing homocysteine as a by-product, but you don’t know until you put it to the test. I’ll cover that next. 

    This is the eleventh in a 12-video series exploring stroke risk. If you missed the last two, see Vegetarians and Stroke Risk Factors: Vitamin B12 and Homocysteine? and How to Test for Functional Vitamin B12 Deficiency.

    This whole creatine angle was new to me. I had long worried about homocysteine levels being too high among those getting inadequate B12 intake, but I didn’t realize there was another potential mechanism for bringing it down other than with vitamin B. Let’s see if it pans out in my final video of the series: The Efficacy and Safety of Creatine for High Homocysteine. 



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  • What About Homocysteine, Vitamin B12, and Vegetarians’ Stroke Risk? 

    What About Homocysteine, Vitamin B12, and Vegetarians’ Stroke Risk? 

    Not taking vitamin B12 supplements or regularly eating B12-fortified foods may explain the higher stroke risk found among vegetarians.

    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 is common in those eating plant-based diets (unless they take B12 supplements or regularly eat B12-fortified foods) and 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 as there is still “a great controversy” surrounding the connection between homocysteine and stroke risk. But, as you can see in the graph below and at 0:57 in my video Vegetarians and Stroke Risk Factors: Vitamin B12 and Homocysteine?, 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 they also seem to be at higher risk for clotting ischemic strokes in observational studies and, more recently, bleeding hemorrhagic strokes, as well as increased risk of dying from cardiovascular disease and all causes put together. 

    Even more convincing are the genetic data. About 10 percent of the population has a gene that increases homocysteine levels by about 2 points, and they appear to have significantly higher odds of having a stroke. Most convincing would be randomized, double-blind, placebo-controlled trials to prove that lowering homocysteine with B vitamins can lower strokes, and, indeed, that appears to be the case for clotting strokes: Strokes with homocysteine-lowering interventions were more than five 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 concentrations than meat-eaters and that low vitamin B12 concentrations cause ischaemic stroke, then the incidence of stroke should be increased among vegetarians…but this is not the case.” However, it has never been studied until now.

    As you can see in the graph below and at 2:16 in my video, the EPIC-Oxford study researchers found that 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 vitamin B12-depleted or B12-deficient, as you can see below and at 2:23, and that resulted in extraordinarily high homocysteine levels.

    Why was there so much B12 deficiency? Because only a small minority were taking a dedicated B12 supplement. And, unlike in the United States, B12 fortification of organic foods isn’t allowed in the United Kingdom. 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, presumably because of the B12 fortification of commonly eaten foods in the United States. 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.

    Start eating strictly plant-based without B12-fortified foods or supplements, and B12 deficiency can develop. However, that was only for those not eating sufficient foods fortified with B12. Those eating plant-based who weren’t careful about getting a regular reliable source of B12 had lower B12 levels and, consequently, higher homocysteine levels, as you can see below and at 3:27 in my video.

    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, “no significant difference” was found between vegetarians and nonvegetarians. They both looked just as bad even though vegetarians tend to have better risk factors, such as lower cholesterol and blood pressure. The researchers suggest that B12 deficiency plays a role, but how do they know? Some measures of artery function weren’t any better either. Again, they surmised that vitamin B12 deficiency was overwhelming the natural plant-based benefits. “The beneficial effects of vegetarian diets on lipids and blood glucose [cholesterol and blood sugars] need to be advocated, and efforts to correct vitamin B12 deficiency in vegetarian diets can never be overestimated.”

    Sometimes vegetarians did even worse. Worse artery wall thickness and worse artery wall function, “raising concern, for the first time, about the vascular health of vegetarians”—more than a decade before the new stroke study. Yes, their B12 was low, and, yes, their homocysteine was high, “suggest[ing] that vitamin B12 deficiency in vegetarians might have adverse effects on their vascular health.” What we need, though, is an interventional study, where participants are given B12 to see if that fixes it, and here we go. The title of this double-blind, placebo-controlled, randomized crossover study gives it away: “Vitamin B-12 Supplementation Improves Arterial Function in Vegetarians with Subnormal Vitamin B-12 Status.” So, 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 “hold[ing] on to the old myth that deficiency of this vitamin is rare and occurs only in a small proportion of vegans.” “A common mistake is to think that the presence of dairy products and eggs in the diet, as in LOV [a lacto-ovo vegetarian diet], can still ensure a proper intake [of B12]…despite excluding animal flesh.”

    Now that we may have nailed the cause, maybe “future studies with vegetarians should focus on identifying ways to convince vegetarians to take vitamin B12 supplements to prevent a deficiency routinely.” 

    I have updated my recommendation for B12 supplementation. I now suggest at least 2,000 mcg (µg) of cyanocobalamin once weekly, 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 have 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 mandate that started on January 1, 2020, the target is 4.5 mcg three times a day.) Please note, though, that those older than the age of 65 have only one option: to take 1,000 micrograms a day. 

    We started this series on what to eat and not eat for stroke prevention, and whether vegetarians really have a higher stroke risk. Check related posts for the last few videos that looked at specific factors.

    Stay tuned for: 



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