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Tag: B12

  • Bone Fractures, Lung Cancer, and Vitamin B12 Supplements? 

    Bone Fractures, Lung Cancer, and Vitamin B12 Supplements? 

    What do randomized controlled trials of high-dose daily vitamin B12 supplementation show about its effects on cancer risk, death, and longevity? 

    In 2019, “Association of High Intakes of Vitamins B6 and B12 from Food and Supplements with Risk of Hip Fracture Among Postmenopausal Women in the [Harvard] Nurses’ Health Study” was published. Note, though, that only the combined high intake of vitamins B6 (≥35 mg/day) and B12 (≥20 mcg/day) was associated with an increased hip fracture risk. We know that treatment with high doses of vitamin B6 may increase hip fracture risk on its own. After a decade or so, those who had been taking high-dose (40 mg) B6 supplements had about a 40 percent higher hip fracture risk, but not those taking B12, as you can see below and at 0:35 in my video Do Vitamin B12 Supplements Cause Bone Fractures and Lung Cancer?.  

    That’s what the Harvard study found, too. High intake of vitamin B12 alone was not associated with increased risk. In fact, some observational studies suggest a slightly lower fracture risk at high B12 blood levels. What we care about most, though, are interventional studies, where people are randomized to B12 so we can see what happens, and when we look at those, we find there is no increased fracture risk among those given B12. In conclusion, based on randomized controlled trials, high doses of vitamin B12 have not been shown to be associated with the risk of fractures.

    Okay, but what about this? In 2017, a study found that men taking vitamin B12 supplements appeared to have increased lung cancer risk. Now, the researchers didn’t find any such association in women, and the increased risk was mostly among men who smoked. Could it be that B12 was feeding budding tumors? It’s hard enough imagining a vitamin being carcinogenic on its own, especially if it somehow only affects men and not also women. “Replication of these findings in additional prospective studies with careful measurement of B vitamin supplement use is warranted.” And, indeed, when you put together all the observational studies, there is no significant correlation between lung cancer and levels of B12 in the blood, whether you’ve smoked or not. If anything, most studies seemed to trend towards higher B12 levels being protective, as you can see below and at 2:03 in my video. 

    Then, in 2018, a new study found an association between overall lung cancer risk and higher circulating levels of B12, again appearing to be more of a concern with smokers, as seen here and at 2:16 in my video. 

    Now, this was another observational study. Those with higher B12 levels were just observed to have higher cancer levels. Those of you who have been following my work know the drill: There are two potential issues that arise in observational studies that prevent us from ascribing cause-and-effect: confounding factors, also known as “lurker variables,” and reverse causation.

    What might be a lurker variable in this case? What might be a third factor associated with both higher B12 levels and cancer that may be the true cause? Well, who has higher levels of B12 circulating in their blood? Those who eat a lot of meat and dairy, which are, in fact, “the most important contributors to serum vitamin B-12,” that is, B12 in our blood. And those who eat more meat do tend to have more lung cancer: “Dose-response analysis showed that consumption of red meat for 120 g per day might increase the risk of lung cancer by 35%, and consumption of processed meat for 50 g per day might increase the risk of lung cancer by 20%.” So, we’re generally talking about 35 percent more risk for every quarter-pound burger eaten each day and about 20 percent increased risk for every breakfast sausage link. It’s no wonder those with higher B12 levels in their blood could have more lung cancer. The B12 could just be a marker for meat intake.

    And, if you remember, reverse causation is when X may not lead to Y, but, instead, Y may lead to X. So, instead of high B12 blood levels leading to cancer, maybe cancer leads to high blood levels of B12. And, indeed, nearly 75 percent of patients diagnosed with cancer exhibit elevated B12 levels. So, elevated B12 levels may simply be a marker for cancer. Besides taking extra B12, there are all sorts of reasons your levels can rise, such as liver problems, kidney problems, bone marrow problems, and cancer, as you can see below and at 3:50 in my video. So, high B12 levels may just be a marker of brewing, but not yet diagnosed, cancer. 

    What about observational studies specifically linking B12 supplement use to lung cancer, though? Those could also be reverse causation: “The consequence of being at risk for cancer is that patients will engage in healthier behaviors, including taking multivitamins (reverse causality). The well-established causes, such as smoking, chronic obstructive pulmonary disease, and previous cancers, are the real lung cancer risks.” So, we’re left with this “chicken or the egg causality dilemma,” which is why, ideally, we need randomized controlled trials to see if there’s any cause and effect.

    This became even more urgent with genetic evidence suggesting that those born with higher lifelong levels may be at increased risk. Thankfully, as you can see below and at 4:47 in my video, we do have randomized controlled trials—more than a dozen randomized controlled trials randomizing thousands of people up to 2,000 micrograms of B12 every single day for years, in fact. 

    The findings? “Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality.” And this includes specifically looking at lung cancer, as seen below and at 5:02 in my video. In fact, if anything, vitamin B supplements may actually lower the risk of the most dangerous form of skin cancer. 

    If you missed my previous video, check out Do Vitamin B12 Supplements Cause Acne?.

    For my other B12 updates, see related posts below. All of these videos can be found in one digital download: Latest Vitamin B12 Recommendations.

    I’ve also explored vitamin B12’s role in stroke risk. See the related posts below. That series is available for digital download, too: Why Do Vegetarians Have Higher Stroke Risk?.



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  • Acne and Vitamin B12 

    Acne and Vitamin B12 

    Acne can be triggered in one in ten people who get vitamin B12 injections.

    “Acne is a disease unique to humans.” Why do we even get it? Well, think about the distribution of those greasy sebaceous glands. They’re “on the face, chest and back; these are exactly the same structures that pose the greatest obstruction during childbirth…Having extra lubrication at these sites would help make the baby more slippery for birth conferring a selective advantage to successful delivery.” Perhaps, but what triggers them to become inflamed into pimples later in life?

    “In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95%” of teens. Not even a single case could be found in some populations where more “traditional” diets are eaten (i.e., minimally processed, high-carb, low-fat diets). “Nutrition counseling” has been suggested “as a first-line or adjunctive therapy…for individuals with mild to moderate acne.” It looks like high glycemic foods and dairy products are “exacerbating factors,” so we’re talking about sugar, soda, refined junky carbohydrates, white flour, breakfast cereal, and dairy products, like milk, cheese, yogurt, and whey, as well as saturated and trans fats, which are concentrated in meat, dairy, junk, and fast food. You can see a table detailing this below and at 1:21 in my video Do Vitamin B12 Supplements Cause Acne?.

    “Acne patients should be encouraged to discontinue any whey protein supplements they might be taking,” for example. “The relationship between milk and acne severity may be explained by the presence in dairy of normal reproductive [sex] steroid hormones or the enhanced production of polypeptide [growth] hormones such as IGF-1…” What if you gave up dairy a month ago and there’s still no change? “It should be noted that changes in acne due to any pharmaceutical treatment or dietary changes are likely to take at least 10 to 12 weeks,” so you have to stick with it.

    “Acne patients,” not surprisingly, “were more than twice as likely to have a non-vegan diet compared with controls,” but the difference did not reach statistical significance. Were the vegans eating a lot of vegan junk? Maybe, but what about the paper entitled, “Vitamin B-12 Induced Acne”? Mammalian herbivores, including nonhuman primates like gorillas, and our fellow great apes, get all the B12 they need by practicing coprophagy, the eating of feces, but my preference would be to take B12 supplements. And you don’t have to worry about getting too much because it’s been reported that “there are no reports of adverse effects associated with excess B12 intake”—but that’s not true. First described back in the 1950s, acne erupts in about one in ten people within days or even hours of getting an injection of vitamin B12, which then disappears rapidly when injection “treatment is discontinued.”

    At the time, we had no idea what the mechanism might be, and the problem remained unsolved until just a few years ago when we finally figured it out: Vitamin B12 modulates the gene expression of the skin bacteria that cause acne. Researchers swabbed the skin of ten people before and after being injected with vitamin B12. As you can see below and at 3:20 in my video, it turns out that the level of B12 on our skin is proportional to the level in our blood, so, after a B12 injection, the bacteria on our skin have to make less of their own B12. As a result, the acne bacteria could concentrate instead on using their cellular machinery to churn out more compounds to attack our face and “induce inflammation in acne.” 

    Indeed, as you can see here and at 3:53 in my video, without excess B12 on the skin (with B12 shown in green), the bacteria have to make most of it on their own at the expense of porphyrins (shown in red), which can trigger acne inflammation. When there is a lot of B12 floating around, the bacteria don’t have to waste resources and, instead, can focus on trying to pimple you up. 

    So, what do you do? We know that individuals on plant-based diets have to take supplemental B12, but we don’t have to get injections. Vitamin B12-related acne tends to occur only “in dosages in excess of 5 to 10 mg per week.” That’s 5,000 to 10,000 micrograms a week, which is well in excess of the 50 micrograms a day or, alternately, the 2,000-microgram single weekly dose that I recommend. The only time you should be taking 5,000 to 10,000 micrograms a week is if you are treating B12 deficiency. If you remember from my previous video, B12 deficiency is treated with 1,000 micrograms a day for a month or more, as shown below and at 4:35 in my video, and that could potentially trigger acne. 

    For example, a vegan woman who hadn’t been taking B12 developed a deficiency and had to be treated with such high doses of the vitamin that her face erupted in acne, as you can see at 4:49 in my video. All the more reason not to become B12-deficient in the first place. But, even if you do get B12 injections, the likelihood of it triggering acne may only be about one in ten.

    For background and my updated recommendations, see my extended look at vitamin B12 in the related posts below. All of these videos can be found in one digital download. Check out Latest Vitamin B12 Recommendations.

    I previously explored vitamin B12’s role in stroke risk, which you can also see in the related posts below. That series is available for digital download, too: Why Do Vegetarians Have Higher Stroke Risk?.

    Up next is Do Vitamin B12 Supplements Cause Bone Fractures and Lung Cancer?.



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  • Testing for Vitamin B12 Deficiency 

    Testing for Vitamin B12 Deficiency 

    Many doctors mistakenly rely on serum B12 levels in the blood to test for vitamin B12 deficiency.

    There were two cases of young, strictly vegetarian individuals with no known vascular risk factors. One suffered a stroke, and the other had multiple strokes. Why? Most probably because they weren’t taking vitamin B12 supplements, which leads to high homocysteine levels, which can attack our arteries.

    So, those eating plant-based who fail to supplement with B12 may increase their risk of both heart disease and stroke. However, as you can see in the graph below and at 0:47 in my video How to Test for Functional Vitamin B12 Deficiency, vegetarians have so many heart disease risk factor benefits that they are still at lower risk overall, but this may help explain why vegetarians were found to have more stroke. This disparity would presumably disappear with adequate B12 supplementation, and the benefit of lower heart disease risk would grow even larger.

    Compared with non-vegetarians, vegetarians enjoy myriad other advantages, such as better cholesterol, blood pressure, blood sugars, and obesity rates. But, what about that stroke study? Even among studies that have shown benefits, “the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. 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 that you might even miss them. What’s more, you develop metabolic vitamin B12 deficiency well before you develop a clinical deficiency, so there’s “a missed opportunity to prevent dementia and stroke” when you have enough B12 to avoid deficiency symptoms, but not enough to keep your homocysteine in check. “Underdiagnosis of this condition results largely from a failure to understand that a normal serum [blood level] B12 may not reflect an adequate functional B12 status.” The levels of B12 in our blood do not always represent the levels of B12 in our cells. We can have severe functional deficiency of B12 even though our blood levels are normal or even high.

    “Most physicians tend to assume that if the serum B12 is ‘normal,’ there is no problem,” but, within the lower range of normal, 30 percent of patients could have metabolic B12 deficiency, with high homocysteine levels. 

    Directly measuring levels of methylmalonic acid (MMA) or homocysteine is a “more accurate reflection of vitamin B12 functional statuses.” Methylmalonic acid can be checked with 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 Hcy [homocysteine] rises in both vitamin B12 and folate deficiencies.” So, “metabolic B12 deficiency is strictly defined by elevation of MMA levels or by elevation of Hcy in folate-replete individuals,” that is, in those getting enough folate. Even without eating beans and greens, which are packed with folate, folic acid is added to the flour supply by law, so, these days, high homocysteine levels 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 subclinical functional vitamin B12 deficiency is dramatically higher than previously assumed…” We’re talking about 10 to 40 percent of the general population, more than 40 percent of vegetarians, and the majority of vegans who aren’t scrupulous about getting their B12. Some suggest that those on plant-based diets should check their vitamin B12 status every year, but you shouldn’t need to if you’re adequately supplementing. 

    There are rare cases of vitamin B12 deficiency that can’t be picked up on any test, so it’s better to just make sure you’re getting enough.

    If you do get your homocysteine tested and it’s still too high, up in the double digits despite B12 supplementation and eating beans and greens, I have a suggestion for you in the final videos of this series, which we’ll turn to next with: Should Vegetarians Take Creatine to Normalize Homocysteine? and The Efficacy and Safety of Creatine for High Homocysteine.

    How did we end up here? To watch the full series if you haven’t yet, check the related posts below. 



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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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