 B12 supplementation is crucial for anyone eating a plant-based diet, but does it have any side effects? Watch this video to find out. Acne is a disease unique to humans. Why do humans get acne? Well, think about the distribution of those greasy sebaceous glands, face, chest, and back— exactly the same structures that pose the greatest obstruction during childbirth. So hey, maybe having a little extra lubrication at those sites would help make the baby more slippery for birth, conferring a selective advantage for successful delivery. OK, but what triggers them to become inflamed into zits later on? While in Westernized societies, acne is a nearly universal skin disease afflicting up to 95% of teens, and some populations eating more traditional diets, not even single cases could be found. This suggests that perhaps nutrition counseling should be a first-line therapy for individuals with mild to moderate acne. It looks like it's the high glycemic foods and dairy products. So we're talking sugar, soda, refined junky carbs, white flour, breakfast cereal, and dairy products like milk, cheese, yogurt, whey, as well as saturated and trans fats concentrated in meat, dairy, junk, and fast food. So, for example, acne patients should be encouraged to discontinue any whey protein supplements that might be taking the relationship between milk and acne severity, maybe explained by the presence in dairy of normal reproductive sex steroid hormones or the enhanced production of growth hormones such as IGF1. And if you're like, wait, I gave up dairy a month ago and still no change, it should be noted that changes in acne due to any dietary changes are likely to take at least 10 to 12 weeks, so you have to stick to it. Not surprisingly, acne patients are more than twice as likely to have a non-vegan diet compared to controls, but the difference did not reach statistical significance. So maybe the vegan's reading a lot of vegan junk. But what about this? Vitamin B12 induced acne. Our fellow great-ape herbivores like gorillas get all the B12 they need practicing 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 there are evidently no reports of adverse effects associated with excess B12 intake, but that's not true. First described back in the 1950s about 1 in 10 people erupt in acne within days or even just within hours of getting an injection of vitamin B12, which then disappears rapidly when you stop injecting them. At the time, we had no idea what the mechanism might be. A problem still unsolved even up until just a few years ago, but then we finally figured it out. Vitamin B12 modulates the gene expression of the skin bacteria that cause acne. They swabbed the skin of 10 people before and after being injected with vitamin B12, turning out the level of B12 on your skin is proportional to the level in your blood. And so after injection, the bacteria on your skin have to make less of their own B12. And so the acne bacteria could concentrate instead on using its cellular machinery to churn out more compounds to attack your face. Without excess B12 on the skin shown here in green, the bacteria has to make most on its own at the expense of porphyrins, which can trigger acne inflammation. When there's lots of B12 floating around the bacteria, it can not waste resources and focus instead on trying to pimple you up. Okay, so wait, what do you do? Those on plant-based diets have to take supplemental B12. Yes, but we don't have to get injections. Vitamin B12-related acne tends to occur only in dosages, in excess of 5,000 to 10,000 micrograms a week. Well, in excess of the 50 micrograms a day, I recommend or alternately my 2,000 single weekly dose. I mean, the only time you'd be taking between 5,000 to 10,000 a week is if you were 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. And that could potentially trigger it, as noted in this vegan woman who wasn't taking B12. Developed B12 deficiency had to be treated with such high doses her face erupted in acne. So all the more reason not to fall B12 deficient in the first place. But look, worse comes to worse. Even if you do get B12 injections, the likelihood of it triggering acne may only be about 1 in 10. In 2019, a study found an association between high intakes of vitamins B6 and B12 from food and supplements with the risk of hip fracture among post-menopausal women in the Harvard Nurses' Health Study. But note it was only the combined high intake of vitamins B6 and B12. We know that treatment with high doses of vitamin B6 may alone increase hip fracture risk. After a decade or so, those who had been taking high dose B6 supplements had about 40% higher hip fracture risk, but not in those taking B12. And 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 slightly lower fracture risk at high B12 blood levels. But what we care about most are interventional studies where people are randomized to B12 so we can see what happens. And when you do that, 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 an increase in lung cancer risk. Now they didn't find any such association. Women, it was mostly among smoking men. I mean, could it be that B12 was like feeding some budding tumors? I mean, it's hard to imagine a vitamin being carcinogenic on its own, especially somehow only in men, not women. The bottom line is that replication of these findings with additional studies is necessary. And indeed, when you put all the observational studies together, there was no significant correlation between levels of B12 in the blood and lung cancer, whether you smoked or not. I mean, if anything, most studies seem to be trending towards higher B12 levels being protected. But 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 smoker thing. Now this was another observational study. Those with higher B12 levels were just observed to have higher cancer levels. And so those of you who've been following my work know the drill. There are two potential issues that arise in observational studies that prevent you from ascribing cause and effect, confounding factors, also known as lurker variables, and reverse causation. What might be a lurker variable in this case? A third factor associated with both higher B12 levels in cancer, and that may be the true cause? Well, who has higher levels of B12 circulating in their blood? Those who eat lots of meat and dairy. In fact, probably the most important contributors. And those who eat more meat do tend to have more lung cancer, about 35% more risk for every about daily quarter pound burger, and 20% increased risk for each like breakfast sausage leg. So 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, instead of x leading to y, maybe y is instead leading to x. So instead of high B12 blood levels leading to cancer, I mean maybe cancer leads to high blood levels, and indeed nearly three-quarters of cancer patients. Exhibit elevated B12 levels. So elevated B12 levels may just be a marker for cancer. There's all sorts of things beyond just taking extra B12 that can raise your levels of liver problems, kidney problems, bone marrow problems, and cancer. So high levels may just be a marker of a brewing, not yet diagnosed cancer. Yeah, but what about observational studies specifically linking supplement use to lung cancer? That too could be reverse causation, where being at risk for cancer, in other words being a smoker, makes you more likely to take vitamins to try to decrease your risk. And basically any behavior tied to smoking could be indirectly tied to lung cancer, but it's the smoking itself, of course. That's the real lung cancer risk. So we're left with this chicken-of-the-egg causality dilemma, which is why ideally we need a randomized controlled trials to see if there's any cause and effect. This became even more urgent, with genetic evidence suggesting that those just born with higher life-long levels may be at increased risk. Thankfully we do have randomized controlled trials over a dozen randomized controlled trials randomizing thousands of people, up to 2,000 micrograms of B12 every single day for years, and vitamin B supplementation does not have any effect on getting cancer, dying from cancer, or dying overall. And this includes specifically looking at lung cancer. In fact, if anything, vitamin B supplements may actually lower the risk of the most dangerous form of skin cancer.