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?.
