"Do Vitamin B12 Supplements Cause Bone Fractures and Lung Cancer?"
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 Postmenopausal 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 a 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.
OK, 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 in women,
and it was mostly among smoking men.
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, and especially somehow only in men but 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 the levels of B12
in the blood and lung cancer, whether you smoked or not.
If anything, most studies seemed to be trending
towards higher B12 levels being protective.
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 have 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 and cancer,
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 link.
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,
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 are all sorts of things beyond just taking extra B12
that can raise your levels: 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.
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 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 just born with higher lifelong 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.