Vitamin B12 supplementation and ageing
There's a debate about whether older people should be taking vitamin B12 supplementations regularly to lower their risk of dementia. Some suggest that they should, but that people do need to be careful.
Norman Swan: Another active debate about supplementation and ageing is around vitamin B12. Should older people be taking B12 routinely to lower their risk of dementia? Some experts think they should but people do need to be careful, as you'll find out.
Martha Morris is an epidemiologist at the Human Nutrition Research Center on Ageing at Tufts University in Boston.
Martha Morris: In the 1960s the estimated prevalence of vitamin B12 deficiency in the elderly was a 1%, and by 1990 the estimate was 5%, and now it's up in the range of 20%.
Norman Swan: So have we changed or has the measure changed?
Martha Morris: The measure has changed. Initially one diagnosed vitamin B12 deficiency by assessing anaemia, but now we know that anaemia doesn't always accompany vitamin B12 deficiency.
Norman Swan: Because it's a very particular kind of anaemia where the red blood cells become larger.
Martha Morris: Right. Well, the first thing that wasn't recognised was that all vitamin B12 deficiency isn't the autoimmune disease, pernicious anaemia, which is where you see that megaloblastic anaemia.
Norman Swan: This is where the stomach loses its acid and you lose the ability to absorb vitamin B12.
Martha Morris: In the autoimmune disease actually the intrinsic factor is the problem, that the cells that produce both the intrinsic factor and the hydrochloric acid are destroyed.
Norman Swan: And the intrinsic factor you need to absorb vitamin B12.
Martha Morris: Right, it's like a carrier protein to actually transport vitamin B12 from the gastrointestinal system into the blood. But we all become somewhat vitamin B12 deficient as we age because of this other problem which is the decrease in hydrochloric acid, and what that is needed for is to release vitamin B12 from food protein. That's the majority of the problem.
Norman Swan: So as we age we produce less acid in the stomach.
Martha Morris: Exactly.
Norman Swan: And therefore the B12 remains trapped.
Martha Morris: Yes. So we might be consuming a lot of it but not absorbing very much of it.
Norman Swan: Then they started to measure B12 levels directly but that wasn't a very good measure either, according to Martha Morris. The step after that was to look at a chemical which rises in the blood when vitamin B12 is too low. The substance is called methylmalonic acid.
But the team at Tufts were dumbfounded when they looked at elderly people from the town of Framingham in Massachusetts who'd been followed for many years and compared their B12 levels to their thinking and memory abilities.
Martha Morris: Our most recent study that was published earlier this year, we showed that those elderly participants in the Framingham original cohort who had vitamin B12 levels below the 40th percentile, which is somewhere in the 258, something like that, range, which is much higher than anyone has ever considered to be a deficient range, they were susceptible to rapid cognitive decline, which was assessed by many mental state examination scores. However, by the time we started to assess nutritional status in these people, they were already quite elderly. And in this study they were followed over about eight years.
Norman Swan: So just to be clear then, so you had a group of people in the Framingham study who, if you like, fell off the cliff in terms of their thinking and memory ability, and it was related to their vitamin B12 level, it was a low level but at a higher level than people thought was a deficiency.
Martha Morris: Right. But there were only about 1,000 of them, but then excluding those with kidney disease et cetera, we ended up with about 500 people. And about half of those people had at one point had their methylmalonic acid levels measured as well, and I found exactly the same thing. Now, high methylmalonic acid is bad, low vitamin B12 is bad, both indicating low B12 status. And if you were above the 60th percentile for methylmalonic acid concentration, you also had a high risk of rapid MMSE score decline over the eight-year period.
Norman Swan: And the 60th percentile is actually just a little bit off the average methylmalonic acid level. You know, if it was going to be really high you'd say, well, it's really only the top 5%, but in fact you're finding that it's the top 40%, which is a really big group.
Martha Morris: Yes, it's shocking and it's scary. I don't want to say that 40% of the elderly are at risk of rapid cognitive decline due to vitamin B12 deficiency. So I did a final thing, and that was to look at those people who were below the 40th percentile for vitamin B12 as well as being above the 60th percentile for methylmalonic acid. And I made categories, I made four categories, either both bad, both good, or one bad, one good. And I found that the only ones who actually were at risk of this rapid cognitive decline were the ones that had both markers showing. And that was still a scary number but it was better than 40%, it was 16%.
Norman Swan: As Martha Morris said, that's still a very high number, and its magnitude may be an error in the way the study was done, but even so, there is a growing acceptance that vitamin B12 can affect brain and nerve function, which could explain why people might fall off the cliff thinking and memory wise.
But all this is just an association, a statistical link between cognitive decline and a low-ish B12 alongside a high-ish methylmalonic acid, if you'll forgive all this jargon. But is there any proof of cause and effect, because that would come from a randomised trial of supplementation.
Martha Morris: No, not a lot of proof, and one of the issues there is if you are really vitamin B12 deficient you may need a lot more B12 supplementation than anybody really realises. There have been some trials, some intervention studies like that but they find that it takes 1,000 micrograms of vitamin B12 to affect any improvements.
Norman Swan: Is the evidence strong enough for you to be swallowing extra B12?
Martha Morris: Personally I'm not doing it. You have to proceed with caution because of the fact that you are usually going to be taking a multivitamin to get that, and the multivitamins have high folic acid doses.
Norman Swan: Which is another supplement that you've been looking at, particularly when you've got folate fortification, and you've got some disturbing information on folate.
Martha Morris: Yes, there has been a lot of observational study about folate and cognition, and folate and depression. What we always saw in pre-fortification days was a dose response relationship where the higher the folate intake…well, there weren't so many studies with intake, but there were studies of circulating levels, and the higher those circulating levels were, the better people performed on cognitive function tests. And there were studies of Alzheimer's disease and other types of dementia.
Norman Swan: But that could have been the cause of a better diet, it might not have been the folate, it might have been something else in people's life.
Martha Morris: That's true, but…
Norman Swan: So the expectation was…
Martha Morris: Yes, the expectation from all these studies was that we were always going to see benefits to higher folate intakes or higher folate status. And so one of the first studies that looked at intake instead of serum levels found just the opposite.
Norman Swan: So high intake in that study, but it wasn't a trial, it was just following people, observing people, which is a bit of a risky methodology to actually assess true risk, but nonetheless it showed high intake in older people, higher cognitive decline.
Martha Morris: Exactly.
Norman Swan: But when they delved into this further, it looked as though the real problem was in people who'd been taking folate supplements. The best thinking at the moment is that folate supplements are good for your brain if your folate levels are low. But with folate added to the food supply these days, most of us have enough on board, so taking folic acid tablets may not help further and could just conceivably be bad for your brain. And if the findings are real, then you don't have to be vitamin B12 deficient to run this risk. If it's real, it could come from folic acid supplements themselves.
Martha Morris: So this kind of gives one pause.
Norman Swan: So what could be going on?
Martha Morris: I am stumped. I have no idea, and I don't think anyone else has any good idea. This is just completely unexpected. There haven't been enough studies yet. Ours is really only the second one to show this in a prospective study.
Norman Swan: So despite the confidence that some in the complementary medicine industry have about vitamin supplements, it's actually a complicated story, and possibly the safest thing if you're concerned about vitamin B12 is to discuss it with your GP and perhaps to take B12 alone, not in a multivitamin. And just to confuse you further, you should check an interview I did with Professor David Spence last year, suggesting there's evidence that if you have kidney damage you've got to be careful about which form of vitamin B12 to take. And we'll have a link to that interview on our website.
I hope all this has been much clearer than mud.
This has been the Health Report and I'm Norman Swan. See you next time.
- Dr Martha Morris
Human Nutrition Research Center on Ageing
- Dr Norman Swan
- Brigitte Seega