Medical B vitamins slow brain shrinkage in the elderly

[SW VandeCarr]

Mild cognitive impairment (MCI) may be slowed with B vitamin supplements according to a recent UK study. Other studies have shown that elevated blood homocysteine levels are associated with MCI and more severe cognitive dysfunction including Alzheimer's disease. B12, B6 and folic acid are known to reduce blood homocysteine levels. 271 elderly subjects with MCI were enrolled in this randomized placebo controlled trial and 168 had a final MRI to evaluate brain shrinkage, the main outcome measure in the trial. The study showed a statistically and clinically significant slowing of brain shrinkage in the group treated with high daily doses of B vitamins for two years vs placebo.

http://www.ox.ac.uk/media/news_stories/2010/100909.html

 

[SW VandeCarr]

Bump.

OK, no comments. I'll lead off. What does slowing brain shrinkage have to do with MCI? The article didn't mention any cognitive testing. I haven't actually seen the paper and I'm not sure it's available yet. It seems reasonable to say that if your brain shrinks a bit, maybe some of your cognitive abilities decline a bit too. But is that scientific? If so, how do the two relate?

Just trying to provoke some discussion.

 

[nismaratwork]

The answer seems to be that there are results here, but that their significance and meaning are unknown.

I don't know if this is... anything, but OPTIMA has been going for a bit less than quarter century and there is nothing definitive in the areas you are asking about. Keep in mind the history of such studies in relation to other diseases and conditions; while these results are interesting, I don't know that they'll ultimately lead to a treatment, diagnostic means, or a dead end.

Here's the homepage for OPTIMA: http://www.medsci.ox.ac.uk/optima

Here's an excerpt from the relevant OPTIMA study (circa 2005) which addresses what the significance of the results you mentioned might be.

What about dietary risk factors?
The Project found that, in the patients who had Alzheimer’s disease, and in some of those with other dementias, the level of an amino acid called homocysteine found in blood plasma was significantly higher than in other people. They also found that the levels of the B vitamins, folic acid and vitamin B12 were significantly lower in the same patients. High levels of homocysteine are known to be associated with strokes, heart disease, and some cancers.
Does this mean that high levels of homocysteine actually cause Alzheimer's disease?
The true answer is that at present we simply do not know. Many other researchers have now found that the levels of folic acid and vitamins B12 are reduced in dementia, and specifically in Alzheimer’s disease, and others have shown high levels of homocysteine, not only in Alzheimer’s disease but in other diseases too. The high levels of homocysteine in the research could be the result of Alzheimer’s disease rather than the cause.

 

[SW VandeCarr]

The answer seems to be that there are results here, but that their significance and meaning are unknown.

I don't know if this is... anything, but OPTIMA has been going for a bit less than quarter century and there is nothing definitive in the areas you are asking about. Keep in mind the history of such studies in relation to other diseases and conditions; while these results are interesting, I don't know that they'll ultimately lead to a treatment, diagnostic means, or a dead end.

Here's the homepage for OPTIMA: http://www.medsci.ox.ac.uk/optima

Here's an excerpt from the relevant OPTIMA study (circa 2005) which addresses what the significance of the results you mentioned might be.

Yes. Thanks for your response. I agree, when you have two observations: high blood homocysteine levels and low B vitamin levels in patients with Alzheimer's disease (AD)and AD is characterized by brain atrophy (although the pattern is important), it is encouraging to see the result of this study. That's why I posted it.

However you have ask, wouldn't it have made sense to have included some cognitive tests in the protocol? After all, MCI is a cognitive disability. Since I've worked in clinical research I know how this works. Suppose the cognitive tests showed a downward progression more or less equally in both treatment arms? Oops, maybe no more money for further studies!

If you ask too many questions, you might not always get the answers you hope to get. In fairness, cognitive testing is not that precise and lot of extraneous factors can influence results. It would be a shame to have a negative result for this outcome measure throw doubt on what could be a significant finding. However at some point, the question: "Do high dose B vitamins daily slow or arrest cognitive decline in the elderly?" has to be addressed directly.

 

[nismaratwork]

Yes. Thanks for your response. I agree, when you have two observations: high blood homocysteine levels and low B vitamin levels in patients with Alzheimer's disease (AD)and AD is characterized by brain atrophy (although the pattern is important), it is encouraging to see the result of this study. That's why I posted it.

However you have ask, wouldn't it have made sense to have included some cognitive tests in the protocol? After all, MCI is a cognitive disability. Since I've worked in clinical research I know how this works. Suppose the cognitive tests showed a downward progression more or less equally in both treatment arms? Oops, maybe no more money for further studies!

If you ask too many questions, you might not always get the answers you hope to get. In fairness, cognitive testing is not that precise and lot of extraneous factors can influence results. It would be a shame to have a negative result for this outcome measure throw doubt on what could be a significant finding. However at some point, the question: "Do high dose B vitamins daily slow or arrest cognitive decline in the elderly?" has to be addressed directly.

I agree that the lack of cognitive testing is odd, especially as the creation of more effective tests is part of what OPTIMA has been doing for 20+ years! Perhaps they felt that it would interfere with their study protocols, but if so, I wonder why there's been no follow up with cognitive tests. I'm still doing some more research into this to see if there are some ongoing studies that are yet to be published.

This is an interesting result on its own... I hope there's more info to be found out there beyond the OPTIMA studies. Let's find out.

 

[SW VandeCarr]

This is an interesting result on its own... I hope there's more info to be found out there beyond the OPTIMA studies. Let's find out.

Oh, there will be. There are few health/medical issues that are more significant than this one. Most families will be faced with dementia in a close relative or spouse sooner or later, and we all get old, like or not. For most, it's still better than the alternative. If something as simple as taking vitamins can have an effect, it would be a boon to society even if thought of in terms of costs alone . Dementia in general is no longer thought to be an inevitable part of the aging process.

 

[rhody]

nismara, SW,

Interesting discussion. If I may relate first hand experience with B vitamins, and folic acid (B9, folacin) in particular. I may not be in the "normal" population to begin with, have excess calcium from sarcoidosis as background. In that context, I have tried a supplement containing all B's (for just the reason you mention, to keep my brain from shrinking) and in less than three months developed stomach problems. I made an appointment with a gastroenterologist a week ahead, suspecting that the B's were causing it, so I stopped taking them. Fast forward three days, things started to get better, by day six I was symptom free so I canceled my appointment.

Second, I had been taking folic acid (my employer hands it out at health fairs), and that was causing nausea, sneezing fits (histamine release), and a nasty drip that is not good for my lung condition, seems to keep O2 uptake down a bit, which I reported on in Lisa's thread: https://www.physicsforums.com/showthread.php?t=418005". As soon as I stopped taking folic acid, the upset stomach, sneezing stopped, the drip was much better. I also added magnesium supplement, which helps in calcium be absorbed in the body. I again added folic acid (only for three days) and the same symptoms returned with a vengeance. I am off it for good now, convinced that that was the cause of my problem. I just had a stress echo-cardiogram and did way better than 4 years ago, got a level 4 this time, and did not feel like I was going to lose my breath at the end of the treadmill test. I was in better shape this time, and off all B's and folic acid as well.

I grew up believing B vitamins were "water soluble" and that for practical purposes you could not build them up in your system. I was on the B's for about a month and a half before developing stomach problems. I am now not convinced that they are "purged" from you system on a daily basis. The symptoms should have appeared at first, and did not.

I have two family members who died from alzeheimer's, my Grandmother, Father, it is not something I care to experience myself. Having said that, B vitamins and the bad side effects are too much. I am concerned that I may have the genes that given certain physical conditions my express themselves and I may develop it as well, but both Dad and Grandmother were smokers and moderate drinkers, Grandma more so than Dad. Plus later in life they became sedentary, I don't believe from any physical condition that would have prevented them from walking.
They were not very engaged with their minds either, both activities research has shown that slow the onset of the disease.

I plan on doing everything in my power to keep off the alzehiemer track. The brain book by Norman Doidge did provide a number of things (besides taking B Vitamins) that you can do to keep you healthy mentally, emotionally, and physically as long as possible. I will use every technique I can find. Might I suggest, as Doidge and a number of researcher's in the book provide case histories for, that engaging the mind seems to keep many elderly still quite with it, highly functional. In the end, it all comes down to personal motivation, and there isn't a pill I know of, yet, that stimulates that.

Rhody...

P. S. There appears to be 4 or 5 "histamine" receptor sites in the brain, it seems that the last two receptor sites from links I have been reading have only been detected in the past decade. Histamine must be fairly important for that many receptor sites and I have a bunch of links to try a fathom the history and will report in Lisa's thread in the future.

 

[nismaratwork]

Oh, there will be. There are few health/medical issues that are more significant than this one. Most families will be faced with dementia in a close relative or spouse sooner or later, and we all get old, like or not. For most, it's still better than the alternative. If something as simple as taking vitamins can have an effect, it would be a boon to society even if thought of in terms of costs alone . Dementia in general is no longer thought to be an inevitable part of the aging process.

Yeah, there is a crunch like this coming in many nations, and these "little lapses" that occur in MCI can still lead to accidents, death, or a lowered quality of life. In the extreme as I've seen firsthand, it's devastating for years. My grandmother died with Alzheimer's; a seven year process where the person within the body was long gone before pneumonia claimed her. That being said, far milder cognitive impairment can still turn people into something less recognizable as a family member or friend.

The problem is that most of the pharmaceutical options that have panned out are stimulants and not a means of prevention or addressing the root of the problem. We also live in a day and age where many people take anti-psychotic medications and others drugs which can have a devastating effect on the brain over the long haul. If you've never seen an MRI of atrophy with ventricular enlargement, it's quite arresting. There needs to be a deeper understanding of how these processes are set into motion, and how to arrest them in the case of natural occurrence, and drug induced situations. You can't simply tell someone who is schizophrenic to stop taking their medications and expect a good outcome, but atrophy of the brain is NOT a good outcome in the long-term either.

This is a problem that requires more research than the targeted types which pharmaceutical companies have to do for R&D, and with the recognition that our mental health system cannot support a large population of such effected people. The solution can't be mass-care, which means it must be medical. Vitamin studies are a good start, but it's just the tip of a wildly complex iceberg; much needs to be done.

 

[shredder666]

as far as I know vitamin B's are important cofactors for energy generation thiamine..pyruvate dehydrogenase catalyzed conversion of pyruvate to acetyl CoA, the other Bs are related to reactions involving the electron carriers, i forgot wat b12 did

but deficiency in thiamine leads to memory loss and demyelination of limb neurons, low B3 leads to dementia, etc etc

so pretty important stuff, this shouldn't be surprising

 

[nismaratwork]

as far as I know vitamin B's are important cofactors for energy generation thiamine..pyruvate dehydrogenase catalyzed conversion of pyruvate to acetyl CoA, the other Bs are related to reactions involving the electron carriers, i forgot wat b12 did

but deficiency in thiamine leads to memory loss and demyelination of limb neurons, low B3 leads to dementia, etc etc

so pretty important stuff, this shouldn't be surprising

Yeah, and you need vitamin C to produce collagen, but that doesn't mean taking lots of it restores collagen lost to the natural aging process. What's interesting here is not that these people could have had a vitamin deficiency, but that increased levels somehow ameliorate atrophy in the absence of deficiency.

 

[litup]

nismara, SW,

Interesting discussion. If I may relate first hand experience with B vitamins, and folic acid (B9, folacin) in particular. I may not be in the "normal" population to begin with, have excess calcium from sarcoidosis as background. In that context, I have tried a supplement containing all B's (for just the reason you mention, to keep my brain from shrinking) and in less than three months developed stomach problems. I made an appointment with a gastroenterologist a week ahead, suspecting that the B's were causing it, so I stopped taking them. Fast forward three days, things started to get better, by day six I was symptom free so I canceled my appointment.

Second, I had been taking folic acid (my employer hands it out at health fairs), and that was causing nausea, sneezing fits (histamine release), and a nasty drip that is not good for my lung condition, seems to keep O2 uptake down a bit, which I reported on in Lisa's thread: https://www.physicsforums.com/showthread.php?t=418005". As soon as I stopped taking folic acid, the upset stomach, sneezing stopped, the drip was much better. I also added magnesium supplement, which helps in calcium be absorbed in the body. I again added folic acid (only for three days) and the same symptoms returned with a vengeance. I am off it for good now, convinced that that was the cause of my problem. I just had a stress echo-cardiogram and did way better than 4 years ago, got a level 4 this time, and did not feel like I was going to lose my breath at the end of the treadmill test. I was in better shape this time, and off all B's and folic acid as well.

I grew up believing B vitamins were "water soluble" and that for practical purposes you could not build them up in your system. I was on the B's for about a month and a half before developing stomach problems. I am now not convinced that they are "purged" from you system on a daily basis. The symptoms should have appeared at first, and did not.

I have two family members who died from alzeheimer's, my Grandmother, Father, it is not something I care to experience myself. Having said that, B vitamins and the bad side effects are too much. I am concerned that I may have the genes that given certain physical conditions my express themselves and I may develop it as well, but both Dad and Grandmother were smokers and moderate drinkers, Grandma more so than Dad. Plus later in life they became sedentary, I don't believe from any physical condition that would have prevented them from walking.
They were not very engaged with their minds either, both activities research has shown that slow the onset of the disease.

I plan on doing everything in my power to keep off the alzehiemer track. The brain book by Norman Doidge did provide a number of things (besides taking B Vitamins) that you can do to keep you healthy mentally, emotionally, and physically as long as possible. I will use every technique I can find. Might I suggest, as Doidge and a number of researcher's in the book provide case histories for, that engaging the mind seems to keep many elderly still quite with it, highly functional. In the end, it all comes down to personal motivation, and there isn't a pill I know of, yet, that stimulates that.

Rhody...

P. S. There appears to be 4 or 5 "histamine" receptor sites in the brain, it seems that the last two receptor sites from links I have been reading have only been detected in the past decade. Histamine must be fairly important for that many receptor sites and I have a bunch of links to try a fathom the history and will report in Lisa's thread in the future.

In your case, if the concept of higher B vitamins actually works to lower the shrinkage rate of the brain, and taking supplements causes stomach problems, maybe it would be better to eat foods with high B content. That seems to me to avoid the kind of problems you mentioned. Another issue could be the amount you took may have been too high. Did you try lower doses?

 

[rhody]

In your case, if the concept of higher B vitamins actually works to lower the shrinkage rate of the brain, and taking supplements causes stomach problems, maybe it would be better to eat foods with high B content. That seems to me to avoid the kind of problems you mentioned. Another issue could be the amount you took may have been too high. Did you try lower doses?

litup,

I try to eat healthy, and most of the B's I need come with food. That being said, I must correct something I said in a previous post. I take Niaspan, which is FDA approved for breaking down fat before it becomes cholesterol in the walls of arteries, veins, etc... 1000 mg before going to sleep. This is essentially B3 (Niacin) packaged in such a way as to achieve a "sustained release". The has been proven by the drug company that sells it through expensive clinical trials and testing. The stuff is pricey too. What makes it that way is the fact that the trials prove absorption in the body is a nice flat line, whereas extended release niacin may have ups and down in how quickly it is absorbed (I asked a pharmacist friend about it).

You were correct about the dosage though, it may have been on the "high end" for some of the B family. I prefer to get what I need from food, and do not experience bad side effects with Niaspan. (sustained release B3). So far this appears to be working. Will know for sure when blood tests show that the good cholesterol numbers are up from previous tests.

Rhody...

 

[SW VandeCarr]

Here's the full paper for those that might be interested.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0012244

 

[Proton Soup]

Yeah, and you need vitamin C to produce collagen, but that doesn't mean taking lots of it restores collagen lost to the natural aging process. What's interesting here is not that these people could have had a vitamin deficiency, but that increased levels somehow ameliorate atrophy in the absence of deficiency.

fwiw, some vit. C may be stored in the adrenals. http://www.ajcn.org/cgi/content/abstract/86/1/145

some collagen may be lost because we have a decreased capacity to produce glycine as we age, making it a conditionally-essential amino acid. http://www.ncbi.nlm.nih.gov/pubmed/20093739

cobalamin (b12) deficiency is common in the elderly. they eat less, and digest what they eat poorly. you can overcome this with megadoses (perfectly safe for this vitamin).

in the US, folic acid is fortified into all our processed grain products by law. so, that is usually not a problem except for a couple of caveats. B12 deficiency will cause the classical sign of megaloblastic anemia. only, excess folic acid in the diet will mask this sign, making it less likely that B12 deficiency is caught before it starts causing neurological damage. the other caveat is that folic acid may not be helpful for persons with MTHFR polymorphisms. for that, you need look elsewhere: http://pamlabs.com/


and, also, there are other ways around this sometimes, like going directly to the methylation problem and supplementing with S-Adenosyl-Methionine, aka SAMe, aka Adomet. http://en.wikipedia.org/wiki/Adomet