This is okay science, and unlike most times people link to these kinds of things on here I’m not going to throw a fit. But a few caveats:
First of all, my totally unfounded opinion is that the guy you’re linking to seems sketchy as hell. His site implies he is a doctor a bunch of times, including his biography talking about when he entered medical school, but the only degree listed is one from a college of “naturopathic medicine”. He founded a sketchy online pharmacy that sells (among other things) homeopathic solutions. He believes that vaccinations cause autism, at least in MTHFR babies (aka 1⁄4 of the population). And he fits a very worrying stereotype of the doctor who prescribes the same cure for almost every disease, and recommends that if it doesn’t work you just need to “optimize” his cure a little more carefully, as opposed to consider that other factors may be involved.
I don’t actually know anything about the research on this subject, but because of the red flags raised above I’ve tried to investigate it very briefly and see what it looks like. You should probably ignore everything below, but just out of curiosity:
Dr. Lynch seems to think that if you have MTHFR, taking more folic acid will be harmful to you. The way I’ve heard it is that taking more folic acid compensates for the lowered activity of MTHFR (see for example Linus Pauling Institute. Studies have also shown that low blood folate raises homocysteine levels.
If that’s correct, then supplementing with MTHF would have similar effects to supplementing with normal folate—ie a mixed bag that seems to include higher risk of many cancers.
And although conventional wisdom is that homocysteine is a harmful amino acid that causes cardiovascular disease, this has been confirmed in correlational studies only and interventional studies have failed to show that decreasing homocysteine lowers heart attack risk.
My guess is that most of the disease associations Dr. Lynch mentions as linked to MTHFR are actually linked to folate in general, and people with MTHFR are more likely to have low folate and therefore disease. For example, Dr. Lynch mentions that MTHFR affects autism risk, Down Syndrome risk, neural tube defect risk, etc, but folic acid in general also affects all of these things. Likewise, this study shows that babies with mutant MTHFR have more autism, but that this effect only holds true in countries without folic acid supplementation—the implication being that in countries with folic acid supplementation, pregnant women have enough folic acid whether they have a gene that decreases their levels slightly or not.
I admit I have tried to read the important parts of his site but I haven’t gotten to all of it, so maybe it explains his unconventional views on folate levels vs. MHTF levels somewhere.
Although Dr. Lynch recommends spending $150+ to get yourself genetically tested, my suggestion if you’re worried about this or any other gene is to sign up for 23andMe and get all your common mutations sequenced in one go for $99. If you already have 23andMe data, you can find your version of the gene Dr. Lynch is talking about by clicking in the gear in the upper left hand corner, going to “Browse Raw Data”, and then searching for SNP rs1801133. 23andMe uses opposite notation from most other sites, so the homozygous normal will be listed as GG, heterozygous as GA, and mutant as AA.
(I seem to be part of the lucky 25% who has the AA version. Maybe this explains my constant addictive infectious depressed demented diabetic cancerous heart attacks)
Your doctor can test you for folate deficiency. If you’re really concerned about your health it’s not a terrible idea, though it’s no more important than about thirty other tests you could also get. If you have the mutant gene, maybe have a slightly more stringent standard than normal for what counts as deficiency? I don’t know. In any case, you can supplement with MTHF if you want, but as mentioned before it will probably have about the same effect as normal folate supplementation—great for people with deficiencies and for pregnant women, probably just a little more cancer in everyone else. You can read more here.
The only exception is that if your psychiatrist recommends it for depression, you will need the MTHF version since the normal version can’t directly enter the brain. Your doctor will recommend an expensive Official Medical Version of it. As far as I know, the MTHF you can get off Amazon for $15 works exactly as well.
I would be really interested in hearing from anyone who knows more about biochemistry or has studied these areas in more depth.
I agree. The reason I chose that specific page is because I did not find an adequate alternative list. I tried Googling site:.gov “symptoms of MTHFR” and site:.edu “symptoms of MTHFR” and only one result comes up—but it’s specifically for homocysteinemia. That one result is reputable (nih.gov) but I know that it does not contain a full list of symptoms. It has left out important symptoms like depression and fatigue, which I know to be associated with MTHFR because I know people with the condition whose medical professionals have said that those symptoms can be caused by MTHFR and whose fatigue and/or depression symptoms were helped immensely by MTHFR treatment, and because I saw research on PubMed (searched it again since I have no idea where it is) linking MTHFR with depression and finding that using methyfolate as part of the treatment has an effect on depression. I could go with the shorter symptom list for homocysteinemia, but since I know that it is inadequate, I figured the longer symptom list would likely result in more people getting MTHFR tests and useful treatment.
There’s an elephant in the room here: why doesn’t there seem to be a good symptom list? If the fact that there are 5073 results for MTHFR on PubMed means anything at all, MTHFR is probably a real mutation with the potential to cause health effects. I suspect that it’s because we discovered MTHFR fairly recently and research results can be confusing because most of them are wrong, so perhaps the credible sources don’t want to take the chance on listing symptoms that they’re not completely certain are associated with MTHFR. This of course would not mean that people are not sick. It would just mean that the only people who have the guts to try to give people some idea of what MTHFR does to you are people who don’t have that kind of credibility to lose.
Perhaps your point here is to give me a heads-up along the lines of “people might get confused and think you are recommending the this guy”. That would be a good heads-up if so. Since it has occurred to me, I decided to add a disclaimer to my P/S/A comment.
if you have MTHFR, taking more folic acid...
As a non-medical doctor having a discussion with a psychiatrist to humor curiosities:
My understanding is that if you have MTHFR, you’ve got a reduced ability to process folic acid into methylfolate, and methylfolate is the usable version. Therefore taking additional folic acid isn’t necessarilly going to result in you utilizing the folic acid. Additionally, if you cannot process the folic acid, it sits around in your system waiting for you to clean it out. If your folic acid is synthetic as opposed to food-based, there can be issues with the synthetic folic acid sitting around not being utilized. The claim I heard was that it’s this unutilized synthetic folic acid that causes autism.
the implication being that in countries with folic acid supplementation
That’s interesting. Have you taken an interest in MTHFR or were your perspectives formed based on research you did after reading this PSA? I’m asking you because if it turns out that you’ve got a significant interest in MTHFR, I’d be interested in hearing what else you know about it. If not, I should probably regard your forays into MTHFR research as being about as useful as mine since, without reading a ton of research, any perspectives we build are going to be suceptible to the “most published research findings are false” problem.
sign up for 23andMe and get all your common mutations sequenced in one go for $99
I chose not to recommend that for the following reasons:
A. (As a non-lawyer) I believe that it is now illegal for U.S. health insurance companies to discriminate against you based on the results of genetic testing, but there may be no protection in other countries that LessWrong readers are from (and 50% of them visit from outside the U.S.).
B. (As a non-lawyer) I believe that it is still legal for U.S. life insurance and disability insurance companies to discriminate against you on the basis of genetic testing.
C. If I remember correctly, the 23 and me test is is not an official medical test. I was told by a doctor that when comparing the 23 and me results to a different test that uses blood instead of saliva and does qualify as a medical test, that the results are very close. I was also told a lot of things about it by a person with a biology degree that made me realize how complicated genetic testing is. I’m not sure whether 23 and me should be recommended in place of a medical test.
D. I was initially very squicked by 23 and me because the only PDF of theirs that I could find that has an accuracy citation produces a 404 error when you click it. I have since gotten citations from them, after bugging the heck out of customer service and explaining what “real citation” means. Upon reviewing the citations, I realized that I was in over my head because I didn’t know a lot of the terms they were using. I am no longer squicked, but it’s mostly because a few people I think are probably trustworthy told me that 23 and me is useful. I still wonder whether I should consider them dodgy due to the failure to provide a real accuracy citation in their PDF.
In any case, you can supplement with MTHF if you want
Self-treating with methylfolate may not be a good idea. Here’s why.
The only exception is that if your psychiatrist recommends it for depression, you will need the MTHF version since the normal version can’t directly enter the brain.
I see now that MTHFR.net actually did not list depression as a symptom by itself. They’ve got depression in post-menopausal women and “Infant depression via epigenetic processes caused by maternal depression” but not plain “depression”. Is your take on it that MTHFR can cause depression and/or that methylfolate can be useful for treating depression?
As far as I know, the MTHF you can get off Amazon for $15 works exactly as well.
I have checked out dozens and dozens of supplement review results on consumerlab.com, perhaps over a hundred. My findings are that many of the brands tested were shown to offer one or more supplements that contain lead, spoiled ingredients, or they did not contain the amount of the substance(s) advertized. I would not go get a random cheap one on Amazon.com. Instead, I would find one of these brands:
Brands with 30 reviews each and a perfect record on consumerlab as of June 2013:
Solgar
Puritan’s Pride
Vitamin World
Nature’s Bounty
Brands with an acceptable record as of June 2013:
Jarrow (17 reviews, all passed except one with a labeling issue)
Note: Puritan’s Pride, Vitamin World and Nature’s Bounty are all related. I think they’re all owned by the same company.
I plan to start a blog containing my supplement research and other life optimizing research at some point in the future (or perhaps find a relevant one to post on, since LessWrong is about rationality, not optimizing one’s life). I can update you when my supplement data is posted if you’d like.
It was written to Yvain. I was under the impression that Yvain was studying psychology, not medicine. Now that his website link has changed, I’m not sure there’s a way for me to look this up.
This is okay science, and unlike most times people link to these kinds of things on here I’m not going to throw a fit. But a few caveats:
First of all, my totally unfounded opinion is that the guy you’re linking to seems sketchy as hell. His site implies he is a doctor a bunch of times, including his biography talking about when he entered medical school, but the only degree listed is one from a college of “naturopathic medicine”. He founded a sketchy online pharmacy that sells (among other things) homeopathic solutions. He believes that vaccinations cause autism, at least in MTHFR babies (aka 1⁄4 of the population). And he fits a very worrying stereotype of the doctor who prescribes the same cure for almost every disease, and recommends that if it doesn’t work you just need to “optimize” his cure a little more carefully, as opposed to consider that other factors may be involved.
I don’t actually know anything about the research on this subject, but because of the red flags raised above I’ve tried to investigate it very briefly and see what it looks like. You should probably ignore everything below, but just out of curiosity:
Dr. Lynch seems to think that if you have MTHFR, taking more folic acid will be harmful to you. The way I’ve heard it is that taking more folic acid compensates for the lowered activity of MTHFR (see for example Linus Pauling Institute. Studies have also shown that low blood folate raises homocysteine levels.
If that’s correct, then supplementing with MTHF would have similar effects to supplementing with normal folate—ie a mixed bag that seems to include higher risk of many cancers.
And although conventional wisdom is that homocysteine is a harmful amino acid that causes cardiovascular disease, this has been confirmed in correlational studies only and interventional studies have failed to show that decreasing homocysteine lowers heart attack risk.
My guess is that most of the disease associations Dr. Lynch mentions as linked to MTHFR are actually linked to folate in general, and people with MTHFR are more likely to have low folate and therefore disease. For example, Dr. Lynch mentions that MTHFR affects autism risk, Down Syndrome risk, neural tube defect risk, etc, but folic acid in general also affects all of these things. Likewise, this study shows that babies with mutant MTHFR have more autism, but that this effect only holds true in countries without folic acid supplementation—the implication being that in countries with folic acid supplementation, pregnant women have enough folic acid whether they have a gene that decreases their levels slightly or not.
I admit I have tried to read the important parts of his site but I haven’t gotten to all of it, so maybe it explains his unconventional views on folate levels vs. MHTF levels somewhere.
Although Dr. Lynch recommends spending $150+ to get yourself genetically tested, my suggestion if you’re worried about this or any other gene is to sign up for 23andMe and get all your common mutations sequenced in one go for $99. If you already have 23andMe data, you can find your version of the gene Dr. Lynch is talking about by clicking in the gear in the upper left hand corner, going to “Browse Raw Data”, and then searching for SNP rs1801133. 23andMe uses opposite notation from most other sites, so the homozygous normal will be listed as GG, heterozygous as GA, and mutant as AA.
(I seem to be part of the lucky 25% who has the AA version. Maybe this explains my constant addictive infectious depressed demented diabetic cancerous heart attacks)
Your doctor can test you for folate deficiency. If you’re really concerned about your health it’s not a terrible idea, though it’s no more important than about thirty other tests you could also get. If you have the mutant gene, maybe have a slightly more stringent standard than normal for what counts as deficiency? I don’t know. In any case, you can supplement with MTHF if you want, but as mentioned before it will probably have about the same effect as normal folate supplementation—great for people with deficiencies and for pregnant women, probably just a little more cancer in everyone else. You can read more here.
The only exception is that if your psychiatrist recommends it for depression, you will need the MTHF version since the normal version can’t directly enter the brain. Your doctor will recommend an expensive Official Medical Version of it. As far as I know, the MTHF you can get off Amazon for $15 works exactly as well.
I would be really interested in hearing from anyone who knows more about biochemistry or has studied these areas in more depth.
I agree. The reason I chose that specific page is because I did not find an adequate alternative list. I tried Googling site:.gov “symptoms of MTHFR” and site:.edu “symptoms of MTHFR” and only one result comes up—but it’s specifically for homocysteinemia. That one result is reputable (nih.gov) but I know that it does not contain a full list of symptoms. It has left out important symptoms like depression and fatigue, which I know to be associated with MTHFR because I know people with the condition whose medical professionals have said that those symptoms can be caused by MTHFR and whose fatigue and/or depression symptoms were helped immensely by MTHFR treatment, and because I saw research on PubMed (searched it again since I have no idea where it is) linking MTHFR with depression and finding that using methyfolate as part of the treatment has an effect on depression. I could go with the shorter symptom list for homocysteinemia, but since I know that it is inadequate, I figured the longer symptom list would likely result in more people getting MTHFR tests and useful treatment.
There’s an elephant in the room here: why doesn’t there seem to be a good symptom list? If the fact that there are 5073 results for MTHFR on PubMed means anything at all, MTHFR is probably a real mutation with the potential to cause health effects. I suspect that it’s because we discovered MTHFR fairly recently and research results can be confusing because most of them are wrong, so perhaps the credible sources don’t want to take the chance on listing symptoms that they’re not completely certain are associated with MTHFR. This of course would not mean that people are not sick. It would just mean that the only people who have the guts to try to give people some idea of what MTHFR does to you are people who don’t have that kind of credibility to lose.
Perhaps your point here is to give me a heads-up along the lines of “people might get confused and think you are recommending the this guy”. That would be a good heads-up if so. Since it has occurred to me, I decided to add a disclaimer to my P/S/A comment.
As a non-medical doctor having a discussion with a psychiatrist to humor curiosities:
My understanding is that if you have MTHFR, you’ve got a reduced ability to process folic acid into methylfolate, and methylfolate is the usable version. Therefore taking additional folic acid isn’t necessarilly going to result in you utilizing the folic acid. Additionally, if you cannot process the folic acid, it sits around in your system waiting for you to clean it out. If your folic acid is synthetic as opposed to food-based, there can be issues with the synthetic folic acid sitting around not being utilized. The claim I heard was that it’s this unutilized synthetic folic acid that causes autism.
That’s interesting. Have you taken an interest in MTHFR or were your perspectives formed based on research you did after reading this PSA? I’m asking you because if it turns out that you’ve got a significant interest in MTHFR, I’d be interested in hearing what else you know about it. If not, I should probably regard your forays into MTHFR research as being about as useful as mine since, without reading a ton of research, any perspectives we build are going to be suceptible to the “most published research findings are false” problem.
I chose not to recommend that for the following reasons:
A. (As a non-lawyer) I believe that it is now illegal for U.S. health insurance companies to discriminate against you based on the results of genetic testing, but there may be no protection in other countries that LessWrong readers are from (and 50% of them visit from outside the U.S.).
B. (As a non-lawyer) I believe that it is still legal for U.S. life insurance and disability insurance companies to discriminate against you on the basis of genetic testing.
C. If I remember correctly, the 23 and me test is is not an official medical test. I was told by a doctor that when comparing the 23 and me results to a different test that uses blood instead of saliva and does qualify as a medical test, that the results are very close. I was also told a lot of things about it by a person with a biology degree that made me realize how complicated genetic testing is. I’m not sure whether 23 and me should be recommended in place of a medical test.
D. I was initially very squicked by 23 and me because the only PDF of theirs that I could find that has an accuracy citation produces a 404 error when you click it. I have since gotten citations from them, after bugging the heck out of customer service and explaining what “real citation” means. Upon reviewing the citations, I realized that I was in over my head because I didn’t know a lot of the terms they were using. I am no longer squicked, but it’s mostly because a few people I think are probably trustworthy told me that 23 and me is useful. I still wonder whether I should consider them dodgy due to the failure to provide a real accuracy citation in their PDF.
Self-treating with methylfolate may not be a good idea. Here’s why.
I see now that MTHFR.net actually did not list depression as a symptom by itself. They’ve got depression in post-menopausal women and “Infant depression via epigenetic processes caused by maternal depression” but not plain “depression”. Is your take on it that MTHFR can cause depression and/or that methylfolate can be useful for treating depression?
I have checked out dozens and dozens of supplement review results on consumerlab.com, perhaps over a hundred. My findings are that many of the brands tested were shown to offer one or more supplements that contain lead, spoiled ingredients, or they did not contain the amount of the substance(s) advertized. I would not go get a random cheap one on Amazon.com. Instead, I would find one of these brands:
Brands with 30 reviews each and a perfect record on consumerlab as of June 2013:
Solgar
Puritan’s Pride
Vitamin World
Nature’s Bounty
Brands with an acceptable record as of June 2013:
Jarrow (17 reviews, all passed except one with a labeling issue)
Note: Puritan’s Pride, Vitamin World and Nature’s Bounty are all related. I think they’re all owned by the same company.
I plan to start a blog containing my supplement research and other life optimizing research at some point in the future (or perhaps find a relevant one to post on, since LessWrong is about rationality, not optimizing one’s life). I can update you when my supplement data is posted if you’d like.
Are you talking to someone other than Yvain, about whom you wrote this remark?
It was written to Yvain. I was under the impression that Yvain was studying psychology, not medicine. Now that his website link has changed, I’m not sure there’s a way for me to look this up.
Yvain has graduated medical school; he is concentrating in psychiatry but it’s still an MD.
Ah, okay. I’ll edit my comment then.