Do nutritional supplements help with mental health? Part 2: Vitamins that do begin with a ‘B’

May 26, 2008 at 4:23 pm 15 comments

This is part two of my series of posts on nutritional supplements and mental health. Yesterday I looked at vitamins that don’t begin with a ‘B’ (see that post for my various caveats and disclaimers). Today I’m going to look at vitamins that do start with a ‘B’. Tomorrow: Those crunchy, crunchy minerals.

Vitamin B1 (thiamin)

Thiamin’s an important vitamin. Deficiency can lead to a variety of neuro-degenerative disorders. Since alcoholism impairs the ability of the body to utilise thiamin, these conditions – Wernicke’s encephalopathy, Korsakoff’s psychosis, etc. – tend to be associated with alcoholism. There doesn’t seem to be much evidence linking thiamin to any mental disorders. Mostly I was only able to find case reports of schizophrenics with thiamin-deficiency as a result of poor diet or co-morbid alcohol disorders.

The one exception was this study from 1989, which added thiamin and a drug called acetazolamide (used to treat glaucoma, absence seizures and altitude sickness) to the drug regime of 24 schizophrenics. This apparently had positive results.

Acetazolamide, incidentally, has recently been investigated as a way to reverse anti-psychotic induced weight gain, and also as a treatment for bipolar disorder.

Vitamin B2 (riboflavin)

This rather equivocal paper from 1992 made cautious links between depression, riboflavin deficiency and thyroxine levels: “The findings suggest that B2 (FAD) activity may serve as a sensitive marker of thyroxine status in certain female psychiatric inpatients and that B2 deficiency may play an etiological role in defects of the methylation pathways in a subset of mentally ill individuals.”

Aside from this, all I could turn up were a number of studies that used riboflavin as a marker to check medication compliance. Excess riboflavin is excreted by the body (turning urine bright yellow) and it glows under UV light. This means that if you combine riboflavin with your patients psychiatric drugs and then collect urine samples every day you can tell if they’ve actually been taking what you’ve prescribed them. This also means that large doses of riboflavin are pointless – the body just gets rid of it.

Vitamin B3 (niacin)

Niacin (which is called niacin because calling it ‘nicotinic acid’ might make people think that cigarettes are full of healthy vitamins) was widely investigated for use in the treatment of schizophrenia in the 1960′s and early 1970′s. This never really added up to much, with one review of the literature concluding that “the data indicate that nicotinic acid has no therapeutic effect of schizophrenia.”.

More recently, the interest in niacin has turned towards its (possible) use as a test for schizophrenia. High doses of niacin cause a flush response of the skin; it turns out that this response is weaker and less often found in schizophrenics. Studies like this have found that the effect is not found in other mental illnesses like bipolar disorder and depression. Another study found that people experiencing their first psychotic episode exhibited the effect, but people who had experienced multiple episodes did not. While this is interesting (and could potentially lead to a test for schizophrenia) it’s not an argument for supplemental niacin.

The only recent paper I could find that did suggest supplemental niacin for mental illnesses was a 1995 paper from the Ukraine:

Participation of nicotinic acid and its derivates in the functioning of nervous system is considered basing on the data from literature. It is supposed that the favourable therapeutic effects of nicotinamide, nicotinic acid and their active biological form–NAD are realized due to the mechanisms of their functioning in the nervous system, for treating schizophrenia, epilepsy and other diseases of the nervous system.

Niacin is dangerous at high doses, although some people seem to recommend it. The following case report shows why you shouldn’t believe everything you read on the internet (I include the stuff I’m writing in that, by the way – check it out for yourself):

A 56-year-old male with a history of schizophrenia presented to the emergency department after orally ingesting 11,000 mg of niacin. The patient cited an Internet resource that recommended high-dose niacin for therapy of schizophrenia as the reason for his ingestion. He stopped his psychiatric medications several weeks prior to his niacin overdose. At presentation, the patient was alert and normothermic. His pulse was 68 beats per minute and his blood pressure was initially 92/41 mmHg. Hypotension with a blood pressure of 58/40 developed over the next few hours and persisted despite intravenous infusion of over 4 liters of normal saline. The physical exam was otherwise unremarkable, specifically without signs of an allergic reaction or cutaneous flushing. He required intravenous dopamine infusion for 12 hours to support a mean arterial blood pressure greater than 60 mmHg. Evaluation for other etiologies of hypotension was unrevealing.

So, there’s very little evidence to suggest that niacin supplementation helps with any mental illnesses, and the high doses sometimes recommended by alternative medicine sites can be harmful.

Vitamin B5 (pantothenic acid)

Pantothenic acid is everywhere. That’s what the word pantothenic means. It’s so prevalent that, to quote Wikipedia: “Pantothenic acid deficiency is exceptionally rare and has not been thoroughly studied. In the few cases where deficiency has been seen (victims of starvation and limited volunteer trials), nearly all symptoms can be reversed with the return of pantothenic acid.”

It looks like there were a couple of studies back in the dark ages of psychiatry about supplementing pantothenic acid for schizophrenia. For example, Partially favorable applications of pantothenic acid in schizophrenic subjects from 1953 or Treatment of chronic schizophrenia by a combination of electroshock, pantothenic acid and nicotinamide from 1954. There’s no details available on pubmed, so I have no idea what they found. I think it speaks for itself that nobody’s repeated them in the fifty years since.

Vitamin B6 (pyridoxine, etc.)

There’s some reasonably good evidence that pyridoxine can help improve neuroleptic-induced tardive dyskinesia and akathasia. These kinds of studies have been going on for a while, but two recent studies from Israel seem to be the biggest and most comprehensive. The akathasia study compared pyridoxine to mianserin (an antidepressant) and a placebo in a group of sixty schizophrenic patients. They concluded that “results indicate that high doses of B(6) and a low dose of mianserin may be a useful addition to current treatments of NIA.” The tardive dyskinesia study involved fifty inpatients with schizophrenia or schizoaffective disorder and reported similarly positive results: “Vitamin B(6) appears to be effective in reducing symptoms of TD. The specific mechanisms by which vitamin B(6) attenuates symptoms of TD are not clear.” Note however, that the ‘high dose’ in both of these studies was 1200m. This is high enough to potentially cause sensory neuropathy. In other words, it’s probably not the kind of thing you want to be doing without medical supervision.

There is also research that suggests a link between low levels of pyridoxine and depression:

In 140 individuals, symptoms of depression were evaluated by the Major Depression Ir to examine whether treatment with vitamin Bnventory, and biochemical markers of vitamin B deficiency were measured. RESULTS: We found that 18 (13%) individuals were depressed. A low plasma level of PLP [pyridoxal phosphate] was significantly associated with the depression score … Our study suggests that a low level of plasma PLP is associated with symptoms of depression. Randomized trials are now justified and needed in orde6 may improve symptoms of depression.

Previous to this, there had been a rather unconvincing trial using pyridoxine to treat co-morbid minor-depression in schizophrenia patients. This involved 9 people in an open label study, of which two showed some improvement. This seems indistinguishable from placebo to me, even though the authors optimistically conclude that “A subgroup of schizophrenic patients with comorbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.” There doesn’t appear to have been any further investigation.

Finally, this paper from way back in 1982 that suggested that since oral contraceptives decrease serum levels of vitamin B6 and vitamin B6 is involved in tryptophan metabolism, which is implicated in depression, anxiety disorders and so on, that supplementation of small amounts of pyridoxine would relieve symptoms of these disorders in women taking oral contraceptives. No studies on this seem to have been carried out, though, so it’s pretty much just speculation. The lower serum levels of B6 are confirmed by this recent study however. As a quick tangent, the authors of that study conclude that “Since low vitamin B6 levels are independently associated with heightened risks for arterial and venous thromboembolism (TE), they could partly account for the increased TE risk of OC users.”

So, currently it looks like vitamin B6 supplementation could help with some of the serious side effects of anti-psychotics, though in doses that could cause other problems. Depressed people seem to have lower levels of pyridoxine in their blood, but it’s not clear whether supplemental B6 would help, nor what kind of dosages would be required if it did. Women taking oral contraceptives might benefit from taking a small dose of supplemental B6, though it’s more persuasive that this could reduce the risk of throboembolism than help with mental illness.

Vitamin B7 (biotin; sometimes called Vitamin H)

To quote from Wikipedia:

Biotin deficiency rarely occurs among healthy people, since the daily requirement of biotin is low, many foods provide adequate amounts of it, intestinal bacteria synthesize small amounts of it, and the body effectively scavenges and recycles it from bodily waste. However, deficiencies can be caused by consuming raw egg whites over a period of months to years. Egg whites contain high levels of avidin, a protein that binds biotin strongly. When cooked, avidin is denatured and becomes entirely non-toxic.

The only relevant paper I could find was a case study of a patient who was gastrointestinally impaired and had been fed intravenously for months, which led to biotin deficiency and a cluster of symptoms which included severe depression. So, if you’re not being fed on a drip and you don’t eat raw egg whites all the time, you probably don’t need supplemental biotin.

Vitamin B9 (folic acid / folate)

There’s been a lot of research into folate over the last decade or so, and plenty before then as well. There’s some fairly substantive evidence that folate deficiency is linked to depression and somewhat less for schizophrenia and bipolar disorder. It’s pretty well established that people with mental illnesses of various kinds tend to have lower serum levels of folate.

Let’s start with depression. A recent review concluded: “Depressed patients with both low and normal folate levels may benefit from augmenting a primary antidepressant medication either initially, at the onset of treatment, or later after some degree of treatment resistance has been recognized.”

Another paper, published last year, concluded that:

“… folate deficiencies may be caused by improper absorption and utilization, often due to genetic polymorphisms. Individuals, therefore, can have insufficient levels or lack needed forms of folate, despite adequate intake. Supplementation with the active form of folate, methyltetrahydrofolate, which is more readily absorbed, may be effective in the prevention and treatment of both depression and dementia.”

Or this paper from 2005:

There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.

Lots of studies seem to have resulted in a positive effect. Research continues.

There isn’t quite this level of confidence with the schizophrenia research. A Korean study from 2006 reported that “findings suggest that folate supplement may be beneficial to some schizophrenic patients with homocysteinemia due to the genetic defect of methylenetetrahydrofolate reductase.” It wasn’t the only study from 2006 to reach this conclusion.

A review of the literature from the previous year was less positive, finding methodological flaws in previous studies and calling for further studies “to clarify the relationship between folate status and schizophrenia”. However the two studies from 2006 mentioned above strike me as enough to be cautiously positive.

Folate supplementation in bipolar disorder has, if anything, less evidence to back it up than in schizophrenia. The most recent study that I could find was from 1997. This measured the folate levels of 45 manic inpatients against a socio-economically matched control group. It concluded:

This indicated that the reduced red-cell folate in mania is associated with the illness and not due to reduced absorption or dietary deficiency of folate. Considering previous studies that showed reduced red-cell folate in depression, our findings suggest that reduced red-cell folate occurred in both phases of bipolar disorders.

Two studies looking at folate and lithium had rather different conclusions. One found that: “These results question the rationale of prescribing folic acid preparations for lithium-treated bipolar disorder patients, but the authors indicate that folate concentrations may be low in lithium-treated unipolar depressives.” While the other, conducted five years previously, went so far as to make this recommendation: “It is suggested that a daily supplement of 300-400 micrograms folic acid would be useful in long-term lithium prophylaxis.”

Here’s my own conclusions. Folate supplementation for people with depression – especially those who are taking anti-depressants – seems fairly well supported by the evidence as these things go. It’s definitely a promising area of investigation. For some people, taking folate may be a sensible decision, probably more so for people who don’t live in areas where foods are commonly enriched with it. The evidence for schizophrenia and bipolar disorder is much more limited, so using folate would be more speculative. However, it seems fairly well established that people with these conditions are more likely to have low folate levels, and since folate is both cheap and safe at the low-ish doses generally suggested, supplements of it may well be justifiable and possibly even sensible.

Vitamin B12 (cobalamins)

Cobalmin is often studied together with pyridoxine (B6) and folic acid, mostly because all three are involved in homocysteine metabolism. Deficiencies can lead to raised levels of homocysteine, which has been suggested as a risk factor for a variety of mental illnesses. Like those other two vitamins, there’s a long history of research into cobalmin as a treatment for depression.

A number of studies have found that people with mental illness tend to have low cobalmin levels. For example, this Israeli study from 2000 looked at the cobalmin levels of 644 psychiatric in-patients: “Vitamin B12 deficiency is common in chronically ill psychotic patients with adequate nutrition and is not readily detected by routine hematology tests.”

The evidence that low cobalmin levels can impair treatment of mental illnesses is contradictory. While this study concluded that cobalmin levels were more important than folate levels in predicting response to treatment in people suffering from major depressive disorder, this study found almost exactly the opposite. The second study was looking specifically at people with treatment-resistant depression, which could conceivably account for this difference, though it doesn’t seem especially likely to me.

As I noted in the section on folic acid, some researchers are already recommending supplementation of cobalmin: “On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.”

The evidence for cobalmin supplementation seems less convincing to me than the evidence for folate. There don’t appear to be any studies that show a benefit from additional cobalmin. It may be worth noting that folic acid supplementation can mask the symptoms of cobalmin deficiency, so it may be prudent for people who are at risk of b12 deficiency (eg. the elderly, alcoholics, elderly alcoholics, etc.) who are taking folic acid supplements to also take a cobalmnin supplement.

Conclusions

The substance of real interest here is vitamin B9 (folic acid). The evidence isn’t absolutely convincing, but it is persuasive, particularly for its use as an adjunct to anti-depressants. There haven’t been any studies that actually use it for bipolar disorder, but it doesn’t seem unreasonable – given the similarly low levels that have been found in manic patients – to provisionally assume that it may help. I’m equivocating here. Folic acid’s dirt cheap and safe enough that various countries fortify bread and cereal products with it. And it looks like a good enough idea that I’m going to start taking it myself.

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Do nutritional supplements help with mental health? Part 1: Vitamins that don’t begin with a ‘B’. About Bloody Time

15 Comments Add your own

  • [...] aren’t one of the B vitamins. Part two, which I’ll hopefully post tomorrow, will be for the eight B vitamins. Parts three and four will be for minerals and other stuff, [...]

  • 2. Jarret Morrow  |  May 26, 2008 at 11:54 pm

    Very informative blog site! I have a dietary supplement site: http://jmorrow50.wordpress.com which has some related content which you might be interested in.

    Cheers,

    Jarret

  • 3. Jurriaan plesman  |  May 27, 2008 at 4:17 am

    For natural food sources of vitamins and minerals see;

    “Rich Sources of Nutrients” at:
    http://www.hypoglycemia.asn.au/articles/rich_sources_nutrients.html

  • 4. Jurriaan plesman  |  May 27, 2008 at 4:20 am

    For natural sources of vitamins and minerals see:

    http://www.hypoglycemia.asn.au/articles/richsources.html

    Sorry the previous comment was a mistake.

  • 5. aikaterine  |  May 27, 2008 at 12:03 pm

    This is good. I have a request for your meta-study of mineral supplements (I think you mentioned on the previous post that you were going to do that one next).

    Is there a difference between regular mineral supplements and ionised mineral supplements. My doctor recommends this one:

    http://www.concentrace.co.uk/index.php

    Which is fine, but ionised mineral supplements are considerably more expensive than regular ones. I would be interested to hear your take on the matter. And, I think it is important to note that different formulations of supplements are metabolised differently in the body (or are they). It’s all convoluted.

    In any case, thanks for doing this it is really great information.

  • 6. experimental chimp  |  May 27, 2008 at 3:18 pm

    Hi Aikaterine

    Nice to hear from you again. That’s an interesting question. I’ll do my best to answer it, although my chemistry is kind of rusty.

    An ion is just an element that’s lost or gained an electron. In order to be stable, an element has to have a certain number of electrons. To do this, elements combine with other elements to form compounds. When the two elements are a metal and a non-metal, they can do this by sharing their electrons. In ordinary table salt, each sodium atom (a metal) donates an electron to a chlorine atom (a non-metal) to form sodium chloride (a salt).

    Almost all the elements that are used as dietary minerals are in the form of salts. Dissolve them and you end up with ions in solution. The entire purpose of the digestive system is to break foods down into their constituents, move the useful stuff into the body and get rid of the stuff that’s of no use. So, by the time a mineral salt has reached the small intestine, it’ll usually be dissolved. Most of the time the real action will happen in the jejunum (the middle bit of the small intestine) where ions are actively pumped into the blood stream using a special class of enzymes.

    So iodised minerals are simply minerals that have been dissolved. Your body does this rather efficiently anyway, so I can’t see any benefit from doing this. It seems pretty likely that other factors have much more effect on the bio-availability of various elements.

    Really, though, living things have been using minerals and other nutrients for their own chemical processes since the first cell made a barrier between itself and the world almost four billion years ago. As living things we’ve had a hell of a lot of practice at using whatever’s around. The idea that our bodies are so fragile that we need these things in extra-special forms just seems extraordinarily pessimistic.

  • 7. aikaterine  |  May 29, 2008 at 10:13 am

    Hey –

    I agree with your logic. However, the whole ionised thing has been recommended by some people who are usually pretty resistant to all the marketing surrounding supplements (and the like). So, it interests me. Here is the key marketing pitch for ionised mineral supplements (I think):

    “You cannot benefit from minerals unless you can absorb them. The absorption of minerals takes place primarily within the small intestine. As food passes through, minerals transfer into the blood stream through the walls of the intestine. This can only happen if the minerals are ionically charged. Although stomach acid helps to ionize the minerals in foods, a mineral supplement should already contain naturally ionized minerals to be fully absorbed.”

    Again, no clue how relevant this actually is. But it would be good to know. And how great would it be if I could convince you to do my research for me. I am a lazy, lazy girl. And I trust your ability to discern relevant data.

    But, apart from my blatant selfishness, if you are going to expand your meta-analysis to the mineral genre then I think this is an important aspect of the question to answer.

    Enjoy your trip to London. It really is good to hear that you finally have an appointment.

  • 8. aikaterine  |  May 29, 2008 at 10:22 am

    Sorry, I left something out. I know that you addressed the digestice system (as is mentioned in the quote a referenced). So, the part of the quote which interests me the most is:

    “This can only happen if the minerals are ionically charged. Although stomach acid helps to ionize the minerals in foods, a mineral supplement should already contain naturally ionized minerals to be fully absorbed.”

    How much truth is there to this? Again, I agree with your logic. But is there some science we are missing which would suggest that the stomach does not adequately dissolve regular supplements?

  • 9. experimental chimp  |  May 29, 2008 at 4:56 pm

    Look at it this way – many drugs are supplied in the form of a salt. For example oxycontin, a powerful opiate painkiller, is usually supplied in the form of oxycodone hydrochloride. It’s a commonly abused drug. If putting it into an ionized form (ie. dissolving it) could make the body absorb it better, supplying the user with more of the drug they want, how come nobody actually does this? Drug users tend to be pretty inventive about the ways that they use substances, so if anyone was going to do this, they would. But they don’t.

    For that matter, why don’t pharmaceutical companies supply their drugs in ionic forms? Manufacturing is not cheap, so if dissolving a drug made it much more easily absorbed, why don’t they do this? Some drugs are supplied in both dissolved and solid forms – dextromethorphan hydrobromide is a good example as you can get cough mixtures or pastilles containing it. The doses of each are the same, because the dissolved form isn’t much better absorbed. And some drugs are elemental – lithium for example, so it applies to them too.

    There are differences in the solubility of different forms of salts. But if it’s going to dissolve in water at room-temperature, it’s going to dissolve in your stomach.

    If there is some science I’ve missed, then I’ve missed it. But the marketing copy I’ve read seems to be nonsense.

  • 10. donny  |  February 10, 2010 at 10:02 pm

    http://www.circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.105.580332v1

    “Riboflavin Lowers Homocysteine in Individuals Homozygous for the MTHFR 677CT Polymorphism”

    There was no effect of riboflavin on homocysteine found for people without this particular MTHFR type. So if riboflavin had an effect on mental health that involved homocysteine metabolism, the effect might be found only in a small subset of the general population of the mentally ill.

    I started taking niacin a while back for its effects on triglycerides and Hdl cholesterol; I would have stopped long ago, except that I accidentally discovered that it completely wipes out chronic pain in a shoulder I whomped at the cottage a few years back. My blood pressure has gone down over this period, from slightly high to ideal, but I only take a few grams a day (still massive compared to normal diet levels), and I also lost some fat and eat a lower carb diet than I used to. If I stop taking the niacin, the shoulder hurts.

  • 11. abbrakile  |  August 21, 2012 at 9:38 am

    Soon autumn, hurry to say goodbye to summer!).

  • 12. bcscpabelxbw  |  April 11, 2013 at 6:12 pm

    dxvzxyemtiiv

  • 13. uhovautyrqco  |  April 12, 2013 at 5:53 am

    rrwicjwemopg

  • 14. vullhewzotvu  |  April 12, 2013 at 5:54 am

    hhygksbfvjxz

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Hi, I'm James. I'm a 26 year old guy from England with bipolar disorder (currently well controlled). I also have a circadian rhythm sleep disorder (not so well controlled). This blog has charted my journey from mental illness, through diagnosis and, recently, into recovery. It's not always easy, but then, what is?

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