Nutritional Supplements and Vitamins

Nutritional Supplements and Vitamins

Nutritional Supplements and Vitamins

Supplements and Depression or Insomnia

Nutritional Supplements and Vitamins

In the summer of 2016 we updated this page with information from a comprehensive review of research on the use of nutritional supplements (or “nutraceuticals”) in the treatment of depression. Since then we have added information every few months.

The authors of the review concluded that there was good data supporting the effectiveness of fish oil supplements and suggestive but not conclusive evidence in favor of SAMe and, to a lesser extent, folate (Sarris, et al; 2016).

Elsewhere we have summarized data on the use of natural supplements for insomnia.

Caveat Emptor – Let the Buyer Beware

For those who are interested in the topic and are concerned about the fact that there are no regulations to ensure that these products are safe and that they contain the ingredients they claim to contain, we strongly recommend visiting this website:

ConsumerLab.com, provides independent test results and information to help consumers and healthcare professionals evaluate health, wellness, and nutrition products. It publishes results of its tests online at www.consumerlab.com, including listings of brands that have passed testing. Products that pass CL’s testing are eligible to bear the CL Seal of Approval. CL addresses a growing need of consumers and healthcare professionals for better information to guide the selection of health, wellness, and nutrition products.

Supplements

Nutritional supplements and vitamins are chemicals that are found in nature (note: supplements don’t have to be any more “natural” in terms of how they are made than prescription drugs, they just have to contain chemicals which exist in nature). Because they are found in nature they are not, in the United States, subject to review and approval by the Food and Drug Administration. Also, because they are found in nature, they tend to be safer than prescription drugs (although that is not necessarily always true) and, at least in our experience, the effects of nutritional supplements and vitamins tend to be more subtle than the effects of medications, which increases the importance of tracking outcomes carefully (mood charting).

We believe in the value of supplements a great deal, but they are certainly not the right answer for everyone. What we have tried to do is summarize the available information on the supplements that have the most importance for those with mood disorders.


SAM-e

S-adenosylmethionine, or SAM-e for short, is one of the few nutritional supplements that has good clinical research to support its safety and effectiveness. Although SAM-e is used for many purposes, we are particularly interested in it as a compound that may have antidepressant properties.

A recent blog post on this site might also be worth reviewing.

Clinical Significance

S-adenosylmethionine (SAMe) is involved in many reactions that involve methylating chemicals (transferring a methyl group to the chemical to change its properties).

Two types of methylation reactions are particularly significant for psychiatry:

  • Reactions involving Catechol-O-Methyl-Transferase (COMT)
  • DNA Methyl-Transferase reactions

Catechol-O-Methyl-Transferase

COMT is one of the main enzymes involved in the breakdown of monoamine neurotransmitters which play a key role in depression (dopamine, norepinephrine, epinephrine).

For COMT to function there must be enough SAMe present.

There is some evidence to suggest that people with a particular form of the COMT enzyme (COMT Val158Met) may be more prone to fearfulness (paranoia) and excessive risk-taking (gambling, drug use), particularly when they are in exposed to high stress situations (“COMT Val158Met polymorphism interacts with stressful life events and parental warmth to influence decision making.” Qinghua He, Gui Xue, Chuansheng Chen, Zhong-Lin Lu, Chunhui Chen, Xuemei Lei, Yuyun Liu, Jin Li, Bi Zhu, Robert K. Moyzis, Qi Dong & Antoine Bechara. Nature Scientific Reports 2, Article number: 677 (2012) doi:10.1038/srep00677). Since this form of COMT is less active, people with this form of the enzyme who are experiencing these symptoms might respond to supplementation with SAMe which could overcome some of the reduced COMT activity.

DNA Methyl-Transferase

DNA Methyl-Transferases play a key role in regulating gene expression. Basically, at birth, a set of these enzymes apply methyl groups to selected locations on your genes. The methylation of the genes determines which genes are active and how active they are and thus plays a huge role in who you are as a person. Since the methylation of genes can be reversed, there is another set of these enzymes that maintain the methylation pattern. All of these DNA methyl-transferase reactions depend on SAMe.

Low Vitamin B12, Folate or Methionine

People with low vitamin B12 (fairly common in the elderly) or low folate or low levels of folate activity (which can be related to having a particular form of the enzyme methylenetetrahydrofolate reductase (MTHFR) may benefit from supplementation with SAMe since B12 and folate are all essential factors in the formation of SAMe in the body.

Clinical Effectiveness

Aside from the interesting possibility that SAMe may play a unique role in the treatment of irritability, paranoia and impulsiveness in people with the COMT Val158Met polymorphism, the use of SAMe that most people are interested in is its potential role in the treatment of depression.

SAMe is one of the most studied natural therapies for treating major depression. Several studies have shown that it is as effective as tricyclic antidepressants in treating major depression (Delle Chiaie, Am J Clin Nutr 2002, Salmaggi, Psychother Psychosom 1993, Kagan, Am J Psychiatry 1990). A more recent study (Papakostas, Am J Psychiatry 2010 clarified in Fleish, Am J Psychiatry 2010) found that it may be helpful in patients with major depressive disorder who did not respond to prescription treatment with a serotonin reuptake inhibitor (SRI). In the study, SAMe was given along with an SRI and 46.1% of patients receiving the combination benefited, versus 35.8% receiving an SRI and a placebo supplement. The results suggest that SAMe may be an effective and safe adjunctive treatment for SRI non-responders.

A recent article summarizing the literature on SAMe had this to say:

“SAMe is a methyl donor and is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine, SAMe has been postulated to have antidepressant properties. A small number of clinical trials with injected or oral SAMe have shown that, at doses of 200-1600 mg/d, SAMe is superior to placebo and is as effective as tricyclic antidepressants in alleviating depression, although some individuals may require higher doses. SAMe may have a faster onset of action than do conventional antidepressants and may potentiate the effect of tricyclic antidepressants. SAMe may also protect against the deleterious effects of Alzheimer disease. SAMe is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients. Overall, SAMe appears to be safe and effective in the treatment of depression, but more research is needed to determine optimal doses.

“Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Mischoulon D, Fava M. Am J Clin Nutr. 2002 Nov;76(5):1158S-61S.Harvard Medical School, Depression Clinical and Research Program, Massachusetts General Hospital, Boston 02114, USA.

Our own experience is that SAMe is not entirely free of one side effect that can be of significant concern for those with bipolar (or manic depressive) disorder: It can definitely induce mania.

Therapeutic Dosages

A typical full dosage of SAMe is 400 mg taken 3 to 4 times per day If this dosage works for you, take it for a few weeks and then try reducing the dosage. As little as 200 mg twice daily may suffice to keep you feeling better once the full dosage has “broken through” the symptoms. However, some people develop mild stomach distress if they start full dosages of SAMe at once. To get around this, you may need to start low and work up to the full dosage gradually.

Recently, SAMe has come on the US market at a recommended dosage of 200 mg twice daily This dosage labeling makes SAMe appear more affordable (if you’re only taking 400 mg per day, you’ll spend only about a third or a fourth of what you’d pay for the proper dosage), but it is unlikely that SAMe will actually work when taken at such a low dosage.

Good sources of SAMe include: GNC, Natrol, Nature Made, Puritan’s Pride, Twinlab and the Vitamin Shoppe . It is often recommended that one start at 200 mg a day and then increase gradually to around 800 mg a day. SAMe should be taken in divided doses (at least 2 times a day and preferably 3 times a day) and improvement can be seen in a few days to 3-4 weeks.

Buyer beware! In its most recent review of these products, Consumer Lab found that almost half of all formulations were unacceptable. For one product the amount was below detectable.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease I am providing you with specific brand information as a courtesy. Gateway Psychiatric Services receives no reimbursement from these companies.


Fish Oil

Ever since May of 1999, and the first publication of a study by Andy Stoll from Brigham and Women’s Hospital at Harvard Medical School, there has been a great deal of interest in the value of omega-3 fatty acids in the prevention and treatment of mood disorders.* The study compared 9.6 grams per day of omega-3 fatty acids from fish oil with olive oil (as a placebo) and found that, on nearly every measure, bipolar patients did better on the fish oil supplement.
Since then there have been several more studies and the results are mixed. In October of 2002 in an article in the most prestigious journal in psychiatry (the Archives of General Psychiatry) Peet and Horrobin from Swallownest Court Hospital, in Sheffield, England found that treatment with ethyl-eicosapentaenoate (one of the principle omega-3 fatty acids in fish oil) at a dosage of 1 g/d was effective in treating depression in patients who remained depressed despite adequate standard therapy. Zanarini and Frankenberg from McLean Hospital (also affiliated with Harvard) found that the same dose (1 gram/day) of ethyl-eicosapentaenoate was effective in treating borderline personality disorder (a condition associated with depression and rapid shifts in mood). Then in May of 2003 Lauren Marengell and colleagues from Baylor College of Medicine in Houston found that 2 grams per day of docosahexaenoic acid (DHA) (the other major omega-3 fatty acid in fish oil) was not effective in treating depression.
A 2008 comprehensive analysis of the available data, in a Cochrane Review concluded that there was modest evidence for the effectiveness of EPA or EPA + DHA in treating bipolar depression but not mania.

Our own experience with fish oil is also mixed, it seems to have helped patients with unstable or cycling mood disorders achieve more stability, but it is often not dramatically helpful. On the other hand, it has no side effects other than a very slight fishy “taste” that reminds you that you took it for a few minutes. And there is some evidence that it may be good for preventing blood vessel disease that can cause strokes, memory loss, and heart disease.

A recent study published in the Journal of the National Cancer Institute reported that men who had higher blood levels of the two fats (DHA and EPA) found in fish oil had a somewhat increased risk of prostate cancer. This study did not ask these men about their diet and it was not a clinical trial (giving people the supplement and observing what happened). Studies that look at associations run the risk of assuming that A (taking fish oil) causes B (prostate cancer) even if there is no such link (A and B are caused by something else – for example, other studies have suggested that fish oil protects against prostate cancer – maybe the subjects who were concerned about prostate cancer decided to take fish oil to prevent it from happening). There is an ongoing large clinical trial of fish oil which will likely answer the question.

The only way to get substantial amounts of those omega-3s is from fish or fish-oil supplements. The least expensive way to get fish-oil supplements is most likely from a membership club, like Kirkland Signature Natural Fish Oil at Costco or Member’s Mark Omega 3 Fish Oil at Sam’s Club . Some other quality brands** are: Spring Valley Natural Fish Oil Concentrate, Walgreen’s Fish Oil Concentrate, Vitasmart Naturals Fish Oil Concentrate (Kmart), Natrol Omega-3, GNC Fish Body Oils.

A recent review suggested that the easiest way to get the required dose is with Viva Labs Ultra Strength Omega – 3 Fish Oil. Two capsules provided as much EPA as 8 capsules of other supplements. Although more expensive per pill, the supplement was no more expensive per mg of EPA.

The dose of EPA you should look for is 1 gram per day.


Saint John’s Wort

Saint John’s Wort ( Hypericum Perforatum ) is a plant that has a long (dating back to Hippocrates) history as an herbal medicine. It is commonly prescribed in Germany for the treatment of depression. A large, but mixed quality, literature, mostly from Germany, supports its use and suggests that it is comparably effective to traditional pharmaceutical antidepressants. It has not been shown to be effective for moderate to severe depression and one large study sponsored by the Pfizer did not find it to be more effective than placebo in the treatment of major depression (April 2002).

It is our experience that St. John’s Wort is a mildly effective antidepressant and, unlike SAMe, we have not seen it induce mania. However, most of the patients who have tried it with moderate or more severe depression have ended up switching to traditional antidepressants. It has a very mild side effect profile.

hypericumThe form of Saint John’s Wort used in the NIMH study and in most research since then is available at Hypericum Buyer’s Club .**

While St. John’s Wort itself has a benign side effect profile, a potentially toxic metal, cadmium, is present in significant quantities in many formulations of the herb. Also, there is a great deal of variability in the quality of product available. Nature Made and Nature’s Plus are two other formulations that are of generally good quality. The optimum dosage of hypericum, based on the majority of medical studies, is 300 mg of hypericum extract three times a day.

Finally, research from the NIH has shown that St. John’s wort interacts with some drugs–including certain drugs used to control HIV infection (such as indinavir). Other research shows that St. John’s wort can interact with anticancer, or chemotherapeutic, drugs (such as irinotecan). The herb may also interact with drugs that help prevent the body from rejecting transplanted organs (such as cyclosporine). Using St. John’s wort limits these drugs’ effectiveness.


Melatonin

Melatonin is a hormone made by your body’s pineal (pih-knee-uhl) gland. When the sun goes down, and darkness comes, the pineal gland “goes to work.” As melatonin production rises, you begin to feel less alert. Body temperature starts to fall as well. Levels are so low during the day that scientists often have difficulty detecting melatonin then.

Few studies have been done on melatonin’s safety, side effects, interactions with drugs, and long-term effects. (Unlike products recognized as “drugs, melatonin does not require extensive testing in animals and people before being sold in the U.S.). How much to take, when to take it, and melatonin’s effectiveness for many groups of people are also unknown.

Our experience is that melatonin is an agent that is not a particularly effective sedative (in other words it doesn’t help that much putting you to sleep), however it can help to re-establish normal circadian (night/day) biorhythms. An alternative approach, that has no side effects at all involves calculating when to expose yourself to light use a jet lag bodyclock .

For more information on melatonin see these blog posts –

Melatonin and Sleep

Natural Supplements and Vitamins for Insomnia

Those of you who are interested in trying this agent are in luck because the quality of melatonin supplements available is generally pretty good. Natrol, Twinlab, Puritan’s Pride and Walgreen’s are among the companies with good products.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease I am providing you with specific brand information as a courtesy. Gateway Psychiatric Services receives no reimbursement from these companies.


Vitamins

For a number of reasons, some obvious, and some not so obvious, many people with mood disorders have trouble eating a healthy diet. At the same time, there is very strong evidence that vitamin deficiencies are related to depression. For this reason, we strongly urge everyone with a mood disorder to at least take a multivitamin every day.

In the sections that follow we will talk a little bit more about the role that various vitamins play in preserving normal mood.

Multivitamin / Multimineral Pills

We recommend that every patient with a mood disorder take a multivitamin / multimineral pill. There are many reasons for this. First, they are inexpensive and safe (with a few exceptions relating to formulations that provide too much of certain vitamins or minerals — those that provide 100% of the Daily Value of vitamins or minerals are always fine). Second, there are a number of deficiencies that can worsen depression, and that may even make a depression resistant to other kinds of treatment, for instance folate deficiency and iron deficiency.

However, a recent test of multivitamins by Consumer Labs (see above) found that 25% failed to meet acceptable standards. Some contained potentially toxic levels of lead in them. Formulations made by Walgreen’s, Puritan’s Pride, GNC and Centrum all passed the tests.

Some general advice:

  • A multi need not cost more than a few cents a day. You don’t need a fancy multi.
  • Look for “USP” on the product label. This means that the pills meet the standards of the US Pharmacopeia for disintegration and it also means that it has been tested under controlled laboratory conditions.
  • Look for 100% of the Daily Value for: vitamin D, vitamin B1 (thiamin), B2 (riboflavin), B3 (niacin), B6, B12 and folic acid (folate). Plus at least 20 micrograms of vitamin K for strong bones.
  • The multivitamin should contain no more than 5,000 IU of vitamin A (that’s 100% of the Daily Value) but at least 40% of it should be in the form of beta carotene.
  • Look for 100% of the Daily Value of: copper, zinc, iodine, selenium (preferably from yeast, but not more than 200 micrograms) and chromium (not more than 200 micrograms).
  • Most multivitamins contain 100% of the Daily Value of vitamin C and E. This may not be enough. We recommend 250 – 500 milligrams of vitamin C per day, but you should get the extra amount from fruits (orange juice) and vegetables (orange and red vegetables) if possible. It is not clear whether higher doses of vitamin E are helpful or not.
  • Calcium is so bulky that you won’t be able to find a multi with enough, so you will probably need a separate calcium supplement. Everyone needs at least 1,000 milligrams of calcium per day in either a supplement or in food. Women over 50 and men over 65 need 1,200 to 1,5000 mg.
  • If your multi contains iron (and it should) don’t take it with food.

Good sources of multivitamins include: Geritol, Kirkland Signature, Nature Made, Nature’s Bounty, One A Day Maximum, Theragran-M, Centrum and Walgreen’s Multivitamin with Iron. Consumer Labs tested multivitamins in September 2000. Their review can be found at ConsumerLabs.com .* In this study 5/15 multivitamins failed their standards.


B Vitamins


There are eight B vitamins:

  • thiamine (B1)
  • riboflavin (B2)
  • niacin (B3)
  • pantothenic acid (B5)
  • pyridoxine (B6)
  • biotin (B7)
  • folate (folic acid, B9)
  • cobalamin (B12)

Like most vitamins, B vitamins must be consumed in diet or supplements because your body needs them but cannot make them.

Three of the B vitamins have a particularly important role in brain function in depression: pyridoxine (B6), folate (B9) and cobalamin (B12). In addition, thiamine (B1) deficiency, especially in people who drink heavily, can be associated with memory deficits, and in one small study thiamine supplementation was found to speed up response to serotonin antidepressants (SSRIs).


Pyridoxine (B6)

In one study, treatment with B6 was found to help women deficient in B6 who had depression associated
with use or oral contraceptives, but it has generally not helped other people suffering from depression (Williams, Family Practice 2005). On the other hand, a number of the studies that have looked at using combinations of B vitamins to help prevent cognitive decline and memory problems in the elderly have included B6, which is why we included it here in the list of important B vitamins for the brain.


Folic Acid and Methylfolate (B9)

A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. Several studies have also found that supplementation with at least 500 micrograms of folate converted some antidepressant nonresponders into good responders.

Folate deficiency is associated with depression and dementia. It is also a critical supplement for women who are pregnant. And some medications (especially Depakote and Lamictal) that may be prescribed to patients with mood disorders tend to inhibit the action of folate.

Although the review on nutritional supplements did not find convincing evidence for the effectiveness of folate supplements, there may be a particular circumstance in which some kind of supplement may be especially useful, some people have a genetic variant of the methylenetetraheydrofolate reductase (MTHFR) gene that puts them at greater risk of a deficit in folate in the brain.

For more on this read this blog post –

Methylfolate and Depression

We have found that methylfolate supplements are more likely to be helpful in those with this genotype, which can be identified using a panel of genetic tests that we often use in patients who fail to respond to initial treatments of depression (the Genocept assay).

Methylfolate is the active form of folate. Folate is the form found in the diet and in most over the counter supplements, but for people with the deficient MTHFR gene, they are not able to convert folate to methylfolate and transport it into the brain, where it is used to make many of the essential neurotransmitters that affect depression.

Folic acid also has particular affects on mood and cognitive and social function. However, folic acid should be used with caution in the presence of vitamin B-12 deficiency or epilepsy. The easiest way to get your daily dose is by taking a daily multivitamin.

Good natural sources of folate include dark green leafy vegetables and oranges.

The recommended daily allowance for most adults is 400 mcg, but for pregnant women it is 600 mcg per day. The upper limit for folic acid is 1000 mcg per day, however, some studies have found benefit at higher doses, at higher doses, though there is some reason for concern about toxicity because folate can make the brain more vulnerable to seizures. More information is available here .


Cyanocobalamin (B12)

B12 deficiency is one of the classic causes of a potentially reversible memory impairment. Most people receive adequate amounts from their diet (it is found in meats, fish, and chicken, but not found in foods from plants) but vegetarians (for obvious reasons) and those who are older than 50 years of age (because of reduced stomach acid and therefore reduced absorption) should take supplements.

The role of B12 in minimizing cognitive decline is suggested by a study which followed several hundred people in their 70’s over an eight year period and found that cognitive decline was faster among those with the lowest blood levels of B12 (under 257 pmol/L) which was the case for 40% of the elderly people in the study (Morris, J Am Geriatr Soc 2012). Normally, people are not considered B12 deficient (and at risk for pernicious anemia) until levels go below about 148 pmol/L (200 pg/mL). The study suggests that it may be beneficial to maintain somewhat higher levels of B12.

Similarly, a large placebo-controlled study in Holland of adults 65 and older suggested that blood levels of B12, particularly in its active form, holotranscobalamin, may indicate who can most benefit from supplementing with B vitamins. In this study, all participants had high homocysteine levels (12 to 50 micromol/L) although many were not actually deficient in B12 (the mean level was 257 pmol/L). After being given folic acid (400 mcg) and B12 (500 mcg) daily for 2 years, compared to placebo, there was a minor reduction in the decline in cognitive functioning. However, those who started the study with lower levels of holotranscobalamin (below 64 pmol/L) had more benefit from supplementation in terms of episodic memory performance (i.e., recall and recognition) and information processing speed (van der Zwaluw, Neurology 2014).

The recommended daily allowance is 2.4 micrograms for most people, but higher doses of up to 500 mcg have been used to prevent heart disease. No upper limit has been established for B12.

Since some older people lack the co-factor that facilitates absorption of B12 we sometimes find it useful to prescribe either B12 injections or an intranasal form of B12 (Nascobal).


B Vitamin Combinations

Not surprisingly, a number of studies have looked at B vitamin combinations as a way to prevent or minimize cognitive deficits in older patients.

In a 2 year placebo controlled study of people aged 70 years or older with mild cognitive impairment, a
combination of B vitamins was found to slow cognitive decline, particularly in those who started with elevated levels of plasma homocysteine (over 11.3 micromoles/L) which can occur with inadequate B vitamin
intake. People in the study were given a daily dose of folic acid (800 mcg), vitamin B12 (500 mcg), and vitamin B6 (20 mg) (de Jager, Int J Geriatr Psy 2011). Further analyses of this study found that the beneficial effects of B vitamins were enhanced when people began the study with blood plasma levels of omega 3
fatty acids in the upper range of normal, In fact, those with low omega 3 levels did not benefit from B vitamin supplementation. In general, the effects were more significant for DHA alone than for EPA the combined levels (Oulhaj, J Alz Dis 2016).

In a similar study, this same B vitamin combination reduced the amount of shrinkage in regions of the brain commonly affected by Alzheimer’s disease. The benefit was found only among people who started the 2 year
study with high homocysteine levels (over 11.06 micromoles/L), but this represented about 50% of the people in the study. Shrinkage was reduced by 8 times compared to the amount of brain shrinkage experienced among those taking placebo (Douaud, PNAS 2013). As with the research noted above by Oulhaj,
further analysis of this study also found that higher blood levels of omega 3 fatty acids enhanced the beneficial effect of the B vitamins (Jerneren, Am J Clin Nutr 2015).

In summary, it is reasonable in those concerned with cognitive decline to receive testing for the level of plasma homocysteine in your blood, and if this is elevated, it makes sense to take a combination of 800 mcg of folate (or one of the active forms of folate discussed above) along with 500 mcg of vitamin B12 (or Nascobal) and 20 mg of vitamin B6 plus fish oil. 

Vitamin D

Vitamin D is a fat-soluble vitamin, unlike the B vitamins that we have been talking about, and fat-soluble vitamins generally require more care with dosing because they can accumulate in fat and reach toxic levels in the body.

This means that vitamin D has a “therapeutic window” – take too much and you suffer adverse consequences just as you do if you have too little.

In addition, there was some controversy about what constitutes a “normal” level of the vitamin in blood. This has largely been resolved and we now understand that there is a normal level for 25-hydroxy vitamin D, which is between 20 nanograms/milliliter to 50 ng/mL, but then there is a level between 12 and 20 nanograms/milliliter which may not be quite “normal” but where supplementation is unlikely to be necessary or beneficial and it’s really only those people below a level of 12 nanograms/milliliter who need and benefit from supplementation.

All of this means that vitamin D supplementation really needs to be guided by blood tests and initiated only if there’s evidence of a deficiency.

A study reported by WebMD in June 2017 suggests that many Americans may be getting too much of the vitamin:

“In 2014, just over 3 percent of U.S. adults took more than 4,000 international units (IUs) of the vitamin daily, exceeding the upper limits of what is considered safe, the researchers said. In 2007-2008, only 0.2 percent did that.

For perspective, the recommended daily amount of vitamin D is only 600 IUs for adults aged 70 and younger. For those over 70, the recommendation is 800 IUs a day.

“More may not always be better with vitamin D,” said study author Mary Rooney, a doctoral student at the University of Minnesota in Minneapolis.

“There’s not much research on longer-term health outcomes on high-dose supplements,” she said. But studies have hinted at potential harm, such as excess calcium in the blood, which can cause deposits in blood vessels, Rooney and her colleagues said.”

References

Jerome Sarris, Jenifer Murphy, David Mischoulon, George I. Papakostas, Maurizio Fava, Michael Berk, and Chee H. Ng. American Journal of Psychiatry. Published online: April 26, 2016   http://dx.doi.org/10.1176/appi.ajp.2016.15091228

de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012 Jun;27(6):592-600. doi: 10.1002/gps.2758. Epub 2011 Jul 21. PubMed PMID: 21780182.

Ghaleiha, A., Davari, H., Jahangard, L. et al. Eur Arch Psychiatry Clin Neurosci (2016). doi:10.1007/s00406-016-0685-6

Morris MS, Selhub J, Jacques PF. Vitamin B-12 and folate status in relation to decline in scores on the mini-mental state examination in the framingham heart study. J Am Geriatr Soc. 2012 Aug;60(8):1457-64. doi: 10.1111/j.1532-5415.2012.04076.x. Epub 2012 Jul 12. PubMed PMID: 22788704; PubMed Central PMCID: PMC3419282.

Oulhaj A, Jernerén F, Refsum H, Smith AD, de Jager CA. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis. 2015;50(2):547-57. doi: 10.3233/JAD-150777. PubMed PMID: 26757190; PubMed Central PMCID: PMC4927899.

van der Zwaluw NL, Dhonukshe-Rutten RA, van Wijngaarden JP, Brouwer-Brolsma EM, van de Rest O, In ‘t Veld PH, Enneman AW, van Dijk SC, Ham AC, Swart KM, van der Velde N, van Schoor NM, van der Cammen TJ, Uitterlinden AG, Lips P, Kessels RP, de Groot LC. Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT. Neurology. 2014 Dec 2;83(23):2158-66. doi: 10.1212/WNL.0000000000001050. Epub 2014 Nov 12. PubMed PMID: 25391305.

Williams AL, Cotter A, Sabina A, Girard C, Goodman J, Katz DL. The role for vitamin B-6 as treatment for depression: a systematic review. Fam Pract. 2005 Oct;22(5):532-7. Epub 2005 Jun 17. Review. PubMed PMID: 15964874.