In some studies, vitamin D supplementation (1,500 IU/day) has been found to improve unipolar depression. Recently, researchers led by Wendy K. Marsh found that compared to placebo, 12 weeks of vitamin D3 supplementation (5,000 IU/day) did not produce greater improvement in depressive symptoms. The study, presented at the 2016 meeting of the Society of Biological Psychiatry, included 33 adult participants whose vitamin D levels remained deficient throughout the study.
Editor’s Note: Caution is urged in interpreting this small study, especially because the participants did not achieve healthy levels of vitamin D.
Low levels of vitamin D are common in children and adults with bipolar disorder. Future research may explore whether raising vitamin D levels to healthy levels has a beneficial effect on mood. There are many other benefits to vitamin D supplementation. It can improve cognition, regulate calcium and phosphorus absorption, and maintain healthy bones and teeth. It may also protect against diseases such as cancer, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. Improved cardiovascular health is also a possible benefit of vitamin D supplementation.
Some studies have suggested that omega-3 fatty acids may be helpful in the treatment of schizophrenia, but data to support this idea have been inconsistent. A recent meta-analysis of research on omega-3s and schizophrenia suggests that this nutritional supplement might be more useful in early-stage schizophrenia than in later illness.
At the 2016 meeting of the Society of Biological Psychiatry, researchers led by Alexander T. Chen presented the findings of their meta-analysis. First they analyzed six studies that shared a common scale for measuring schizophrenia symptoms. In these studies, omega-3 fatty acids did not outperform placebo when used as an add-on treatment to antipsychotics for people with schizophrenia.
In four remaining studies of omega-3 fatty acids and schizophrenia, the omega-3s were associated with improvement only in patients in the early stages of schizophrenia. Compared to placebo, the supplements decreased non-psychotic symptoms, decreased the dosage of antipsychotic medication patients required, and improved early treatment response (but not late treatment response) in patients in their first episode of schizophrenia.
In the same study, omega-3 fatty acids also reduced conversion to full-blown schizophrenia and psychotic symptom severity in patients at high risk for schizophrenia who were having preliminary symptoms of the illness.
Editor’s Note: Researcher Paul E. Keck has also found that omega-3 fatty acids may be more effective early in bipolar disorder rather than later. He reported that younger patients with bipolar depression and rapid cycling showed more improvement when taking the omega-3 fatty acid EPA than when taking placebo. In contrast, patients with bipolar depression who were over the age of 45 did worse on EPA than on placebo.
Part of the ambiguity about whether omega-3 fatty acids can help treat or prevent mental illness may be explained by the supplements working better in younger people or earlier in the course of an illness.
In 1996, the US began to require that enriched cereal grain products be fortified with folate, a vitamin that is particularly important to fetal brain development. A new study of children born before and after this policy change suggests that the increased folate in commercial foods after 1996 led to increases in cortical thickness in the children born after the change.
At the 2016 meeting of the Society of Biological Psychiatry, Joshua L. Roffman and colleagues described their research into the effects of folate fortification. The researchers identified 3,309 children born between 1993 and 2001 who had had a magnetic resonance imaging (MRI) brain scan. Analysis of the scans showed that children born after folate fortification began had thicker cortices than those born before the change. The frontal and temporal regions of the brain were particularly affected.
A thin cortex is a risk factor for schizophrenia and other cognitive problems.
Editor’s Note: Folate supplementation has also been shown to enhance the effects of selective serotonin reuptake inhibitor (SSRI) antidepressants in adults with lingering symptoms of depression.
Up to a third of the population may have a deficit of MTHFR, an enzyme important for folate metabolism, and for these people, l-methylfolate is recommended rather than folate itself.
Vitamin B12 deficiency is a risk associated with a vegan diet. B12 deficiency can lead to depression, anemia, and even irreversible neuron damage, according to researcher Drew Ramsey, who spoke on the topic at the 2016 meeting of the American Psychiatric Association.
A study of vegans showed that 52% were deficient in vitamin B12, while another 23% had insufficient levels of the vitamin. B12 is found in the highest concentrations in certain seafoods and liver. It is also found in dairy products, eggs, fortified breakfast cereals, and is available in supplement form.
Women who eat a vegan diet while pregnant may not be providing their offspring with enough nutrients, according to researcher Emily Deans, who also spoke at the meeting. A case report on 30 vegan mothers found that 60% of their offspring had developmental delays and 37% showed cerebral atrophy.
Deans said that eating no meat is associated with higher rates of depression, anxiety, and worse quality of life.
Ramsey believes that while the North American diet is probably weighted too heavily toward animal products, seafood remains an important source of B12.
A long-term study of 130,000 nurses and other health professionals found that eating more plants lowered risk of death over several decades. A 3% increase in calories from plant protein was associated with a 10% lower risk of death during the study period.
The research, by Mingyang Song and colleagues in the journal JAMA Internal Medicine, found that the more animal protein consumed, the higher the risk of death from cardiovascular disease during the study. A 10% increase in the proportion of calories from animal protein was associated with a 2% increase in deaths. This association was worse for people who were obese or heavy drinkers.
Song and colleagues suggest that plants are a better source of calories than are animal products, and that fish or chicken are better choices than processed red meat.
Researcher Dariush Mozaffarian recommends eating plant-based foods like fruits, nuts, seeds, beans, and non-starchy vegetables, but avoiding those like French fries or white bread that have little nutritional value.
MTHFR is an enzyme needed for the body to break down vitamin B9, also known as folate or folic acid. It also helps convert the toxic amino acid homocysteine into the antidepressant amino acid s-adenysl-methionine. However, a significant segment of the population (some estimate 40%) have a genetic mutation in the MTHFR gene that interferes with the body’s ability to break down B vitamins and is linked to higher levels of homocysteine. MTHFR mutations are also linked to depression.
A 2016 study by Arnold W. Mech and Andrew Farah in the Journal of Clinical Psychiatry found that treating people with major depression and a MTHFR deficiency using a combination of micronutrients and already-broken-down B vitamins improved their depression and reduced their homocysteine levels compared to placebo.
The study included 330 adult patients with major depression and one of two genetic variants in the MTHFR gene—C677T or A1298C. Of those who received the metabolized vitamins, 82.4% showed reduced homocysteine levels. Those who received placebo showed a small average increase in homocysteine. The vitamin group also saw a large drop in depression symptoms on average after 8 weeks, with 42% achieving full remission. There were no side effects.
These findings suggest that homocysteine levels play a role in depression and that metabolized B vitamins can be an effective treatment for depression, particularly in those with a MTHFR deficiency. A metabolized form of folate that is commercially available is called L-methylfolate.
A new study suggests that the nutritional supplement vitamin B1, also known as thiamine, can improve symptoms of depression when taken with an antidepressant. Edith Holsboer-Trachsler and colleagues presented the research from their randomized, double-blind, placebo-controlled study at a recent scientific meeting. In a 12-week study, about 50 adults (averaging 35 years of age) with major depression were prescribed a selective-serotonin reuptake inhibitor (SSRI) antidepressant. In addition, half received thiamine supplements while the other half were given placebos. Starting at six weeks, those receiving thiamine with their antidepressant showed more improvement in their depressive symptoms than those receiving the antidepressant alone.
Thiamine is an essential nutrient for humans. It is found in foods such as yeast, pork, cereal grains, and certain vegetables. Thiamine deficiency has been linked to irritability and symptoms of depression, while thiamine supplementation can improve mood and reduce feelings of stress. No side effects were reported in the study.
Holsboer-Trachsler and colleagues hope that thiamine supplementation may help patients adhere to their antidepressant regimens by decreasing the time it takes until their moods begin to lift.
Many psychiatric illnesses, including bipolar disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), and anxiety disorders may stem from abnormalities in brain development that begin before birth. Researchers are trying to determine whether dietary supplements taken by pregnant mothers or infants can reduce the risk of such illnesses. At a recent scientific meeting, researcher Randal Ross and colleagues reported that compared to placebo, choline supplements reduced problems with a brain process called sensory gating in one-month-old infants and also improved the children’s attention span and social skills at age 3.
Sensory gating is the process by which the brain filters out unimportant information, to avoid flooding higher cortical centers with irrelevant stimuli. Deficits in the way the brain inhibits response to this type of irrelevant information are associated with mental illnesses such as schizophrenia.
In Ross’s study, healthy pregnant mothers received either a placebo or 6300 mg of choline, a nutrient found in liver, egg yolks, and meat. After delivery, the infants also received 700 mg of supplemental choline per day. In children who carried CHRNA7, a risk gene for schizophrenia discovered by Ross’s colleague Robert Freedman, choline reversed the associated risk of sensory gating problems and normalized their behavior at age 3.
Saffron, the expensive yellow spice derived from the plant Crocus sativus, was the subject of a recent meta-analysis in the journal Human Psychopharmacology. The meta-analysis included six studies of a total of 230 adult outpatients with major depressive disorder. In two of these studies, 30mg/day of saffron extract was as effective as 20mg/day of the antidepressant fluoxetine and 100mg/day imipramine for the treatment of mild to moderate depression had been in other studies.
Saffron is suggested to have anticancer, anti-inflammatory, antioxidant, and antiplatelet effects, and current clinical trials are exploring whether it could prevent and treat Alzheimer’s disease.
The current study was an effort to systematically analyze clinical trials on saffron to establish treatment parameters such as dosage in addition to safety information.
Researchers are exploring the therapeutic potential of nutraceuticals, or nutritional treatments. Folate, also known as folic acid or vitamin B9, is one of the most important nutritional elements for mental health.
The folate found in foods such as dark leafy greens must be broken down further in order to be used in the body. Folate first breaks down into dihydrofolate (DHF), which is turned into tetrahydrofolate (THF). At the 2014 meeting of the International Society for Bipolar Disorders, researcher J.H. Baek described a pathway by which THF is turned into a form called 5,10 MTHF, which is turned into a form called 5 MTHF. 5 MTHF is important for the function of the enzyme tryptophan hydroxylase and for clearing homocysteine, an amino acid that is cardio- and neuro-toxic.
L-methylfolate, the active ingredient in the medication Deplin, is an already-broken-down form of folate that the brain can use more readily than the folate from food. L-methylfolate is converted directly to 5 MTHF, so it is effective in 15% to 35% of the normal population who have a deficiency in the enzyme MTHF reductase, which converts THF to 5 MTHF. One genetic variant (a C to T allele variation 677) that results in one type of deficiency in MTHF reductase has a 42% incidence among Asians, 34% among Caucasians, and 8% among Africans, and these individuals would benefit from l-methylfolate.
Folate and Medications for Bipolar Disorder
Certain medications lead to deficits in folate, so patients should consider taking a nutritional supplement.
The anticonvulsant drug lamotrigine inhibits the conversion of folate to DHF and DHF to THF, so folate supplementation is a good idea for those patients taking lamotrigine.
The mood stabilizer valproate inhibits the conversion of toxic homocysteine to methionine and then to s-adenosyl methionine (SAMe), which acts like an internally-produced antidepressant. Thus valproate increases homocysteine, and patients on valproate should be routinely treated with folate and vitamin B12 to help lower homocysteine levels in the blood.
Folate supplements are recommended for depressed patients who are having an inadequate response to antidepressants, since the nutrient helps antidepressants work better even when patients do not have a folate deficiency. Researcher Andrew Stoll recommends folate (1mg for women and 2mg for men). However, those patients who have one of the genetic conditions that leads to a deficiency in MTHF reductase should take l-methylfolate instead of regular folate. Researcher Mauricio Fava and colleagues showed that l-methylfolate at doses of 15mg (but not 7.5mg) was more effective than placebo in patients with unipolar depression.