While the nutritional supplement folate (also known as folic acid or vitamin B9) can be useful for depression, there appears to be one instance when augmentation with regular folate could be counterproductive. In those with a transport defect associated with a MTHR (methyl tetrahydrofolate reductase) deficiency, folate can compete with l-methylfolate for uptake into the brain. Folate would thus limit the beneficial effects of l-methylfolate supplementation, which is required for this 15% of the population.
Severe malnutrition in the first year of life even when corrected for the rest of a person’s life leaves a legacy of permanent cognitive deficits, marked deficits in attention, and increases in depression, conduct disorders, and medical disorders compared to carefully matched controls. Jamina Galler, a researcher at Harvard Medical School, gave a plenary talk at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry on the long-term effects of even short-term childhood malnutrition, including marasmus (calorie deficiency) and kwashiorkor (protein deficiency).
Galler’s studies followed three generations of people born in Barbados and observed the consequences of prior malnutrition, which was completely eliminated in Barbados by 1980. The consequences of malnutrition in the first year of life not only affected the first (G1) generation, but subsequently their offspring in the G2 generation who also suffered an excess of attention-deficit hyperactivity disorder, low IQ, and low annual income into adulthood. That is, the early malnutrition had transgenerational effects.
Malnutrition is a huge problem worldwide and is especially bad in sub-Saharan Africa and some parts of Asia. Globally, malnutrition accounts for 50% of the deaths of children under age five. However, even in the US hunger is a problem for one in four children, or about 16 million individuals, and the long-term consequences of hunger remain to be further studied.
Studies in animals indicate that early malnutrition has epigenetic effects that can be passed on to four future generations before they are reversed. Epigenetic effects refer to environmental factors that cannot change the sequence of DNA, but change how easily it is transcribed by adding or taking away acetyl and methyl groups on DNA and histones, the structures around which DNA is wound. Malnutrition (defined as 6–8% casein, a type of protein, in the diet instead of the normal 25%) in rodents affects cognitive abilities and blood pressure and can lead to diabetes, obesity, and other metabolic abnormalities. The next generation is also affected because a previously malnourished mother huddles too much with her offspring, and they become obese as a result of these poor parenting skills. The second generation also exhibits epigenetic changes in the prefrontal cortex (such as too few glucocorticoid receptors due to methylation of the glucocorticoid promoter) and fewer neurons in the hippocampus.
Editor’s Note: Other data indicate similar long-lasting epigenetic and transgenerational effects of other types of childhood adversity, such as verbal, physical, or sexual abuse. These findings in humans are also paralleled by findings in animals, and give strong credence to the idea that the environment can have long-lasting effects on neurobiology and behavior via epigenetic effects that can be superimposed on whatever genetic effects are inherited.
Data from this editor (Robert Post) and colleagues on verbal abuse in childhood is striking; this supposedly less severe form of abuse is still associated with a more difficult course of bipolar disorder and an increase in medical comorbidities. Thus, the experience of early abuse, even just verbal abuse, appears to have long-lasting consequences for psychiatric and medical health into adulthood.
Several studies in adults and children suggest that omega-3 fatty acid supplementation may have antidepressant effects. At the 2013 meeting of the American Academy of Child and Adolescent Psychiatry in October, Melissa DelBello, a professor at the University of Cincinnati, reported on a new study of omega-3 fatty acids in depressed children who had a parent with bipolar disorder. The children taking omega-3 fatty acids were more likely to improve than those taking a placebo, but the findings were only of marginal significance.
Cold-water fish are a good source of omega-3 fatty acids, and DelBello said salmon is by far the best in this regard. People who live in countries where fish is consumed in greater quantities are less likely to suffer from depression. Other sources of omega-3 fatty acids include shellfish, plant and nut oils, English walnuts, flaxseed, algae oils, and fortified foods.
The omega-3 fatty acids from fish are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), while the omega-3 fatty acids from plants are alpha-linolenic acid (ALA), which breaks down into EPA and DHA. All of these are anti-inflammatory, though one must consume much greater quantities of ALA to match the benefits of EPA and DHA. In contrast, omega-6 fatty acids, which are much more common in the typical American diet, are pro-inflammatory.
In DelBello’s study of 56 depressed children of a parent with bipolar disorder, the participants were randomized to either 1.8 g of omega-3 fatty acids (1.2 g of EPA and 0.6 g of DHA) or placebo (olive oil). Those who received the omega-3 fatty acids had a 55.6% rate of remission versus 34.5% for those who received placebo, but while the odds ratio of 2.4 favored the omega-3 fatty acids, the difference in remission rates was not statistically significant, likely because of the small size of the study. However, improvement on the Children’s Depression Rating Scale was significantly different across the two groups, with children taking omega-3s improving more. Omega-3 fatty acids are known to have an anticoagulant effect (preventing the clotting of blood), and four children in the study did have prolonged clotting times (but no clinical problems with bleeding).
Editor’s Note: Given the existing literature on omega-3 fatty acids and the trend in this study, omega-3s are worthy of consideration for the treatment and potentially for the prevention of depression in children. This later possibility is further suggested by findings from Australia that, when compared to placebo, omega-3 fatty acids significantly reduced the rate of conversion from prodromal (preliminary) psychotic symptoms to a full-blown diagnosis of schizophrenia.
A recent study confirmed that low levels of vitamin D can increase risk of death and determined a safe upper limit for vitamin D levels. The research, published by Yosef Dror et al. in the Journal of Clinical Endocrinology & Metabolism, showed that safe blood levels of vitamin D are between 20 and 36ng/mL. People with levels above or below this range were at greater risk of mortality or acute coronary syndrome.
Dror suggests that calcium supplement dosages should be specifically tailored to individuals based on levels in their blood.
The research comes from 54 months of data collection during which 422, 822 members of Clalit Health Services, an Israeli health maintenance organization, were tested for vitamin D levels. Only 3% percent of this population were at risk because of high levels of the vitamin, while 62% were at risk due to low levels of vitamin D.
Editor’s Note: Watch out for low vitamin D3. Even if a patient’s levels of D3 are in the normal range, supplementation can help antidepressants work better. According to a study published in the Australian and New Zealand Journal of Psychiatry, adding 1500 IU of vitamin D3 to the treatment regimen of depressed patients taking fluoxetine (Prozac) improved their response significantly.
In a study of over 60,000 women, Swedish researcher Karl Michaëlsson et al. found that those women with the highest intakes of calcium (>1400mg/day) were at higher risk of mortality, particularly from cardiovascular causes such as cardiovascular disease and heart disease (but not stroke), than women with calcium intakes of between 600 and 1000mg/day. The research was published in the journal BMJ in 2013.
While calcium dietary supplements were not associated with elevated risk per se, those women with the highest calcium intake levels who also took supplements had a risk of mortality from all causes that was more than 2.5 times that of women with similar total calcium intake who did not take supplements.
Calcium levels in blood are tightly controlled by the body, but very low or very high calcium intake levels can override this control, causing imbalances.
The efficacy of calcium supplements for conditions such as osteoporosis or chronic kidney disease has not been established, and a healthy balanced diet and avoidance of water filters that remove calcium from drinking water may be best.
A study published in the Lancet reports that even mild iodine deficiency during pregnancy can have adverse effects on IQ and cognitive development in the fetus. This occurs because of the deficiency’s effects on thyroid function.
Editor’s Note: Eat fish, drink milk and take a vitamin supplement with 140 to 150mcg of iodine.
Very dark chocolate made mostly from cocoa beans may be good for you. Cocoa is high in flavanols, which belong to a class of antioxidants called flavonoids. Dark chocolate has been associated with lowered risk of heart attack and stroke, improvements in cognition, lower body mass index (BMI, a weight to height ratio), dilation of blood vessels and lower blood pressure, and improved cholesterol profiles. This is despite containing a lot of saturated fat (a good trick, indeed). Among a study of 37,000 Swedish men, individuals who ate at least 1.8oz of dark chocolate a week had a 17% lower risk of stroke than those who ate less than 0.4oz a week.
Moderation is important. Two ounces of dark chocolate contain about 440 calories, so while a little may be good, a lot may not be so good. Watch out for milk chocolate and highly processed chocolates with great quantities of sugar added, they contain more calories and fewer health benefits.
A balanced diet and regular exercise are keys to good health, but don’t feel too badly if you top off a balanced meal with a tantalizing piece of the dark stuff.
A recent study of patients taking fluoxetine (Prozac) for major depression found that adding 1500 IU of vitamin D3 to their treatment regimen improved their response significantly. The article was published in the Australian and New Zealand Journal of Psychiatry.
According to the Mayo Clinic:
The term “vitamin D” refers to several different forms of this vitamin. Two forms are important in humans: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D2 is synthesized by plants. Vitamin D3 is synthesized by humans in the skin when it is exposed to ultraviolet B (UVB) rays from sunlight. Foods may be fortified with vitamin D2 or D3.
Editors Note: Here is another augmenting agent that could be considered for the treatment of those with residual depression. While vitamin D has not been studied directly in bipolar depression, we could ask, “Why not try it?” Other nutritional supplements in this category might be folate and N-acetylcysteine.
Vitamin D supplements are definitely indicated for the large percentage of those in the US who are vitamin D deficient. Given the data from this randomized trial, vitamin D3 could be considered in those with normal levels of vitamin D as well.
A study of 85,000 children in Norway that was recently published in the Journal of the American Medical Association showed that women who took folic acid during pregnancy were 40% less likely to have a child who developed autism.
A summary of the research by National Public Radio explained:
Folic acid is the synthetic version of a B vitamin called folate. It’s found naturally in foods such as spinach, black-eyed peas and rice. Public health officials recommend that women who may become pregnant take at least 400 micrograms of folic acid every day to reduce the chance of having a child with spina bifida.
The folic acid’s effect reduced the most severe cases of autism but did not seem to have an effect on the incidence of more mild forms, such as Asperger syndrome. The benefits were seen in those women who had been taking folic acid for 4 weeks before conception and continued to take the supplement during the first 8 weeks of pregnancy.