Folate and depression - A neglected problem

Journal of psychiatry & neuroscience: JPN (Impact Factor: 5.86). 04/2007; 32(2):80-2.
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    • "In fact, some researchers theorize that psychiatric diseases with defect in communication as autism, attention deficit hyperactivity disorder, dyslexia, dyspraxia and schizophrenia can be characterized as " phospholipid spectrum of disorders " . This could explain why these conditions often overlap, why they tend to cluster in families, and why they often share similar clinical features (Richardson and Ross, 2000; Young, 2007). Exploration of these mechanisms of action has inspired the pursuit of new treatment protocols that feature PUFA as an adjunctive or as a monotherapy for treatment of these diseases, with many surprising results (Prior and Galduróz, 2012). "
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    ABSTRACT: Polyunsaturated fatty acids (PUFAs) are not only essential for energy production, but they also exhibit a range of immunomodulatory properties that progress through T cell mediated events. Autoimmunity may have a pathogenic role in a subgroup of autistic children. This study is the first to investigate the relationship between serum levels of anti-myelin basic protein (anti-MBP) brain-specific auto-antibodies and reduced plasma levels of PUFAs in autistic children. Plasma levels of PUFAs (including linoleic, alphalinolenic, arachidonic "AA" and docosahexaenoic "DHA" acids) and serum anti-MBP were measured in 80 autistic children, aged between 4 and 12 years, and 80 healthy-matched children. Autistic patients had significantly lower plasma levels of PUFAs than healthy children. On the other hand, ω6/ω3 ratio (AA/DHA) was significantly higher in autistic patients than healthy children. Low plasma DHA, AA, linolenic and linoleic acids were found in 67.5%, 50%, 40% and 35%, respectively of autistic children. On the other hand, 70% of autistic patients had elevated ω6/ω3 ratio. Autistic patients with increased serum levels of anti-MBP auto-antibodies (75%) had significantly lower plasma DHA (P<0.5) and significantly higher ω6/ω3 ratio (P<0.5) than patients who were seronegative for these antibodies. In conclusions, some autistic children have a significant positive association between reduced levels of plasma DHA and increased serum levels of anti-MBP brain-specific auto-antibodies. However, replication studies of larger samples are recommended to validate whether reduced levels of plasma PUFAs are a mere association or have a role in the induction of the production of anti-MBP in some autistic children. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Neuroimmunology 01/2015; 280. DOI:10.1016/j.jneuroim.2015.01.009
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    • "The pathway is unknown Benton and Donohoe, 1999 Folic acid Folic acid deficiency is associated with depressed mood. The pathway is unknown Coppen and Bolander-Gouaille, 2005; Young, 2007 Ghrelin Linked to stress mediated food reward behavior, depression, and anxiety via ghrelin receptor signaling pathway Schanze et al., 2008; Barim et al., 2009; Kluge et al., 2009, 2011; Perello et al., 2010; Chuang et al., 2011; Diz-Chaves, 2011; Kumar et al., 2013 Serotonin Linked to food intake, depression, and anxiety via serotonin receptor signaling pathway Wurtman and Wurtman, 1989; Benton and Donohoe, 1999; Pepino et al., 2009; Shabbir et al., 2013 Dopamine Linked to food reward behavior and mood via dopamine receptor signaling pathway Cantello et al., 1989; Diehl and Gershon, 1992; Fochtmann and Fink, 1992; Berridge, 1996; Black et al., 2002; Davis et al., 2009; Cawley et al., 2013 Leptin Linked to food intake, depression, anxiety, and mood disorder via leptin receptor signaling pathway Collin et al., 2000; Asakawa et al., 2003; Lu et al., 2006; Finger et al., 2010; Liu et al., 2010; Sharma et al., 2010; Yamada et al., 2011; Guo et al., 2012, 2013 Adiponectin Linked to depression and mood disorder. May involve adiponectin-induced inhibition of GSK-3β pathway Arita et al., 1999; Maeda et al., 2001; Milan et al., 2002; Cnop et al., 2003; Delporte et al., 2004; Ryo et al., 2004; Leo et al., 2006; Narita et al., 2006; Hanley et al., 2007; Weber-Hamann et al., 2007; Ye et al., 2007; Yilmaz, 2008; Zeman et al., 2009; Jeong et al., 2012; Wilhelm et al., 2013 Resistin Indirect link to depression. "
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    ABSTRACT: Food is a potent natural reward and food intake is a complex process. Reward and gratification associated with food consumption leads to dopamine (DA) production, which in turn activates reward and pleasure centers in the brain. An individual will repeatedly eat a particular food to experience this positive feeling of gratification. This type of repetitive behavior of food intake leads to the activation of brain reward pathways that eventually overrides other signals of satiety and hunger. Thus, a gratification habit through a favorable food leads to overeating and morbid obesity. Overeating and obesity stems from many biological factors engaging both central and peripheral systems in a bi-directional manner involving mood and emotions. Emotional eating and altered mood can also lead to altered food choice and intake leading to overeating and obesity. Research findings from human and animal studies support a two-way link between three concepts, mood, food, and obesity. The focus of this article is to provide an overview of complex nature of food intake where various biological factors link mood, food intake, and brain signaling that engages both peripheral and central nervous system signaling pathways in a bi-directional manner in obesity.
    Frontiers in Psychology 09/2014; 5:925. DOI:10.3389/fpsyg.2014.00925
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    • "In addition to omega-3 fatty acids, vitamin B (e.g., folate), and magnesium deficiencies have been linked to depression [9,13,14]. Randomized, controlled trials that involve folate and B12 suggest that patients treated with 0.8 mg of folic acid/day or 0.4 mg of vitamin B12/day will exhibit decreased depression symptoms [9]. In addition, the results of several case studies where patients were treated with 125 to 300 mg of magnesium (as glycinate or taurinate) with each meal and at bedtime led to rapid recovery from major depression in less than seven days for most of the patients [14]. "
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    ABSTRACT: According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD). Most antidepressants and other prescription drugs cause severe side effects, which usually discourage patients from taking their medications. Such noncompliant patients who have mental disorders are at a higher risk for committing suicide or being institutionalized. One way for psychiatrists to overcome this noncompliance is to educate themselves about alternative or complementary nutritional treatments. Although in the cases of certain nutrients, further research needs to be done to determine the best recommended doses of most nutritional supplements, psychiatrists can recommend doses of dietary supplements based on previous and current efficacious studies and then adjust the doses based on the results obtained.
    Nutrition Journal 02/2008; 7(1):2. DOI:10.1186/1475-2891-7-2
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Questions & Answers about this publication

  • Simon N Young added an answer in Nutraceuticals:
    What is the role of nutrition and diet in the clinical management of mood disorders?

    Specific nutraceuticals (nutrients) and traditional dietary patterns have shown some benefitis to improve mood state and even decrease risk for depression.

    I would like to open a discussion about this topic. Are nutritional interventions part of daily clinical management of people with mood disorders?

    Simon N Young

    There are a number of comments in this discussion that need clarifying or correcting, and an important issue that has not been raised.

    1. The statement that Fernstrom and Wurtman “have proved that the level of serotonin in your brain is directly influenced by the amount of L-tryptophan in your diet” is not quite true. They demonstrated that tryptophan administration can increase brain serotonin synthesis in rat brain and many others have also demonstrated that this is true for human brain. However, they also demonstrated that tryptophan is transported into brain by a transporter that is active towards all large neutral amino acids, i.e. not only tryptophan but also phenylalanine, tyrosine, leucine, isoleucine and valine. There is competition between the various amino acids for the transporter and as a result brain tryptophan can, as a rough approximation, be predicted by the ratio of plasma tryptophan to the sum of the plasma concentration of the other large neutral amino acids (trp/LNAA). Tryptophan happens to be the least abundant amino acid in most proteins, so when tryptophan (i.e. protein) is ingested as a part of a normal diet plasma tryptophan will increase but the LNAA will increase even more. As a result trp/LNAA, brain tryptophan and brain serotonin will decrease. The effect in humans is so small as not be significant. This is all discussed in detail in the paper you will find here:

    2. You have to distinguish between nutrition and the use of components of the diet in purified form at high doses. For example, tryptophan when given at doses of 3g per day or more has an antidepressant effect (see Cochrane review at presumably because of the increase in brain serotonin synthesis. However, as discussed above, the 0.7 to 1.0 g per day of tryptophan that most people ingest as part of a normal diet will not raise brain tryptophan or serotonin and is certainly not an antidepressant. To me, tryptophan in purified form is a drug, and regulatory agencies in the Canada and the UK approved it as a prescription drug for the treatment of depression (although I believe it is now available over the counter in the UK). In the USA it is available over the counter as a dietary supplement. Another dietary constituent discussed by Lakh and and Vieira (see comment by Joan for the link) is S-adenosylmethionine (SAM). It is an antidepressant at a dose of 1g per day or more which is orders of magnitude large than the amount ingested in the diet. Again to me that is a drug. The article by Hulksen et al (see comment by Vincent for the link) discusses the effects of alpha-lactalbumin, which is a minor constituent of milk that contains unusually high levels of tryptophan does in fact raise brain tryptophan a bit (although not as much as tryptophan because it does contain LNAA). You might want to call that a dietary supplement, but I cannot see why anyone would use it. A search of websites selling alpha-lactalbumin and tryptophan suggests that tryptophan in purified form is cheaper than the tryptophan in alpha-lactalbumin.

    3. The Hulksen article does not talk about real diet. It discusses work with alpha-lactalbumin and the acute tryptophan depletion technique (see neither of which have anything to do with real diets. Their conclusion about the U-shaped curve for plasma tryptophan levels and mood is based on non-nutritional studies of that type and is not even supported particularly well by the data they present.

    4. Maryam says that “Food with high glycemic index and tryptophan reduces the time it takes to fall asleep.” It is important to clarify that tryptophan refers to purified tryptophan, not tryptophan in food. In relation to the comment that milk two hours before going to sleep is useful, I know that this is folklore but I am not aware of any controlled trials demonstrating this. Can anyone enlighten me?

    5. There are now many studies suggesting that those with poor diets are more likely to become depressed than those with good diets (e.g. the Mediterranean diet, the New Nordic diet). Of course this type of epidemiological study does not imply anything about cause and effect. It is likely that those with depressed mood that later becomes clinical depression might select worse diets than those with good mood. Furthermore, not all the studies controlled for possible confounding variables such as exercise, given that those with good diet are more likely to exercise and that may be a protective factor against depression.

    6. A recent meta-analysis concluded that omega-3 polyunsaturated fatty acid supplements are effective in the treatment of depression. 

    7. An old literature suggests that the incidence of folate deficiency is higher in depressed patients than in the general population. This is not surprising as depression is associated with anorexia. However, in rats and possibly in human folate deficiency causes a decrease in serotonin synthesis. A number of studies suggest that folate or methyl-folate enhance the recovery of depressed patients being treated with depression. While folate is probably not often a cause of depression folate deficiency that occurs due to depression and inadequate diet may help prevent recovery. This is discussed here, and a recent high quality study showing that methyl-folate can help recovery from depression is here

    8. The question was “Are nutritional interventions part of daily clinical management of people with mood disorders?” Good diet might help, but there is no evidence that it will help cure depression. Tryptophan, SAM, omega-3 polyunsaturated fatty acids and folate or methyl-folate are all dietary components that may be helpful in the treatment of some depressed patients.

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      ABSTRACT: Tryptophan is important both for protein synthesis and as a precursor of niacin, serotonin and other metabolites. Tryptophan is an unusual amino acid because of the complexity of its metabolism, the variety and importance of its metabolites, the number and diversity of the diseases it is involved in, and because of its use in purified form as a pharmacological agent. This review covers the metabolism of tryptophan, its presence in the diet, the disorders associated with low tryptophan levels due to low dietary intake, malabsorption, or high rates of metabolism, the therapeutic effects of tryptophan and the side effects of tryptophan when it is used as a drug including eosinophilia myalgia syndrome.
      Amino Acids 03/1996; 10(1):21-47. DOI:10.1007/BF00806091

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