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Although one of the first biological treatments of a major psychiatric disorder was the dietary treatment of pellagra, the use of diet and dietary components in the study of psychopathology has not aroused much interest. This article reviews three areas in which the dietary approach has provided interesting information. The tryptophan depletion strategy uses a mixture of amino acids devoid of tryptophan to lower brain tryptophan in order to study the symptoms that can be elicited. One effect of tryptophan depletion is a lowering of mood, the magnitude of which seems to depend on the baseline state of the subject. Therefore, recovered depressed patients often undergo an acute relapse, while normal subjects show more moderate changes of mood. Totally euthymic subjects show no lowering of mood, but subjects with high normal depression scale scores or subjects with a family history of depression show a moderate lowering of mood. These data indicate that low serotonin levels alone cannot cause depression. However, serotonin does have a direct effect on mood, and low levels of serotonin contribute to the etiology of depression in some depressed patients. Folic acid deficiency causes a lowering of brain serotonin in rats, and of cerebrospinal fluid 5-hydroxyindoleacetic acid in humans. There is a high incidence of folate deficiency in depression, and there are indications in the literature that some depressed patients who are folate deficient respond to folate administration. Folate deficiency is known to lower levels of S-adenosylmethionine, and S-adenosylmethionine is an antidepressant that raises brain serotonin levels. These data suggest that low levels of serotonin in some depressed patients may be a secondary consequence of low levels of S-adenosylmethionine. They also suggest that the dietary intake and psychopharmacological action of methionine, the precursor of S-adenosylmethionine, should be studied in patients with depression. Normal meals have definite effects on mood and performance in humans. The composition of the meal, in terms of protein and carbohydrate content, can influence these behaviors. Because protein and carbohydrate meals can influence brain serotonin in rats, these effects in humans have usually been interpreted in terms of altered serotonin functioning. However, the current balance of evidence is against the involvement of serotonin in the acute effects of protein and carbohydrate meals in humans. The underlying mechanisms involved are unknown, but there are a variety of possibilities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The use of diet and dietary components in the study of factors controlling affect in humans: a review. 829 22

The deterioration of functional and mental capacity is one of the major problems of the elderly. This deterioration may be caused or worsened by folate deficiency. The aim of this investigation was to analyze the relationship between mental and functional capacities and folate status in a group of 177 elderly Spanish people. Folate deficiency is common in the Spanish population. In this study, 48.6% of the elderly subjects had folate intakes below recommended values (200 microg/day), 34.9% had serum concentrations < 14 nmol/L and 6.6% had <360 nmol/L erythrocyte folate. Subjects took part in a series of tests: Katz' scale of activities of daily living, Lawton's scale of instrumental activities of daily living, Pfeiffer's mental status questionnaire, Folstein's Mini-Mental State Test and the Geriatric Depression scale of Yesavage. The results for Lawton's scale of instrumental activities of daily living were significantly better (indicating greater independence and capacity) when folate intake and serum or erythrocyte folate concentrations were adequate (i.e., folate intake no less than recommended, > or = 14 nmol/L serum folate or > or = 360 nmol/L erythrocyte folate). Subjects with adequate Mini-Mental State Exam results (> or = 28 points) had serum and erythrocyte folate concentrations significantly higher than those with less adequate results (<28 points). Thus, there is evidence to suggest that the folate status of the elderly should be monitored and, if possible, improved.
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PMID:Functional and psychic deterioration in elderly people may be aggravated by folate deficiency. 875 71

Folate and vitamin B12 are required both in the methylation of homocysteine to methionine and in the synthesis of S-adenosylmethionine. S-adenosylmethionine is involved in numerous methylation reactions involving proteins, phospholipids, DNA, and neurotransmitter metabolism. Both folate and vitamin B12 deficiency may cause similar neurologic and psychiatric disturbances including depression, dementia, and a demyelinating myelopathy. A current theory proposes that a defect in methylation processes is central to the biochemical basis of the neuropsychiatry of these vitamin deficiencies. Folate deficiency may specifically affect central monoamine metabolism and aggravate depressive disorders. In addition, the neurotoxic effects of homocysteine may also play a role in the neurologic and psychiatric disturbances that are associated with folate and vitamin B12 deficiency.
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PMID:Folate, vitamin B12, and neuropsychiatric disorders. 915 10

Homocysteine (Hcy) may represent a metabolic link in the pathogenesis of atherosclerotic vascular diseases and old-age dementias. Hyperhomocysteinemia is an independent risk factor for coronary artery disease and peripheral vascular disease, and is also associated with cerebrovascular disease; specifically, the risk of extracranial carotid atherosclerosis significantly increases in relation to Hcy levels. Hcy is a reliable marker of vitamin B12 deficiency, a common condition in the elderly which is known to induce neurological deficits including cognitive impairment; a high prevalence of folate deficiency has been reported in psychogeriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAMe), a major methyl donor in CNS; therefore, deficiencies in either of these vitamins lead to a decrease in SAMe and increase in Hcy, which can be critical in the aging brain. Another pathogenetic mechanism linking high Hcy levels to reduced cognitive performances in the elderly might be represented by excitotoxicity, since hyperhomocysteinemia may lead to an excessive production of homocysteic acid and cysteine sulphinic acid, which act as endogenous agonists of NMDA receptors. Considering the reasonably high prevalence in the general population of a genetic predisposition to a thermolabile form of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), hyperhomocysteinemia can be seen as the result of multiple genetic and environmental factors leading to vascular and/or neurodegenerative disorders where age-related involutive phenomena represent a common pathogenetic ground. Systematic studies in different psychogeriatric conditions monitoring Hcy levels and clinical features before and after vitamin supplementation are therefore highly recommended.
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PMID:Role of homocysteine in age-related vascular and non-vascular diseases. 935 35

A recent major theory was that a meal high in carbohydrate increased the rate that tryptophan enters the brain, leading to an increase in the level of the neurotransmitter serotonin that modulates mood. Although such a mechanism may be important under laboratory conditions it is unlikely to be of significance following the eating of any typical meal. As little as 2-4% of the calories of a meal as protein will prevent an increased availability of tryptophan. Arguably the food with the greatest impact on mood is chocolate. Those who crave chocolate tend to do so when they feel emotionally low. There have been a series of suggestions that chocolate's mood elevating properties reflect 'drug-like' constituents including anandamines, caffeine, phenylethylamine and magnesium. However, the levels of these substances are so low as to preclude such influences. As all palatable foods stimulate endorphin release in the brain this is the most likely mechanism to account for the elevation of mood. A deficiency of many vitamins is associated with psychological symptoms. In some elderly patients folate deficiency is associated with depression. In four double-blind studies an improvement in thiamine status was associated with improved mood. Iron deficiency anaemia is common, particularly in women, and is associated with apathy, depression and rapid fatigue when exercising.
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PMID:The effects of nutrients on mood. 1061 80

Several reports indicate that biopterin and folate pathways may interact. We examined folate metabolism in PKU patients where hyperphenylalaninaemia leads to a likely excess of THB. We found an increase in total HPLC determined red cell folate in PKU (p=0.0422): specifically, there was an increase in total formyl-H(4)folate (p=0.0002) and H(4)folate (p< or =0.0001), and decrease in total 5-methyl-H(4)folate in PKU patients. At the level of individual oligo-gamma-glutamyl coenzymes, we found that formyl-H(4)folate polyglutamates were virtually all increased in PKU (p=0.0223, 0.0004, 0.0004, 0.0012, and 0.0008 for di-, tri-, tetra-, penta-, and deca-gamma-glutamyl formyl-H(4)folate coenzymes, respectively). Hcy levels did not differ between clinical groups, indicating that folate dependent-Hcy remethylation is not compromised as a consequence of an altered PKU folate disposition. In nature, pentaglutamyl folates are considered the metabolically favoured coenzymes (optimum K(m) for dependent enzymes). The presented data support this-we found that red cell pentaglutamates gave the best measure of metabolism; pentaglutamyl formyl-H(4)folate increased in PKU (p=0.0012) and related methenyls behaved similarly, while, pentaglutamyl 5-methyl-H(4)folate and pentaglutamyl H(4)folate decreased (p< or =0.0001 and 0.0265, respectively). Furthermore, pentaglutamates showed the best correlations between one-carbon oxidation states of folate, as well as with Hcy (p=0.0003 r=-0.54, 95% CI; -0.724 to -0.272). That PKU might influence folate metabolism in some way is unsurprising: patients with DHPR deficiency accumulate DHB and develop secondary folate deficiency-responsive only to reduced folates, while CSF levels of THB are significantly correlated to monoamines and red cell folate in depression. Further studies to confirm the present findings and to ascertain precisely what mechanism operates in PKU that impacts upon folate homeostasis so profoundly are required.
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PMID:The impact of phenylketonuria on folate metabolism. 1220 35

Although most researchers are concerned with the major side effects of oral contraceptives, swelling, nausea, depression, poor circulation, and weight gain are labeled ''minor'' and ignored. A few researchers have found that these side effects seem related to nutritional depletion in oral contraceptive users, especially: 1) Vitamin-B6, which is linked to depression and tryptophan level abnormalities in pill users and may be associated with nausea and weight gain. Studies show a daily need 10-30 times greater than that for women not on the pill. 2) Folic acid deficiency, common among women but a 25% deficiency rate has been noted in pill users. This has been associated with cell malformation and may be a reason for the high spontaneous abortion rate in women who conceive immediately after discontinuing the pill. 3) B1 and B12, the vitamins affecting energy, skin, and hair. Although not linked to any side effects, levels are low in pill users. 4) Vitamin-C, definitely depleted in pill users. This may be part of the bodily change resulting in cardiac problems and thrombosis. Full vitamin supplementation is recommended for all women taking oral contraceptives, including these vitamins as well as Vitamin-E and bioflavinoids. Vitamin supplements are routine for pregnancy. They should also be routine for the pseudopregnancy of oral contraception.
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PMID:Women on the pill are opening up a small case of side effects every morning. 1222 10

This study takes into consideration whether low serum folate levels may contribute to depressive mood in patients with chronic epilepsy. The serum folate levels and the score on the Self-Rating Depression Scale (SDS) were examined in 46 patients with chronic epilepsy. Patients with a score indicating at least minor depression on the SDS had a significantly lower serum folate level than patients with a normal score on SDS. There was a significant negative correlation between the serum folate levels and the SDS score. A serum folate level below 7.5 ng/ml was significantly associated with a pathological score on SDS. Because a serum folate level of 7.5 ng/ml is in the normal range for many laboratories, further studies using total plasma homocysteine as a sensitive measure of functional folate deficiency are required to elucidate the impact of folate metabolism on depressive mood in patients with chronic epilepsy.
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PMID:Low serum folate levels as a risk factor for depressive mood in patients with chronic epilepsy. 1255 73

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.
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PMID:[Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences]. 1510 81

The objective of this review was to determine the effectiveness, adverse effects and acceptability of folate in the treatment of depression. Electronic databases (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register) and reference lists were searched, and authors, experts and pharmaceutical companies contacted to identify randomized controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, for patients with a diagnosis of depressive disorder. Three randomized trials (247 participants) were included. Two studies assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale (HDRS) scores on average by a further 2.65 points [95% confidence interval (CI) 0.38-4.93]. Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The remaining study found no statistically significant difference when folate alone was compared with trazodone. The identified trials did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.
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PMID:Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. 1526 Sep 15


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