The Folate Studies for Depression

Folate or folic acid (vitamin B-9) is probably the most important single vitamin supplement.  It lowers the risk of some birth defects including spina bifida, with additional evidence that it helps prevent strokes, heart disease, Alzheimer's disease, and some cancers.  It may be of value in preventing Parkinson's disease as well.  See, the Folic Acid page on this website for those studies.  The U.S. government has required supplementation of cereals with 140 mcg of folic acid per serving to help prevent spina bifida.  Since the law was passed, researchers have found added evidence for some of the other benefits as well.  

The depression research is fairly impressive.  It is reviewed below, starting with the five published double-blind studies, followed by 27 more research studies supporting the findings  of the double-blind studies.  I recommend children take at least 400 mcg. per day, and adults and depressed children at least 800 mcg. per day.  For psychiatric patients, I recommend 1000-1600 mcg per day.  That should cost no more than 4 cents a day at the high 1600 mcg dose, a real health bargain.

It is recommended that older adults also take vitamin B-12, since folic acid may cover-up evidence of anemia which is a symptom of a serious B-12 deficiency.  B-12 deficiency can also cause neurological damage.  Therefore, I recommend that everyone over age 50 take B-12 500 mcg every other day in addition to the folic acid.  B-12 is stored in the liver, so there is no need to take a dose everyday and 500 mcg is a lot more than the minimum daily dosage.  That would add about 1-2 cents per day.  

Individual Studies Below:

Low Folate, not Low B-12, Slows Improvement on Fluoxetine (Prozac): In a study of 110 adults with Major Depression who responded to an 8-week trial of fluoxetine, patients with initial low folate levels (</=2.5 ng/ml) were much more likely to experience a later onset of clinical improvement than patients with normal levels (p=0.0028). The delayed improvement average 1 1/2 weeks. B12 and homocysteine level status did not predict time to clinical improvement (p>0.05). The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine. Papakostas GI, Petersen T, et al. MGH-Harvard. Int J Neuropsychopharmacol. 2005 May 9;:1-6.

Low Folate and B(12) in Small Study: In a study of 33 elderly with depression and 33 healthy controls, depressed patients had significantly lower levels of folate and vitamin B(12). Homocysteine was significantly higher in depressed individuals than in controls. Correlation of folate, vitamin B(12) and homocysteine plasma levels with depression in an elderly Greek population. Dimopoulos N, et al. University of Athens, Greece. Clin Biochem 2007 Jan 26.

Low Folate, High Homocysteine Linked to Depression; Not B-12: A random subsample of 412 persons ages 60-64 from a larger community sample found that being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Sachdev PS, Parslow RA, et al. University of New South Wales, Sydney, Australia. Psychol Med. 2005 Apr;35(4):529-38.

Folic Acid and B-12 for Depression Urged: Both low folate and low vitamin B12 have been found in studies of depressive patients. An association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are linked to a poor response to antidepressants, and treatment with folic acid improves response to antidepressants. High vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is overrepresented among depressive patients. The authors suggest that folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression. Treatment of depression: time to consider folic acid and vitamin B12. Coppen A, Bolander-Gouaille C. Epsom, Surrey, UK. J Psychopharmacol. 2005 Jan;19(1):59-65.

DB Folic Acid Adds to Fluoxetine; Reduces Depression and Side-Effects: A DB PC study of 127 patients with Major Depression had HAM-D depression scores >20 at the beginning of the 12-week study. They were treated with placebo or 500 micrograms folic acid plus fluoxetine 20 mg/day. Researchers found 94% of women had a >50% decrease in depression with folate vs. 61% with placebo. Female remission of depression occurred in 72% with folate vs. 47% with placebo. Side-effects were less (13% vs. 30%) with folate!. There was no benefit in males, although the author notes research showing that men need more folate to lower homocysteine and men in this study did not experience decreased homocysteine while the women did. Therefore, give men more folate. Improvement was related to lowered homocysteine, but not folate levels. Low folate in plasma and RBCs is common in depression. Folate is important for the synthesis of tetrahydrobiopterin, the co-factor for hydroxylation of phenylalanine and tryptophan and is the rate-limiting step synthesizing DA, NE, and 5HT. High homocysteine risk factor for heart attack, Alzheimer's disease, and stroke, all of which higher in depression. Fewer side-effects occurred (8 vs. 19) with folate. A. Coppen, England, J Affective Dis 00;60:121-30, Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. 

DB 5-Methyl tetrahydrofolic Acid as Good as Trazodone:  A DB PC study of 96 patients with mild to moderate dementia and depression were treated with folate 50 mg/day or trazodone 100 mg/day added to their normal psychiatric meds for 8 weeks. There was no difference after four weeks and the combination worked best at 8 weeks. Passeri M, Cucinotta D, Abate G, et al. Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. Aging (Milano). 1993;5:63–71.

DB Methylfolate Adjunct Helps Depression & Schizophrenia: In a DB PC study of 41 patients (33%) out of 123 with major depression (24) or schizophrenia (17) had low RBC folate [<200microg/l] or borderline folate. They were treated with placebo or 15 mg methylfolate with regular meds for 6 months. Folate patients did better in social recovery and the difference grew with time. The HAM-D depression scores increased in those depressed patients treated with placebos from 8.0 to 11.25 but decreased from 9.62 to 8.31 with folate. Schizophrenics had decreased depression with folate from 5.22 to 3.44 at 3 months and then to 2.22, but showed no change with placebo going from 5.63 to 5.87. Two-thirds of people with megaloblastic anemia have psychiatric difficulties. Low folate in 22% in average study and low B-12 in 5%. Have not been able to prove that low folate is due to inadequate dietary intake. All schizophrenics and 19 depressed were on psychotropics. Few had macrocytosis (enlarged Red Blood Cells [RBCs]) which is an inadequate screen for B-12 or folate deficiency. SAM gets its methyl group from methylfolate via methionine and both affect serotonin and dopamine turnover. Godfrey, King’s College, Lancet ’90;336:392; Br J Psychiatry 8/91

DB Folate Added to Lithium Helped Depression: In a DB PC study, placebo or folate 200 microg/day was added to lithium in 75 patients with depression. There was a 40% decrease in depression with folate. The author recommends adding 300-400 microg/day. Coppen, J Aff Disorder ’86;10:9-13

DB Folate Helps Depression: In a placebo controlled trial of folic acid 15 mg daily for four months in 24 folate deficient depressed subjects with mild cognitive impairment, Botez et al reported significant improvement in the Wechsler IQ memory scale and Kohs block design test. Mood also improved. Botez MI, Botez T, Leveille J, Bielmann P, Cadotte M. Neuropsychological correlates of folic acid deficiency: facts and hypotheses. In: Botez MI, Reynolds EH, eds. Folic acid in neurology, psychiatry and internal medicine. New York: Raven, 1979:435-461.

Low Folate Linked to Increased White Spots on MRI Scans; Respond More Poorly to Treatment: In a study of 50 out-patients with major depression and free of psychotropic medications for at least 2 weeks, MRI scans found that low blood folate, hypertension and age independently predicted a greater severity of total brain, as well as subcortical, white matter hyperdensities. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I). Iosifescu DV, et al. Massachusetts General Hospital, Harvard. Psychiatr Res 2005 Dec 30;140(3):291-9 and 140(3):301-7.

Low Folate Linked to Slower Improvement on Anti-Depressants: In a study of 110 outpatients with major depression who responded to an 8-week trial of fluoxetine, patients with low folate levels (<or=2.5 ng/ml) were more likely to experience a later onset of clinical improvement than eufolatemic patients ( p =0.0028). B12 and homocysteine level status did not predict time to clinical improvement ( p >0.05). The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine. Papakostas GI, et al. Massachusetts General Hospital, Harvard. . Int J Neuropsychopharm 2005 Dec;8(4):523-8.

Low Folate Again Linked to Depression in Israel: In a study of folate and B-12 levels in 224 newly admitted psychiatric in-patients, there was no difference in B-12 levels vs. controls. However, about 30% of patients had low folate values compared to 2.5% in the control group (P<0.0001). Mean folate level in controls was significantly higher than in patients (P<0.0001), where a positive correlation was found between low folate levels and depression. Researchers suggest that folate levels be assessed in patients admitted to psychiatric wards, especially in those with depression. Further study is needed to evaluate the role of folate and cobalamin in psychiatric illness. Vitamin B12 and folate serum levels in newly admitted psychiatric patients. Lerner V, et al. Ben-Gurion University of the Negev, Israel. . Clin Nutr 2006 Feb;25(1):60-7.

Low Folate Linked to Depression in Australia, Too: In a random subsample of 412 persons ages 60-64, being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was also associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. The effects of folic acid and homocysteine are overlapping but distinct. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Sachdev PS, et al. University of New South Wales, Sydney, Australia. . Psychol Med 2005 Apr;35(4):529-38. Ed: Low folate is a cause of increased homocysteine.

Low Folate Linked to Depression Relapse During Anti-Depressant Treatment: In a study of 71 adults with Major Depressive Disorder treated with fluoxetine (Prozac) 40 mg/day for 28 weeks, the presence of low serum folate levels (p =.004), but not low B12 (p >.05) or elevated homocysteine levels (p >.05), was associated with relapse during continuation treatment with fluoxetine. The relapse rates for patients with (N = 7) and without (N = 64) low folate levels were 42.9% versus 3.2%, respectively. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy. Papakostas GI, Petersen T, et al. Massachusetts General Hospital, Harvard. J Clin Psychiatry. 2004 Aug;65(8):1096-8

Low Folate Strongly Linked to Poor Anti-Depressant Response: In a 4-week DB study of 55 adults with major depressive disorder (MDD) who had previously failed to respond to open treatment with fluoxetine 20 mg/day, patients were given either (1) fluoxetine dose increase, (2) lithium augmentation of fluoxetine, or (3) desipramine augmentation of fluoxetine. Low serum folate levels (p =.04), but not elevated homocysteine (p >.05) or low vitamin B12 levels (p >.05), were associated with poorer response to treatment. The response rates for patients with (N = 14) and without (N = 38) low folate levels were 7% versus 45%, respectively. Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression. Papakostas GI, Petersen T, et al. Massachusetts General Hospital, Harvard. J Clin Psychiatry. 2004 Aug;65(8):1090-5

Folate Low In Interictal Psychosis: In a study of the interictal "schizophrenia-like" psychosis (interictal psychosis ) of epilepsy, researchers checked the plasma folate, vitamin B12, and homocysteine levels of 32 age- and sex-matched epileptic patients with or without interictal psychosis. The epileptic patients with interictal psychosis had significantly lower folate levels and higher homocysteine levels than those without interictal psychosis. Folate supplementation, in addition to antipsychotics, might play a beneficial role in the treatment of interictal psychosis in epileptic patients. Plasma folate and homocysteine levels may be related to interictal "schizophrenia-like" psychosis in patients with epilepsy. Monji A, Yanagimoto K, et al. Kyushu University, Japan. J Clin Psychopharmacol. 2005 Feb;25(1):3-5  

Smokers Had Lower Folate: In a study of 374 patients (272 Alzheimer's, 40 Mild Cognitive Impairment, and 42 Major depression) researchers found significantly lower HDL levels in smokers and previous smokers in comparison to non-smokers, p<0,05. The LDL: HDL ratio in smokers was significant higher (+20%) compared to previous smokers and non-smokers, p < 0.05. The mean levels of folic acid were statistically significant (p<0.05) lower (-24%) in smokers compared to non-smokers. Patients with MCI and Alzheimer's disease and also major depression who are "smokers" show serum levels of HDL and folic acid that are known to be strong risk factors for vascular damage and increased risk for vascular brain damage and impaired cognitive function. Cessation of smoking, and substitution with folate or statin therapy of smoking patients to slow down further cognitive decline. The influence of smoking on plasma folate and lipoproteins in Alzheimer disease, mild cognitive impairment and depression. Stuerenbrug HJ, et al. Median-Klinik Bad Suelze, Germany. . Neuro Endocrinol Letter 2005 Jun;26(3):261-3.

Folate Helped Memory, Not Depression, in Normals: In a study of 211 healthy women from young to old who took either 750 microg of folate with 15 microg of vitamin B-12 and 75 mg of vitamin B-6 or a placebo daily for 35 days, researchers found that folate helped memory performance, but not depression scores. Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly helped memory performance but not mood in women of various ages. Bryan J, Calvaresi E, Hughes D. J Nutr 2002 Jun;132(6):1345-56. Ed: Since normal adults are usually not clinically depressed, it is more difficult to show an impact of any anti-depressant.  Still, this study is important in that it gives evidence of benefit on brain functioning in even normal adults.

Folate May Have Helped SSRI Treatment at Harvard: In a poor quality study from Harvard, 22 Major Depressive Disorder patients, who were non-responsive or partially responsive to SSRI, were treated with an addition of leucovorin (folinic acid) 15-30 mg/day.  This increased blood folate levels from 28 to 301 in an open trial study. The HAM-Depression scores decreased from 19.1 to 12.8 for a modest but clinically significant benefit.  However, because of the poor design of the study, no scientific conclusions can be drawn. Massachusetts General Hospital. Folinic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory depression. Alpert JE, Mischoulon D, Rubenstein GE, Bottonari K, Nierenberg AA, Fava M. Ann Clin Psychiatry 2002 Mar;14(1):33-8

Genetics: Impaired 1-Carbon Metabolism in Depression; MTHFR 677C>T and Hyperhomocysteinemia: In a study of 5,948 adults ages 46-49 and 70-74 from the Hordaland Homocysteine Study cohort, hyperhomocysteinemia (odds ratio = 1.90) and T/T methylenetetrahydrofolate reductase genotype (OR = 1.69), but not low plasma folate or vitamin B-12 levels, were significantly related to depression without comorbid anxiety disorder. Plasma folate level was inversely associated with depression only in the subgroup of middle-aged women. Researcher says plasma folate measurements are imprecise and cell levels are what is important. Measures for homocysteine more precise. None of the investigated parameters showed a significant relationship to anxiety. Evidence of a role of impaired 1-carbon metabolism in depression. U Bergen. Folate, Vitamin B12, Homocysteine, and the MTHFR 677C->T Polymorphism in Anxiety and Depression: The Hordaland Homocysteine Study. Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Arch Gen Psychiatry. 2003 Jun;60(6):618-26

Genetics: Folate MTHFR Polymorphism Linked to Stroke: Methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations were examined. MRI examinations were performed on 1721 adults free of any history of stroke. Silent brain infarcts (SBI) were found in 10.3%. In adults 60 or older (n=849), the prevalence of SBI was significantly higher with the TT polymorphism than with TC+CC (27.7% versus 16.6%; Prevalence of moderately advanced white matter lesions was also significantly higher in TT (60.7% versus 49.0%). After correction for other risk factors, the MTHFR TT genotype was independently associated with SBI (odds ratio [OR]; P=0.018) and moderately advanced white matter lesions (OR, 1.58). Stroke. 2003 May;34(5):1130-5. 

Homocysteinenia and 677TT MTHFR Gene Increased Schizophrenia Risk: Homozygosity for the 677C --> T polymorphism (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene in 254 well-defined schizophrenic patients and 414 healthy controls found a 60% increased risk of schizophrenia and heterozygosity a 30% increased risk. Plasma homocysteine concentrations in 62 patients with schizophrenia and 432 controls found an increased risk for schizophrenia in the fourth and third quartile versus the lowest quartile [odds ratio (OR) = 3.3; and OR = 3.1; respectively]. Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: A dutch population based case-control study. Muntjewerff JW, Hoogendoorn ML, et al. Nijmegen, The Netherlands. Am J Med Genet B Neuropsychiatr Genet. 2005 Apr 1;135B(1):69-72

Low Folate Found in Depressed Young Adults: A Tufts University study of 2,948 Americans ages 15-39 found that, after adjustment for sociodemographic factors, serum vitamin B(12) concentration, alcohol consumption over the past year and current status as to overweight and use of vitamin/mineral supplements, cigarettes and illegal drugs, subjects who met criteria for a lifetime diagnosis of major depression had folate concentrations in serum and RBCs that were lower than those of subjects who had never been depressed. Subjects who met criteria for dysthymia alone had lower RBC folate concentrations than never-depressed subjects, but the serum folate concentrations of the two groups were comparable. Serum tHcy concentration was not related to lifetime depression diagnoses. Low folate status was found to be most characteristic of recently recovered subjects, and a large proportion of such subjects were folate deficient. Depression and folate status in the US Population. Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH. Psychother Psychosom. 2003 Mar-Apr;72(2):80-7

Seizure Patients Low in Folate More Depressed: A very small German study from Univ. of Ulm looked at 46 patients with chronic epilepsy. Patients with a score indicating at least minor depression on the Self-rating Depression Scale had a significantly lower serum folate level than patients with a normal score on SDS. Low serum folate levels as a risk factor for depressive mood in patients with chronic epilepsy. Rosche J, Uhlmann C, Froscher W. J Neuropsychiatry Clin Neurosci. 2003 Winter;15(1):64-6

Folate Increases SAMe by 43%: 3-month supplementation of patients having colon polyps with folic acid (5 mg/day) led to a 35% decrease in abnormally high ornithine decarboxylase activity in polyps that was accompanied by a 43% increase of S-adenosylmethionine content in polyps. Ann N Y Acad Sci 2001 Dec;952:175-6 The effect of high doses of folic acid on the overexpression of ornithine decarboxylase and S-adenosylmethionine content in human colon adenomatous polyps. Bukin YUV, Draudin-Krylenko VA, Levchuk AA, Poddubniy BK, Mazurov ST. (Ed: Even though several studies have proven that SAMe helps with depression, don't waste your money on this expensive supplement.  Taking the much cheaper folic acid is very likely to accomplish the same effect.)

Folate Higher, Cognitive Functioning Higher: A study of blood levels of vitamins B-12, C, and folate found that only folate correlated with cognitive functioning in elderly. J Am Coll Nutr 2000 Feb;19(1):68-76

Folate Low in Strokes, Dementia: In a prospective study of 1,171 Canadians over 65, the lowest quartile for serum folate had an increased likelihood of stroke. Those with low folate levels were more likely to be demented, institutionalized and depressed. In the cognitively impaired but not demented group, those with low folate levels scored lower on the Modified Mini Mental State and had more short-term memory problems. Age Ageing 1998 Jul;27(4):485-91. Folates function as a single carbon donor in the synthesis of serine from glycine, in the synthesis of nucleotides form purine precursors, indirectly in the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin, which is used in the re-methylation of homocysteine to methionine. Oral folates are generally available in two supplemental forms, folic and folinic acid. Administration of folinic acid bypasses the deconjugation and reduction steps required for folic acid. Folinic acid also appears to be a more metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect.

Folate in RBC Low in Mania: Forty-five hospitalized patients with DSM-III-R diagnosis of mania, were found to have a mean red-cell folate level of 193 nmol/l, as compared to 896 nmol/l in the control group (P < 0.00001). Assessment of serum folate in both groups showed no significant differences in the levels. Furthermore the manic patients and the controls were matched by the socio-economic status. This indicated that the reduced red-cell folate in mania is associated with the illness and not due to reduced absorption or dietary deficiency of folate. Considering previous studies that showed reduced red-cell folate in depression, it suggests that reduced red-cell folate occurred in both phases of bipolar disorders. J Affect Disord 1997 Nov;46(2):95-9

Folates and Depression: A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways. Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15-38% of adults diagnosed with depressive disorders. Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified. Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutr Rev. 1997;55:145–149.

Low Folate Less Responsive to Fluoxetine: Subjects with low folate levels were more likely to have melancholic depression and were significantly less likely to respond to fluoxetine. Homocysteine and B12 levels were not associated with depressive subtype or treatment response. MGH, Fava, Am J Psychiatry 1997 Mar;154(3):426-8

Geriatric Depressed Folate Predict Benefit SSRI, Nortriptyline: Depressed geriatric patients have lower levels of folate (FOL) than controls. FOL supplement can reduce depressive morbidity. FOL deficiency causes a lowering of CNS serotonin that contributes to depression. Compared an SSRI (sertraline) with a nonspecific tricyclic antidepressant (nortriptyline) in geriatric depressed. Measured FOL in 22 depressed patients older than 60 years. Both treatments were effective. At baseline, FOL levels normal range. Higher FOL levels at baseline predicted greater improvement.For the group treated with the SSRI, baseline FOL level was a more efficient predictor of improvement. Prediction of Treatment Response in Geriatric Depression From Baseline Folate Level: Interaction With an SSRI or a Tricyclic Antidepressant. Alpert M, Silva RR, Pouget ER. J Clin Psychopharmacol. 2003 Jun;23(3):309-13

Low Folate Latino Women Twice as Likely to be Depressed: In 1510 elderly in the Sacramento Area Latino Study on Aging (SALSA), folate deficiency was less than 1%. For men, no significant association was found between folate level and depression. However, women in the lowest third in blood folate levels were more than twice as likely to be depression as those in the highest third (OR = 2.04; (P < 0.001). Plasma folate concentrations are associated with depressive symptoms in elderly Latino women despite folic acid fortification. Ramos MI, Allen LH, et al. University of California, Davis. Am J Clin Nutr. 2004 Oct;80(4):1024-8.

Low Folate Linked to Cognitive Decline in Prospective Study: High homocysteine concentration is a risk factor for cognitive decline and Alzheimer's disease.  In a 7-year follow-up of 499 high-functioning elderly ages 70-79, those with elevated homocysteine levels, or low levels of folate or vitamin B-6 showed worse baseline cognitive functioning.  After adjustments, those in the bottom quarter of folate had a 160% increased risk (p=0.04) of being in the worst quartile of 7-year cognitive decline.  Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine levels. Homocysteine versus the vitamins folate, b(6), and B(12) as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Kado DM, Karlamangla AS, et al. University of California, Los Angeles. Am J Med. 2005 Feb;118(2):161-7.

Fruit, Vegetables, OJ Increase Folate: In 5533 middle-aged and elderly from the Hordaland Homocysteine Study, folate levels increased as fruit, vegetable, and orange juice consumption increased. Levels decreased as comsumption of milk and bread increased. Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study. Brevik A, Vollset SE, et al. Universities of Oslo and Bergen, Norway. Am J Clin Nutr. 2005 Feb;81(2):434-9.

Thomas E. Radecki, M.D., J.D.

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