1. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits.
Arch Gerontol Geriatr. 1998 Jan-Feb;26(1):1-13.
ABSTRACT:
The relevance of low folate levels as determinants of cognitive deficits and the usefulness of folate supplementation in the treatment of cognitive deficits was reviewed from the literature. Over 40 papers and book chapters published in English, French, German, Italian and Spanish were examined. This represents those papers published in the international literature in the last 10 years which were identified by various key words including folate, cognition and aging (or ageing). Among these papers, only 13 articles specifically addressed issues relevant to the criteria adopted for this review. The remaining papers were principally concerned with depression and or with other pathologies of the aged associated with folate deficiency. Although the specific role of low folate levels in the physiopathology of dementia is still under debate, a growing consensus is emerging in the literature where low folate as well as cobalamin levels in aged patients with cognitive deficits are being considered as a sign of functional problems in the absorption and utilization of vitamins, and not merely as a sign of bad eating habits. In studies where folate compounds were evaluated for treatment effects, the results of a majority of investigations indicated that folate treatment was effective in lessening cognitive deficits. Treatment efficacy, however, has not yet been sufficiently demonstrated by these results because there were no controlled studies and the methodology was heterogeneous for the evaluation of cognitive characteristics. An ad hoc double-blind, controlled versus placebo pilot study was undertaken to evaluate the efficacy of folic acid in 30 aged patients with abnormal cognitive decline and folate level below 3 ng/ml to better understand the value of this type of intervention. Our results from this preliminary study demonstrated that patients treated with folic acid for 60 days showed a significant improvement on both memory and attention efficiency when compared with a placebo group. The intensity of memory improvement was positively correlated with initial severity of folate deficiency. On the contrary, the severity of initial cognitive decline was unrelated to the degree of folate deficiency.

2. [Efficacy of a combination therapy with vitamins B6, B12 and folic acid for general feeling of ill-health. Results of a non-interventional post-marketing surveillance study]
MMW Fortschr Med. 2008 Jan 17;149 Suppl 4:162-6.
ABTRACT:
OBJECTIVE: In the present non-interventional postmarketing surveillance study, patients with symptoms of an inadequate supply of vitamins were tested for how a treatment with a combination vitamin injection consisting of vitamins B6, B12 and folic acid affects mood and fitness. The evaluation of the efficacy and tolerability as well as the documentation of adverse drug reactions were carried out by the physician. METHODS: The patient collective included 1430 patients (70.8% women, average age 67.1 years, average BMI 25.5 kg/m2). The average duration of treatment was 4.5 weeks with an average of 8.3 intramuscular injections. The principal method for determining the efficacy was the self-assessment scale of well-being (Bf-S) according to Zerssen (sum score with a value range between 0 and 56 points). RESULTS: The sum score of the Bf-S decreased from 37.5 (+/-10.1) points at admission to 15.6 (+/- 9.4) points after four weeks of treatment.The subjective impression improved correspondingly in 96.3% of the patients. The improvement of the Bf-S was equally good in women and men.The number of injections correlated with the improvement in the sum score. The tolerability was mainly rated as very good or good. CONCLUSIONS: Eight vitamin infections over four weeks led to a clear improvement in the mood and vitality of patients with symptoms of intracellular vitamin B deficiency.

3. The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases.
Clin Chem Lab Med. 2007;45(12):1590-606.
Hyperhomocysteinemia (HHcy) is related to central nervous system diseases. Epidemiological studies show a positive, dose-dependent relationship between plasma total homocysteine (tHcy) concentration and neurodegenerative disease risk. tHcy is a marker of B-vitamin (folate, B(12), B(6)) status. Hypomethylation, caused by low B-vitamin status and HHcy, is linked to key pathomechanisms of dementia; B-vitamin supplementation could potentially reduce neurological damage. In retrospective studies, the association between tHcy and cognition is impressive; there is also evidence that tHcy-lowering treatment could be effective in primary and secondary stroke prevention. Increased tHcy and low serum folate occur in patients with Parkinson's disease, especially those receiving L-dopa. There is also an association between HHcy and multiple sclerosis, and between B-vitamin status and depression. Studies also confirm a causal role for tHcy in epilepsy, and certain anti-epileptics enhance HHcy. B-vitamin status should be optimized by ensuring sufficient intake in patients with neuropsychiatric diseases. HHcy occurs commonly in the elderly and can contribute to age-related neurodegeneration. Treatment with folic acid, B(12) and B(6) lowers tHcy. For secondary and primary prevention from several neuropsychiatric disorders, it seems prudent to actively identify deficient subjects and ensure sufficient vitamin intake.

4. Dietary intake of folate equivalents and risk of myocardial infarction in the European Prospective Investigation into Cancer and Nutrition (EPIC)--Potsdam study.
Public Health Nutr. 2006 Jun;9(4):465-71.
ABSTRACT:
OBJECTIVE:To assess the relationship between intake of dietary folate equivalents and risk of myocardial infarction in a German cohort. DESIGN: Intake of dietary folate equivalents was assessed by a validated food-frequency questionnaire. Cox proportional hazard models were used to evaluate the association between intake of dietary folate equivalents and risk of myocardial infarction. SETTING: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort, Germany. SUBJECTS: Subjects were 22,245 apparently healthy non-users of vitamin supplements aged 35-64 years. RESULTS: During 4.6 years of follow-up, 129 incident cases of myocardial infarction were identified. Compared with intake below the median (103 microg), higher intake of dietary folate equivalents was associated with a multivariate-adjusted hazard ratio (HR) of 0.57 (95% confidence interval (CI) 0.36-0.91). The inverse association of folate intake and myocardial infarction risk was stronger in participants with an ethanol intake equal to or above the sex-specific median (HR=0.37, 95% CI 0.18-0.79) and attenuated in those with a low ethanol intake (HR=0.67, 95% CI 0.37-1.22). CONCLUSION: An increased intake of dietary folate equivalents was observed to be associated with decreased risk of myocardial infarction in a German study population, pointing towards the importance of folate intake with respect to primary prevention of myocardial infarction.