Background In cross-sectional studies, elevated plasma homocysteine levels have been associated with poor cognition and dementia. Studies of newly diagnosed dementia are required in order to establish whether the elevated homocysteine levels precede the onset of dementia or result from dementia-related nutritional and vitamin deficiencies. Methods A total of 1092 subjects without dementia (667 women and 425 men; mean age, 76 years) from the Framingham Study constituted our study sample. We examined the relation of the plasma total homocysteine level measured at base line and that measured eight years earlier to the risk of newly diagnosed dementia on follow-up. We used multivariable proportional-hazards regression to adjust for age, sex, apolipoprotein E genotype, vascular risk factors other than homocysteine, and plasma levels of folate and vitamins B12 and B6. Results Over a median follow-up period of eight years, dementia developed in 111 subjects, including 83 given a diagnosis of Alzheimer's disease....

https://www.nejm.org/doi/pdf/10.1056/NEJMoa011613

Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease

Background In 1996, the Food and Drug Administration issued a regulation requiring all enriched grain products to be fortified with folic acid to reduce the risk of neural-tube defects in newborns. Fortification (140 μg per 100 g) began in 1996, and the process was essentially complete by mid-1997. Methods To assess the effect of folic acid fortification on folate status, we measured plasma folate and total homocysteine concentrations (a sensitive marker of folate status) using blood samples from the fifth examination (January 1991 to December 1994) of the Framingham Offspring Study cohort for base-line values and the sixth examination (January 1995 to August 1998) for follow-up values. We divided the cohort into two groups on the basis of the date of their follow-up examination: the study group consisted of 350 subjects who were seen after fortification (September 1997 to March 1998), and the control group consisted of 756 subjects who were seen before fortification (January 1995 to September 1996). Resu...

https://www.nejm.org/doi/pdf/10.1056/NEJM199905133401901

The Effect of Folic Acid Fortification on Plasma Folate and Total Homocysteine Concentrations

Genomic DNA methylation decreases in response to moderate folate depletion in elderly women

Objective: To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis. Design: Randomized, double-bli...

Supplementation with Folic Acid during Methotrexate Therapy for Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial

OBJECTIVE —Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). RESEARCH DESIGN AND METHODS —We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991–1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995–1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 μmol/l in each phenotypic category and differences between categories were assessed with regression models. RESULTS —The mean age of the subjects was 54 years (range 28–82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 μmol/l) and those without (9.4 μmol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 μmol/l) compared with those with 1 or no phenotype (9.3 μmol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). CONCLUSIONS —Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

https://care.diabetesjournals.org/content/diacare/24/8/1403.full.pdf

Fasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome: The Framingham Offspring Study

Microbiological assay is still widely used for estimating folic acid derivatives in serum and other biological samples. We describe here a modification of this procedure involving use of 96-well microtiter plates. This procedure, used with modern, computer-interfaced microtiter-plate readers and data-reduction software, greatly shortens the time and minimizes reagent costs for this assay. Under the conditions of our assay procedures, all folic acid derivatives tested gave equal growth response for Lactobacillus casei. Results for assays of rat liver extracts showed excellent agreement between the standard bioassay and the 96-well procedure.

Lactobacillus casei microbiological assay of folic acid derivatives in 96-well microtiter plates.

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Lactobacillus casei microbiological assay of folic acid derivatives in 96-well microtiter plates.