Effects of Folic Acid Supplementation on Serum Folate and Plasma Homocysteine Concentrations in Older Adults: A Dose-Response Trial

Atherosclerosis is a chronic disease that can seriously endanger human life. Folic acid supplementation modulates several disorders, including atherosclerosis, via its antiapoptotic and antioxidative properties. This study investigated whether folic acid alleviates atherogenesis by restoring homocysteine levels and antioxidative capacity in atherosclerosis Wistar rats. To this end, 28 Wistar rats were randomly divided into 4 groups (7 rats/group) as follows: (i) wild-type group, fed only the AIN-93 semi-purified rodent diet (folic acid: 2.1 mg/kg); (ii) high-fat + folic acid-deficient group (HF+DEF) (folic acid: 0.2 mg/kg); (iii) high-fat + normal folic acid group (folic acid: 2.1 mg/kg); and (iv) high-fat + folic acid-supplemented group (folic acid: 4.2 mg/kg). After 12 weeks, histopathological changes in the atherosclerotic lesions of the aortic arch were determined. In addition, serum folate levels, plasma homocysteine levels, plasma S-adenosyl-homocysteine levels, antioxidant status, oxidant status, and lipid profiles were evaluated. The results show aggravated atherosclerotic lesions in the HF+DEF group. Folic acid supplementation increased concentrations of serum folate. Further, folic acid supplementation increased high-density lipoprotein-cholesterol, decreased plasma homocysteine levels, and improved antioxidant capacity in atherogenic rats. These findings are consistent with the hypothesis that folic acid alleviates atherogenesis by reducing plasma homocysteine levels and improving antioxidant capacity in rats fed a high-fat diet.

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No effect of folic acid supplementation in the course of 1 year on haemostasis markers and C-reactive protein in older adults

Thrombosis and Haemostasis ◽

10.1160/th04-08-0524 ◽

2005 ◽

Vol 94 (07) ◽

pp. 96-100 ◽

Cited By ~ 16

Author(s):

Mariska Klerk ◽

Jane Durga ◽

Evert G. Schouten ◽

Cornelis Kluft ◽

Frans J. Kok ◽

...

Keyword(s):

Older Adults ◽

Folic Acid ◽

Disease Risk ◽

Controlled Trial ◽

Folic Acid Supplementation ◽

Serum Folate ◽

Tissue Type ◽

C Reactive Protein ◽

Acid Supplementation ◽

Reactive Protein

SummaryElevated homocysteine levels are associated with an increased cardiovascular disease (CVD) risk, but the underlying mechanism is still unclear. High homocysteine might affect the endothelium, and consequently lead to impaired haemostasis. In a randomized placebo controlled trial among 276 older adults with plasma total homocysteine concentrations above 13 mM at screening, we investigated the effect of homocysteine lowering by folic acid supplementation (0.8 mg/day) for 1 year on markers of endothelial function (vonWillebrand factor), coagulation (tissue factor, factor VIIa, fragments 1+2), and fibrinolysis (fibrin degradation products, tissue-type plasminogen activator), and inflammation (C-reactive protein). Despite a 24% reduction in plasma homocysteine concentration and four-fold increase in serum folate concentration in the folic acid group compared to the placebo group, there was no clear change in any of the haemostasis markers, nor CRP. Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by one-year folic acid supplementation does not influence haemostasis markers.

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Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial

Yearbook of Psychiatry and Applied Mental Health ◽

10.1016/s0084-3970(08)70862-4 ◽

2008 ◽

Vol 2008 ◽

pp. 288-289

Author(s):

J.C. Ballenger

Keyword(s):

Older Adults ◽

Folic Acid ◽

Cognitive Function ◽

Controlled Trial ◽

Folic Acid Supplementation ◽

Double Blind ◽

Acid Supplementation

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Faculty Opinions recommendation of Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1065777.518705 ◽

2007 ◽

Author(s):

Kay Tee Khaw

Keyword(s):

Older Adults ◽

Folic Acid ◽

Cognitive Function ◽

Controlled Trial ◽

Folic Acid Supplementation ◽

Double Blind ◽

Acid Supplementation

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Folic acid supplementation does not attenuate thermoregulatory or cardiovascular strain of older adults exposed to extreme heat and humidity

Experimental Physiology ◽

10.1113/ep087049 ◽

2018 ◽

Vol 103 (8) ◽

pp. 1123-1131 ◽

Cited By ~ 4

Author(s):

Daniel Gagnon ◽

Steven A. Romero ◽

Matthew N. Cramer ◽

Ken Kouda ◽

Paula Y S. Poh ◽

...

Keyword(s):

Older Adults ◽

Folic Acid ◽

Folic Acid Supplementation ◽

Extreme Heat ◽

Acid Supplementation ◽

Cardiovascular Strain

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Folate: In Vitro and in Vivo Effects on VLDL and LDL Oxidation

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.77.1.66 ◽

2007 ◽

Vol 77 (1) ◽

pp. 66-72 ◽

Cited By ~ 7

Author(s):

McEneny ◽

Couston ◽

McKibben ◽

Young ◽

Woodside

Keyword(s):

Folic Acid ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Folic Acid Supplementation ◽

Serum Folate ◽

Ldl Oxidation ◽

Low Density ◽

Acid Supplementation

Raised total homocysteine (tHcy) levels may be involved in the etiology of cardiovascular disease and can lead to damage of vascular endothelial cells and arterial wall matrix. Folic acid supplementation can help negate these detrimental effects by reducing tHcy. Recent evidence has suggested an additional anti-atherogenic property of folate in protecting lipoproteins against oxidation. This study utilized both an in vitro and in vivo approach. In vitro: Very-low-density lipoprotein (VLDL) and low density lipoprotein (LDL) were isolated by rapid ultracentrifugation and then oxidized in the presence of increasing concentrations (0→ μmol/L) of either folic acid or 5-methyltetrahydrofolate (5-MTHF). In vivo: Twelve female subjects were supplemented with folic acid (1 mg/day), and the pre- and post-VLDL and LDL isolates subjected to oxidation. In vitro: 5-MTHF, but not folic acid, significantly increased the resistance of VLDL and LDL to oxidation. In vivo: Following folic acid supplementation, tHcy decreased, serum folate increased, and both VLDL and LDL displayed a significant increase in their resistance to oxidation. These results indicated that in vitro, only the active form of folate, 5-MTHF, had antioxidant properties. In vivo results demonstrated that folic acid supplementation reduced tHcy and protected both VLDL and LDL against oxidation. These findings provide further support for the use of folic acid supplements to aid in the prevention of atherosclerosis.

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