Hope for healing hearts with high-dose folic acid

Dyslipidemia and increases in plasma homocysteine usually occur at end-stage renal disease; both are recognized as risk factors for atherosclerosis. Folate administration reduces homocysteine concentration. In this study we determined the effect of a high dose of folic acid (40 mg intravenous injection three times a week) on plasma and red blood cell lipid profiles in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (baseline) and after 21, 42, and 64 days of treatment. Folic acid supplementation decreased plasma homocysteine. Plasma triglyceride levels decreased whereas polyunsaturated fatty acid values increased after 21 days; then they returned to baseline levels at the end of treatment. Total cholesterol and low-density lipoprotein (LDL) cholesterol were higher than those of the baseline during all the study, whereas high-density lipoprotein (HDL) cholesterol was reduced. In erythrocyte membranes, folic acid therapy enhanced cholesterol/phospholipid ratios and the fluorescence anisotropy of diphenyl-hexatriene. We conclude that large doses of folic acid produce a favorable effect, reducing plasma homocysteine levels and protecting patients from atherosclerosis. However, as this therapy induces significant alterations in both plasma and erythrocyte membrane lipid profiles, plasma lipid values should be controlled throughout the treatment of patients with renal failure.

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High dose folic acid supplementation in women with epilepsy: Are we sure it is safe?

Seizure ◽

10.1016/j.seizure.2015.02.030 ◽

2015 ◽

Vol 27 ◽

pp. 51-53 ◽

Cited By ~ 11

Author(s):

Ali A. Asadi-Pooya

Keyword(s):

Folic Acid ◽

Folic Acid Supplementation ◽

High Dose ◽

Acid Supplementation

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Effects of dietary supplementation of high-dose folic acid on biomarkers of methylating reaction in vitamin B12-deficient rats

Nutrition Research and Practice ◽

10.4162/nrp.2009.3.2.122 ◽

2009 ◽

Vol 3 (2) ◽

pp. 122 ◽

Cited By ~ 8

Author(s):

Hyesun Min

Keyword(s):

Folic Acid ◽

Vitamin B12 ◽

Dietary Supplementation ◽

High Dose

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Differential effects of low and high dose folic acid on endothelial dysfunction in a murine model of mild hyperhomocysteinaemia

European Journal of Pharmacology ◽

10.1016/j.ejphar.2006.08.085 ◽

2006 ◽

Vol 551 (1-3) ◽

pp. 92-97 ◽

Cited By ~ 16

Author(s):

Zoe L. Clarke ◽

Stuart J. Moat ◽

Alastair L. Miller ◽

Michael D. Randall ◽

Malcolm J. Lewis ◽

...

Keyword(s):

Folic Acid ◽

Endothelial Dysfunction ◽

Murine Model ◽

High Dose ◽

Differential Effects ◽

Mild Hyperhomocysteinaemia

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High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans

Redox Biology ◽

10.1016/j.redox.2020.101724 ◽

2020 ◽

Vol 37 ◽

pp. 101724 ◽

Cited By ~ 1

Author(s):

Kyohei Koseki ◽

Yukina Maekawa ◽

Tomohiro Bito ◽

Yukinori Yabuta ◽

Fumio Watanabe

Keyword(s):

Oxidative Stress ◽

Folic Acid ◽

Caenorhabditis Elegans ◽

Folic Acid Supplementation ◽

High Dose ◽

Acid Supplementation

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Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis

Journal of Investigative Medicine ◽

10.1136/jim-2019-001025 ◽

2019 ◽

Vol 67 (8) ◽

pp. 1110-1117 ◽

Cited By ~ 2

Author(s):

Clóvis Paniz ◽

Maylla Rodrigues Lucena ◽

Juliano Felix Bertinato ◽

Felipe Rebello Lourenço ◽

Bruna Cipriano A Barros ◽

...

Keyword(s):

Folic Acid ◽

Mrna Expression ◽

Hereditary Spherocytosis ◽

Elevated Serum ◽

Interferon Γ ◽

Serum Folate ◽

Total Serum ◽

High Dose ◽

Healthy Controls ◽

Serum Concentrations

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.

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Influence of High-Dose Folic Acid on Methotrexate Efficacies and Safety in Japanese Rheumatoid Arthritis Patients

Drug Research ◽

10.1055/s-0043-117498 ◽

2017 ◽

Vol 67 (12) ◽

pp. 705-709 ◽

Cited By ~ 1

Author(s):

Shun Kameyama ◽

Yuko Kase ◽

Saori Kurihara ◽

Fumiko Yoshida ◽

Masamitu Noda ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Folic Acid ◽

Adverse Effects ◽

Patient Characteristics ◽

High Dose ◽

Major Conclusion ◽

Dose Methotrexate ◽

Higher Doses ◽

Patient Subgroups

Abstract Backgrounds Folic acid dose at ≦5 mg/week has been recommended for rheumatoid arthritis (RA) patients to decrease risk of methotrexate adverse effects. However, higher doses of folic acid is used in some cases. We examined the influence of high-dose folic acid on methotrexate efficacies and safety in Japanese RA patients. Methods 502 RA patients of four hospitals prescribed methotrexate and folic acid were included. These patients were divided into two subgroups according to the threshold of folic acid dose by 5 mg/week. Basic patient characteristics, methotrexate doses, and the efficacies or adverse effects of methotrexate were retrospectively compared between the two patient subgroups. Results The frequency of folic acid use at doses higher than 5 mg/week was significantly different between the four hospitals (P<0.001). The prevalence of methotrexate adverse effects was not significantly different between the patients taking folic acid less and more than 5 mg/week. However, in the lower dose methotrexate subgroup (≦8 mg/week), the prevalence of patients exhibiting abnormal serum ALT concentrations in the patients using higher (>5 mg/week) dose of folic acid was significantly higher than that in the lower (≦5 mg/week) folic acid-treated subgroup (P=0.029). Folic acid dose between patients taking methotrexate less and more than 8 mg/week was not significantly different. Major conclusion Folic acid dose was dependent on the hospitals, while efficacies and hepatotoxicity of methotrexate was not basically different between patients taking less and more than 5 mg/week of folic acid.

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Laying hens can convert high doses of folic acid added to the feed into natural folates in eggs providing a novel source of food folate

British Journal Of Nutrition ◽

10.1017/s0007114508995647 ◽

2008 ◽

Vol 101 (2) ◽

pp. 206-212 ◽

Cited By ~ 18

Author(s):

Leane Hoey ◽

Helene McNulty ◽

Elizabeth M. E. McCann ◽

Kelvin J. McCracken ◽

John M. Scott ◽

...

Keyword(s):

Folic Acid ◽

Laying Hens ◽

Optimal Dose ◽

Leafy Vegetables ◽

Natural Food ◽

High Dose ◽

Green Leafy Vegetables ◽

Cost Efficient ◽

High Doses ◽

Food Folate

There are few good sources of natural food folates apart from green leafy vegetables and these may have a limited potential to increase folate status because of substantial losses that can occur during cooking. Fortified foods can overcome this but are controversial because of safety concerns regarding chronic exposure to high-dose folic acid (FA; the synthetic form). The aim of the present study was to develop eggs with an enriched natural folate content and minimal unmetabolised FA. Forty-eight, 30-week-old laying hens were randomised to receive the basal feed (formulated to provide 1 mg folate/kg feed) to which had been added one of the following FA levels (0, 2, 4, 8, 16, 32 mg/kg feed). Total folate was measured in eggs collected throughout the 12-week study period and the FA content estimated at 12 weeks. Results showed that the maximal egg folate content was achieved by adding 16 mg FA/kg feed. At this optimal dose, the total folate content per egg was 75 μg (compared with 32 μg in a regular egg) of which FA represented at most 10 %, a level which would probably be converted into natural folates by humans after ingestion. The results demonstrate that it is possible to use synthetic FA at high doses to produce novel animal foods enriched with natural folates in a cost-efficient process. Such foods may be particularly relevant to European populations without access to FA fortification and therefore dependent on natural food folate sources for the primary prevention of folate-related disease.

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