scholarly journals Flaxseed Increases Animal Lifespan and Reduces Ovarian Cancer Severity by Toxically Augmenting One-Carbon Metabolism

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5674
Author(s):  
William C. Weston ◽  
Karen H. Hales ◽  
Dale B. Hales
Keyword(s):  
Liver Function ◽  
Carbon Metabolism ◽  
Vitamin B6 ◽  
Ovarian Tumor ◽  
Tumor Metastasis ◽  
Plasma Homocysteine ◽  
Elevated Plasma ◽  
Polyamine Biosynthesis ◽  
Reduced Body ◽  
One Carbon Metabolism

We used an LC-MS/MS metabolomics approach to investigate one-carbon metabolism in the plasma of flaxseed-fed White Leghorn laying hens (aged 3.5 years). In our study, dietary flaxseed (via the activity of a vitamin B6 antagonist known as “1-amino d-proline”) induced at least 15-fold elevated plasma cystathionine. Surprisingly, plasma homocysteine (Hcy) was stable in flaxseed-fed hens despite such highly elevated cystathionine. To explain stable Hcy, our data suggest accelerated Hcy remethylation via BHMT and MS-B12. Also supporting accelerated Hcy remethylation, we observed elevated S-adenosylmethionine (SAM), an elevated SAM:SAH ratio, and elevated methylthioadenosine (MTA), in flaxseed-fed hens. These results suggest that flaxseed increases SAM biosynthesis and possibly increases polyamine biosynthesis. The following endpoint phenotypes were observed in hens consuming flaxseed: decreased physiological aging, increased empirical lifespan, 9–14% reduced body mass, and improved liver function. Overall, we suggest that flaxseed can protect women from ovarian tumor metastasis by decreasing omental adiposity. We also propose that flaxseed protects cancer patients from cancer-associated cachexia by enhancing liver function.

Genetic Variation: Impact on Folate (and Choline) Bioefficacy

2010 ◽  
Vol 80 (45) ◽  
pp. 319-329 ◽  
Author(s):  
Allyson A. West ◽  
Marie A. Caudill
Keyword(s):  
Carbon Metabolism ◽  
Genetic Variants ◽  
Plasma Homocysteine ◽  
Water Soluble ◽  
Gene Interactions ◽  
Dietary Folate ◽  
Methyl Donors ◽  
Common Genetic Variants ◽  
One Carbon Metabolism ◽  
The Impact

Folate and choline are water-soluble micronutrients that serve as methyl donors in the conversion of homocysteine to methionine. Inadequacy of these nutrients can disturb one-carbon metabolism as evidenced by alterations in circulating folate and/or plasma homocysteine. Among common genetic variants that reside in genes regulating folate absorptive and metabolic processes, homozygosity for the MTHFR 677C > T variant has consistently been shown to have robust effects on status markers. This paper will review the impact of genetic variants in folate-metabolizing genes on folate and choline bioefficacy. Nutrient-gene and gene-gene interactions will be considered along with the need to account for these genetic variants when updating dietary folate and choline recommendations.

B-Vitamine und Lungenkrebsrisiko

2017 ◽  
Vol 49 (04) ◽  
pp. 195-197
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Clin Oncol ◽  
Carbon Metabolism ◽  
Vitamin B6 ◽  
Lung Cancer Risk ◽  
Vitamin B ◽  
One Carbon Metabolism

Brasky TM, White E, Cheng C-L. Long-term, supplemental, one-carbon metabolism-related vitamin B use in relation to lung cancer risk in the Vitamins and Lifestyle (VITAL) Cohort. J Clin Oncol 2017; 35: 3440–3448 Die jahrelange Einnahme von hoch dosierten Vitamin-B6- oder -B12-Einzelpräparaten ging in einer prospektiven Kohortenstudie bei älteren Männern mit einem stark erhöhten Lungenkrebsrisiko (2- bis 4-fach) einher.

Nutrition Throughout Life: Folate

2012 ◽  
Vol 82 (5) ◽  
pp. 348-354 ◽  
Author(s):  
Helene McNulty ◽  
Kristina Pentieva ◽  
Leane Hoey ◽  
JJ Strain ◽  
Mary Ward
Keyword(s):  
Scientific Evidence ◽  
Plasma Homocysteine ◽  
Health Issues ◽  
Elevated Plasma ◽  
Cvd Risk ◽  
Gene Encoding ◽  
Folate Status ◽  
Increased Risk ◽  
One Carbon Metabolism ◽  
Meta Analyses

Scientific evidence supports a number of roles for folate in maintaining health from early life to old age. Folate is required for one-carbon metabolism, including the remethylation of homocysteine to methionine; thus elevated plasma homocysteine reflects functional folate deficiency. Optimal folate status has an established role in preventing NTD and there is strong evidence indicating that it also has a role in the primary prevention of stroke. The most important genetic determinant of homocysteine in the general population is the common 677C → T variant in the gene encoding the folate-metabolising enzyme, MTHFR; homozygous individuals (TT genotype) have reduced enzyme activity and elevated plasma homocysteine concentrations. Meta-analyses indicate that the TT genotype carries a 14 to 21 % increased risk of CVD, but there is considerable geographic variation in the extent of excess CVD risk. A novel interaction between this folate polymorphism and riboflavin (a co-factor for MTHFR) has recently been identified. Intervention with supplemental riboflavin targeted specifically at individuals with the MTHFR 677TT genotype was shown to result in significant lowering of blood pressure in hypertensive people and in patients with CVD. This review considers the established and emerging roles for folate throughout the lifecycle, and some public health issues related to optimising folate status.

scholarly journals Effects of vitamin B6 on one‐carbon metabolism in oral contraceptive users

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Luisa Rios‐Avila ◽  
Maria Ralat ◽  
Bonnie Coats ◽  
Peter W. Stacpoole ◽  
Jesse F. Gregory
Keyword(s):  
Oral Contraceptive ◽  
Carbon Metabolism ◽  
Vitamin B6 ◽  
One Carbon Metabolism

The Vitamins Involved in One-Carbon Metabolisms are Associated with Reduced Risk of Breast Cancer in Overall and Subtypes

2020 ◽  
Vol 90 (1-2) ◽  
pp. 131-140 ◽  
Author(s):  
Mahshid Hatami ◽  
Farhad Vahid ◽  
Mohammad Esmaeil Akbari ◽  
Mahya Sadeghi ◽  
Fatemeh Ameri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin B12 ◽  
Carbon Metabolism ◽  
Vitamin B6 ◽  
Regulation Of Gene Expression ◽  
Folate Intake ◽  
Her2 Status ◽  
Total Intake ◽  
One Carbon Metabolism ◽  
The Relationship

Abstract. Background: Some micronutrients like folate, vitamin B12, B6, and B2 are the source of coenzymes, which participate in one-carbon metabolism. Any disruption in this metabolism can interfere with DNA replication, repair and regulation of gene expression and ultimately promote the likelihood of carcinogenesis. This study aimed at investigating the relationship between the intakes of micronutrients involved in one-carbon metabolism with breast cancer (BrCa) and its subtype’s odds. Methods: Nutrients’ intake from diet and supplements were collected through interviewing 151 cases and 154 controls by a 168-item semiquantitative food frequency questionnaire. Logistic regression was used to determine the relationship between dietary and/or total intake of studied nutrients and odds of BrCa and its subtypes. Results: After adjusting the effects of confounding variables in the models, the odds of BrCa was significantly lower in the highest intake quartile compared with the lowest quartile for total intake of vitamin B2 (OR = 0.17, 95% CI, 0.07–0.39; Ptrend < 0.001), vitamin B6 (OR = 0.11, 95% CI, 0.05–0.27; Ptrend < 0.001), vitamin B12 (OR = 0.20, 95% CI, 0.09–0.43; Ptrend < 0.001) and folate (OR = 0.09, 95% CI, 0.04–0.21; Ptrend < 0.001). Also, those with the highest quartile of vitamin B6, B12, B2 and folate intake compared with the lowest quartile were less likely to develop estrogen receptor (ER)+ and progesterone receptor (PR)+ subtypes, ER- status, PR- and human epidermal growth factor receptor 2 (HER2)+ subtypes and HER2- status. Conclusion: High intakes of vitamins B2, B6 and folate are associated with reduced odds of BrCa in overall and all ER, PR and HER2 subtypes. Also, high intakes of vitamin B12 reduced the odds of all subtypes of BrCa except ER- subtype.

scholarly journals B vitamin blood concentrations and one-carbon metabolism polymorphisms in a sample of Italian women and men attending a unit of transfusion medicine: a cross-sectional study

2020 ◽  
Author(s):  
Renata Bortolus ◽  
Francesca Filippini ◽  
Silvia Udali ◽  
Marianna Rinaldi ◽  
Sabrina Genesini ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Carbon Metabolism ◽  
Vitamin B6 ◽  
Blood Donors ◽  
Cross Sectional Study ◽  
Transfusion Medicine ◽  
Sectional Study ◽  
Cross Sectional ◽  
Plasma Folate ◽  
One Carbon Metabolism

Abstract Purpose To define blood status of folate, vitamin B12, vitamin B6, homocysteine, and major one-carbon metabolism-related polymorphisms in healthy, males and females blood donors, aged 18–65 years were evaluated. General characteristics and lifestyle factors were also investigated. Methods An explorative cross-sectional study design was used to evaluate a sample of blood donors attending the Unit of Transfusion Medicine of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women of whom 155 of childbearing age). Major clinical characteristics including lifestyle and dietary habits, B vitamins and homocysteine were analyzed. The MTHFR 677 C>T, cSHMT 1420 C>T, DHFR 19 bp ins/del, RFC1 80 G>A polymorphisms were also determined. Results Mean plasma concentrations of folate, vitamin B12, vitamin B6 and homocysteine were 14.2 nmol/L (95% CI 13.7–14.8), 271.9 pmol/L (95% CI 262.6–281.5), 51.0 nmol/L (95% CI 48.7–53.4) and 13.5 µmol/L (95% CI 13.1–14.0), respectively. Plasma folate, was adequate (> 15 nmol/L) in 44.7% of all subjects, 39.0% of males and 42.5% of women < 45 years. Similarly, vitamin B12 was adequate (> 350 pmol/L) in 25.1% of all subjects and in 20.3% of men ≥ 45 years. The rare allele frequencies were 0.21 for MTHFR 677TT, 0.11 for cSHMT 1420TT, 0.18 for DHFR 19 bp del/del, 0.20 for RFC1 80AA, and a gene–nutrient interaction was confirmed for folate concentrations according to MTHFR 677C>T and DHFR 19 bp del/del. Conclusion An Italian sample of healthy blood donors shows that an adequate concentration of plasma folate and vitamin B12 is reached only in a limited percentage of subjects, thus encouraging consideration for specific public health strategies.

57 The Saga of Just One QTL; From Laying Hen Bone Strength to One Carbon Metabolism

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 32-32
Author(s):  
Ian C Dunn ◽  
Heather McCormack ◽  
Dirk-Jan de Koning ◽  
Alejandro Rodríguez Navarro ◽  
Matthias Schmutz ◽  
...  
Keyword(s):  
Bone Strength ◽  
Bone Quality ◽  
Carbon Metabolism ◽  
Complex Traits ◽  
Laying Hens ◽  
Differentially Expressed Gene ◽  
Plasma Homocysteine ◽  
Egg Laying ◽  
Chromosome 1 ◽  
One Carbon Metabolism

Abstract Skeletal damage is a challenge for laying hens, as the adaptations for egg laying make them susceptible to osteoporosis. We know that activity, growth and puberty influence skeletal quality genetics. However, in this story, we follow the process of resolving a QTL for skeletal quality to a single gene. Providing both a nutritional and a genetic solution and illustrating another level of complexity. Using divergently selected populations in an F2 cross, a QTL for skeletal quality was described. Utilising a series of experiments in the commercial founder line the QTL was fine mapped on chromosome 1 and the differences in physiology of hens that segregated for markers at the locus defined e.g. tibia breaking strength 200.4 vs 218.1 Newton (p&lt; 0.002). Transcriptome profiling of tibia from the high and low bone strength genotype revealed a highly differentially expressed gene co localising to the QTL, the enzyme cystathionine beta synthase (CBS). CBS is a component of one carbon metabolism. Plasma homocysteine, the substrate of CBS had a higher concentration in the genotype associated with poor bone quality. Homocysteine interferes with crosslinking of the collagen matrix, critical to bone formation. Homocysteine can be re-methylated into methionine, a limiting amino acid in laying hens, using betaine as a methyl donor. Testing the hypothesis that reducing plasma homocysteine by feeding betaine, a widely available feed additive, would improve bone quality in laying hens proved successful.This is just one component of a complex trait and its elucidation took us along unexpected routes. However, I am optimistic that with modern tools and an open mind we can progress more quickly. Alongside understanding the factors that determine skeletal quality genetics, the discovery of the mechanisms behind complex traits, although rarely easy, offer the potential for novel interventions to improve animal health and production.

scholarly journals Formate can differentiate between hyperhomocysteinemia due to impaired remethylation and impaired transsulfuration

2012 ◽  
Vol 302 (1) ◽  
pp. E61-E67 ◽  
Author(s):  
Simon G. Lamarre ◽  
Anne M. Molloy ◽  
Stacey N. Reinke ◽  
Brian D. Sykes ◽  
Margaret E. Brosnan ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Folate Metabolism ◽  
Methionine Synthase ◽  
Vitamin B ◽  
Metabolomic Analysis ◽  
Elevated Plasma ◽  
H Nmr ◽  
Transsulfuration Pathway ◽  
One Carbon Metabolism ◽  
The One

Formate can differentiate between hyperhomocysteinemia due to impaired remethylation and impaired transsulfuration. Am J Physiol Endocrinol Metab 301: E000–E000, 2011. First published September 20, 2011; 10.1152/ajpendo.00345.2011.—We carried out a1H-NMR metabolomic analysis of sera from vitamin B12-deficient rats. In addition to the expected increases in methylmalonate and homocysteine (Hcy), we observed an approximately sevenfold increase in formate levels, from 64 μM in control rats to 402 μM in vitamin B12-deficient rats. Urinary formate was also elevated. This elevation of formate could be attributed to impaired one-carbon metabolism since formate is assimilated into the one-carbon pool by incorporation into 10-formyl-THF via the enzyme 10-formyl-THF synthase. Both plasma and urinary formate were also increased in folate-deficient rats. Hcy was elevated in both the vitamin B12- and folate-deficient rats. Although plasma Hcy was also elevated, plasma formate was unaffected in vitamin B6-deficient rats (impaired transsulfuration pathway). These results were in accord with a mathematical model of folate metabolism, which predicted that reduction in methionine synthase activity would cause increased formate levels, whereas reduced cystathionine β-synthase activity would not. Our data indicate that formate provides a novel window into cellular folate metabolism, that elevated formate can be a useful indicator of deranged one-carbon metabolism and can be used to discriminate between the hyperhomocysteinemia caused by defects in the remethylation and transsulfuration pathways.

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