Dietary nutrients in one-carbon metabolism linked to colorectal cancer risk
image: Key steps of 1C metabolism DHFR: dihydrofolate reductase; FH2: dihydrofolic acid; FH4: tetrahydrofolic acid; MTHFD: methylenetetrahydrofolate dehydrogenase; SHMT: hydroxymethyltransferase; MTHFR: methylenetetrahydrofolate reductase; NADPH: nicotinamide adenine dinucleotide phosphate; 5-mTHF: 5-methyltetrahydrofolat; MTR: N5-methyltetrahydrofolate-homocysteine methyltransferase (methionine synthase); AHCY: adenosylhomocysteinase; BHMT: betaine-homocysteine methyltransferase; Hcy: homocysteine; SAM: S-adenosyl methionine; SAH: S-adenosylhomocysteine; DMG: dimethylglycine; CSE: cystathionine γ-lyase; CBS: cystathionine β-synthase; TCA: tricarboxylic acid cycle.
Credit: Lin Deng, Yu-chan Huang-fu, Yan-hui Ma.
This review article explores the role of dietary nutrients involved in one-carbon (1C) metabolism—such as folate, B vitamins (B6, B12), methionine, and serine—in modulating colorectal cancer (CRC) risk. Key findings include:
1C Metabolism Pathways: Folate and methionine cycles are central to nucleotide synthesis, DNA methylation, and redox homeostasis, all critical for CRC development.
Nutrient Impact:
- Folate shows a dual role: protective at moderate levels but potentially promoting CRC in pre-existing lesions.
- Vitamin B6 and B12 are cofactors in 1C metabolism, with observational studies suggesting protective effects, though clinical trials remain inconclusive.
- Methionine and serine influence methylation and immune responses, with dietary restrictions showing antitumor potential in preclinical models.
Mechanisms: Dysregulation of 1C metabolism disrupts DNA synthesis/methylation, increases oxidative stress, and alters gut microbiota, contributing to CRC.
Clinical Implications: Targeting 1C metabolism (e.g., folate inhibitors, serine deprivation) offers therapeutic potential, but precision nutrition is needed due to individual variability.
The study highlights the need for further research to clarify nutrient-CRC relationships and optimize dietary or therapeutic interventions.