Glándulas (ganglios linfáticos inflamados)

Beetroot-derived betaine supports whole-body methylation by donating methyl groups to homocysteine (producing methionine) and indirectly raising S-adenosylmethionine (SAMe) levels. This supports DNA methylation, neurotransmitter synthesis, and hepatic methylation reactions.

Betaine is a direct methyl donor that remethylates homocysteine to methionine via betaine-homocysteine methyltransferase (BHMT), independently of folate and B12. This BHMT pathway is a critical alternative methylation route. Clinical trials confirm betaine supplementation reliably lowers plasma homocysteine, and it is classified as a canonical methyl nutrient in peer-reviewed literature.

Bovine liver is the single most concentrated food source of the three principal dietary methyl-donor nutrients: folate (natural food-form 5-MTHF), B12 (as methylcobalamin), and choline (convertible to betaine). These collectively drive the one-carbon/methylation cycle, which regulates DNA methylation, homocysteine metabolism, and neurotransmitter synthesis.

Brussels sprouts are a good dietary source of folate, the primary one-carbon donor in the methylation cycle. Dietary folate supports the methionine cycle by donating a methyl group to convert homocysteine to methionine, thereby sustaining S-adenosylmethionine (SAM) — the universal methyl donor for DNA, RNA, protein, and lipid methylation.

Choline is the metabolic precursor to betaine (trimethylglycine). Through choline dehydrogenase oxidation, it is converted to betaine, which donates methyl groups to homocysteine via BHMT, supporting SAMe regeneration. Choline deficiency reduces hepatic SAMe and impairs methylation. It is classified as a canonical methyl nutrient in multiple PubMed reviews.

Curcumin, the major polyphenol of turmeric, inhibits DNA methyltransferases (DNMTs) and modulates histone-modifying enzymes, altering promoter methylation patterns. A 2025 PMC systematic review (PMC12554032) identifies curcumin among the most frequently studied food-derived DNMT modulators. Evidence is primarily preclinical (in vitro and animal models).

Dimethylglycine (DMG) is the immediate metabolic product of betaine after methyl donation via BHMT, and it continues to provide methyl groups to the folate cycle via dimethylglycine dehydrogenase. Supplementation with DMG provides methyl donors to the one-carbon cycle and has been used clinically since the 1970s. It is tracked as a biomarker of BHMT methylation pathway activity.

EGCG, the major catechin of green tea, competitively inhibits DNMT1 and DNMT3 (DNA methyltransferases), reactivating epigenetically silenced genes. A 2025 PMC systematic review (PMC12554032) of 76 studies identifies EGCG as the most frequently studied food-derived DNMT modulator. Evidence is primarily from in vitro and animal studies.

FMN and FAD are obligate cofactors for MTHFR, the enzyme central to the one-carbon/methylation cycle that generates 5-methylTHF for homocysteine remethylation and downstream methylation reactions. Riboflavin supplementation stabilizes MTHFR activity specifically in 677TT carriers, supporting methylation flux. This is a well-characterized biochemical and clinical relationship.

Folic acid is the synthetic oxidized form of folate used in supplements and food fortification. It requires enzymatic conversion to active 5-MTHF to participate in the methylation cycle. Widely shown to lower homocysteine and support methylation pathway function across numerous RCTs; standard form in public health folate programs worldwide.

Folinic acid feeds directly into the folate/one-carbon cycle, supplying the methyl groups carried by 5-MTHF needed to remethylate homocysteine and regenerate SAM (S-adenosylmethionine)—the universal methyl donor for DNA, RNA, protein, lipid, and neurotransmitter methylation. Because it bypasses DHFR, it is particularly useful for supporting methylation in individuals with MTHFR polymorphisms or antifolate drug exposure.

Genistein, the principal soy isoflavone, inhibits DNMT activity in a dose-dependent manner and induces gene-specific methylation changes. A 2025 PMC systematic review (PMC12554032) ranks genistein among the most studied food-derived DNMT modulators. Evidence includes preclinical models and some human observational data; dietary intake levels may be insufficient for DNMT effects.

L-methionine is the essential amino acid and direct precursor to SAMe. Dietary methionine availability directly determines SAMe synthesis capacity and thus the overall cellular methylation rate. Multiple PMC-indexed studies confirm that methionine dietary levels alter hepatic SAMe/SAH ratios, histone methylation marks, and global DNA methylation patterns.

L-serine is the principal endogenous donor of one-carbon units to the folate cycle via the serine hydroxymethyltransferase reaction, generating the methyl groups ultimately used for DNA, RNA, and protein methylation through the S-adenosylmethionine pathway. Human tracer studies confirm serine contributes approximately 100% of folate-dependent one-carbon units for homocysteine remethylation.

Liver fractions are among the most concentrated dietary sources of vitamin B12 and folate — the two nutrients most critical to the methylation cycle. B12 (as methylcobalamin) donates methyl groups to convert homocysteine to methionine, and folate regenerates the methyl donor 5-MTHF. The methylation-support claim is scientifically grounded in well-established B12/folate biochemistry.

Magnesium is a required cofactor for methionine adenosyltransferase (MAT), the ATP-dependent enzyme that converts methionine to SAMe. Multiple methylation-cycle references confirm Mg2+ is essential for SAMe synthesis and for other methylation-pathway enzymes. It is listed as a key methylation support mineral in multiple authoritative methylation references.

Methylcobalamin is the active coenzyme form of vitamin B12 that directly participates in the remethylation of homocysteine to methionine via methionine synthase (MTR). It is a key cofactor in the methionine cycle and supplies methyl groups for SAMe regeneration. Clinical RCTs confirm it lowers elevated homocysteine, the primary biomarker of impaired methylation.

P-5-P is the active coenzyme form of vitamin B6 that directly serves as cofactor for cystathionine β-synthase in the transsulfuration pathway, clearing homocysteine from the methylation cycle. A 2024 RCT confirmed significant homocysteine reduction when P-5-P was combined with methylfolate and methylcobalamin. It is also used in prescription medical foods for methylation-related endothelial dysfunction.

PC is synthesized de novo in the liver via the PEMT pathway, which requires three sequential methyl group transfers from S-adenosylmethionine. Conversely, choline from PC catabolism provides betaine, a methyl donor for homocysteine remethylation. PC thus sits at a critical intersection of the one-carbon metabolic network.

Resveratrol, a polyphenol from grape skins, modulates DNA methylation by inhibiting DNMT activity and modulating TET enzymes, decreasing promoter methylation of specific genes. A 2025 PMC systematic review (PMC12554032) and PMC12841049 identify resveratrol among the food-derived bioactives with demonstrated effects on DNA methylation via DNMT inhibition. Evidence is primarily preclinical.

SAMe is the body's universal methyl donor, directly fueling hundreds of methylation reactions involving DNA, RNA, proteins, and phospholipids. It is synthesized from methionine and ATP and is a prescription drug in several European countries. Multiple PubMed-indexed reviews confirm its central mechanistic role in transmethylation. Its depletion in chronic liver disease correlates with impaired methylation.

Spinach is a primary dietary source of folate, the key methyl donor in one-carbon metabolism. Folate drives the methylation of homocysteine to methionine, generating S-adenosyl-methionine (SAM), the universal methyl donor for DNA, RNA, protein, and lipid methylation reactions throughout the body.

Sulforaphane, derived from glucoraphanin in cruciferous vegetables, modulates DNA methylation by downregulating DNMT1/3A/3B expression and inhibiting HDAC activity, contributing to epigenetic reactivation of silenced genes. Multiple PMC reviews (PMC12554032, PMC10375321, PMC12841049) consistently identify sulforaphane as a documented dietary DNMT modulator with chemopreventive epigenetic effects.

Trimethylglycine (TMG) is chemically identical to betaine and supports methylation as a direct methyl donor via BHMT, converting homocysteine to methionine independently of folate and B12. It is widely used in methylation support formulations and increasingly as a companion to NMN supplements to offset increased methylation demand from NAD+ catabolism.

Vitamin B12 (cobalamin) is essential as cofactor for methionine synthase, which remethylates homocysteine to methionine using 5-MTHF, directly sustaining the SAMe/methylation cycle. B12 deficiency stalls this reaction, trapping folate in the methyl-folate trap and elevating homocysteine. It is among the most robustly evidenced methylation-support nutrients.

Riboflavin (vitamin B2) is the obligate coenzyme (as FAD) for MTHFR, the enzyme converting 5,10-methyleneTHF to 5-MTHF. NCBI Bookshelf (NBK6145) documents that riboflavin deficiency impairs MTHFR activity, reduces 5-MTHF levels, and elevates homocysteine, especially in MTHFR 677TT genotype individuals where plasma homocysteine is inversely related to riboflavin status.

Vitamin B6, as pyridoxal-5-phosphate (PLP), supports methylation by enabling the transsulfuration pathway—the CBS-catalyzed conversion of homocysteine to cystathionine and glutathione. This clears homocysteine from the methylation cycle and supports methionine production for SAMe synthesis. Multiple PubMed reviews classify it as a canonical methyl nutrient.

Folate (vitamin B9) facilitates transport of methyl groups in the one-carbon pathway for DNA methylation and homocysteine remethylation. Deficiency produces global hypomethylation and impaired SAMe synthesis. It is among the most extensively studied methylation-supporting nutrients, with strong mechanistic, epidemiological, and clinical evidence.

5-Methyltetrahydrofolate (5-MTHF) is the bioactive folate form that donates its methyl group to homocysteine (via methionine synthase/B12) to regenerate methionine and sustain SAMe production. Particularly important for individuals with MTHFR gene variants, clinical RCTs demonstrate significant homocysteine reduction with 5-MTHF supplementation.

Zinc is a structural cofactor for DNA methyltransferases (DNMTs), enzymes that execute cytosine methylation. It is also required for BHMT (betaine-homocysteine methyltransferase) function in the BHMT methylation pathway. A 2022 PMC systematic review (PMC9530842) reviews multiple studies confirming the association between zinc levels and DNA methylation status.