From the Guidelines
Functional medicine approaches to over-methylation should prioritize reducing methyl donors and supporting methylation balance through targeted interventions, including dietary modifications, antioxidant support, and lifestyle interventions. When considering treatment for over-methylation, it is essential to focus on balancing methylation pathways. Treatment typically begins with laboratory testing to confirm methylation status, including genetic testing for MTHFR and other methylation-related genes, homocysteine levels, and methylation metabolites.
- For confirmed over-methylation, treatment generally involves reducing methyl donors and supporting methylation balance.
- This includes limiting or avoiding supplements containing methyl donors such as SAMe, methionine, and methylated B vitamins (particularly methylfolate and methylcobalamin).
- Instead, practitioners may recommend non-methylated forms of B vitamins like niacin (B3, 50-100mg daily), pyridoxine (B6, 50-100mg daily), and hydroxocobalamin (a form of B12, 1000mcg daily) 1. Some studies have investigated the use of hypomethylating agents, such as azacitidine and decitabine, in the treatment of myelodysplastic syndromes (MDS) 1.
- However, these studies are not directly applicable to the treatment of over-methylation in the context of functional medicine.
- The goal of treatment is to restore methylation balance, as proper methylation is crucial for numerous bodily functions, including neurotransmitter synthesis, detoxification, immune function, and DNA repair.
- Treatment duration varies by individual, with regular monitoring of symptoms and laboratory markers to guide adjustments to the protocol.
- Antioxidant support with vitamin C (500-1000mg daily) and vitamin E (400IU daily) may help manage oxidative stress associated with methylation imbalances.
- Lifestyle interventions, including stress management techniques, adequate sleep, and moderate exercise, are also important components of treatment.
From the Research
Functional Medicine Diagnosis and Treatment of Over-Methylation
- Over-methylation is a condition that can be caused by various factors, including genetic disorders, environmental toxins, and nutritional deficiencies 2.
- The diagnosis of over-methylation can be challenging, as it often presents with non-specific symptoms such as fatigue, anxiety, and depression 2.
- Biochemical tests, such as plasma S-adenosylmethionine and S-adenosylhomocysteine, can be used to clarify the diagnosis of isolated hypermethioninemia, a hallmark of methylation disorders 2.
- A low-methionine diet may be beneficial in patients with methionine adenosyltransferase I/III deficiency, and S-adenosylmethionine supplementation may be useful in patients with this deficiency 2.
Nutritional Factors and Methylation
- Vitamin B12 and folate play critical roles in the methionine remethylation cycle, and deficiencies in these nutrients can disrupt methylation processes 3.
- Maternal micronutrient imbalance, including folic acid and vitamin B12 deficiency, can have adverse effects on fetal brain development and programming, and may increase the risk of neurodegenerative disorders in later life 4.
- Dietary folate and vitamin B-12 intake have been associated with genome-wide changes in DNA methylation in blood, and may have implications for cancer risk and treatment 5.
Clinical Implications of Methylation
- Methylation at DNA, RNA, and protein levels plays critical roles in many cellular processes, and is associated with diverse differentiation events, physiological activities, and human diseases, including cancer 6.
- DNA methylation is the most well-studied type of methylation, and has been largely translated into clinical use for early diagnosis and treatment of cancer 6.
- Further research is needed to translate the onco-therapeutic and prognostic values of RNA and protein methylations into clinical use, and to explore the clinical potential of simultaneous examination of methylations at multiple levels or together with other forms of molecular markers 6.