MTHFR Testing in Adelaide: Optimizing Methylation and Folate Metabolism

Author: Rohan Smith | Functional Medicine Practitioner | Adelaide, SA

In the world of functional medicine, the MTHFR gene plays a key regulatory role in folate metabolism and methylation. For patients in Adelaide, understanding this genetic blueprint can be an important step in addressing issues such as chronic fatigue, mood disorders, and hormonal imbalance. At Elemental Health and Nutrition, we don’t simply identify genetic variants—we assess how those genes are expressed in real-world physiology.

Quick Answer: What Is MTHFR Testing?

MTHFR testing identifies variations in the Methylenetetrahydrofolate Reductase gene, which encodes an enzyme responsible for converting folic acid into 5-methyltetrahydrofolate (5-MTHF or L-methylfolate)—the biologically active form of folate (1,2). Up to 50% of the population carries at least one variant, which may reduce enzyme efficiency by approximately 30–70% (3,15).

This reduction can affect the methylation cycle, a biochemical pathway involved in DNA repair, neurotransmitter synthesis, and detoxification processes (4,10).

The Science of the Methylation Cycle

Methylation refers to the transfer of a methyl group to another molecule—a process occurring billions of times per second throughout the body. When MTHFR enzyme activity is reduced, folate-dependent steps within this cycle may become less efficient.

Clinically, two commonly observed effects include:

• Elevated homocysteine: When homocysteine is not efficiently recycled to methionine, levels may rise and are associated with increased cardiovascular risk (5,6).
• Reduced neurotransmitter synthesis: Active folate acts as a key co-factor in the production of serotonin, dopamine, and adrenaline, which may explain associations between MTHFR variants and mood disorders in some individuals (7,12).

Understanding Your Results: C677T vs A1298C

Not all MTHFR variants have identical clinical implications. In practice, the two most commonly assessed single nucleotide polymorphisms (SNPs) are:

• C677T: More commonly associated with reduced enzyme activity and elevated homocysteine, with implications for cardiovascular and neurological health (1,8).
• A1298C: More often linked to altered neurotransmitter balance, chronic pain patterns, and ammonia clearance within the central nervous system (9,13).

Individuals who are homozygous (two copies) for a variant typically show greater reductions in enzyme activity than those who are heterozygous (one copy) (2,11).

The Functional Medicine Perspective: Beyond the SNP

A common limitation of genetic testing is focusing on the variant alone rather than its functional impact. Not everyone with an MTHFR variant requires methylated nutrients, and excessive methyl donor intake may provoke symptoms such as agitation or anxiety in susceptible individuals (4,14).

As part of a functional medicine assessment in Adelaide, MTHFR genetics are interpreted alongside:

• Homocysteine and vitamin B12 status to determine whether a metabolic bottleneck is present.
• Organic acids testing, such as the Mosaic Diagnostics Organic Acids Test, which evaluates metabolic intermediates related to neurotransmitter and mitochondrial pathways.
• Environmental exposure, including intake of synthetic folic acid from fortified foods, which may be less efficiently processed in individuals with reduced MTHFR activity (3,15).

Frequently Asked Questions

Should I avoid folic acid if I have an MTHFR variant?

Many individuals with MTHFR variants have difficulty converting synthetic folic acid into active folate. Dietary folate from leafy greens or practitioner-guided use of L-methylfolate may be better tolerated (3,10).

How does MTHFR relate to fatigue?

Methylation supports the production of compounds involved in mitochondrial energy generation, including CoQ10 and carnitine. Reduced efficiency in this cycle may contribute to symptoms seen in chronic fatigue presentations (4,13).

Can MTHFR be fixed?

Genetic variants cannot be changed, but gene expression can be influenced. Precision nutrient therapy may help support methylation pathways by supplying appropriate cofactors such as riboflavin (B2), pyridoxine (B6), cobalamin (B12), and folate in forms appropriate to individual needs (8,14).

Key Insights

• MTHFR is involved in the conversion of folate into its active form (1,2).
• Variants may be associated with elevated homocysteine and altered neurotransmitter synthesis (5,7).
• Careful interpretation by a practitioner experienced in methylation and fatigue-related conditions is important to avoid adverse effects from inappropriate supplementation.
• Targeted methylation support may form part of a broader strategy to address brain fog and systemic inflammation (12,15).

Optimize Your Biochemistry

Genetic testing can provide valuable insight into individual biochemistry when interpreted correctly. If you would like guidance on MTHFR testing and personalised methylation support, consultations are available at Elemental Health and Nutrition in Adelaide.

References

1. Frosst P, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995.
2. Tsang BL, et al. Association between MTHFR gene polymorphisms and neurological outcomes. Mol Neurobiol. 2015.
3. Obeid R, et al. 5-Methyltetrahydrofolate vs folic acid. J Perinat Med. 2013.
4. Bailey SW, Ayling JE. Folate metabolism and methylation biochemistry. Proc Natl Acad Sci USA. 2009.
5. Rozen R. Genetic predisposition to hyperhomocysteinemia. Thromb Haemost. 1997.
6. Wald DS, et al. Homocysteine and cardiovascular disease. BMJ. 2002.
7. Bottiglieri T. Folate, homocysteine, and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005.
8. McNulty H, et al. Riboflavin lowers blood pressure in MTHFR 677TT genotype. Circulation. 2006.
9. Weisberg I, et al. A second MTHFR polymorphism. Mol Genet Metab. 1998.
10. Smith AD, et al. Homocysteine lowering and brain atrophy. PLoS One. 2010.
11. Nelen WL, et al. Genetic risk factors for pregnancy loss. Lancet. 1998.
12. Wan L, et al. MTHFR polymorphisms and psychiatric disorders. Front Genet. 2018.
13. Groff JL, Gropper SS. Advanced Nutrition and Human Metabolism. Wadsworth. 2000.
14. Stahl SM. L-methylfolate in depressive disorders. J Clin Psychiatry. 2008.
15. McCaddon A, et al. Folate metabolism and neurological function. Clin Chem Lab Med. 2011.