Personalised nutraceutical treatment grounded in one-carbon metabolism support was associated with clinically meaningful reductions in psychological distress in a real-world primary care cohort, with outcomes comparable across MTHFR genotypes when treatments were appropriately tailored.
Key Findings
Results
Mean K10 psychological distress scores significantly decreased by four points over approximately three months of personalised nutraceutical treatment across the full cohort.
Study included 50 adults attending an integrative general practice clinic for anxiety and/or depression.
Psychological distress was measured using the Kessler-10 (K10) scale at baseline and approximately three months later.
Mean K10 scores decreased by four points over the treatment period.
72% of patients showed clinical improvement.
The decrease was described as statistically significant.
Results
Reductions in psychological distress were observed across all MTHFR genotypes, including individuals with homozygous variant genotypes.
37 of 50 patients received MTHFR genotyping as part of their clinical assessment.
Outcomes were described as comparable across MTHFR genotypes when treatments were appropriately tailored.
This included patients with homozygous variant genotypes, who might be expected to have the greatest reduction in MTHFR enzymatic activity.
Results suggest that genotype and biomarker-informed nutraceutical strategies may mitigate potential metabolic disadvantages associated with MTHFR variants.
Results
Patients receiving methylfolate or SAMe showed improvement in psychological distress scores, though differences were not statistically significant compared to those not receiving these supplements.
Supplement-specific analyses evaluated whether L-methylfolate and SAMe were associated with greater improvement.
Both supplements are associated with support of one-carbon metabolism and methylation capacity.
Differences in improvement between supplement groups were not statistically significant.
Secondary analyses were conducted with Benjamini-Hochberg FDR-adjusted p-values and are described as hypothesis-generating.
Results
Nutraceutical treatment was associated with significant increases in serum vitamin B12 and modest reductions in homocysteine, but these biomarker shifts did not correlate strongly with K10 symptom change.
Biomarker analyses were conducted following nutraceutical treatment.
Serum vitamin B12 increases were described as significant.
Reductions in homocysteine were described as modest.
Biomarker shifts did not correlate strongly with changes in K10 scores.
The disconnect between biomarker change and symptom change was noted as a secondary finding.
Results
No serious adverse events or clinically significant abnormalities in liver or renal function were identified during the treatment period.
Safety and tolerability were evaluated as a secondary outcome.
No serious adverse events were reported across the cohort of 50 adults.
Liver function and renal function were monitored and showed no clinically significant abnormalities.
The nutraceutical regimens included B-vitamins, folate, and adjunctive metabolic interventions.
Methods
The study was a retrospective cohort design of 50 adults receiving personalised nutraceutical treatment informed by clinical assessment, laboratory testing, and MTHFR genotyping alongside usual care.
Design was retrospective cohort, conducted at an integrative general practice clinic.
All 50 participants received personalised nutraceutical treatment; 37/50 received MTHFR genotyping.
Treatments targeted one-carbon metabolism through B-vitamins, folate, and adjunctive metabolic interventions.
Nutraceutical treatment was applied alongside usual care, not as a replacement.
Secondary analyses used Benjamini-Hochberg FDR-adjusted p-values and are described as hypothesis-generating.
What This Means
This research suggests that a personalised supplement-based approach targeting a specific metabolic pathway (called one-carbon metabolism) may help reduce symptoms of anxiety and depression in adults seen in a general practice setting. In a group of 50 patients, psychological distress scores dropped meaningfully over about three months, and nearly three-quarters of patients showed clinical improvement. The supplements used included forms of folate (such as L-methylfolate), B-vitamins, and SAMe — nutrients that support the body's methylation processes, which are involved in producing brain chemicals related to mood.
A notable aspect of this study was that it incorporated genetic testing for a common gene variant (MTHFR) that can reduce the body's ability to process folate. The researchers found that patients with this variant — including those with the most impactful version of it — improved similarly to those without the variant, suggesting that tailoring supplements to an individual's genetic profile may help overcome biological disadvantages. Blood tests showed that vitamin B12 levels increased and homocysteine (a marker linked to methylation problems) decreased modestly, though these changes did not directly predict who improved the most symptom-wise.
This research suggests that precision nutraceutical approaches — personalising supplement regimens based on genetics and lab tests — may be a safe and potentially useful addition to standard care for people with anxiety and depression. However, because this was a small, retrospective, uncontrolled study conducted in a real-world clinic, the findings cannot prove that the supplements caused the improvements. The authors call for larger controlled trials to confirm these results, and note that several of their secondary analyses (such as comparisons by genotype or specific supplement) should be considered exploratory rather than definitive.
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Beer C, Rae F, Watt M, Trzaskowski M, Yates C, Semmler A, et al.. (2026). Personalised Nutraceutical Treatment Guided by MTHFR Genotype in Mental Health: A Retrospective Cohort Study.. Nutrients. https://doi.org/10.3390/nu18172791