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Tryptophan and Brain Disorders / Nutrition, Genetics, and Disease · Journal article
Nutrients · August 26, 2026
Early or partial results. Treat as a signal, not a conclusion.
This retrospective single-site cohort of 50 adults found that personalised nutraceutical treatment informed by MTHFR genotyping and clinical assessment was associated with a mean 4-point K10 score reduction and 72% clinical improvement rate over three months, with no serious adverse events. The absence of a control group, concurrent usual care, and single-centre design mean this observational finding cannot establish causal efficacy and should be viewed as hypothesis-generating evidence supporting the need for controlled trials.
Retrospective cohort study. 50 adults presenting to an integrative general practice clinic with anxiety and/or depression.. Intervention: Personalised nutraceutical treatment informed by clinical assessment, laboratory testing, and MTHFR genotyping, including B-vitamins, folate, methylfolate, SAMe, and adjunctive metabolic interventions tailored to one-carbon metabolism supp…. n = 50. Single integrative general practice clinic; specific location not stated..
Mean K10 scores decreased by 4 points over approximately three months across the full cohort 72% of patients showed clinical improvement in psychological distress Reductions in psychological distress were seen across all MTHFR genotypes, including homozygous variant carriers
No serious adverse events or clinically significant abnormalities in liver or renal function were identified
The findings suggest personalised nutraceutical treatment may be safe and potentially beneficial for anxiety and depression in primary care settings. However, the lack of a control arm means clinicians cannot yet distinguish the effect of genotype-guided nutraceuticals from concurrent usual care, placebo, or natural recovery; controlled trials are necessary before changing practice.
Retrospective cohort study without control group in a single integrative practice clinic; shows feasibility and safety but lacks comparison arm and rigorous design needed to establish efficacy of genotype-guided nutraceutical treatment.
As stated by the source record.
Quoted from the source exactly as published.
The findings suggest personalised nutraceutical treatment may be safe and potentially beneficial for anxiety and depression in primary care settings. However, the lack of a control arm means clinicians cannot yet distinguish the effect of genotype-guided nutraceuticals from concurrent usual care, placebo, or natural recovery; controlled trials are necessary before changing practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background & Aims: One-carbon metabolism plays a central role in neurotransmitter synthesis, methylation capacity, and neurobiological resilience. Variants in the methylenetetrahydrofolate reductase (MTHFR) gene can reduce enzymatic activity, affecting folate- and methionine-cycle functions and potentially influencing biological pathways relevant to mood and anxiety disorders. Personalised nutraceutical treatment strategies, particularly those addressing methylation capacity through targeted B-vitamin, folate, and adjunctive metabolic interventions are increasingly implemented in integrative clinical practice, yet evidence regarding their clinical outcomes remains limited. Methods: We conducted a retrospective cohort study of 50 adults attending an integrative general practice clinic for anxiety and/or depression. All received personalised nutraceutical treatment informed by clinical assessment, laboratory testing and, for 37/50 patients, MTHFR genotyping. Psychological distress was measured using the Kessler-10 (K10) scale at baseline and approximately three months later. Secondary analyses evaluated whether outcomes differed by MTHFR genotype, whether specific supplements (e.g., L-methylfolate and SAMe) were associated with greater improvement, whether biomarker changes correlated with symptom change, and the safety/tolerability profile. Results: Across the full cohort, mean K10 scores significantly decreased by four points over the treatment period, with 72% of patients showing clinical improvement. Reductions in psychological distress were seen across all MTHFR genotypes, including individuals with homozygous variant genotypes. Supplement-specific analyses showed improvement among those receiving methylfolate or SAMe, although the differences were not statistically significant. Following nutraceutical treatment, biomarker analyses demonstrated significant increases in serum vitamin B12 and modest reductions in homocysteine, but biomarker shifts did not correlate strongly with K10 change. No serious adverse events or clinically significant abnormalities in liver or renal function were identified. Conclusions: In this real-world primary care cohort, personalised nutraceutical treatment, grounded in one-carbon metabolism support and applied alongside usual care, was associated with clinically meaningful reductions in psychological distress. Outcomes were comparable across MTHFR genotypes when treatments were appropriately tailored, suggesting that genotype and biomarker-informed nutraceutical strategies may mitigate potential metabolic disadvantages. These findings support further controlled research into precision nutraceutical psychiatry for anxiety and depression. Secondary analyses of genotype subgroup, specific supplements, and biomarker–outcome associations are reported alongside Benjamini–Hochberg FDR-adjusted p-values and should be interpreted as hypothesis-generating.
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