Nutrigenomics & Personalised Nutrition

Discovery paper identifying the C677T single nucleotide polymorphism in the MTHFR gene, reducing enzyme activity by ~70% in homozygous individuals (TT genotype, ~10% of Caucasian populations). Impaired MTHFR activity reduces conversion of dietary folate to 5-methyltetrahydrofolate (5-MTHF), the biologically active form. This elevates homocysteine, a pro-inflammatory amino acid associated with cardiovascular disease and neural tube defects. Carriers require methylfolate (5-MTHF) from leafy greens or supplements, not synthetic folic acid.

Reviewed dietary and supplementation strategies for MTHFR C677T carriers with elevated homocysteine. 5-Methyltetrahydrofolate (methylfolate) supplementation at 400–800 mcg/day lowered homocysteine by 15–25% in C677T TT carriers, outperforming equivalent doses of folic acid. Rich dietary sources of natural folates (not fortified with synthetic folic acid) — leafy greens, legumes, asparagus — provide a mix of folate forms including 5-MTHF. Vitamin B12 and B6 are co-factors and should be optimised alongside folate in affected individuals.

GWAS study (n=38,759) identifying the FTO rs9939609 variant as the first replicated common genetic obesity locus. Each A allele of rs9939609 (~38% allele frequency) associated with 0.4 kg/m² higher BMI and 1.2× greater obesity odds. FTO encodes an m6A RNA demethylase influencing energy expenditure and fat storage via hypothalamic pathways. Importantly, the FTO effect on obesity is not deterministic: physical activity in FTO risk-allele carriers reduces the genetic BMI effect by ~30% — demonstrating gene-lifestyle interaction.

Analysed gene-lifestyle interaction in 20,430 adults, examining whether physical activity modifies genetic obesity risk from 12 BMI-associated variants including FTO. Among physically active participants, the combined genetic risk score showed 40% attenuated effect on BMI compared to sedentary individuals. FTO specifically showed the largest attenuation. This provides direct evidence that lifestyle interventions — particularly structured exercise — can substantially override genetic predisposition to weight gain, validating the exercise-logging approach of this platform.

Systematic review of 50+ dietary intervention studies stratified by APOE genotype. APOE4 carriers (~25% of the population) show significantly greater LDL-cholesterol responses to high saturated fat intake — up to 3× greater LDL rise per gram of saturated fat versus APOE2/3 carriers. APOE4 is also the primary genetic risk factor for late-onset Alzheimer's disease, and a Mediterranean-pattern diet (high omega-3, low saturated fat) specifically attenuates APOE4-associated cognitive decline risk. Personalised dietary fat guidance is meaningfully different across APOE genotypes.

Comprehensive review of clinically relevant gene-diet interactions across 12 nutrigenomics loci. Key interactions: APOE4 + saturated fat → elevated LDL risk; FTO + high-fat diet → amplified obesity risk vs standard diet; MTHFR TT + low dietary folate → elevated homocysteine; TCF7L2 + high-GI carbohydrate → elevated T2DM risk. Establishes the scientific case for personalised nutrition (matching dietary guidance to individual genotype) as a clinically valid — though currently expensive — precision tool.

Reviews the genetics and evolution of the LCT C/T-13910 variant conferring lactase persistence — continued production of lactase enzyme into adulthood. Lactase persistence is common in Northern Europeans (~90%) but absent in most East Asians (~5–10%), Africans, and Southeast Asians (~10–25%). Lactase non-persistent individuals who avoid dairy miss the highest-DIAAS protein source (whey/casein) and primary dietary calcium source — creating a nutritional disadvantage that must be compensated through lactose-free dairy, fermented products (lower lactose), or non-dairy calcium and protein alternatives.

RCT (n=90) demonstrating that higher dairy intake (≥4 servings/day vs standard 2 servings) during a caloric deficit enhanced fat loss (−5.8 vs −3.8 kg) and lean mass retention (+0.7 vs −0.5 kg) over 16 weeks — an effect mediated by whey protein's high leucine content, casein's slow-digestion profile, and dairy calcium's role in reducing dietary fat absorption. In lactase-persistent individuals, dairy represents one of the highest evidence-quality protein and calcium sources for body composition optimisation.