Abstract: N‑of‑1 (single-case) trials can provide higher-level evidence than randomized controlled trials in determining which treatment regimen is optimal for an individual, and this study design is also well-suited for validation testing in personalized nutrition. This systematic review aims to synthesize nutrition-related studies conducted using the N‑of‑1 design. Inclusion criteria were: study participants were adults; intervention/exposure factors were any nutrient, food, beverage, or dietary pattern; control settings included baseline levels, no intervention/placebo control, or other alternative interventions; outcome measures included dietary changes, body weight, biochemical indicators, clinical symptoms, quality of life, or disease outcomes resulting from different nutritional conditions. Databases searched included Medline, Embase, Scopus, Cochrane Central, and PsychInfo. Based on study type, the reporting quality of the literature was evaluated using either the CONSORT extension for N‑of‑1 trials (CENT) or the STROBE guidelines for observational epidemiological studies. After screening 211 articles, 7 studies were ultimately included, distributed across 5 countries, involving a total of 83 participants. The diseases/scenarios covered by the studies included prediabetes, diabetes, irritable bowel syndrome, weight management, and exploring the effects of diet on healthy populations. The reporting quality of the included studies was mostly acceptable, while the quality of dietary assessment varied from poor to good. The existing body of evidence is limited but demonstrates the main characteristics of the N‑of‑1 study design and provides a reference for subsequent research in the era of personalized medical nutrition therapy.
