Table 3.

Summary of clinical trial designs for evaluating functional foods.

Trial Design	Primary Objective	Advantages	Limitations	References
Randomized controlled trial (RCT)	Assess efficacy and safety under controlled conditions	High internal validity, minimizes bias, provides high-quality evidence, gold standard in clinical evaluation	Time-consuming, resource-intensive, limited for pre/post-market evaluations, consumer behavior variability introduces bias	[100,101,102]
Crossover trial	Compare treatments within the same subjects	Requires fewer participants, reduces inter-subject variability	Risk of carry-over effects, longer study duration	[103,104]
Parallel-group trial	Compare outcomes between separate groups	Simple design, no carry-over effects	Requires larger sample sizes	[105,106]
Open-label trial	Evaluate treatment effect when blinding is not feasible	Easier to conduct, reflects real-world conditions	Increased risk of observer and participant bias	[107,108]
Blinded (single/double/triple)	Reduce bias in reporting and assessment	Enhances credibility of findings	Complex logistics, not always feasible in nutrition studies	[109]
Observational cohort study	Monitor outcomes in natural settings over time	Reflects real-life conditions, useful for long-term effects, explores prevention guidelines	Cannot establish causality, more confounding factors	[110,111]
Cross-sectional study	Examine correlations at a single point in time	Useful for identifying associations and informing hypotheses	Cannot establish causality, depends on timing of data collection	[112,113]