Cardiometabolic risk factors and glycaemic control in randomised crossover trials
Evidence basis: randomised trials
Small short randomised crossover trials found that eating on a regular schedule improved the thermic effect of food and lowered glucose and insulin responses versus an irregular pattern.
Population: Very small samples of women: nine healthy lean women aged 18-42 in one randomised crossover trial, eleven normal-weight women aged 18-40 in the other,. The observational half of the evidence is recorded as its own outcome. The supporting review covered cross-sectional and prospective cohort studies plus two randomised controlled intervention studies in lean and obese women, and noted that social jet lag affects a large share of the population.
Research details
Summary
The randomised evidence is consistent in direction but very small in scale. In a randomised controlled trial, eleven normal-weight women aged 18-40 completed two 14-day isoenergetic diet periods, one with a regular meal pattern of six meals per day and one with an irregular pattern of three to nine meals per day, separated by a 14-day washout; meal regularity was associated with a greater thermic effect of food and lower glucose responses. An earlier randomised crossover trial in nine healthy lean women found that the overall thermic effect of food over three hours after a test meal was significantly lower after the irregular meal pattern (P = 0.003), with no significant differences in body weight, three-day mean energy intake, fasting resting metabolic rate, or subjective appetite. In the irregular period, mean energy intake on the day when nine meals were eaten was significantly greater than when six or three meals were consumed (P = 0.0001), showing that irregularity changed intake within the pattern. A review of meal irregularity and cardiometabolic consequences reported that only a few cross-sectional and prospective cohort studies were identified, most suggesting that eating meals irregularly is associated with a higher risk of the metabolic syndrome and cardiometabolic risk factors including BMI and blood pressure, and that this was supported by two randomised controlled intervention studies showing that consuming meals regularly for two weeks versus an irregular meal pattern led to lower peak insulin and lower fasting total and LDL-cholesterol in both lean and obese women.
Why this certainty
Rated Limited rather than Moderate because the randomised trials have sample sizes in the single or low double digits, durations of two weeks per condition, and intermediate outcomes only, and the supporting evidence is largely observational. It is not rated Very limited because two independent randomised crossover trials using isoenergetic diets and controlled meal patterns found the same direction for thermic effect of food and glucose response, and a review found the observational literature pointed consistently the same way.
Limitations
The randomised trials are extremely small (nine and eleven participants), short (14 days per condition), and restricted to healthy normal-weight or lean women, so they cannot speak to men, older adults, people with obesity, or long-term outcomes. All measured outcomes are intermediate physiological markers - thermic effect of food, glucose response, peak insulin, LDL-cholesterol - rather than clinical events, so the outcome tests a physiological mechanism and not a disease endpoint. The observational literature is cross-sectional or prospective cohort, cannot establish causation, and the reviewers themselves described it as limited. Meal patterns were imposed, so adherence and real-world sustainability are untested, and the review noted the need for large-scale studies with detailed dietary assessment.
Effect estimate
Thermic effect of food over 3 h after a test meal in 9 healthy lean women: significantly lower after an irregular meal pattern than a regular one (P = 0.003) (Farshchi 2004). Meal regularity versus irregularity in 11 normal-weight women over 14-day isoenergetic periods: greater thermic effect of food and lower glucose responses with regularity (Alhussain 2016).
- Decreased thermic effect of food after an irregular compared with a regular meal pattern in healthy lean women.
- Irregular meal-pattern effects on energy expenditure, metabolism, and appetite regulation: a randomized controlled trial in healthy normal-weight women.
- Meal irregularity and cardiometabolic consequences: results from observational and intervention studies.
