2.1. Epidemiological Studies about the Effects of Meal Frequency on Cholesterol, Body Weight and Diabetes
The origin of the firm belief that eating three meals per day is the better healthy choice is a mix of cultural heritage [4,5,6] and early epidemiological studies . The available epidemiological studies have not primarily investigated cardiovascular diseases (CVDs), but rather some risks factors such as cholesterol and body weight [8,9]. These studies observed a worsening of blood lipids associated with a “gorging” (a reduced meal frequency, one or two meals daily) diet compared to “nibbling” (the consumption of frequent smaller meals or snacks). In these early studies, authors stated that a reduced meal frequency is associated with an increased risk of cardiovascular disease . Subsequent studies seemed to confirm these previous findings, reporting a lower age-adjusted total and LDL (low-density lipoprotein) cholesterol in subjects who reported eating four or more meals daily, compared to those reporting one or two . The association was also confirmed after adjustment for alcohol, smoking, systolic blood pressure, anthropometric measurements as WHR (waist to hip ratio) and BMI (body mass index), and macronutrient intake. In a 1989 paper, authors compared a very high frequency of meals (17) to a lower frequency (3) and found an improvement of total and LDL cholesterol with the higher frequency; however, this particular approach is clearly atypical in ordinary life . A recent study within the European Prospective Investigation into Cancer (EPIC) project showed a lower concentration of total and LDL cholesterol in subjects reporting a higher (≥6 times/day) meal frequency compared to those who ate 1 or 2 times a day, even when adjusted for age, BMI, physical activity, smoking, total energy intake, and macronutrient distribution . Again, a recently published cross-sectional analysis within the prospective Seasonal Variation of Blood Cholesterol Study in Worcester County, Massachusetts (SEASONS) showed that a frequency higher than four times per day leads to a lower risk of obesity compared to a frequency lower than three times per day, even after adjustment for age, sex, physical activity, and total energy intake .
Another large cohort study, the Malmo Diet and Cancer study, reported that eating more than six meals per day reduces the risk of obesity compared to less than three meals daily; moreover, after adjustment for diet and lifestyle, frequent eaters had lower waist circumference . Regarding diabetes, a 16-year follow-up study showed an increased risk of type 2 diabetes mellitus in men who ate 1-2 times a day compared to those who ate three meals a day (relative risk RR 1.26) after adjustments for age, BMI, and other relevant factors . These data are in contrast to another study that found no correlation between increased meal frequency and type 2 diabetes risk in women after six years follow up (3 times a day: RR 1.09, ≥6 times a day: RR 0.99) . Despite the numerous studies examining risk factors, only one prospective cohort study investigated the relationship between meal frequency and coronary heart disease (CHD) risk. Cahill et al.  found that men eating 1-2 meals per day hadan RR for CHD of 1.10, men eating 4-5 meals per day hadan RR of 1.05, and men eating ≥6 times hadan RR 1.26, as compared to who ate three times a day after adjustment for total energy intake, diet composition, and other risk factors. In general, conflicting results are depending on the outcome investigated and the methodology used.
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However, as also suggested by other authors [19,20], the correlation between a reduced meal frequency and a higher risk of CHD in these studies appears to be weak considering the cross-sectional nature of these studies, making it difficult to establish the causality or temporality of this association.