Impact of a High-Calorie Diet on Metabolic Health, Carotid Intima-Media Thickness, and Endothelial Function in Individuals with Constitutional Thinness.

Background Constitutional thinness (CT) is an uncommon condition, allegedly non-pathological, defined by a persistently low body mass index (BMI <18 kg/m²) enduring from childhood through to later stages of life, without underlying chronic illnesses or hormonal abnormalities. Although CT is not associated with poor health outcomes, its long-term cardiovascular and metabolic implications remain unclear. Given that patients with CT often aim to achieve weight gain, and considering the lack of studies examining the outcomes of high-calorie dietary interventions in this population, we aimed to evaluate vascular and metabolic risk factors associated with atherosclerosis in CT individuals. Methods This prospective before-and-after study involved 60 non-smoking, normotensive, normoglycemic participants with CT, all exhibiting normal lipid profiles (HDL: 55.8 ± 16 mg/dL; LDL: 66 ± 19.9 mg/dL). Changes in carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), fasting and postprandial blood glucose levels before (T0) and after (T1) a 3-month high-calorie diet intervention were assessed using paired Student's t-test. In addition, postprandial insulin levels were evaluated to capture potential metabolic adaptations. Results No significant changes were observed in CIMT (p = 0.54), FMD% (p = 0.423), BMI (p = 0.978), fasting (p = 0.297) or postprandial (p = 0.511) glucose levels, or lipid profiles (total cholesterol p = 0.138, HDL p = 0.858, LDL p = 0.66) after the 3-month high-calorie diet intervention. Both CIMT and FMD% remained within normal ranges at baseline and follow-up, suggesting that in the short term, individuals with CT do not experience substantial alterations in vascular or metabolic parameters despite increased caloric intake. A post-hoc power analysis based on postprandial insulin (p = 0.007) showed a large effect size (Cohen's d = 0.71), with a power of 82% using G*Power software. Conclusions Short-term high-calorie dietary intervention does not lead to significant cardiovascular or metabolic changes in individuals with CT. However, these findings should be interpreted with caution due to the small sample size and short duration. Further studies with longer follow-up and larger sample sizes, or different dietary compositions, may be necessary to evaluate long-term effects. Keywords: constitutional thinness, carotid intima-media thickness, flow-mediated dilation, high-calorie diet, cardiovascular health, metabolic stability.