Alterations in Tryptophan Metabolic Pathways in Obese Individuals Adhering to Low-Carbohydrate Intermittent Fasting: Contributions to Oxidative Stress and Hypertension

Abstract

Low-carbohydrate diets and intermittent fasting (IF) are increasingly used for weight control, particularly in obese women. Modifying dietary behavior forces the body to adapt alternative pathways for energy and nutrient supply. Obesity is associated with oxidative stress and hypertension due to excess body fat. Tryptophan (Trp), an essential amino acid, is metabolized mainly via the kynurenine, 5-hydroxytryptophan (5-HT), and indole pathways. This study examined the effects of lifestyle on Trp metabolism, focusing on the kynurenine and 5-HT pathways, and their association with oxidative stress and hypertension. A total of 120 premenopausal women were enrolled: 40 controls (BMI<25 kg/m²), 40 non-adherent obese (BMI≥30 kg/m²), and 40 obese adherent to low-carb and IF. Serum analyses included lipid profile, total oxidant status (TOS), total antioxidant capacity (TAC), 8-hydroxydeoxyguanosine (8-OHdG), kynurenine, and 5-HT. Non-adherent obese participants showed significantly higher TOS, 8-OHdG, and kynurenine, with lower TAC and Trp than controls. Adherent obese participants exhibited improvements in TOS, TAC, and kynurenine compared to non-adherent obese, though 8-OHdG and Trp remained unchanged. Oxidative stress correlated with kynurenine in non-adherent obese and with 5-HT in adherent obese. A metabolic shift from kynurenine to 5-HT was observed in the adherent group, negatively correlated with BMI. Kynurenine was associated with increased hypertension risk in both obese groups.In conclusion, adherence to a low-carb diet and IF can shift Trp metabolism from the kynurenine to the 5-HT pathway, reduce oxidative stress, and lower hypertension risk in obese premenopausal women, highlighting the metabolic benefits of lifestyle interventions beyond weight reduction.