Background Lower total carbohydrate intakes could have beneficial effects on cardiometabolic risk markers. However, the effects of low carbohydrate diets (LCD) on lipid markers and clinical end-points remain largely unknown. This study aimed to examine the associations between LCD and cardiovascular conventional risk factors and investigate whether these associations are mediated by body mass index (BMI), waist circumference (WC) and haemoglobin A1c (HbA1c).

Methods We included adults aged 45-80 years from the UK NDNS programme (2008-2016) with data on dietary intake, anthropometric and biochemical parameters. Four interventions were examined including LCD, Low Carbohydrate and High Fibre Diet (LCHF), Low Carbohydrate and High Saturated Fat Diet (LCHS), and Low Carbohydrate and High Unsaturated Fat Diet (LCHU). Obesity was measured by BMI and WC. Biochemical markers included HbA1c, total cholesterol, HDL and LDL cholesterol, triglycerides, systolic and diastolic blood pressure and C-reactive protein (CRP). BMI, WC and HbA1c were used as mediators of the effects. The analysis was adjusted for sociodemographic status, lifestyle factors and antihypertensive medication. Causal mediation analysis was used to investigate the total, indirect and direct effect of LCD on CVD markers.

Results BMI, WC and HbA1c fully mediated the association between LCD and triglycerides and fully mediated the effects of LCHF on LDL, although BMI and WC were sufficient to fully mediate the effects of LCHF on triglycerides and CRP. BMI alone fully mediated the effects of LCHS on HbA1c, triglycerides, LDL and CRP. None of these mediators explained the effect of LCHU on CVD risk markers.

Conclusion This study demonstrated that individuals on LCHF improved their CVD markers as expected, but those on LCD who increase fat intake had no effects on CVD markers mediated by obesity and diabetes. More research on the mechanisms underlying the significant increase in HDL cholesterol in people consuming LCD is needed.