Do markers of adiposity and glycaemia mediate the association between low carbohydrate diet and cardiovascular risk factors: findings from the UK National Diet and Nutrition Survey (NDNS) 2008-2016.

Objectives: To examine the associations between low carbohydrate diet (LCD) and conventional cardiovascular risk factors and investigate whether these associations are mediated by body mass index (BMI), waist circumference (WC) and haemoglobin A1c (HbA1c) applying causal mediation analyses.

Methods: We included 3640 adults aged 45-80 years from the UK National Diet and Nutrition Survey programme (2008-2016) with data on dietary intake, anthropometric and biochemical parameters. Four hypothetical interventions were examined: (1) LCD, (2) Low carbohydrate (LC) and high fibre diet (LCHF), (3) LC and high saturated fat diet (LCHS) and (4) LC and high unsaturated fat diet (LCHU). BMI and WC were used as markers of obesity. Biochemical markers included HbA1c, total cholesterol, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, triglycerides, systolic and diastolic blood pressure and C reactive protein (CRP). BMI, WC and HbA1c were used as a mediator of the effects. The analysis was adjusted for sociodemographic characteristic, smoking, estimated total energy intake, alcohol consumption and antihypertensive medication. To identify a potential causal effect of LCD on cardiovascular disease (CVD) risk, we estimated the average treatment effect, and corresponding p values and CI for the total, indirect and direct effect of the treatment on the outcome.

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 not 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: The causal hypotheses tested in this study demonstrate that individuals on LCD with high fibre intakes 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.