In a randomized trial, published in Cell Reports Medicine, researchers examined the metabolic and gut microbiome impacts of restricting free sugars versus overall carbohydrates in 60 adults over 12 weeks.

Compared with a moderate-sugar diet, a low-sugar diet (< 5% energy) and ketogenic diet (< 8% energy from carbohydrate) both decreased fat mass without altering physical activity levels but had differing effects on cardiometabolic health. The researchers noted that a 12-week restriction of free sugars or total carbohydrates reduced body fat in healthy adults. 

The ketogenic diet also impaired glucose tolerance and increased atherogenic lipoproteins, increasing the postprandial glucose incremental area under the curve (AUC) during a mixed meal at week 4 (P = .002) and week 12 (P = .03). Peak postprandial glucose was higher at week 4 (P = .002). In skeletal muscle, the ketogenic diet increased pyruvate dehydrogenase kinase 4 protein at week 4 (P = .04) and decreased glucose transporter 4 at week 12 (P = .03) vs control. Neither diet changed physical activity energy expenditure compared with moderate-sugar control.

Differences in lipid metabolism were also observed. At week 4, the ketogenic diet raised fasting apolipoprotein B by 16 mg/dL (95% confidence interval [CI] = 5–28 mg/dL) and triacylglycerols (P = .04). Nuclear magnetic resonance spectroscopy showed increased particle concentrations of all low-density lipoprotein (LDL) subclasses and lipid content in medium VLDL to small LDL (all P < .05). The low-sugar diet did not have these effects, but lowered LDL cholesterol by 0.5 mmol/L (95% CI = 0.1–1.0 mmol/L) at week 12 (P = .01). Free-sugar restriction lowered LDL cholesterol without major metabolic or microbiome effects

The ketogenic diet transiently increased C-reactive protein at week 4 (P < .05) and altered gut microbial diversity at week 12 (P = .04), decreasing Bifidobacterium abundance at both timepoints (q ≤ 0.04). Both diets lowered leptin (P ≤ .006), while the ketogenic diet additionally reduced fasting and postprandial fibroblast growth factor 21 at week 12 (P ≤ .01).

Using an objective intake-balance method, the researchers found the low-sugar and ketogenic diets decreased calculated energy intake over 12 weeks by 352 kcal/d (95% CI = 145–560 kcal/d) and 398 kcal/d (95% CI = 92–703 kcal/d), respectively. Adherence was monitored through frequent participant contact, detailed diet records, and biomarkers like respiratory exchange ratio and continuous glucose monitoring.

Declaration of interests can be found in the study.