Ketogenic vs. low-sugar diet: Study reveals distinct metabolic effects and fat loss benefits

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Aug 7 2024

A recent study published in the journal Cell Reports Medicine compares the effects of a ketogenic diet with reduced free sugar intake on cardiometabolic health.

Study: Ketogenic diet but not free-sugar restriction alters glucose tolerance, lipid metabolism, peripheral tissue phenotype, and gut microbiome: RCT. Image Credit: Sea Wave / Shutterstock.com

Free-sugar restriction

Many modern and natural sweet foods contain free sugars like glucose and fructose. Restricting free sugar to less than 5% of total energy intake can reduce energy intake by 100 kcal/ day.

However, this approach has not been shown to reduce fat mass. An earlier study by the current study's authors did not identify any significant change in energy balance within 24 hours of free-sugar restriction. This discrepancy may be due to other factors in the energy cycle or inaccurate self-reporting of energy intake.  

Carbohydrate restriction

The ketogenic diet involves reducing carbohydrate intake for weight loss and altering one’s metabolism. These effects are attributed to the hepatic production of ketone bodies as fuel for peripheral tissues.

Previous studies suggest that the ketogenic diet reduces physical activity energy expenditure (PAEE) levels compared to high-carbohydrate diets. Nevertheless, how the ketogenic diet affects the energy cycle and cardiometabolic health remains unclear.

Energy metabolism in skeletal muscle and fatty tissue can be affected by physical activity and nutrition. The gut microbiome, which produces short-chain fatty acids (SCFAs), also contributes to the regulatory inputs of these peripheral tissues on fasting and postprandial metabolism.  

About the study

The researchers of the current study randomized 60 healthy adults to a ketogenic or low-free-sugar diet for 12 weeks. A third control group was allowed moderate sugar intake.

The ketogenic and low-free sugar groups reported consuming less than 8% and 5% of their total energy as carbohydrates, respectively. In the moderate-sugar group, 18% of energy was provided by free sugars.

At 12 weeks, study participants in both intervention groups lost fat mass due to lowered energy intake. PAEE was not reduced in either group.

The low-free sugar group had reduced total energy intake, total cholesterol, and low-density cholesterol (LDL-C) levels compared to controls. In fasting and postprandial states, the ketogenic diet group had a reduced respiratory exchange ratio (RER), thus indicating lower carbohydrate breakdown for energy.

Fasting glucose levels were also reduced in the ketogenic group at four weeks until ultimately returning to baseline levels at 12 weeks. Glucose tolerance worsened at both time points in this group.

Lipoproteins containing apolipoprotein B are responsible for the increased risk of atherosclerosis with higher cholesterol levels. Although apolipoprotein B levels increased in the ketogenic group, no change in total, LDL, or high-density lipoprotein (HDL) cholesterol levels was observed at week 12.

In the ketogenic group, lower concentrations of amino acids (AAs) were used to synthesize glucose and higher levels of branched-chain AAs were observed. The metabolism of skeletal muscle and fatty tissue shifted, suggesting impaired glucose uptake by skeletal muscle after a meal.

The ketogenic group also exhibited higher levels of the inflammatory marker C-reactive protein (CRP) at week four. Non-esterified fatty acid (NEFA) levels also increased after meals, thus indicating that lipolysis provides free fatty acids for energy in individuals following the ketogenic diet.

These changes were not observed by week 12 despite these individuals continuing to exhibit ketosis throughout the study period. A shift in the beta diversity of the gut microbiome was also observed in the ketogenic group, with an increased prevalence of Bifidobacterium adolescentis and Planococcus.

Both restriction groups reported an increased desire for sweet foods by week 12 as compared to baseline.

Conclusions

Restricting free sugars or overall carbohydrates reduces energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles, and gut microbiome.”

The study findings emphasize that low carbohydrate or free sugar intake preserves PAEE in healthy adults. In contrast, reducing PAEE has been reported after skipping breakfast or alternate-day fasting, possibly due to the absence of energy intake.

Reducing free sugar intake by 1% caused self-reported energy intake to decrease by 14 kcal/day, corroborating previous research. However, objective measurements indicate that the reduction in energy intake may be more significant at about 17 kcal/day.

In the current study, reduced energy intake led to decreased fat and total body mass, thus indicating that these dietary interventions are effective long-term strategies for weight loss. However, the ketogenic diet only observed gut microbiome shifts and unfavorable metabolic changes at peripheral and whole-body levels. Thus, reducing free sugar intake may be an optimal dietary approach for attaining cardiometabolic health benefits.