Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults

Abstract

Ketogenic diets (KDs) often contain high levels of saturated fat, which may increase liver fat, but the lower carbohydrate intake may have the opposite effect. Using a controlled feeding design, we compared liver fat responses to a hypocaloric KD with a placebo (PL) versus an energy-matched low-fat diet (LFD) in overweight adults. We also examined the added effect of a ketone supplement (KS). Overweight adults were randomized to a 6-week KD (KD + PL) or a KD with KS (KD + KS); an LFD group was recruited separately. All diets were estimated to provide 75% of energy expenditure. Weight loss was similar between groups (p > 0.05). Liver fat assessed by magnetic resonance imaging decreased after 6 week (p = 0.004) with no group differences (p > 0.05). A subset with nonalcoholic fatty liver disease (NAFLD) (liver fat > 5%, n = 12) showed a greater reduction in liver fat, but no group differences. In KD participants with NAFLD, 92% of the variability in change in liver fat was explained by baseline liver fat (p < 0.001). A short-term hypocaloric KD high in saturated fat does not adversely impact liver health and is not impacted by exogenous ketones. Hypocaloric low-fat and KDs can both be used in the short-term to significantly reduce liver fat in individuals with NAFLD.

Keywords: NAFLD; exogenous ketones; ketogenic diet; liver fat; low carbohydrate.

Figure 1

(A) Mean and (B) individual participant changes in total liver fat after 6-week ketogenic and low-fat diets. (C). total liver fat in a subset of participants with nonalcoholic fatty liver disease (NAFLD). ** = p < 0.01 from baseline. KD = ketogenic diet. KS = ketone supplement. LFD = low-fat diet WK0 = baseline. WK6 = post-intervention.

Figure 2

Daily measurements of fasted βHB recorded before breakfast and at least 10 h after supplement ingestion. All values reported as mean ± SEM. KD + KS and KD + PL ketones increased significantly from baseline (***) (p < 0.001) and were significantly higher than LFD (p < 0.001). Distinct letters denote significant differences between KD + KS and KD + PL.

Figure 3

(A) Association of the absolute change in liver fat versus weight loss (R = 0.006, p > 0.05). (B) Association of the absolute change in liver fat versus baseline liver fat (R = −0.91, p < 0.05). Within the NAFLD group, the correlation was R = −0.96 for the ketogenic group (n = 7) and R = −0.40 for the low-fat diet group (n = 5).