Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets

Abstract

Background: Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy.

Methods: A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual's energy expenditure. On Day 7, ketone buildup from FK was measured.

Results: A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p < 0.0058. Using a Fisher LDS pair-wise comparison, higher significant levels of acetone buildup were found for diets with 79% fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R(2) = 0.92), and lower body mass index (R(2) = 0.71) was observed during FK.

Figure 1

Layout of the NK and FK diet study portion of the present work.

Figure 2

Changes in acetone during phase 3, starvation, after different diet compositions for 11 subjects. The diets are defined by the ratio of fat to total carbohydrate and protein by mass, which are plotted on the x-axis. The change in acetone in ppmV is plotted on the y-axis.

Figure 3

Breath ketone, acetone, measured during the starvation day (Day 6) for 11 subjects after Diet B. Time zero was set for 10:00 am in the morning, after 12 hours from last meal (10:00 pm on Day 5).

Figure 4

Correlation of breath acetone levels with blood ketone and urine ketone as well as blood glucose collected from different subjects on their fasting days.

Figure 5

Correlation of acetone buildup on starvation day (Day 6) after diet C (on Day 5) with different physiological parameters. (A) Exponentially decaying correlation of acetone buildup with BMI (R² = 0.46), (B) Exponentially decaying correlation of acetone buildup with Body Fat % (R² = 0.71), and (C) Exponentially increasing correlation of acetone buildup with TEE (TEE = PAL × REE, for more details see experimental section) (R² = 0.92 for n = 9). Two subjects with lowest BMI (marked in circles) did not follow the trend likely due to non-compliance of energy balanced diet on Day 5 of the diet.