High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial

Journal Title (Medline/Pubmed accepted abbreviation): Nutr. & Metab.
Year: 2011
Volume: 8
First Page 26 (12 pages)
doi (if applicable): http://www.nutritionandmetabolism.com/content/8/1/26

Summary of Background and Research Design

Background: Negative energy balance, achieved by a low energy diet and/or an increase in energy expenditure, is often accompanied by a reduction in lean muscle mass. The mechanism of this phenomenon may be explained by the regulation of liver glycogen; under low energy conditions, glycogen stores are low and gluconeogenesis (the biochemical process that makes glucose from amino acids or other compounds) contributes most of the body’s glucose. Over all, glucose introduction to the blood is slower than under conditions of energy balance

Hypothesis: By increasing protein intake under negative energy balance, the higher amount of gluconeogenic precursors will allow glucose production to occur at rates similar to the energy balanced state.

Subjects: Healthy men that resembled fitness characteristics of infantry soldiers or competitive athletes were recruited. There were 26 men, divided into 2 age groups: 18-29 and 30-35.

Experimental design: randomized into 3 groups

Treatments and protocol: For days 1-4, participants were in energy balance (energy consumed = energy burned). Two groups consumed 0.9 g protein per kg body weight and the other group consumed 1.8 g protein/kg; all diets contained 55% carbohydrate. On days 5-11, all subjects increased energy expenditure 1000 kcal/day with endurance exercises (treadmill, elliptical, stationary bicycle) at 50-65% their VO2max for approximately 80 min total. The exercise was voluntarily spread out into 15 min intervals throughout the day. One of the groups that consumed 0.9 g protein/kg on days 1-4 increased energy intake to compensate, thus remaining in energy balance (BAL-MP, for balanced, moderate protein). The other 2 groups continued with the same caloric intake as on days 1-4 (DEF-MP for deficient, moderate protein and DEF-HP for deficient, high protein). At baseline and on day 11, height, weight, and body composition were measured.
    The rate of glucose production was measured using labeled isotopes on days 4 and 12. Glucose labeled with deuterium (2H, a hydrogen atom with similar chemical properties as 1H but, since it is only present as 0.015% of the hydrogen atoms in nature, it can be traced) and glycerol labeled with 13C (13C is 1.1% of all natural carbons, 98.9% of carbon is 12C) were the isotopes used. Subjects were infused with a priming dose of labeled glucose and labeled glycerol and then a continuous dose of the labeled molecules for 4 hrs. Nine blood samples were acquired during those 4 hours and assessed for the isotopes in the plasma. Non-enriched glucose was from endogenous glucose stores. Glucose that was enriched with 13C was likely synthesized from the labeled glycerol.
    The fasting blood sample, acquired before the isotope study, was assessed for glucose, glycerol, free fatty acids, β-hydroxybutyrate (ketoacid), glucagon and insulin.

Summary of research findings
  • The DEF-MP and DEF-HP groups lost 2.4 ± 0.6 kg and 2.9 ± 1.0 kg, respectively in the 7 days of energy deficiency. These losses were partitioned as 0.9 ± 1.1% (DEF-MP) and 1.3 ± 0.9% (DEF-HP) fat mass and 1.6 ± 1.0 kg (DEF-MP) and 1.4 ± 0.9 kg (DEF-HP) fat free mass. Those in the BAL-MP group did not lose weight.
  • Glucose production decreased when exercise was increased in the DEF-MP group but remained at the same rate in the BAL-MP and DEF-HP groups. This observation supported the authors’ hypothesis that the reduction in glucose production was rescued with a higher amount of dietary protein.
  • There were higher rates of gluconeogenesis on day 12 compared to day 4, regardless of group.
  • Glycogen breakdown was higher in the BAL-MP group than in either DEF group.
  • Glucagon and insulin both decreased from day 4 to day 12 for all groups. In the DEF-MP group, the change was statistically significant for glucagon.
  • Resting energy expenditure and oxidation rates were similar in all groups on both days of data collection.
  • β-hydroxybutyrate was significantly higher on day 12 compared to day 4 for the DEF groups but not for the BAL group. This compound is a ketoacid and can provide energy in times of low glucose.

Interpretation of findings/Key practice applications

A sudden increase in energy expenditure (on the day-week time scale) can cause the production of endogenous glucose to decrease. However, this decrease can be attenuated with an increase in dietary protein. A high protein diet may be a way to preserve muscle mass and potentially reduce tiredness when trying to lose weight. The DEF-HP group lost a little less fat free mass than the DEF-MP group, but these subjects were only energy deficient for 7 days. It would be interesting to extend this study for a longer period of time.


This study only investigated men, so one must be cautious when translating the findings to women. Also, the subjects were highly trained soldiers who typically consume about 3767 ± 700 kcal per day. Their physiology, therefore, may be slightly different than the average person or even the average athlete.
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