Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy

Rick Hursel, Eveline A P Martens, Hanne K J Gonnissen, Henrike M Hamer, Joan M G Senden, Luc J C van Loon, Margriet S Westerterp-Plantenga, Rick Hursel, Eveline A P Martens, Hanne K J Gonnissen, Henrike M Hamer, Joan M G Senden, Luc J C van Loon, Margriet S Westerterp-Plantenga

Abstract

Background: Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates.

Objective: To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake.

Methods: A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans.

Results: After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620).

Conclusions: In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake.

Trial registration: Clinicaltrials.gov NCT01551238.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow diagram (CONSORT) of a…
Fig 1. Flow diagram (CONSORT) of a substudy in two diet groups (12 weeks High Protein or Low Protein diet), with n = 20 eligible men and women.
Fig 2. Mean (+SEM) plasma Phe (A)…
Fig 2. Mean (+SEM) plasma Phe (A) concentration (μmol L-1) and plasma L-[ring-2H5]Phe (B) enrichment (MPE) after 12 weeks on a HP (grey) vs LP (black) diet.
n = 15. Data were analyzed with a two-factor ANOVA (time x treatment). *Treatment effect P<0.001.
Fig 3. Mean (+SEM) basal whole-body protein…
Fig 3. Mean (+SEM) basal whole-body protein metabolism expressed as the AUC (μmol Phe/kg/h) after 12 weeks on a HP (grey) vs LP (black) diet.
n = 15. Data were analyzed with a two-factor ANOVA (time x treatment). *Treatment effect P

Fig 4. Mean (+SEM) mixed muscle protein…

Fig 4. Mean (+SEM) mixed muscle protein fractional synthesis rates (%/h) in the basal state…

Fig 4. Mean (+SEM) mixed muscle protein fractional synthesis rates (%/h) in the basal state after 12 weeks on a HP (grey) vs LP (black) diet.
n = 15. Data were analyzed with a one-way ANOVA.

Fig 5. Mean (+SEM) protein intake, excretion…

Fig 5. Mean (+SEM) protein intake, excretion and balance (g/d) at baseline and after 12…

Fig 5. Mean (+SEM) protein intake, excretion and balance (g/d) at baseline and after 12 weeks on a HP (grey) vs LP (black) diet.
n = 15. Data were analyzed with a two-factor repeated measures ANOVA (time x treatment). *Treatment effect P
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This work was supported by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 266408. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Fig 4. Mean (+SEM) mixed muscle protein…
Fig 4. Mean (+SEM) mixed muscle protein fractional synthesis rates (%/h) in the basal state after 12 weeks on a HP (grey) vs LP (black) diet.
n = 15. Data were analyzed with a one-way ANOVA.
Fig 5. Mean (+SEM) protein intake, excretion…
Fig 5. Mean (+SEM) protein intake, excretion and balance (g/d) at baseline and after 12 weeks on a HP (grey) vs LP (black) diet.
n = 15. Data were analyzed with a two-factor repeated measures ANOVA (time x treatment). *Treatment effect P

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