- BIOMARKERS TO DEFINE OPTIMAL PROTEIN REQUIREMENT
- Di Girolamo, Filippo Giorgio
Subject
- Sarcopenia
- protein
- aging
- hypoxia
- inactivity
- SCUOLA DI DOTTORATO DI RICERCA IN BIOMEDICINA MOLECOLARE
- MED/09 MEDICINA INTERNA
Description
- 2013/2014
- Dietary proteins are the source of the amino acids required by the body for tissue growth and maintenance. The Population Reference Intake (PRI) for proteins, as defined by the European Food Safety Authority (EFSA) for healthy adults, including the elderly, is 0.83 g/kg body weight/day. This amount is defined on the net balance of body protein (or “nitrogen balance”, given by the difference between dietary nitrogen intake and losses) equivalent to 0.66 g/kg/day plus a safety factor for interpersonal variability and differences in proteins quality of mixed diets. The PRI, however, is the minimum daily amount of protein needed to maintain the nitrogen balance and avoid a progressive loss of lean body mass in healthy people with moderate physical activity. Therefore nitrogen balance may not be adequate to define protein requirement in adults and especially in ageing characterized by loss of muscle mass and function (sarcopenia). Furthermore until recently the prevalent idea was that a protein intake above PRI had no further benefits and on the contrary could impair health. These believes are now under discussion, diets with higher protein intake have been shown beneficial in the prevention and treatment of conditions such as sarcopenia, COPD and type 2 diabetes mellitus. There is a need of more precise methods to define protein requirement. AIM. The aim of the present thesis is to investigate in human healthy volunteers new biomarkers adequate to define optimal protein intake. Recent studies have determined protein needs by measuring whole-body protein metabolism using stable labeled isotope-amino acids. METHODS. Our research group has applied two different metabolic methods based on the most widely used tracer, i.e. D5-Phe stable isotope, in two experimental bed rest campaigns (FP7 PLANHAB and INTERREG PANGaA) in healthy volunteers. BR is a suitable model to investigate physiologic adaptation to inactivity. MAIN RESUTLTS. FP7 PLANHAB. We applied the stable isotope infusion technique, to assess the effect of physical inactivity and/or hypoxic condition on whole body protein turnover as previously described in Biolo et al 2008. Chronic hypoxia has been associated with an overall reduction in protein synthesis and in total plasma and skeletal muscle protein content. During the PLANHAB study we investigated, through a crossover randomization, the net effects of 10 days normobaric hypoxia (4000 mt.), associated with either ambulatory conditions or BR, in 11 young (age 24±4 yr), healthy and normal weight male subjects maintained on eucaloric diets. Main results. Hypoxia in ambulatory conditions significantly decreased whole body protein turnover by reducing both protein synthesis (-8±2%) and protein degradation (-8±3%). Hypoxia during bed rest did not caused significant changes in protein metabolism. INTERREG PANGaA. The skeletal muscle loss in aging is caused mainly by the “anabolic resistance” i.e. the inadequate increase in the rate of protein synthesis in response to nutritional-metabolic stimuli, including exercise, protein and amino acid intake as well as insulin and insulin-like growth factor stimulation. As a consequence, the net protein balance becomes negative leading to sarcopenia. The effects of ageing on the anabolic resistance induced by inactivity are poorly investigated. During the PANGeA study we had the opportunity to perform the second documented experimental BR in in healthy elderly volunteers and the first comparing aged with young subjects. To evaluate the anabolic resistance associated with ageing and inactivity, we enrolled 7 young (23±1yr) and 8 elderly (59±1yr) normal weight individuals, in a 14-d experimental BR protocol. We replaced our previous infusion method with a new, simpler, safer and quicker technique, by which tracers are given orally instead of parenterally, the all procedure is completed in two hours, instead of 6, and only two blood draws versus 7 are sufficient. Main results. At baseline parameters of anabolic sensitivity were comparable between young and elderly individuals. The anabolic resistance significantly increased after BR in both groups (bed-rest effect p<0.01), with a statistically significant bed-rest×group interaction (p=0.01). Anabolic resistance increased significantly in elderly (18.5%±7.3%) more than in young (5.2%±9.4%) subjects. DISCUSSION. In the PLANHAB study, hypoxia in ambulatory conditions reduced by the same level both protein synthesis and catabolism, as measured by isotope infusions, suggesting an adaptive mechanism: the lower energy production and availability induced by hypoxia associated with ambulatory condition. These modifications could not have been revealed by the use of nitrogen balance method, showing the relevance of more sophisticated analysis. The direct evaluation of the muscle protein metabolism through an infusion of stable-labeled isotope tracer, considered the golden standard methodology, gave us, in the PLANHAB study, reliable results in the early protein metabolism changes during hypoxia and/or BR. This method however has the limit of being complex, onerous and invasive, therefore being unsuitable for clinical evaluation. In the PANGeA study we could confirm the presence of a reduced sensitivity to anabolic stimuli in the elderly population compared to the young men. The elderly subjects are therefore, more at risk to develop changes of protein metabolism induced by inactivity. The simpler, timesaving and less invasive method we have developed for the PANGeA study, on the other hand, could be applied to a wider ranges of experimental conditions and clinical settings.
- XXVII Ciclo
- 1983
Date
- 2015-06-09T08:25:37Z
- 2015-06-09T08:25:37Z
- 2015-04-28
Type
- Doctoral Thesis
Format
- application/pdf
Identifier
urn:nbn:it:units-14066