Bernard Beaufrere

The rate of protein digestion affects protein gain differently during aging in humans

In young men ingesting protein meals, slowly digested proteins (caseins: CAS) induce a higher protein gain than those that are rapidly digested (whey proteins: WP). Our aim was to assess whether or not this is true in elderly men receiving mixed meals. The effects of meals containing either CAS or two different amounts of WP (WP‐iN: isonitrogenous with CAS, or WP‐iL: providing the same amount of leucine as CAS) on protein metabolism (assessed by combining oral and intravenous leucine tracers) were compared in nine healthy, elderly (mean ±s.e.m. age 72 ± 1 years) and six young men (24 ± 1 years). In both age groups, WP‐iL and WP‐iN were digested faster than CAS (P < 0.001, ANOVA). Proteolysis was inhibited similarly whatever the meal and age groups (P= NS). Protein synthesis was higher with WP‐iN than with CAS or WP‐iL (P < 0.01), irrespective of age (P= NS). An age‐related effect (P < 0.05) was found with postprandial leucine balance. Leucine balance was higher with CAS than with WP‐iL (P < 0.01) in young men, but not in elderly subjects (P= NS). In isonitrogenous conditions, leucine balance was higher with WP‐iN than with CAS (P < 0.001) in both age groups, but the magnitude of the differences was higher in the elderly men (P= 0.05). In conclusion, during aging, protein gain was greater with WP (rapidly digested protein), and lower with CAS (slowly digested protein). This suggests that a ‘fast’ protein might be more beneficial than a ‘slow’ one to limit protein losses during aging.

Albumin and fibrinogen syntheses increase while muscle protein synthesis decreases in head-injured patients

The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion of L-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients (P < 0.02). Fractional muscle protein synthesis rate decreased by 50% (P < 0.01) after injury. Fractional and absolute fibrinogen synthesis rates were multiplied by two and nine, respectively, after injury (P < 0.001). Albumin levels were lower in patients (25.2 +/- 1.2 g/l, means +/- SE) than in controls (33.7 +/- 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 +/- 1.0%/day) compared with controls (7.3 +/- 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion ofl-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients ( P < 0.02). Fractional muscle protein synthesis rate decreased by 50% ( P < 0.01) after injury. Fractional and absolute fribrinogen synthesis rates were multiplied by two and nine, respectively, after injury ( P< 0.001). Albumin levels were lower in patients (25.2 ± 1.2 g/l, means ± SE) than in controls (33.7 ± 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 ± 1.0%/day) compared with controls (7.3 ± 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.

Effects of 14 weeks of progressive endurance training on energy expenditure in elderly people

Effects of progressive endurance training on energy expenditure (EE) were studied in thirteen elderly sedentary subjects (62.8 (SD 2.3) years) after 7 and 14 weeks of training. Daily EE (DEE) and energy cost of the various usual activities were measured over 48 h by whole-body indirect calorimetry. Free-living DEE (DEEFLC) was calculated from 7 d activity recordings and the energy costs of activities were measured in the calorimeters using the factorial method. DEEFLC did not vary significantly throughout the training period despite the additional energy cost of training sessions (0.60 (SD 0.15) MJ/d), because energy expended during free-living activities (EEACT) decreased by 4.8 (SD 7.1)% (P < 0.05) and 7.7 (SD 8.6)% (P < 0.01) after 7 and 14 weeks of training respectively. Measurements in the calorimeters showed that sleeping metabolic rate transiently increased by 4.6 (SD 3.2)% after 7 weeks of training (P < 0.001) and returned to its initial level after 14 weeks of training. BMR was 7.6 (SD 7.0)% (P < 0.01) and 4.1 (SD 6.1)% (P = NS) higher after 7 and 14 weeks of training respectively, than before training. Likewise, diet-induced thermogenesis increased from 3.7 (SD 2.5) to 7.2 (SD 2.8)% energy intake after 7 weeks of training (P < 0.05), and returned to its initial level after 14 weeks of training (4.2 (SD 2.6)% energy intake). Despite these changes, energy expended during activities and the corresponding DEE did not vary throughout the training period. It was concluded that: (1) DEEFLC remained constant throughout the training period due to a compensatory decrease in free-living EEACT; (2) progressive endurance training induced a transient increase in sleeping metabolic rate, BMR and diet-induced thermogenesis after 7 weeks which was not reflected in the energy expended during activities and DEE.

Gut mucosal protein synthesis in fed and fasted humans

Fractional protein synthesis rate (FSR) of duodenal mucosa was measured in two groups of six healthy young men, either in the fed state at the end of a 10-day standardized diet or after a 36-h fast. Protein synthesis rate was measured during a 9-h intravenous infusion of [13C]leucine and [2H5]phenylalanine. The fed group also received an intragastric tracer, [2H3]leucine, mixed with the liquid diet. At the end of the tracer infusion, an endoscopy was performed to take duodenal mucosal biopsies. The major results were that 1) duodenal mucosal protein synthesis was high, 48.0 +/- 8.5% (SE)/day by use of intravenous leucine tracer and intracellular leucine enrichment; 2) it was not affected by feeding whatever the tracer or the precursor pool used for the calculations; 3) the two intravenous tracers gave different FSR values; and 4) with the intragastric tracer, FSR was 25-220% of the rate calculated with the intravenous tracer, depending on the precursor pool used for the calculation. Thus absolute values of FSR should be taken with caution, because they depend on the precursor pool chosen, the route of tracer administration, and the tracer itself. However, gut mucosal protein synthesis as assessed by an intravenous tracer is not affected by feeding in humans.

Critical evaluation of the factorial and heart-rate recording methods for the determination of energy expenditure of free-living elderly people

The aim of the present study was to validate against the doubly-labelled water (DLW) technique the factorial method and the heart rate (HR) recording method for determining daily energy expenditure (DEE) of elderly people in free-living conditions. The two methods were first calibrated and validated in twelve healthy subjects (six males and six females; 70.1 (SD 2.7) years) from open-circuit whole-body indirect calorimetry measurements during three consecutive days and during 1 d respectively. Mean energy costs of the various usual activities were determined for each subject using the factorial method, and individual relationships were set up between HR and energy expenditure for the HR recording method. In free-living conditions, DEE was determined over the same period of time by the DLW, the factorial and the HR recording methods during 17, 14 and 4 d respectively. Mean free-living DEE values for men estimated using the DLW, the factorial and the HR recording methods were 12.8 (SD 3.1), 12.7 (SD 2.2) and 13.5 (SD 2.7) MJ/d respectively. Mean free-living DEE values for women were 9.6 (SD 0.8), 8.8 (SD 1.2) and 10.2 (SD 1.5) MJ/d respectively. No significant differences were found between the three methods for either sex, using the Bland & Altman (1986) test. Mean differences in DEE of men were -0.9 (SD 11.8) % between the factorial and DLW methods, and + 4.7 (SD 16.1) % between the HR recording and DLW methods. Similarly, in women, mean differences were -7.7 (SD 12.7) % between the factorial and DLW methods, and + 5.9 (SD 8.8) % between the HR recording and DLW methods. It was concluded that the factorial and the HR recording methods are satisfactory alternatives to the DLW method when considering the mean DEE of a group of subjects. Furthermore, mean energy costs of activities calculated in the present study using the factorial method were shown to be suitable for determining free-living DEE of elderly people when the reference value (i.e. sleeping metabolic rate) is accurately measured.

Alterations of Sensory Perceptions in Healthy Elderly Subjects during Fasting and Refeeding

Background: Sensory perception losses may contribute to age-related malnutrition by affecting food selection and consumption. Objective: To determine the effects of a 36-hour fast followed by a 6-hour refeeding period on sensory perceptions in 7 healthy elderly subjects (65–80 years of age) and 6 healthy young subjects (18–35 years of age). Methods: Self-perceived hunger and olfactory ratings were recorded on visual analogue scales in response to three different classes of odorant stimuli (salt, sweet and sour). Odorant stimuli were administered three times during the study, twice during the fasting period (12 and 24 h fasted) and once at the end of the re-nutrition period. Results: A significant difference was found between the two groups for the self-perceived hunger ratings in response to the sour stimuli. A significant difference was observed between the two groups for olfactory ratings as regards the salt and sour odorant stimuli. Among the metabolic changes associated with fasting and refeeding, blood glucose was significantly related (r2 = 0.97, p = 0.001) to the perception of hunger in the control group subjects, but no such relationship was found for the elderly subjects (r2 = 0.16, p = NS). Conclusion: (1) Self-perceived hunger and olfactory ratings are specifically affected in healthy elderly. (2) Nutritional status can modulate sensory perceptions in elderly and young during the transition from fasting to refeeding.

Short-Term Administration of a Combination of Recombinant Growth Hormone and Insulin-Like Growth Factor-I Induces Anabolism in Maintenance Hemodialysis

CONTEXT Resistance to GH and IGF-I is a significant complication of severe chronic kidney disease, which contributes to muscle wasting. Pharmacological doses of recombinant human (rh) GH or rhIGF-I have been proposed to treat this catabolic condition. OBJECTIVE This study was undertaken to examine the potential additive anabolic effects of rhGH + rhIGF-I compared with rhIGF-I. DESIGN We studied eight well-nourished hemodialysis patients in a random crossover design and compared the metabolic effects of a 3-d administration of moderate dose of rhIGF-I (40 microg/kg per 12h) with an association of rhIGF-I + rhGH (50 microg/kg/d). Leucine kinetics, plasma amino acids (AAs), serum insulin, and IGF binding proteins (IGFBP)-1 and -3 were measured. RESULTS The net protein balance was not affected by rhIGF-I alone, whereas serum insulin and IGFBP-3 decreased (P < 0.05) and IGFBP-1 increased (P < 0.01). With the combination rhGH + rhIGF-I, an increase of IGFBP-3 (P < 0.01) and insulin (P < 0.01) as well as a decrease of IGFBP-1 (P < 0.01) occurred. Plasma essential AAs (P = 0.01) as well as the essential to nonessential AA ratio (P < 0.001) decreased. Whole-body protein net balance increased significantly (P < 0.05) with a 22% decrease in leucine oxidation and a 15% increase in nonoxidative leucine disposal. CONCLUSIONS In dialysis patients, rhIGF-I administration at a moderate dose has no protein metabolic effect, but the association with a moderate dose of rhGH is followed by a significant anabolic response.

Oxidative stress status and antioxidant status are apparently not related to carotenoid status in healthy subjects.

Several lines of evidence suggest that carotenoids may have a beneficial effect on health as a result of their antioxidant properties. In addition to beta-carotene, five other carotenoids are recovered in noticeable amounts from human plasma and tissues. Although the effect of beta-carotene on in vivo lipid peroxidation has been documented, few data are available on the effects of the other carotenoids. We evaluated the ability of the main human carotenoids to reduce lipid peroxidation by determining the correlations between plasma carotenoid concentration and plasma antioxidant capacity (in 79 healthy volunteers) and between carotenoid status and breath pentane excretion (in a subgroup of 24 subjects). Carotenoid intake was assessed by means of a 3-day food recall. Carotenoid status was evaluated by measurement of beta-carotene, lycopene, lutein/zeaxanthin, and alpha-carotene in plasma and buccal mucosal cells. Antioxidant status was evaluated by measurement of the total antioxidant capacity of the plasma. Oxidative stress status was evaluated by breath pentane measurements. Food recall data and the carotenoid concentrations in plasma and buccal mucosal cells showed that the subjects had normal carotenoid intake and normal carotenoid status. The total antioxidant capacity of the plasma was not related to the concentration of any specific carotenoid. The level of expired air pentane was not related to the carotenoid status of the subjects. These results show that normal concentrations of carotenoids in plasma and tissues are not correlated with these clinical markers of antioxidant and oxidative stress status.

Age-related changes in plasma lycopene concentrations, but not in vitamin E, are associated with fat mass.

The aim of the present study was to assess the influence of age on plasma concentration of alpha-tocopherol, retinol and carotenoids with a special attention paid to natural differences in body composition. Forty healthy subjects were recruited: twenty were less than 35 years old and twenty above 60 years old. Males and females were equally represented in each age group. Subjects were kept in energy balance and received controlled diets for 36 h. Fat mass and fat-free mass were determined with the (18)0-enriched water dilution technique. Plasma vitamins A and E, and carotenoid levels were determined after 12 h fasting and were shown to be similar in women and men. Plasma alpha-tocopherol concentration increased with age (+44 % elderly v. young), and correlated with % fat mass and plasma cholesterol. After adjustment for plasma cholesterol, the effect of age and % fat mass disappeared. In contrast, plasma lycopene level was 2-fold lower in the elderly than in the young group, and was inversely correlated with fat mass. When lycopene values were adjusted for fat mass, the effect of age disappeared. These results suggest that plasma levels of vitamin E and lycopene differed in the two age groups and that differences in plasma cholesterol and fat mass might participate in such an effect. Short-term vitamin intake did not appear to influence plasma vitamin concentrations.

Aging and protein metabolism.

During aging, there are qualitative and quantitative modifications of proteins in various tissues. In muscle, myofibrillar and mitochondrial proteins are affected, resulting in a loss of strength and, to a lesser degree, endurance. Mechanisms of sarcopenia remain not well known and probably involve loss of motoneurons, muscle disuse and hormonal alterations. Partial prevention of muscle loss is possible by resistance training. In all tissues, and particularly in the brain, oxidative changes in proteins are likely to alter various functions of proteins.