Use of oral supplements in malnourished elderly patients living in the community: a pharmaco-economic study.

BACKGROUND & AIMS: Inadequate nutritional support in elderly patients is likely to be responsible for increased morbidity and increased associated costs. Conversely prescribing oral supplements to ensure sufficient protein and energy intake should be beneficial. Even though this claim makes sense there is a lack of objective data to support the evidence. The objective of the present study was to assess the cost of malnutrition and related comorbidities among elderly patients living in the community and to determine the impact of nutritional support practice on these outcomes. METHODS: Observational, prospective, longitudinal, cohort study with a 12 months follow-up conducted with 90 general practitioners in France. Two groups of physicians were selected based on historical prescribing practice: group 1 with rare and group 2 with frequent prescription of oral nutrition supplements. The resulting study population was 378 elderly malnourished patients aged over 70, living in the community, either at home or in institutions. Nutritional status at baseline was determined using the Mini Nutritional Assessment (MNA) scale. Main outcome measures were nutritional status, malnutrition-related comorbidities and medical care consumption. RESULTS: Populations in the two groups of patients were balanced for age, gender, weight and body mass index but differed significantly in terms of housing status (P < 0.005) and nutritional status (P < 0.001). After adjustment for baseline characteristics, MNA improved within both groups over time but improvement was significantly higher in group 2 than in group 1 (P < 0.01). The adjusted cost per patient of hospital care (EUR -551), nursing care (EUR -145) and other medical care was significantly reduced in group 2 as compared to group 1, with cost savings of EUR -723 per patient (90% CI: EUR -1.444 to EUR -43). Including the costs related to nutritional products, the total cost savings per patient attributable to nutrition support were EUR -195 (90% CI: EUR -929 to EUR +478). CONCLUSION: Appropriate nutrition support can address the problem of malnutrition among elderly individuals living in the community and may contribute to reduce the costs of health care.

Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons.

BACKGROUND: Undernutrition is a main cause of immunodeficiency. Many confounding factors limit the interpretation of immune function in hospitalized elderly patients. OBJECTIVE: We compared the effects of short-term fasting and refeeding on lymphocyte subset distribution and neutrophil function in healthy subjects. DESIGN: Seven young adult (x +/- SE age: 24 +/- 2 y) and 8 elderly (71 +/- 3 y) subjects were fed standardized diets (1.6 x predicted resting energy expenditure; 16% protein) for 7 d. They then fasted for 36 h and were refed for 4 h (42 kJ/kg). Lymphocyte subsets were quantified by using fluorochrome-conjugated monoclonal antibodies. Neutrophil chemotactic migration was evaluated by using a 2-compartment chamber. Neutrophil reactive oxygen species production was measured by using a luminol-amplified chemiluminescence assay and oxidation of 2'7'-dichlorofluorescein diacetate. RESULTS: Baseline total and cytotoxic T lymphocyte subpopulations were lower in elderly than in adult subjects (P < 0.01). Nutritional state had a significant effect (P < 0.05) on total, helper, and cytotoxic T and B lymphocyte counts in all subjects, and the response of lymphocyte subpopulations to nutritional fluctuations was significantly affected by age. The chemotactic index was lowered by fasting in both groups (P < 0.05 compared with basal values). After refeeding, neutrophil migration was restored in adult but not elderly subjects. The superoxide anion production rate increased with fasting and reverted to prefasting values with refeeding in both groups (P < 0.05). Fasting induced a significant decrease in hydrogen peroxide production in stimulated neutrophils that was reversed by refeeding in adult but not elderly subjects. CONCLUSION: The lack of response of lymphocyte subpopulation counts and neutrophil function to nutritional changes may help to explain the proneness of elderly persons to infection.

Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe disease characterized by neurogenic amyotrophy and degeneration of upper and lower motor neurons. Although ALS patients usually experience reductions in fat-free mass (FFM), hypermetabolism via an undetermined source has also been reported. OBJECTIVE: The objective was to clarify the metabolic level of ALS patients. DESIGN: We measured the resting energy expenditure (REE) of 62 patients (32 men and 30 women) with ALS and investigated the factors correlated with metabolic level. Nutritional evaluation included bioelectrical impedance analysis, indirect calorimetry, and calculation of the body mass index. Neurologic assessment included an evaluation of peripheral and central neurologic deficit. Forced vital capacity was measured and smoking status was noted. A complete blood cell count was made and thyroid hormone and C-reactive protein concentrations were measured. RESULTS: Patients were hypermetabolic, by an average of approximately 10% more than in a reference healthy population. FFM, age, and the neutrophil count were significantly associated with REE. The only variable that contributed to the prediction of REE, REE/Z100 kHz (bioimpedance at 100 kHz), REE adjusted for FFM, or the ratio of measured REE to calculated REE was the neutrophil count, which explained only a small percentage of variance in the multiple regression analysis. Hypermetabolism was not associated with a reduction in respiratory function, tobacco use, hyperthyroidism, spasticity and fasciculation intensities, or infection. CONCLUSIONS: Our study corroborates the surprising finding that ALS patients are hypermetabolic. FFM, age, sex, manual muscular testing, the modified Norris limb score, weight, and an increase in circulating neutrophil counts correlated with the hypermetabolic state. Other factors may play a role in pathophysiologic processes that involve mitochondrial energy production or even sympathoadrenergic activation.

Weightlessness as an accelerated model of nutritional disturbances.

Food intake and eating patterns, body functions and composition are significantly altered by short-duration space flight. Prolonged missions lasting weeks or months further aggravate these changes, and are responsible for acute or chronic physical impairments at return to ground conditions. Current projects of missions to Mars, resulting in 2 years of microgravity conditions, stress the critical need for the development of optimal nutritional programs and physical countermeasures to prevent body mass and function alterations. This review outlines ground models of microgravity simulation, summarizes the major effects of weightlessness on body composition, protein metabolism, hormonal pattern, and muscle function, and addresses contradictory findings related to the oxidative stress secondary to space flight. Potential countermeasures, such as nutrient intake and physical conditioning, as well as areas of interest for future research both in ground and space medicine, are discussed.

Energetic cost of protein turnover in healthy elderly humans.

OBJECTIVE: Whole body protein turnover (PTO) and resting energy expenditure (REE) are both correlated to fat-free mass (FFM), in young and elderly subjects, and REE is positively correlated to PTO in young adults. Thus, the aim of this study was to compare the energetic cost of PTO in young (n=39, 23.4+/-3.1 y) and elderly (n=41, 67.5+/-3.6 y) healthy volunteers. MEASUREMENTS: REE (indirect calorimetry), PTO ((13)C-leucine isotopic dilution) and body composition (bioelectrical impedance analysis with age-specific equations) were measured in the postabsorptive state. RESULTS: Elderly subjects had a higher fatness (30.5+/-7.1 vs 18.2+/-5.5%, elderly vs young, P<0.001), a similar REE (0.97+/-0.13 vs 1.06+/-0.15 kcal min(-1)), and a lower PTO (1.28+/-0.22 vs 1.44+/-0.18 micromol kg(-1) min(-1), P<0.001). PTO, REE and FFM were significantly correlated and after adjustment for FFM, REE was positively correlated to PTO (r=0.61, P<0.001). The slope of this relationship was the same in both groups, while the adjusted mean REE was lower in elderly subjects (0.97+/-0.09 vs 1.05+/-0.07 kcal min(-1), P<0.01). CONCLUSION: In comparison with young subjects, the energetic cost associated with PTO in elderly subjects is not different, but the proportion of REE not associated with PTO is lower.

Isomerization increases the postprandial oxidation of linoleic acid but not alpha-linolenic acid in men.

Human lipid intake contains various amounts of trans fatty acids. Refined vegetable and frying oils, rich in linoleic acid and/or alpha-linolenic acid, are the main dietary sources of trans-18:2 and trans-18:3 fatty acids. The aim of the present study was to compare the oxidation of linoleic acid, alpha-linolenic acid, and their major trans isomers in human volunteers. For that purpose, TG, each containing two molecules of [1-(13)C]linoleic acid, alpha-[1-(13)C]linolenic acid, [1-(13)C]-9cis,12trans-18:2, or [1-(13)C]-9cis,12cis,15trans-18:3, were synthesized. Eight healthy young men ingested labeled TG mixed with 30 g of olive oil. Total CO(2) production and (13)CO(2) excretion were determined over 48 h. The pattern of oxidation was similar for the four fatty acids, with a peak at 8 h and a return to baseline at 24 h. Cumulative oxidation over 8 h of linoleic acid, 9cis,12trans-18:2, alpha-linolenic acid, and 9cis,12cis,15trans-18:3 were, respectively, 14.0 +/- 4.1%, 24.7 +/- 6.7%, 23.6 +/- 3.3%, and 23.4 +/- 3.7% of the oral load, showing that isomerization increases the postprandial oxidation of linoleic acid but not alpha-linolenic acid in men.

Dietary trans alpha-linolenic acid from deodorised rapeseed oil and plasma lipids and lipoproteins in healthy men: the TransLinE Study.

TRANS: isomers of alpha-linolenic acid, which are formed by deodorization of refined vegetable oils, can be found in significant amounts in edible oils. Effects of trans alpha-linolenic acid on plasma lipoproteins are unknown. We therefore investigated the effects of trans alpha-linolenic acid on plasma lipids and lipoproteins in healthy European men. Eighty-eight healthy men from three European countries (France, Scotland, UK and the Netherlands) first consumed for 6 weeks a diet with experimental oils 'free' of trans fatty acids (run-in period). For the next 6 weeks, they were randomly allocated to a diet with experimental oils 'high' or 'low' in trans alpha-linolenic acid. Daily total trans alpha-linolenic acid intake in the high trans group was 1410 (range 583-2642) mg. Experimental oils were provided as such, or incorporated into margarines, cheeses, muffins and biscuits. The high trans alpha-linolenic acid diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % (95 % CI 1.4, 15.3; and the total cholesterol:HDL-cholesterol ratio by 5.1 % (95 % CI 0.4, 9.9; compared with the low-trans diet. This was largely explained by an increase in LDL-cholesterol on the high-trans diet, while no change was observed in the low-trans group (mean treatment effect of 4.7 % (95 % CI -0.8, 10.5; No effects were found on total cholesterol and HDL-cholesterol, triacylglycerols, apolipoprotein B and A-1, and lipoprotein(a) concentrations. In conclusion, trans alpha-linolenic acid may increase plasma LDL-:HDL-cholesterol and total cholesterol:HDL-cholesterol ratios. Whether diet-induced changes in these ratios truly affects the risk for CHD remains to be established.

Reduced whole-body fat oxidation in women and in the elderly.

OBJECTIVE: To test the hypothesis that the increase in fat mass observed with aging might be related to a decrease in whole-body fat oxidation. SUBJECTS AND MEASUREMENTS: Forty volunteers had measurements of sleeping and 24 h substrate oxidation in calorimetric chambers, body composition with the (18)O dilution technique, VO(2)max, and fiber composition analysis from a biopsy of vastus lateralis. They were divided into 10 young women, 10 young men, 10 elderly women and 10 elderly men. RESULTS: Sleeping fat oxidation and 24 h fat oxidation were lower in women than in men and in elderly than in young participants. Sleeping fat oxidation was correlated to fat-free mass and energy balance (multivariate analysis). Twenty four hour fat oxidation was correlated to total energy expenditure and energy balance (multivariate analysis). After adjustment for differences in these factors, sleeping and 24 h fat oxidation were no longer different between age and sex groups. None of the parameters of macronutrient metabolism was correlated with muscle fiber composition. CONCLUSION: Our data suggest that fat oxidation is lower in elderly subjects. This difference could favour fat mass gain if fat intake is not adequately reduced. Differences in fat-free mass and in total energy expenditure appear to participate in the reduction in fat oxidation. International Journal of Obesity (2001) 25, 39-44

Differential insulin sensitivities of glucose, amino acid, and albumin metabolism in elderly men and women.

Regulation of glucose homeostasis by insulin is modified during aging, but whether this alteration is associated with changes in protein metabolism is less defined. Insulin dose responses of whole body glucose, leucine, and albumin metabolism have been investigated using isotopic dilution of D-[6, 6-(2)H(2)]glucose and L-[1-(13)C]leucine in 14 young (Y; 24.0 +/- 0.9 yr; mean +/- SEM, 20.5 +/- 0.4 kg/m(2)) and 12 healthy elderly subjects (E; 69.4 +/- 0.6 yr; 24.6 +/- 0.8 kg/m(2)) using a euglycemic and euaminoacidemic hyperinsulinemic clamp at two insulin infusion rates of 0.2 and 0.5 mU/kg.min (CL1 and CL2, respectively). Despite significantly higher plasma insulin in E than in Y, the glucose disposal rate was lower in E than in Y at both insulin levels, whereas glucose production was normally suppressed. Whole body protein breakdown was less inhibited by insulin in E than in Y at CL1 (-13.5 +/- 1.4% vs. -8.8 +/- 1.3%, Y vs. E, P < 0.05), but not significantly at CL2 (-22.0 +/- 1.4% vs. -18.8 +/- 1.7%, Y vs. E, P = NS). The albumin synthesis rate was identical and stimulated to the same extent by insulin in groups Y and E. Gender affected basal leucine metabolism, but the response to insulin was similar in both groups. In conclusion, decreased insulin action on glucose disposal is associated with a reduced insulin sensitivity for protein breakdown in healthy elderly subjects at low insulin concentrations. Higher insulin levels compensate for a reduced insulin action on protein metabolism in elderly subjects.

The digestion rate of protein is an independent regulating factor of postprandial protein retention.

To evaluate the importance of protein digestion rate on protein deposition, we characterized leucine kinetics after ingestion of "protein" meals of identical amino acid composition and nitrogen contents but of different digestion rates. Four groups of five or six young men received an L-[1-13C]leucine infusion and one of the following 30-g protein meals: a single meal of slowly digested casein (CAS), a single meal of free amino acid mimicking casein composition (AA), a single meal of rapidly digested whey proteins (WP), or repeated meals of whey proteins (RPT-WP) mimicking slow digestion rate. Comparisons were made between "fast" (AA, WP) and "slow" (CAS, RPT-WP) meals of identical amino acid composition (AA vs. CAS, and WP vs. RPT-WP). The fast meals induced a strong, rapid, and transient increase of aminoacidemia, leucine flux, and oxidation. After slow meals, these parameters increased moderately but durably. Postprandial leucine balance over 7 h was higher after the slow than after the fast meals (CAS: 38 +/- 13 vs. AA: -12 +/- 11, P < 0.01; RPT-WP: 87 +/- 25 vs. WP: 6 +/- 19 micromol/kg, P < 0.05). Protein digestion rate is an independent factor modulating postprandial protein deposition.

Muscle fatty acid oxidative capacity is a determinant of whole body fat oxidation in elderly people.

In sedentary elderly people, a reduced muscle fatty acid oxidative capacity (MFOC) may explain a decrease in whole body fat oxidation. Eleven sedentary and seven regularly exercising subjects (65.6 +/- 4. 5 yr) were characterized for their aerobic fitness [maximal O(2) uptake (VO(2 max))/kg fat free mass (FFM)] and their habitual daily physical activity level [free-living daily energy expenditure divided by sleeping metabolic rate (DEE(FLC)/SMR)]. MFOC was determined by incubating homogenates of vastus lateralis muscle with [1-(14)C]palmitate. Whole body fat oxidation was measured by indirect calorimetry over 24 h. MFOC was 40.4 +/- 14.7 and 44.3 +/- 16.3 nmol palmitate. g wet tissue(-1). min(-1) in the sedentary and regularly exercising individuals, respectively (P = nonsignificant). MFOC was positively correlated with DEE(FLC)/SMR (r = 0.58, P < 0. 05) but not with VO(2 max)/kg FFM (r = 0.35, P = nonsignificant). MFOC was the main determinant of fat oxidation during all time periods including physical activity. Indeed, MFOC explained 19.7 and 30.5% of the variance in fat oxidation during walking and during the alert period, respectively (P < 0.05). Furthermore, MFOC explained 23.0% of the variance in fat oxidation over 24 h (P < 0.05). It was concluded that, in elderly people, MFOC may be influenced more by overall daily physical activity than by regular exercising. MFOC is a major determinant of whole body fat oxidation during physical activities and, consequently, over 24 h.

No effect of dietary trans isomers of alpha-linolenic acid on platelet aggregation and haemostatic factors in european healthy men. The TRANSLinE study.

The aim of this study was to investigate the effect of trans alpha-linolenic acid on platelet aggregation and blood haemostasis. A randomized, double blind dietary intervention trial was carried out with healthy male volunteers (n=88) in three European centers. After a 6-week washout period where subjects avoided foods containing all trans fats, subjects either continued for 6 weeks with a low trans diet or a diet where trans alpha-linolenic acid provided 0.6% of energy (supplied as oil, margarine, cheese, muffins, and biscuits). At the end of the washout period the intake of trans polyunsaturated fats was 58+/-115 mg/day; this increased in patients on the high trans diet by +1344+/-328 mg/day, compared with +10+/-67 mg/day in patients on the low trans diet (p<0.01). The change in trans alpha-linolenic acid in plasma cholesteryl esters was 0.26+/-0. 20 on the high trans and 0.00+/-0.07% of fatty acids on the low trans diet (p<0.001). No effect of the high trans diet was observed on platelet aggregation: collagen EC(50) high trans 157+/-100, low trans 152+/-90 ng/mL (NS); U44619 EC(50) high trans 81+/-61, low trans 59+/-27 nM (NS). The high trans diet did not affect platelet thromboxane production, fibrinogen levels, factor VII, activated factor VIIa, or plasminogen activator inhibitor activity. There were no center-specific differences in response to the high trans diet. A relatively high amount of trans alpha-linolenic acid for 6 weeks does not increase the risk of coronary heart disease by promoting platelet aggregation and blood coagulation.

Fat and protein redistribution with aging: metabolic considerations.

Aging is associated with a redistribution of both fat and lean tissue within the body. Intra-abdominal fat (IAF) accumulates more rapidly than total fat while the loss of lean body mass is mostly due to sarcopenia. Increase of visceral fat plays a major role in the pathogenesis of insulin resistance, which leads to type II diabetes and also to cardiovascular diseases. This review is focussed on the relationships that exist between the accumulation of IAF and insulin resistance during aging. The various methods available for assessing IAF are briefly reviewed; imaging techniques are the only reference methods, and their availability is limited. Insulin resistance that appears with aging is caused by accumulation of IAF, rather than by aging per se. Studies done in type II diabetic patients suggest that the metabolic link between increased IAF and insulin resistance could well be the increased availability and/or oxidation of free fatty acids. Physical inactivity certainly enhances both IAF accumulation and, more directly, insulin resistance. Independent and significant effects of menopause or of sarcopenia on insulin resistance remain to be established. The influence of hormonal changes, reduced fatty acid utilization, and resistance to leptin on IAF accumulation are also discussed. Although it is difficult to determine the independent influence of each of these factors, IAF accumulation seems to be a central and important determinant of cardiovascular risk. The last part of this review is devoted to protein metabolism and focused on the preservation of protein metabolism in the liver during aging.

Aging: a barrier to renutrition? Nutritional and immunologic evidence in rats.

BACKGROUND: Previous reports suggest that correcting the malnourished state is more difficult in elderly people than in younger ones and that protein requirements may be higher in elderly than in younger adults. OBJECTIVE: The aim of this study was to establish whether malnourished old rats respond to protein-supplemented nutritional repletion as do young adult rats. DESIGN: Adult (3 mo old) and old (22 mo old) rats were submitted to dietary restriction programs that induced similar metabolic and nutritional alterations. Malnourished adult and old rats were then killed (R groups) or refed for 1 wk with a high-protein diet (HPD; 23% protein) or a very-high-protein diet (VHPD; 27% protein). Control groups at both ages were fed ad libitum throughout the experiment. Effects of food repletion were evaluated in terms of protein metabolism, intestinal histomorphometry, and nonspecific immune status. RESULTS: In adult rats, HPD sufficed to increase body weight and restore basal values of liver weight and protein content (P: < 0.01 compared with the R adult group), nitrogen balance (P: < 0.01 compared with the R adult group), and hydrogen peroxide production by polymorphonuclear neutrophils and monocytes (P: < 0.01 compared with the R group); VHPD had no supplementary effect except on nitrogen balance. In old rats, HPD was less effective and greater benefit was observed with VHPD in terms of body weight gain (10%; P: < 0.01 compared with the old group fed HPD), albuminemia, muscle weight and protein content, plasma arginine concentration, and hydrogen peroxide production by stimulated polymorphonuclear neutrophils and monocytes compared with the old R group (P: < 0.01). CONCLUSION: Aging is a significant variable affecting the response to nutritional support.

Large-scale preparation of (9Z,12E)-[1-(13)C]-octadeca-9,12-dienoic acid, (9Z,12Z,15E)-[1-(13)C]-octadeca-9,12,15-trienoic acid and their [1-(13)C] all-cis isomers.

Several grams of labelled trans linoleic and linolenic acids with high chemical and isomeric purities (>97%) have been prepared for human metabolism studies. A total of 12.5 g of (9Z, 12E)-[1-(13)C]-octadeca-9,12-dienoic acid and 6.3 g of (9Z,12Z, 15E)-[1-(13)C]-octadeca-9,12,15-trienoic acid were obtained in, respectively, seven steps (7.8% overall yield) and 11 steps (7% overall yield) from 7-bromo-heptan-1-ol. The trans bromo precursors used for the labelling were synthesised by using copper-catalysed couplings. The trans fatty acids were then obtained via the nitrile derivatives. A total of 23.5 g of (9Z,12Z)-[1-(13)C]-octadeca-9, 12-dienoic acid and 10.4 g of (9Z,12Z,15Z)-[1-(13)C]-octadeca-9,12, 15-trienoic acid were prepared in five steps in, respectively, 32 and 18% overall yield. Large quantities of bromo and chloro precursors were synthesised from the commercially available acid according to Barton's procedure. In all cases, the main impurities (>0.5%) of each labelled fatty acid have been characterised.

Protein feeding pattern does not affect protein retention in young women.

This study was undertaken to determine whether a pulse protein feeding pattern was more efficient than a spread pattern to improve protein anabolism in young women as was already shown in elderly women. After a 15-d adaptive period [1.2 g protein/(kg fat-free mass. d)], 16 young women (age 26 +/- 1 y) were given a 14-d diet providing 1.7 g protein/(kg fat-free mass. d), using either a pulse pattern (protein consumed mainly in one meal, n = 8), or a spread pattern (spreading daily protein intake over four meals, n = 8). Nitrogen balance was determined at the end of both the 15-d adaptive and the 14-d experimental periods. Whole-body protein turnover was determined at the end of the 14-d experimental period using [(15)N]glycine as an oral tracer. Nitrogen balance was 17 +/- 5 mg N/(kg fat-free mass. d) during the adaptive period. It was higher during the experimental period, but not significantly different in the women fed the spread or the pulse patterns [59 +/- 12 and 36 +/- 8 mg N/(kg fat-free mass. d) respectively]. No significant effects of the protein feeding pattern were detected on either whole-body protein turnover [5.5 +/- 0.2 vs. 6.1 +/- 0.3 g protein/(kg fat-free mass. d) for spread and pulse pattern, respectively] or whole-body protein synthesis and protein breakdown. Thus, in young women, these protein feeding patterns did not have significantly different effects on protein retention.

Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets.

This study was undertaken to determine whether the protein feeding pattern could induce chronic adaptation of protein turnover. After a 15-day adaptive period, elderly (68 yr) and young (26 yr) women received, for 14 days, a diet providing 200 KJ x kg fat-free mass (FFM)(-1) x day(-1), where the daily protein intake (1.7 g protein x kg FFM(-1) x day(-1)) was either spread over 4 meals in the spread pattern or mainly (80%) consumed at noon in the pulse pattern. One day after the end of the dietary treatment, whole body leucine kinetics were measured by use of a continuous [(13)C]leucine infusion, both in the postabsorptive state and in the same fed state. The pulse pattern was able to induce, in young as in elderly women, a lower postabsorptive leucine oxidation and endogenous leucine flux than the spread pattern and improved the responsiveness of nonoxidative leucine disposal during 4-h oral feeding. Thus the pulse pattern was able to induce chronic regulation of protein metabolism in young as in elderly women.