Joseph J. Kehayias

Exercise Training and Nutritional Supplementation for Physical Frailty in Very Elderly People

BACKGROUND Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied. METHODS We conducted a randomized, placebo-controlled trial comparing progressive resistance exercise training, multinutrient supplementation, both interventions, and neither in 100 frail nursing home residents over a 10-week period. RESULTS The mean (+/- SE) age of the 63 women and 37 men enrolled in the study was 87.1 +/- 0.6 years (range, 72 to 98); 94 percent of the subjects completed the study. Muscle strength increased by 113 +/- 8 percent in the subjects who underwent exercise training, as compared with 3 +/- 9 percent in the nonexercising subjects (P < 0.001). Gait velocity increased by 11.8 +/- 3.8 percent in the exercisers but declined by 1.0 +/- 3.8 percent in the nonexercisers (P = 0.02). Stair-climbing power also improved in the exercisers as compared with the nonexercisers (by 28.4 +/- 6.6 percent vs. 3.6 +/- 6.7 percent, P = 0.01), as did the level of spontaneous physical activity. Cross-sectional thigh-muscle area increased by 2.7 +/- 1.8 percent in the exercisers but declined by 1.8 +/- 2.0 percent in the nonexercisers (P = 0.11). The nutritional supplement had no effect on any primary outcome measure. Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation. CONCLUSIONS High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people. In contrast, multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty.

Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation.

The cytokines IL-1 beta and TNF-alpha cause cachexia and hypermetabolism in animal models, but their role in human inflammation remains controversial. The relationship between in vitro cytokine production and metabolism was examined in 23 adults with RA and 23 healthy control subjects matched on age, sex, race, and weight. Body composition was measured by multicompartmental analysis of body cell mass, water, fat, and bone mass. Resting energy expenditure (REE) was measured by indirect calorimetry. Cytokine production by PBMC was measured by radioimmunoassay. Usual energy intake, physical activity, disability scores, medication use, and other confounders were also measured. Body cell mass was 13% lower (P < 0.00001), REE was 12% higher (P < 0.008), and physical activity was much lower (P < 0.001) in subjects with RA. Production of TNF-alpha was higher in RA than controls, both before and after stimulation with endotoxin (P < 0.05), while production of IL-1 beta was higher with endotoxin stimulation (P < 0.01). In multivariate analysis, cytokine production was directly associated with REE (P < 0.001) in patients but not in controls. While energy and protein intake were similar in the two groups and exceeded the Recommended Dietary Allowances, energy intake in subjects with RA was inversely associated with IL-1 beta production (P < 0.005). In this study we conclude that: loss of body cell mass is common in RA; cytokine production in RA is associated with altered energy metabolism and intake, despite a theoretically adequate diet; and TNF-alpha and IL-1 beta modulate energy metabolism and body composition in RA.

Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders

To assess muscle remodeling and functional adaptation to exercise and diet interventions, 26 men and women aged 72-98 yr underwent a vastus lateralis biopsy before and after placebo control condition, and progressive resistance training, multinutrient supplementation, or both. Type II atrophy, Z band, and myofibril damage were present at baseline. Combined weight lifting and nutritional supplementation increased strength by 257 ± 62% ( P = 0.0001) and type II fiber area by 10.1 ± 9.0% ( P = 0.033), with a similar trend for type I fiber area (+12.8 ± 22.2%). Exercise was associated with a 2.5-fold increase in neonatal myosin staining ( P = 0.0009) and an increase of 491 ± 137% ( P < 0.0001) in IGF-I staining. Ultrastructural damage increased by 141 ± 59% after exercise training ( P = 0.034). Strength increases were largest in those with the greatest increases in myosin, IGF-I, damage, and caloric intake during the trial. Age-related sarcopenia appears largely confined to type II muscle fibers. Frail elders respond robustly to resistance training with musculoskeletal remodeling, and significant increases in muscle area are possible with resistance training in combination with adequate energy intakes.

The Boston FICSIT study : the effects of resistance training and nutritional supplementation on physical frailty in the oldest old

Research indicates that lower extremity muscle weakness in the elderly is consistently related to impaired mobility and fall risk. Reversible components of the muscle weakness of aging include underuse syndromes and undernutrition, both of which are prevalent in nursing home populations. The Boston FICSIT study is a nursing home‐based intervention to improve muscle strength through progressive resistance training of the lower extremities and/or multi‐nutrient supplementation in chronically institutionalized subjects aged 70–100. Baseline measurements of falls, medical status, psychological variables, functional status, nutritional intake and status, body composition, muscle mass and morphology, muscle function, and gait and balance are taken. The nursing home residents are then randomly assigned to one of four treatment groups for 10 weeks: (1) high intensity progressive resistance training of the hip and knee extensors 3 days per week; (2) multi‐nutrient supplementation with a 360‐kcal high carbohydrate, low fat liquid supplement every day; (3) a combination of groups (1) and (2); and (4) a control group. Both non‐supplemented groups receive a liquid placebo every day, and both non‐exercising groups attend three sessions of “leisure activities” every week in order to control for the attentional aspects of the exercise and nutritional interventions. At the end of the 10‐week period, all baseline measurements are re‐assessed.

Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?

BACKGROUND The cancer cachexia syndrome occurs in patients with non-small cell lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This increase in REE leads to weight loss, which in turn confers a poor prognosis. This study was undertaken to determine whether the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC. METHODS In this case-control study, 18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy controls on age (+/- 5 years), gender, and body mass index (+/- 3 kg/m2). Only 4 cancer patients had experienced > 5% weight loss. Cancer patients and controls were compared on the basis of: (1) unadjusted REE, as measured by indirect calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40 measurement; and (4) REE adjusted for total body water, as measured by tritiated water dilution. RESULTS We observed no significant difference in unadjusted REE or in REE adjusted for total body water. However, with separate adjustments for lean body mass and body cell mass, cancer patients manifested an increase in REE: mean difference +/- standard error of the mean: 140+/-35 kcal/day (p = 0.001) and 173+/-65 kcal/day (p = 0.032), respectively. Further adjustment for weight loss yielded similarly significant results. CONCLUSIONS These results suggest that the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and raise the question of whether clinical trials that target cancer cachexia should be initiated before weight loss.

Use of the Zetatron D-T neutron generator for the simultaneous measurement of carbon, oxygen, and hydrogen in vivo in humans

Abstract A small sealed D-T neutron generator is used for the pulsed (4–8 kHz) production of fast neutrons. Carbon and oxygen are detected in vivo by counting the 4.44 and 6.13 MeV gamma rays resulting from the inelastic scattering of the fast neutrons. Hydrogen is detected by thermal neutron capture. BGO detectors (127 mm diameter × 76 mm thick) were found more tolerant to neutron exposure and improved the signal to background ratio for the carbon detection by a factor of 6, compared to 152 × 152 mm NaI(Tl). The elemental analysis of the body is used to study the changes of body composition with aging. We investigate the causes of depletion of lean body mass and the development of ways of maintaining functional capacity and quality of life of the elderly.

Aging and body composition: possibilities for future studies.

Three approaches are being taken to the development of techniques for measuring body composition: 1) improving present methods, 2) formulating and devising new body composition measuring techniques and 3) focusing on specific problems of body composition changes in aging. The improvement of multi-frequency bioelectrical impedance, computerized tomography, magnetic resonance and dual-photon absorptiometry imaging belong under the first category. Recent developments in low radiation exposure measurement of body carbon and oxygen by neutron inelastic scattering and body protein by gamma-ray resonance are examples of new technology applied to the direct assessment of body composition of the elderly. The third category remains the most important one and should motivate the evolution of existing methods and the development of new. Current questions focus on distribution of regional body fat and its role in cardiovascular diseases and the depletion of lean body mass with age and its relation to functional capacity, quality of life and resistance to injury or disease. The relationship between the distribution of fat, the depletion of muscle tissue and changes in cellular function with age will become the focus of the future studies of body composition.

Dual Photon Absorptiometry: Validation of Mineral and Fat Measurements

Photons passing through human tissue undergo attenuation in relation to the specific chemical substances with which they interact. Soft tissues, consisting largely of water and organic compounds, reduce photon flux to a lesser extent than bone mineral, which contains the intermediate-Z element calcium. By selecting two appropriate photon energies and recording their attenuation, the investigator can solve simultaneous equations that subdivide body mass into two components: soft tissue and bone mineral ash (Heymsfield, et al., 1989b). Systems are now available that use either a 153-Gadolinium (153Gd) source that generates photons with energies at 100 KeV and 44 KeV or filtered X-rays with energies at about 70 KeV and 40 KeV. Instruments that rely on these sources are referred to as dual photon absorptiometers (DPA) and dual energy X-ray absorptiometers (DEXA), respectively.

Water homeostasis, frailty and cognitive function in the nursing home

ObjectiveTo develop and test a practical clinical method to assess frailty in nursing homes; — To investigate the relationship between cognitive status of the elderly and the balance between water compartments of their body composition.Design and subjectsCross-sectional study, conducted at two nursing homes in Boston-MA.MethodsBody mass and height (Ht) were evaluated to calculate BMI (body mass index, in Kg/m2). The cognitive decline was evaluated based on the scores obtained from the Mini-Mental State Examination (MMSE); The extracellular to total body water ratio (ECW/TBW) was calculated after the analysis of TBW from deuterium and tritium dilution and ECW from bromide dilution. Single-frequency BIA analysis data were investigated for resistance (R) and reactance (Xc), plotted in an R/Ht Xc/Ht graph (vectorial analysis-BIVA). The BIVA results of nursing home residents were compared against the data obtained from the NHANES III study. TBW and ECW values were compared with a group of free-living elderly volunteers.ResultsThe ECW/TBW was significantly higher in nursing home residents than in the free-living individuals. BIVA analysis showed significantly higher Xc/Ht values in the reference subjects. The MMSE did not present a significant correlation with ECW/TBW for either gender.ConclusionWe proposed the ECW/TBW ratio and BIVA as surrogate methods for the clinical assessment of frailty. We tested successfully both approaches with nursing home patients and free-living volunteers and compared them to a national data base. The advent of new, portable instruments will enable field tests to further validate our proposed “Frailty Factor” in future studies. We found no correlation between frailty and cognitive decline in the nursing home.

Neutron activation analysis determination of body composition.

The nutritional status of patients can be evaluated by monitoring changes in body composition, including the depletion of protein and muscle, adipose tissue distribution and changes in hydration status, bone or cell mass. Neutron activation analysis is a unique reference tool for the in-vivo determination of body composition. In this review we describe the recent changes in the field that followed the advent of new portable generators of fast neutrons, capable of performing elemental analysis in the clinical environment. New models were developed based on the partition of the measurable elements of the body. The recent developments help evaluate new treatments for wasting and obesity, in which change in body composition is the main outcome.