Guest guest Posted September 9, 2006 Report Share Posted September 9, 2006 Hi All, The results from the CALORIE intervention with CR compared with exercisers who did not CR and healthy lifestyle controls who were not to (but did a little) CR have been published for the results to 1 year. All human subjects were not obese, but were overweight. The below paper is pdf-availed. Racette SB, Weiss EP, Villareal DT, Arif H, Steger-May K, Schechtman KB, Fontana L, Klein S, Holloszy JO. One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J Gerontol A Biol Sci Med Sci. 2006 Sep;61(9):943-50. PMID: 16960025 http://tinyurl.com/zw57t ... Caloric restriction (CR) increases maximal life span in short-lived organisms, and its effects are being explored in nonhuman primates. The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity. ... A randomized, controlled trial was conducted with 48 healthy, nonobese women and men, aged 57 +/- 1 (mean +/- standard error [sE]) years, with body mass index 27.3 +/- 0.3 kg/m(2). Participants were randomly assigned to a 20% calorically-restricted diet (CR, n=19), exercise designed to produce a similar energy deficit (EX, n=19), or a healthy lifestyle control group (HL, n=10) for 1 year. Assessments included weight, body composition by dual-energy x-ray absorptiometry, abdominal adipose tissue by magnetic resonance imaging, and energy intake by doubly labeled water. ... The average level of CR achieved by the CR group was 11.5 +/- 2.1%, and the EX group completed 59 +/- 6.7% of their prescribed exercise. Weight changes were greater (p </=.0005) in the CR (-8.0 +/- 0.9 kg) and EX (-6.4 +/- 0.9) groups as compared to the HL group (-1.3 +/- 0.9 kg), corresponding to reductions of 10.7%, 8.4%, and 1.7% of baseline weights, respectively. Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly (p <.005) and comparably in the CR and EX groups, but did not change in the HL group. ... CR for 1 year was feasible, but the level of CR achieved was less than prescribed. CR and exercise were equally effective in reducing weight and adiposity. ... little is known regarding the effects of long-term CR with good nutrition in nonobese humans. ... Cross-sectional data on the effects of longer-term CR were obtained from men and women who had been following a CR diet voluntarily for 6 years (5,6). These individuals had dramatically lower body mass index (BMI), body fat, blood pressure, total and LDL cholesterol, C-reactive protein, and carotid artery intima media thickness (5), as well as greater cardiac function (6), relative to healthy controls. Although these studies in humans were not prospective, they set the stage for controlled CR trials in humans. A set of feasibility studies for human CR, referred to as CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), was completed recently. ... We hypothesized that weight loss induced by exercise would result in proportionately greater fat loss than weight loss induced by CR. ... Healthy, nonobese men and postmenopausal women, aged 50–60 years with a BMI between 23.5 and 29.9 kg/m2, were recruited from the St. Louis metropolitan area ... Exercise training more than twice per week was exclusionary, as were smoking, recent weight loss, eating disorder symptoms, and medications that would affect the outcome measures. ... participants were randomly assigned to the CR, exercise (EX), or healthy lifestyle (HL, control) group in a 2:2:1 sequence. Forty-eight adults (30 women, 18 men) began the intervention, and their data are included in these analyses ... The objective of the CR intervention was to decrease daily energy intake by 16% for the initial 3 months of the intervention and by 20% for the remaining 9 months. ... CR intervention ... Each participant received a prescription of total calories to consume daily (and number of calories to remove relative to their baseline intake), but the macronutrient composition was flexible to accommodate individual preferences. Meals were provided from the General Clinical Research Center metabolic kitchen for 5 consecutive days at week 4 (16% CR) and after the 3-month time point (20% CR) to educate participants on the appropriate serving sizes. Participants attended individual and/or group meetings led by a registered dietitian and behavioral psychologist weekly for the first 6 months of the intervention, and less frequently throughout the last 6 months. The curriculum addressed using food scales, reading nutrition labels, modifying recipes and meals to contain fewer calories, incorporating meal replacements, and using various behavior modification strategies from the LEARN manual (7). CR participants were instructed to set weekly behavioral goals and to attend weekly weigh-in sessions throughout the intervention, and were encouraged to use food diaries or the BalanceLog program (HealtheTech, Inc., Golden, CO) on Palm handhelds (Palm, Inc., Sunnyvale, CA) as a means of daily monitoring to enhance adherence. A multivitamin with mineral supplement was given to participants in all groups. EX Intervention ... The goal of the exercise intervention was to induce an energy deficit comparable to the CR intervention by increasing daily energy expenditure through exercise without changing caloric intake. To enable adaptation to exercise, the EX prescription began at 16% and then increased to 20%. Exercise physiologists and trainers worked with EX participants individually to establish and monitor their exercise routines, which could be performed in our exercise facility (containing treadmills, a track, cycle ergometers, rowing ergometers, elliptical machines, and stairclimbers), a health club, participants' homes, or outdoors. All EX participants were instructed to attend weekly weigh-in sessions throughout the intervention. Because this was not a training study, exercise intensity was not prescribed, and the number of weekly exercise sessions was individualized. Healthy Lifestyle ... The HL group received general information about a healthy diet and was offered free yoga classes, but did not receive a diet or exercise prescription, and had minimal contact with our research team. This group served as a control. ... fat mass (FM), fat-free mass (FFM) ... Total energy expenditure (TEE) .... Energy intake was assessed by [doubly distilled water (DLW)] and food diaries. ... heart rate (HR) ... maximum HR (HRmax) ... Seven-Day Physical Activity Recall Questionnaire (PAR) (11,12) .... metabolic equivalents (METs) ... RESULTS ... Forty-six participants (96%) completed the study; one woman dropped out at 6 months due to inability to adhere to the CR prescription, and one man dropped out of the EX group at 9 months for medical reasons unrelated to the intervention ... Ten eligible individuals withdrew before completing baseline testing (n=7 for study issues; n=3 for personal issues). Attendance at the weekly weigh-in sessions with the dietitians (CR group) and exercise trainers (EX group) was comparable, averaging 84.6±2.8% of the total intervention weeks in the CR group and 85.0±3.2% in the EX group. Adverse events among CR participants included hunger and constipation, whereas EX participants experienced muscle soreness and joint pain. One serious adverse event occurred in CR and one in EX; both were deemed unrelated to the interventions. Table 1. Baseline Characteristics and Intervention Prescriptions. ======================================== Variable CR (N=19) EX (N=19) HL (N=10) ======================================== Age, y* 55.6±0.8 58.8±0.6 56.0±0.9 Gender Female 12 (63%) 12 (63%) 6 (60%) Male 7 (37%) 7 (37%) 4 (40%) Race African American/Black 0 1 (5%) 2 (20%) White 17 (89%) 17 (90%) 7 (70%) Other 2 (11%) 1 (5%) 1 (10%) Education < College degree 4 (21%) 6 (32%) 6 (60%) College degree 4 (21%) 4 (21%) 2 (20%) Graduate school 11 (58%) 9 (47%) 2 (20%) Body mass index, kg/m2 27.2±0.6 27.2±0.4 27.9±0.4 Total daily energy expenditure, kcal/d 2493±114 2508±94 2550±138 Prescribed reduction in energy intake, kcal/d 524±33 0 0 Prescribed increase in energy expenditure, kcal/d 0 563±18 0 ======================================== Notes: Values represent mean±standard error or N (% of participants). *p =.007 for difference between groups. CR=caloric restriction; EX=exercise; HL=healthy lifestyle. Body Weight and Composition ... At baseline, most participants were overweight, with a mean BMI of 27.3±0.3 kg/m2, and body fat of 39±1% in women and 25±1% in men. After 1 year, weight losses were 8.0±0.9 kg in the CR group, 6.4±0.9 kg in the EX group, and 1.3±0.9 kg in the HL group (Table 2), which corresponded to reductions of 10.7%, 8.4%, and 1.7% of baseline body weights, respectively. The time course of weight loss is depicted in Figure 2. There was no correlation between the amount of weight lost and the number of weekly weigh-in sessions attended. BMI values after 1 year were 24.4±0.6 kg/m2, 25.0±0.5 kg/m2, and 27.4±0.5 kg/m2 in the CR, EX, and HL groups, respectively (p <.0001 CR vs HL; p =.0005 EX vs HL). As with the decreases in weight and BMI, reductions in whole-body FM were significantly greater in the CR and EX groups than in the HL group, with no significant difference observed between the CR and EX interventions (Table 2). FM comprised 77% of total weight loss in CR and 87% in EX (median values, p =.31 between groups by Wilcoxon's test). Table 2. Body Weight and Body Composition. ============================================== Variable Time CR EX HL pBetween groups >1 year ============================================== Weight, kg Baseline 78.5±2.3 77.5±2.4 81.9±3.7 3 mo 73.8±2.3 75.4±2.4 80.9±3.7 6 mo 71.7±2.3* 73.3±2.4* 79.8±3.7^§ 9 mo 70.9±2.3 71.9±2.4 80.0±3.7 <.0001 CR vs HL 1 y 70.5±2.3* 71.0±2.4* 80.7±3.7 .0005 EX vs HL % Fat mass Baseline 33.1±1.1 31.7±1.0 32.4±1.0 3 mo 30.5±1.2 29.6±1.0 31.6±1.0 6 mo 28.7±1.2* 27.9±1.0* 31.4±1.1 9 mo 27.8±1.2 27.1±1.0 31.7±1.0 <.0001 CR vs HL 1 y 27.7±1.2* 26.7±1.0* 32.4±1.0 <.0001 EX vs HL Fat mass, kg Baseline 25.9±1.2 24.4±1.3 26.3±1.0 3 mo 22.4±1.2 22.0±1.3 25.2±1.0 6 mo 20.6±1.2* 20.3±1.3* 24.9±1.0^§ 9 mo 19.8±1.2 19.3±1.3 25.0±1.0 <.0001 CR vs HL 1 y 19.7±1.2* 18.9±1.3* 25.9±1.0 <.0001 EX vs HL Fat-free mass, kg Baseline 53.6±1.1 53.9±1.0 56.9±1.1 3 mo 52.2±1.1 54.0±1.0 56.9±1.1 6 mo 51.9±1.1^§ 53.9±1.0 56.4±1.1 9 mo 52.0±1.1 53.2±1.0 56.1±1.1 1 y 51.9±1.1^§ 53.0±1.0 56.2±1.1 ============================================== Notes: Values represent least square means±standard error; body composition measures were adjusted for gender and age. p between groups after 1 year reflects the equality of changes from baseline to 1 year by statistical contrasts, only when overall p </=.05. *p </=.0001, ^§p </=.05 for change within group by contrasts for baseline to 6 mo and baseline to 1 y. CR=caloric restriction; EX=exercise; HL=healthy lifestyle. ... visceral and subcutaneous abdominal adipose tissue decreased significantly in the CR and EX groups, but not in the HL group (Figure 3). Although it appears that exercise caused a greater reduction in visceral fat than did CR, the relative changes were comparable (–39% in EX, –37% in CR), and the absolute changes were not statistically different between CR and EX (p =.46) when the baseline differences were accounted for ... [The healthy lifestyle group had about 1/3 the decrease in the subcutaneous fat and a1/2 of the average visceral fat of the other two groups.] Adherence to CR ... Table 3, energy intake decreased significantly (p <.0001) in the CR group during the first 6 months, as assessed by both DLW and food diaries, with adherence lower during the second half of the intervention. Averaged over the entire year, the CR group achieved 11.5±2.1% CR ... the EX group did not restrict their energy intake, whereas the HL group had an average 2.5±2.1% CR. Self-reported energy intake estimated from the food diaries was consistently lower than DLW-determined intake for all groups. Table 3. Energy Intake Estimated From DLW-Derived Energy Expenditure With DXA-Derived Changes in Body Energy Stores or 7-Day Food Diaries. ================================================ Energy Intake time/interval CR EX HL Overall p between groups ================================================ Energy Intake by DLW/DXA, kcal/d Baseline 2541±122 2471±100 2550±146 Baseline–3 mo 2195±123 2443±100 2468±14 3 mo–6 mo 2156±123* 2435±101 2450±156 6 mo–9 mo 2259±123 2501±102 2512±154 9 mo–1 y 2375±124 2532±103 2501±151 .0 Energy Intake by food diaries, kcal/d Baseline 2081±105 2052±103 2201±151 3 mo 1739±106 2100±103 2075±153 6 mo 1766±105* 2104±104 2149±159 9 mo 1812±105^§ 2132±105 2139±157 1 y 1737±106 2062±107 2265±156 .01 ================================================ Notes: Values represent least square means±standard error from the mixed model. Overall p between groups reflects the equality of changes from baseline to 1 year (however, statistical contrasts between CR and EX or CR and HL did not reach significance). *p </=.0001, ^§p </=.005 for change within group by contrasts for baseline to 6 mo and baseline to 1 y. DLW=doubly labeled water; DXA=dual energy x-ray absorptiometry; CR=caloric restriction; EX=exercise; HL=healthy lifestyle. Adherence to EX ... EX participants exercised 5.8±0.6 sessions/wk, 62.5±4.3 min/session, at an intensity of 72±0% of HRmax, and expended 317±39 kcal/d throughout the intervention, which corresponded to 58.7±6.7% of the exercise prescription. This latter value is likely to be an underestimate, however, because HR data were not recorded for 12.8±4.0% of the exercise sessions .... The most frequently used modes of exercise were walking and/or jogging, using elliptical machines, and using cycle ergometers. .... Table 4, results from the PAR questionnaire indicate that physical activity increased only in the EX group. Likewise, absolute VO2max increased only in the EX group, which contrasts the reduction observed in the CR group, providing additional evidence that weight loss was achieved by CR in the CR participants and by exercise in the EX participants. Table 4. Physical Activity and Fitness at Baseline and After 1 Year of Intervention. ========================================= Variable Time CR EX HL pBetween groups ater 1 Year ========================================= Physical Activity from PAR: MET-h/d above rest Baseline 11.0±0.6 10.4±1.0 9.5±1.4 .002 CR vs EX 1 y 10.1±0.5 14.3±1.0^§ 10.7±1.3 VO2max, L/min Baseline 2.11±0.13 1.97±0.15 2.18±0.23 <.0001 CR vs EX 1 y 1.95±0.05* 2.37±0.05* 1.95±0.07 <.0001 EX vs HL VO2max, ml/kg/min Baseline 26.5±1.1 25.3±1.4 26.0±1.8 .0003 CR vs EX 1 y 27.4±1.0^§ 32.8±1.0* 24.7±1.3 <.0001 EX vs HL ========================================= Notes: Values represent least square means±standard error. Rest was assumed to equal 24 MET-h/d; PAR data were analyzed using ranked values. *p </=.001, ^§p </=.05, for change within group from baseline to 1 y. pBetween groups after 1 year reflects the equality of changes from baseline to 1 y by statistical contrasts. CR=caloric restriction; EX=exercise; HL=healthy lifestyle; PAR=Stanford Seven-Day Physical Activity Recall Questionnaire; MET=metabolic equivalent; VO2max=maximal oxygen uptake. DISCUSSION ... CALERIE is the first clinical trial of CR in nonobese humans, and the present study is the first that directly compares the effects of a long-term, diet-induced energy deficit with a comparable exercise-induced energy deficit on whole-body and abdominal adiposity. Our results support the feasibility of long-term, modest CR, and demonstrate that 1 year of CR reduces whole-body adiposity and abdominal adipose tissue significantly and comparably to exercise. Novel features of this study, as compared to many previous studies of energy restriction, are the relatively long duration of the intervention and the focus on nonobese individuals. Consistent with our observation that, compared to CR, exercise did not significantly enhance the mobilization of visceral adipose tissue stores, Ross and colleagues reported comparable reductions in visceral adipose tissue in response to 3 months of diet- or exercise-induced weight loss among men [the free full text http://www.annals.org/cgi/reprint/133/2/92.pdf paper] and premenopausal women (15) with abdominal obesity. In contrast to our results, however, they found that exercisers lost more total FM than did dieters (14,15), and that female exercisers lost more abdominal subcutaneous adipose tissue than did female dieters (15). This discrepancy with our results may be explained by differences in study design, including the older age and lower BMI of our participants, or the longer duration of our intervention. A potential adverse consequence of CR in the present and previous (14) studies is a reduction in FFM, which was accompanied in the present study by a small decrement in absolute VO2max (i.e., L/min). The clinical importance of these changes is unclear. As expected (16,17), exercise helped to preserve lean mass during weight loss and promoted increases in VO2max in the present study. One of the most dramatic effects of life-prolonging CR in rodents is prevention of the large increase in body fat that normally occurs with advancing age in sedentary animals fed ad libitum. It has been hypothesized that maintenance of leanness is importantly involved in the mechanism by which CR slows aging (18). In support of this hypothesis, Blüher and colleagues (19) reported that adipocyte-specific insulin receptor knockout mice have lower FM and increased maximal life span despite normal food intake. As shown in the present study, exercise without CR can be as effective as CR alone in reducing body fat stores, and people who regularly engage in endurance exercise generally stay lean (20). However, although regular exercise helps protect against secondary aging (i.e., physiological declines and disease processes attributable to modifiable lifestyle factors), there is no evidence that exercise slows primary aging (i.e., physiological declines attributable to the aging process itself). Research on rats, in which aging over the life span can be studied under controlled conditions, has shown clearly that maintenance of leanness by means of exercise does not slow primary aging (i.e., does not increase maximal life span). In these studies (21–23), male rats given access to running wheels were compared to sedentary animals in which food intake was restricted 30% to match their body weights to those of the runners. As in many previous studies, the CR rats had increases in average and maximal longevity. In contrast, the runners had a 10% increase in average longevity but no increase in maximal longevity (21 [= the free full-text http://tinyurl.com/qgxe3 paper] –23), despite the observation that exercise prevents body fat accumulation and insulin resistance with advancing age more effectively than CR does (24,25). Therefore, although CR and exercise have many similar benefits, CR has a unique ability to slow primary aging in short-lived organisms. A comparison of long-term CR and exercise in humans may reveal the adaptive response unique to CR that could be involved in slowing primary aging. ... adherence to the prescribed CR and EX regimens was less than 100%. It is difficult for adults in our society to follow a CR diet long-term, as evidenced by the high prevalence of overweight and obese individuals (26). Despite relatively high adherence to the CR diet for the first 6 months, participants in the present study were unable to maintain 20% CR during the final 6 months. Furthermore, the large volume of exercise needed to achieve a 20% increase in daily energy expenditure required approximately 90 minutes every day. Nevertheless, our results provide strong evidence that the CR group did follow a calorically-restricted diet throughout the intervention, and that the EX group lost weight through exercise and not by dieting. Importantly, our CR participants were responsible for purchasing and preparing their own meals, and we did not provide financial incentives for adherence or study completion. Another limitation is that a few HL participants lost a significant amount of weight by 6 months, which may be attributable to the fact that individuals who enrolled in this study were ready to make lifestyle changes, and were able to do so with minimal intervention from the research team. The low rate of study attrition (4%) is encouraging as we prepare to initiate phase 2 of the CALERIE trial. Summary ... Our results support the feasibility of long-term, albeit modest, CR, and provide evidence for beneficial changes in whole-body adiposity and abdominal visceral and subcutaneous adipose tissue that are comparable to exercise-induced alterations. -- Al Pater, alpater@... -- Al Pater, PhD; email: old542000@... __________________________________________________ Quote Link to comment Share on other sites More sharing options...
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