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1.  Effect of Diet Composition on Energy Expenditure during Weight Loss: The POUNDS LOST Study 
Background
Weight loss reduces energy expenditure, but the contribution of different macronutrients to this change is unclear.
Hypothesis
We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss.
Design
A sub-study of 99 participants from the POUNDS LOST trial had total energy expenditure (TEE) measured by doubly labeled water and resting energy expenditure (REE) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants. Participants were randomly assigned to one of 4 diets with either 15% or 25% protein and 20% or 40% fat.
Results
TEE and REE were positively correlated with each other and with fat free mass and body fat, at baseline and 6 months. The average weight loss of 8.1±0.65 kg (LSmean±SE) reduced TEE by 120±56 kcal/d and REE by 136±18 kcal/d. A greater weight loss at 6 months was associated with a greater decrease in TEE and REE. Participants eating the high fat diet lost significantly more fat free mass (1.52±0.55 kg) than the low fat diet group (p<0.05). Participants eating the low fat diet had significantly higher measures of physical activity than the high fat group.
Conclusion
A greater weight loss was associated with a larger decrease in both TEE and REE. The low fat diet was associated with significant changes in fat free body mass and energy expenditure from physical activity compared to the high fat diet.
doi:10.1038/ijo.2011.173
PMCID: PMC3289771  PMID: 21946707
2.  Control in the Middle (CIM) for Three Period Crossover Studies 
Planta Medica  2011;77(13):1473-1476.
Three period crossover studies can be efficient and convenient methods of conducting Phase II clinical trials. Non-randomly placing control in the middle (CIM) has not been practiced, but may be extremely useful in studies testing herbal products for which placebos are not available, or for distinguishing between behavioral and biological effects. Furthermore, this design can serve as a valuable addition to classical studies of either (a) two competing treatments or (b) treatment versus placebo versus an open label “nothing” as the control. Therefore, we propose rigorous designs that will help practitioners efficiently answer research questions where (1) two active treatments need to be compared against each other with treatment vs. placebo comparisons of secondary importance; (2) a single active treatment needs to be tested where no placebo is available; or (3) the placebo effect is of interest in a treatment vs. placebo trial. For studies where no placebo is available, deception will be required, with participants told that in one randomly selected period (#1 or #3) they will receive the active treatment, and that they will receive a new experimental inert placebo in the other period. Assuming this design is approved by an ethics committee, it can be very useful in biomedical research.
doi:10.1055/s-0030-1271044
PMCID: PMC3296130  PMID: 21509714
blinding; crossover study; deception; phase II clinical trial; placebo; washout
3.  An Exploratory Analysis of the Effects of a Weight Loss Plus Exercise Program on Cellular Quality Control Mechanisms in Older Overweight Women 
Rejuvenation Research  2011;14(3):315-324.
Abstract
Obese older adults are particularly susceptible to sarcopenia and have a higher prevalence of disability than their peers of normal weight. Interventions to improve body composition in late life are crucial to maintaining independence. The main mechanisms underlying sarcopenia have not been determined conclusively, but chronic inflammation, apoptosis, and impaired mitochondrial function are believed to play important roles. It has yet to be determined whether impaired cellular quality control mechanisms contribute to this process. The objective of this study was to assess the effects of a 6-month weight loss program combined with moderate-intensity exercise on the cellular quality control mechanisms autophagy and ubiquitin-proteasome, as well as on inflammation, apoptosis, and mitochondrial function, in the skeletal muscle of older obese women. The intervention resulted in significant weight loss (8.0 ± 3.9 % vs. 0.4 ± 3.1% of baseline weight, p = 0.002) and improvements in walking speed (reduced time to walk 400 meters, − 20.4 ± 16% vs. − 2.5 ± 12%, p = 0.03). In the intervention group, we observed a three-fold increase in messenger RNA (mRNA) levels of the autophagy regulators LC3B, Atg7, and lysosome-associated membrane protein-2 (LAMP-2) compared to controls. Changes in mRNA levels of FoxO3A and its targets MuRF1, MAFBx, and BNIP3 were on average seven-fold higher in the intervention group compared to controls, but these differences were not statistically significant. Tumor necrosis factor-α (TNF-α) mRNA levels were elevated after the intervention, but we did not detect significant changes in the downstream apoptosis markers caspase 8 and 3. Mitochondrial biogenesis markers (PGC1α and TFAm) were increased by the intervention, but this was not accompanied by significant changes in mitochondrial complex content and activity. In conclusion, although exploratory in nature, this study is among the first to report the stimulation of cellular quality control mechanisms elicited by a weight loss and exercise program in older obese women.
doi:10.1089/rej.2010.1132
PMCID: PMC3136739  PMID: 21631380
4.  Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels 
Appetite  2010;55(1):37-43.
Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low-calorie sweeteners may be an efficacious weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels. Design: 19 healthy lean (BMI = 20.0 – 24.9) and 12 obese (BMI = 30.0 – 39.9) individuals 18 to 50 years old completed three separate food test days during which they received preloads containing stevia (290 kcal), aspartame (290 kcal), or sucrose (493 kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20 minutes after the lunch preload. Despite the caloric difference in preloads (290 vs. 493 kcals), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia = 301 kcal, p < .01; aspartame = 330 kcal, p < .01). Self-reported hunger and satiety levels did not differ by condition. Stevia preloads significantly lowered postprandial glucose levels compared to sucrose preloads (p < .01), and postprandial insulin levels compared to both aspartame and sucrose preloads (p < .05). When consuming stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload.
doi:10.1016/j.appet.2010.03.009
PMCID: PMC2900484  PMID: 20303371
Stevia; Aspartame; Sucrose; Food Intake; Satiety; Hunger; Insulinogenic Index; Insulin Sensitivity
5.  The Impact of Behavioral Intervention on Obesity Mediated Declines in Mobility Function: Implications for Longevity 
Journal of Aging Research  2011;2011:392510.
A primary focus of longevity research is to identify prognostic risk factors that can be mediated by early treatment efforts. To date, much of this work has focused on understanding the biological processes that may contribute to aging process and age-related disease conditions. Although such processes are undoubtedly important, no current biological intervention aimed at increasing health and lifespan exists. Interestingly, a close relationship between mobility performance and the aging process has been documented in older adults. For example, recent studies have identified functional status, as assessed by walking speed, as a strong predictor of major health outcomes, including mortality, in older adults. This paper aims to describe the relationship between the comorbidities related to decreased health and lifespan and mobility function in obese, older adults. Concurrently, lifestyle interventions, including diet and exercise, are described as a means to improve mobility function and thereby limit the functional limitations associated with increased mortality.
doi:10.4061/2011/392510
PMCID: PMC3195552  PMID: 22013527
6.  Adherence is a multi-dimensional construct in the POUNDS LOST trial 
Journal of behavioral medicine  2009;33(1):35-46.
Research on the conceptualization of adherence to treatment has not addressed a key question: Is adherence best defined as being a uni-dimensional or multi-dimensional behavioral construct? The primary aim of this study was to test which of these conceptual models best described adherence to a weight management program. This ancillary study was conducted as a part of the POUNDS LOST trial that tested the efficacy of four dietary macro-nutrient compositions for promoting weight loss. A sample of 811 overweight/obese adults was recruited across two clinical sites, and each participant was randomly assigned to one of four macronutrient prescriptions: (1) Low fat (20% of energy), average protein (15% of energy); (2) High fat (40%), average protein (15%); (3) Low fat (20%), high protein (25%); (4) High fat (40%), high protein (25%). Throughout the first 6 months of the study, a computer tracking system collected data on eight indicators of adherence. Computer tracking data from the initial 6 months of the intervention were analyzed using exploratory and confirmatory analyses. Two factors (accounting for 66% of the variance) were identified and confirmed: (1) behavioral adherence and (2) dietary adherence. Behavioral adherence did not differ across the four interventions, but prescription of a high fat diet (vs. a low fat diet) was found to be associated with higher levels of dietary adherence. The findings of this study indicated that adherence to a weight management program was best conceptualized as being multi-dimensional, with two dimensions: behavioral and dietary adherence.
doi:10.1007/s10865-009-9230-7
PMCID: PMC3153914  PMID: 19856202
Adherence; Overweight; Obesity; Randomized controlled trial; Lifestyle behavior modification
7.  Early behavioral adherence predicts short and long-term weight loss in the POUNDS LOST study 
Journal of behavioral medicine  2010;33(4):305-314.
The primary aim of this study was to test the association of early (first 6 months) adherence related to diet, self-monitoring, and attendance with changes in adiposity and cardiovascular risk factors. This study used data from the 24-month POUNDS LOST trial that tested the efficacy of four dietary macronutrient compositions for short-and long-term weight loss. A computer tracking system was used to record data on eight indicator variables related to adherence. Using canonical correlations at the 6 and 24 month measurement periods, early behavioral adherence was associated with changes in percent weight loss and waist circumference at 6 months (R = 0.52) and 24 months (R = 0.37), but was not associated with cardiovascular disease risk factor levels. Early dietary adherence was associated with changes in insulin at 6 months (R = 0.19), but not at 24 months (R = 0.08, ns). Early dietary adherence was not associated with changes in adiposity.
doi:10.1007/s10865-010-9253-0
PMCID: PMC3150109  PMID: 20195742
Obesity; Weight management; Adherence; Computer tracking; Waist circumference; Insulin
8.  Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial 
Background:
Obesity and a sedentary lifestyle are associated with physical impairments and biologic changes in older adults. Weight loss combined with exercise may reduce inflammation and improve physical functioning in overweight, sedentary, older adults. This study tested whether a weight loss program combined with moderate exercise could improve physical function in obese, older adult women.
Methods:
Participants (N = 34) were generally healthy, obese, older adult women (age range 55–79 years) with mild to moderate physical impairments (ie, functional limitations). Participants were randomly assigned to one of two groups for 24 weeks: (i) weight loss plus exercise (WL+E; n = 17; mean age = 63.7 years [4.5]) or (ii) educational control (n = 17; mean age = 63.7 [6.7]). In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions within their community each week. During exercise sessions, participants engaged in brisk walking and lower-body resistance training of moderate intensity. Participants in the educational control group attended monthly health education lectures on topics relevant to older adults. Outcomes were: (i) body weight, (ii) walking speed (assessed by 400-meter walk test), (iii) the Short Physical Performance Battery (SPPB), and (iv) knee extension isokinetic strength.
Results:
Participants randomized to the WL+E group lost significantly more weight than participants in the educational control group (5.95 [0.992] vs 0.23 [0.99] kg; P < 0.01). Additionally, the walking speed of participants in the WL+E group significantly increased compared with that of the control group (reduction in time on the 400-meter walk test = 44 seconds; P < 0.05). Scores on the SPPB improved in both the intervention and educational control groups from pre- to post-test (P < 0.05), with significant differences between groups (P = 0.02). Knee extension strength was maintained in both groups.
Conclusion:
Our findings suggest that a lifestyle-based weight loss program consisting of moderate caloric restriction plus moderate exercise can produce significant weight loss and improve physical function while maintaining muscle strength in obese, older adult women with mild to moderate physical impairments.
doi:10.2147/CIA.S17001
PMCID: PMC3131984  PMID: 21753869
obesity; weight loss; physical function; oxidative stress; inflammation; walking speed
9.  An Environmental Intervention to Prevent Excess Weight Gain in African American Students: A Pilot Study 
Purpose
Examine the influence of an environmental intervention to prevent excess weight gain in African American children.
Design
Single-group repeated measures.
Setting
The intervention was delivered to a school composed of African American children.
Subjects
Approximately 45% (N = 77) of enrolled second through sixth grade students.
Intervention
The 18-month intervention was designed to alter the school environment to prevent excess weight gain by making healthier eating choices and physical activity opportunities more available.
Measures
Body Mass Index Percentile was the primary outcome variable. Body mass index Z-score was also calculated, and percent body fat, using bioelectrical impedance, was also measured. Total caloric intake (kcal), and percent kcal from fat, carbohydrate, and protein were measured by digital photography. Minutes of physical activity and sedentary behavior were self-reported.
Analysis
Mixed models analysis was used, covarying baseline values.
Results
Boys maintained while girls increased percent body fat over 18-months (p = .027). All children decreased percent of kcal consumed from total and saturated fat, and increased carbohydrate intake and self-reported physical activity during the intervention (p values < .025). body mass index Z-score, sedentary behavior, and total caloric intake were unchanged.
Conclusion
The program may have resulted in maintenance of percent body fat in boys. Girl's percent body fat steadily increased, despite similar behavioral changes as boys. School-based interventions targeting African American children should investigate strategies that can be effective across gender.
PMCID: PMC2871317  PMID: 20465148
blacks; obesity; children; nutrition; physical activity; Manuscript format: research; Research purpose: intervention testing/program evaluation; Study design: quasi-experimental; Outcome measure: behavioral; Setting: school; Health focus: weight control; Strategy: environmental change; Target population age: youth; Target population circumstances: race/ethnicity
10.  Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives 
Clinics in geriatric medicine  2009;25(4):715-732.
Synopsis
Evidence from animal models and preliminary studies in humans indicate that calorie restriction (CR) delays cardiac aging and can prevent cardiovascular disease. These effects are mediated by a wide spectrum of biochemical and cellular adaptations, including redox homeostasis, mitochondrial function, inflammation, apoptosis and autophagy. Despite the beneficial effects of CR, its large-scale implementation is challenged by applicability issues as well as health concerns. However, preclinical studies indicate that specific compounds, such as resveratrol, may mimic many of the effects of CR, thus potentially obviating the need for drastic food intake reductions. Results from ongoing clinical trials will reveal whether the intriguing alternative of CR mimetics represents a safe and effective strategy to promote cardiovascular health and delay cardiac aging in humans.
doi:10.1016/j.cger.2009.07.002
PMCID: PMC2786899  PMID: 19944269
Cardiovascular disease; oxidative stress; inflammation; apoptosis; autophagy; calorie restriction mimetics
11.  Beneficial Effects of a Q-ter® Based Nutritional Mixture on Functional Performance, Mitochondrial Function, and Oxidative Stress in Rats 
PLoS ONE  2010;5(5):e10572.
Background
Mitochondrial dysfunction and oxidative stress are central mechanisms underlying the aging process and the pathogenesis of many age-related diseases. Selected antioxidants and specific combinations of nutritional compounds could target many biochemical pathways that affect both oxidative stress and mitochondrial function and, thereby, preserve or enhance physical performance.
Methodology/Principal Findings
In this study, we evaluated the potential anti-aging benefits of a Q-ter® based nutritional mixture (commercially known as Eufortyn®) mainly containing the following compounds: terclatrated coenzyme Q10 (Q-ter®), creatine and a standardized ginseng extract. We found that Eufortyn® supplementation significantly ameliorated the age-associated decreases in grip strength and gastrocnemius subsarcolemmal mitochondria Ca2+ retention capacity when initiated in male Fischer344 x Brown Norway rats at 21 months, but not 29 months, of age. Moreover, the increases in muscle RNA oxidation and subsarcolemmal mitochondrial protein carbonyl levels, as well as the decline of total urine antioxidant power, which develop late in life, were mitigated by Eufortyn® supplementation in rats at 29 months of age.
Conclusions/Significance
These data imply that Eufortyn® is efficacious in reducing oxidative damage, improving the age-related mitochondrial functional decline, and preserving physical performance when initiated in animals at early midlife (21 months). The efficacy varied, however, according to the age at which the supplementation was provided, as initiation in late middle age (29 months) was incapable of restoring grip strength and mitochondrial function. Therefore, the Eufortyn® supplementation may be particularly beneficial when initiated prior to major biological and functional declines that appear to occur with advancing age.
doi:10.1371/journal.pone.0010572
PMCID: PMC2868025  PMID: 20485503
12.  The association between energy intake and viewing television, distractibility, and memory for advertisements 
Background
The effect of television viewing (TVV) with and without advertisements (ads) on energy intake is unclear.
Objective
To test: 1) the effect of TVV, with and without ads, on energy intake compared to a control and reading condition, and 2) the association of distractibility and memory for ads with energy intake and body weight.
Design
Forty-eight (26 female) adults (age 19 to 54 years) with body mass index 20 to 35 kg/m2 completed this laboratory-based study. All participants completed four buffet-style meals in random order: 1) control, 2) reading, 3) TV-with food and non-food ads (TV-ads), 4) TV-no ads. Energy intake was quantified by weighing foods. Distractibility and memory for ads in the TV-ads condition were quantified with a norm-referenced test and recognition task, respectively.
Results
Repeated measures analysis of variance indicated that energy and macronutrient intake did not differ significantly among the four conditions (p-values>0.65). Controlling for sex, memory for advertisements was associated with body weight (r=0.36, p<0.05) and energy intake, but only when viewing TV (r=0.39, p<0.05 during the TV-no ads condition and r=0.29, p=0.06 during the TV-ads condition). Controlling for sex, distractibility was associated with body weight (r=0.36, p<0.05), but not energy intake. Distractibility, however, accounted for 13% of the variance in men's energy intake (p=0.11).
Conclusions
TVV did not affect energy intake, but individual characteristics (memory for advertisements) were associated with body weight and energy intake in certain conditions. These characteristics should be considered in food intake and intervention studies.
doi:10.3945/ajcn.2008.26310
PMCID: PMC2615456  PMID: 19056603
food intake; television; advertisements; energy intake; television viewing
13.  Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates 
The New England journal of medicine  2009;360(9):859-873.
BACKGROUND
The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year.
METHODS
We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content.
RESULTS
At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels.
CONCLUSIONS
Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize.
doi:10.1056/NEJMoa0804748
PMCID: PMC2763382  PMID: 19246357
14.  Effects of Chromium Picolinate on Food Intake and Satiety 
Abstract
Background
Chromium picolinate (CrPic) has been shown to attenuate weight gain, but the mechanism underlying this effect is unknown.
Methods
We assessed the effect of CrPic in modulating food intake in healthy, overweight, adult women who reported craving carbohydrates (Study 1) and performed confirmatory studies in Sprague-Dawley rats (Study 2). Study 1 utilized a double-blind placebo-controlled design and randomly assigned 42 overweight adult women with carbohydrate cravings to receive 1,000 μg of chromium as CrPic or placebo for 8 weeks. Food intake at breakfast, lunch, and dinner was directly measured at baseline, week 1, and week 8. For Study 2, Sprague-Dawley rats were fasted for 24 h and subsequently injected intraperitoneally with 0, 1, 10, or 50 μg/kg CrPic. Subsequently, rats were implanted with an indwelling third ventricular cannula. Following recovery, 0, 0.4, 4, or 40 ng of CrPic was injected directly into the brain via the intracerebroventricular cannula, and spontaneous 24-h food intake was measured.
Results
Study 1 demonstrated that CrPic, as compared to placebo, reduced food intake (P < 0.0001), hunger levels (P < 0.05), and fat cravings (P < 0.0001) and tended to decrease body weight (P = 0.08). In study 2, intraperitoneal administration resulted in a subtle decrease in food intake at only the highest dose (P = 0.03). However, when administered centrally, CrPic dose-dependently decreased food intake (P < 0.05).
Conclusions
These data suggest CrPic has a role in food intake regulation, which may be mediated by a direct effect on the brain.
doi:10.1089/dia.2007.0292
PMCID: PMC2753428  PMID: 18715218
15.  Effects of Chromium Picolinate on Food Intake and Satiety 
Background:
Chromium picolinate (CrPic) has been shown to attenuate weight gain, but the mechanism underlying this effect is unknown.
Methods:
We assessed the effect of CrPic in modulating food intake in healthy, overweight, adult women who reported craving carbohydrates (Study 1) and performed confirmatory studies in Sprague-Dawley rats (Study 2). Study 1 utilized a double-blind placebo-controlled design and randomly assigned 42 overweight adult women with carbohydrate cravings to receive 1,000 mg of CrPic or placebo for 8 weeks. Food intake at breakfast, lunch, and dinner was directly measured at baseline, week 1, and week 8. For Study 2, Sprague-Dawley rats were fasted for 24 h and subsequently injected intraperitoneally with 0, 1, 10, or 50 μg/kg CrPic. Subsequently, rats were implanted with an indwelling third ventricular cannula. Following recovery, 0, 0.4, 4, or 40 ng of CrPic was injected directly into the brain via the intracerebroventricular cannula, and spontaneous 24-h food intake was measured.
Results:
Study 1 demonstrated that CrPic, as compared to placebo, reduced food intake (P < 0.0001), hunger levels (P < 0.05), and fat cravings (P < 0.0001) and tended to decrease body weight (P = 0.08). In study 2, intraperitoneal administration resulted in a subtle decrease in food intake at only the highest dose (P = 0.03). However, when administered centrally, CrPic dose-dependently decreased food intake (P < 0.05).
Conclusions:
These data suggest CrPic has a role in food intake regulation, which may be mediated by a direct effect on the brain.
doi:10.1089/dia.2007.0292
PMCID: PMC2753428  PMID: 18715218
16.  Calorie Restriction and Bone Health in Young, Overweight Individuals 
Archives of internal medicine  2008;168(17):1859-1866.
Background
Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life.
Methods
Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR+EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months.
Results
Mean± SE body weight was reduced by -1.0% ± 1.1% (control), -10.4% ± 0.9% (CR), -10.0%±0.8% (CR+EX), and -13.9%±0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23%±10%; CR+EX, 22%±9%; and LCD, 74%±16% vs control, 4%±10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23%±10%) but were unchanged in the CR+EX, LCD, and control groups.
Conclusions
Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrientdense diets have no deleterious effect on bone health.
doi:10.1001/archinte.168.17.1859
PMCID: PMC2748345  PMID: 18809812
17.  Long-Term Effects of Caloric Restriction or Exercise on DNA and RNA Oxidation Levels in White Blood Cells and Urine in Humans 
Rejuvenation research  2008;11(4):793-799.
Excessive adiposity is associated with increased oxidative stress and accelerated aging. Weight loss induced by negative energy balance reduces markers of oxidation in experimental animals and humans. The long-term effects of weight loss induced by calorie restriction or increased energy expenditure induced by exercise on measures of oxidative stress and damage have not been studied in humans. The objective of the present study was to compare the effects of 20% caloric restriction or 20% exercise alone over 1 year on oxidative damage to DNA and RNA, as assessed through white blood cell and urine analyses. Eighteen men and women aged 50 to 60 years with a body mass index (BMI) between 23.5 to 29.9 kg/m2 were assigned to one of two conditions — 20% CR (n = 9) or 20% EX (n = 9) — which was designed to produce an identical energy deficit through increased energy expenditure. Compared to baseline, both interventions significantly reduced oxidative damage to both DNA (48.5% and 49.6% reduction for the CR and EX groups, respectively) and RNA (35.7% and 52.1% reduction for the CR and EX groups, respectively) measured in white blood cells. However, urinary levels of DNA and RNA oxidation products did not differ from baseline values following either 12-month intervention program. Data from the present study provide evidence that negative energy balances induced through either CR or EX result in substantial and similar improvements in markers of DNA and RNA damage to white blood cells, potentially by reducing systemic oxidative stress.
doi:10.1089/rej.2008.0712
PMCID: PMC2724865  PMID: 18729811
18.  Long-Term Effects of Caloric Restriction or Exercise on DNA and RNA Oxidation Levels in White Blood Cells and Urine in Humans 
Rejuvenation Research  2008;11(4):793-799.
Abstract
Excessive adiposity is associated with increased oxidative stress and accelerated aging. Weight loss induced by negative energy balance reduces markers of oxidation in experimental animals and humans. The long-term effects of weight loss induced by calorie restriction or increased energy expenditure induced by exercise on measures of oxidative stress and damage have not been studied in humans. The objective of the present study was to compare the effects of 20% caloric restriction or 20% exercise alone over 1 year on oxidative damage to DNA and RNA, as assessed through white blood cell and urine analyses. Eighteen men and women aged 50 to 60 years with a body mass index (BMI) between 23.5 to 29.9 kg/m2 were assigned to one of two conditions — 20% CR (n = 9) or 20% EX (n = 9) — which was designed to produce an identical energy deficit through increased energy expenditure. Compared to baseline, both interventions significantly reduced oxidative damage to both DNA (48.5% and 49.6% reduction for the CR and EX groups, respectively) and RNA (35.7% and 52.1% reduction for the CR and EX groups, respectively) measured in white blood cells. However, urinary levels of DNA and RNA oxidation products did not differ from baseline values following either 12-month intervention program. Data from the present study provide evidence that negative energy balances induced through either CR or EX result in substantial and similar improvements in markers of DNA and RNA damage to white blood cells, potentially by reducing systemic oxidative stress.
doi:10.1089/rej.2008.0712
PMCID: PMC2724865  PMID: 18729811
19.  Examination of Cognitive Function During Six Months of Calorie Restriction: Results of a Randomized Controlled Trial 
Rejuvenation research  2007;10(2):179-190.
Background
Calorie restriction increases longevity in many organisms, and calorie restriction or its mimetic might increase longevity in humans. It is unclear if calorie restriction/dieting contributes to cognitive impairment. During this randomized controlled trial, the effect of 6 months of calorie restriction on cognitive functioning was tested.
Methods
Participants (n = 48) were randomized to one of four groups: (1) control (weight maintenance), (2) calorie restriction (CR; 25% restriction), (3) CR plus structured exercise (CR + EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), or (4) low-calorie diet (LCD; 890 kcal/d diet until 15% weight loss, followed by weight maintenance). Cognitive tests (verbal memory, visual memory, attention/concentration) were conducted at baseline and months 3 and 6. Mixed linear models tested if cognitive function changed significantly from baseline to months 3 and 6, and if this change differed by group. Correlation analysis was used to determine if average daily energy deficit (quantified from change in body energy stores) was associated with change in cognitive test performance for the three dieting groups combined.
Results
No consistent pattern of verbal memory, visual retention/memory, or attention/concentration deficits emerged during the trial. Daily energy deficit was not significantly associated with change in cognitive test performance.
Conclusions
This randomized controlled trial suggests that calorie restriction/dieting was not associated with a consistent pattern of cognitive impairment. These conclusions must be interpreted in the context of study limitations, namely small sample size and limited statistical power. Previous reports of cognitive impairment might reflect sampling biases or information processing biases.
doi:10.1089/rej.2006.0502
PMCID: PMC2664681  PMID: 17518698
20.  A novel method to remotely measure food intake of free-living people in real-time 
The British journal of nutrition  2008;101(3):446-456.
The aim of this study was to report the first reliability and validity tests of the Remote Food Photography Method (RFPM), which consists of camera-enabled cell phones with data transfer capability. Participants take and transmit photographs of food selection and plate waste to researchers/clinicians for analysis. Following two pilot studies, adult participants (N=52, 20≤BMI≤35) were randomly assigned to the dine-in or take-out group. Energy intake (EI) was measured for three days. The dine-in group ate lunch and dinner in the laboratory. The take-out group ate lunch in the laboratory and dinner in free-living conditions (participants received a cooler with pre-weighed food that they returned the following morning). Energy intake was measured with the RFPM and by directly weighing foods. The RFPM was tested in laboratory and free-living conditions. Reliability was tested over three days and validity was tested by comparing directly weighed EI to EI estimated with the RFPM using Bland-Altman analysis. The RFPM produced reliable EI estimates over three days in laboratory (r=.62, p<.0001) and free-living (r=.68, p<.0001) conditions. Weighed EI correlated highly with EI estimated with the RFPM in laboratory and free-living conditions (r’s>.93, p<.0001). In two laboratory-based validity tests, the RFPM underestimated EI by -4.7% (p=.046) and -5.5% (p=.076). In free-living conditions, the RFPM underestimated EI by -6.6% (p=.017). Bias did not differ by body weight or age. The RFPM is a promising new method for accurately measuring the EI of free-living people. Error associated with the method is small compared to self-report methods.
doi:10.1017/S0007114508027438
PMCID: PMC2626133  PMID: 18616837
digital photography; food intake; energy intake; measurement; self-report
21.  Measurement of Dietary Restraint: Validity Tests of Four Questionnaires 
Appetite  2006;48(2):183-192.
This study tested the validity of four measures of dietary restraint: Dutch Eating Behavior Questionnaire, Eating Inventory (EI), Revised Restraint Scale (RS), and the Current Dieting Questionnaire. Dietary restraint has been implicated as a determinant of overeating and binge eating. Conflicting findings have been attributed to different methods for measuring dietary restraint. The validity of four self-report measures of dietary restraint and dieting behavior was tested using: 1) factor analysis, 2) changes in dietary restraint in a randomized controlled trial of different methods to achieve calorie restriction, and 3) correlation of changes in dietary restraint with an objective measure of energy balance, calculated from the changes in fat mass and fat-free mass over a six-month dietary intervention. Scores from all four questionnaires, measured at baseline, formed a dietary restraint factor, but the RS also loaded on a binge eating factor. Based on change scores, the EI Restraint scale was the only measure that correlated significantly with energy balance expressed as a percentage of energy require d for weight maintenance. These findings suggest that that, of the four questionnaires tested, the EI Restraint scale was the most valid measure of the intent to diet and actual caloric restriction.
doi:10.1016/j.appet.2006.08.066
PMCID: PMC1941699  PMID: 17101191
dietary restraint; validity; assessment measures; calorie restriction; exercise; diet; energy balance

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