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“Restriction of Dietary Fat, but Not Carbohydrate, Alters Brain Reward Circuitry in Adults With Obesity”, Darcey et al 2022

“Restriction of dietary fat, but not carbohydrate, alters brain reward circuitry in adults with obesity”⁠, Valerie L. Darcey, Juen Guo, Amber Courville, Isabelle Gallagher, Jason A. Avery, W. Kyle Simmons, John E. Ingeholm et al (2022-04-20; ):

Weight loss diets often restrict either fat or carbohydrate, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. To investigate whether reductions in dietary fat versus carbohydrate alter brain reward circuitry, we measured dopamine D2/​3 receptor binding potential (D2BP) using PET and neural activity in response to visual food cues using fMRI in 17 inpatient adults with obesity during an eucaloric baseline diet and on the fifth day of isocaloric diets selectively reduced in either dietary fat or carbohydrate, in random order. Reduction of dietary fat, but not carbohydrate, decreased D2BP and decreased neural activity to food cues in brain reward regions. After the reduced fat diet, ad libitum intake shifted towards foods high in both fat and carbohydrates. These results suggest that dietary fat restriction increases tonic dopamine in brain reward regions thereby affecting food choice in ways that may hamper diet adherence.

“Shared Brain and Genetic Architectures between Mental Health and Physical Activity”, Zhang et al 2022

“Shared brain and genetic architectures between mental health and physical activity”⁠, Wei Zhang, Sarah E. Paul, Anderson Winkler, Ryan Bogdan, Janine D. Bijsterbosch (2022; ⁠, ; similar):

Physical activity is correlated with, and effectively treats various forms of psychopathology. However, whether biological correlates of physical activity and psychopathology are shared remains unclear.

Here, we examined the extent to which the neural and genetic architecture of physical activity and mental health are shared. Using data from the UK Biobank (n = 6,389), canonical correlation analysis was applied to estimate associations between the amplitude and connectivity strength of sub-networks of three major neurocognitive networks (default mode, DMN; salience, SN; central executive networks, CEN) with accelerometer-derived measures of physical activity and self-reported mental health. We estimated the genetic correlation between mental health and physical activity measures, as well as putative causal relationships by applying linkage disequilibrium score regression, genomic structural equational modeling, and latent causal variable analysis to genome-wide association summary statistics (GWAS n = 91,105–500,199).

Physical activity and mental health were associated with connectivity strength and amplitude of the DMN, SN, and CEN (all r ≥ 0.12, all p < 0.048). These neural correlates exhibited highly similar loading patterns across mental health and physical activity models even when accounting for their shared variance⁠. This suggests a largely shared brain network architecture between mental health and physical activity. Mental health and physical activity were also genetically correlated (|rg| = 0.085–0.121), but we found no evidence for causal relationships between them.

Collectively, our findings provide empirical evidence that mental health and physical activity have shared brain and genetic architectures and suggest potential candidate sub-networks for future studies on brain mechanisms underlying beneficial effects of physical activity on mental health.

“Does Quitting Smoking Increase Obesity? Evidence From Accounting for Misreporting”, Tchernis et al 2022

“Does Quitting Smoking Increase Obesity? Evidence From Accounting for Misreporting”⁠, Rusty Tchernis, Keith F. Teltser, Arjun Teotia (2022-01; ; similar):

Smoking and obesity are the 2 leading causes of preventable deaths in the United States. Because smoking is subject to heavy government intervention, understanding the effect of smoking on obesity is important in determining the extent of unintended costs or benefits of such intervention. The existing literature on this question is mixed among studies using experimental and observational data, which we attempt to reconcile by accounting for misreporting in observational data.

We use self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS), cigarette taxes to instrument for changes in smoking, and survey completion to instrument for misreporting.

Starting with the baseline 2-stage least squares (2SLS) estimator common in the earlier observational literature, we obtain similar estimates suggesting quitting smoking substantially reduces BMI⁠. However, we find the results are sensitive to specification, functional form, and the presence of misreporting. We show that accounting for misreporting using the 2-step estimator developed by Nguimkeu et al 2019 yields estimates consistent with the experimental literature; quitting smoking has a small positive [increasing] effect on BMI.

Our preferred estimate suggests reduced smoking accounts for 6% of the concurrent rise in obesity.

“Deletion of SA Β-Gal+ Cells Using Senolytics Improves Muscle Regeneration in Old Mice”, Dungan et al 2021

“Deletion of SA β-Gal+ cells using senolytics improves muscle regeneration in old mice”⁠, Cory M. Dungan, Kevin A. Murach, Christopher J. Zdunek, Zuo Jian Tang, Georgia L. VonLehmden, Camille R. Brightwell et al (2021-12-13; ; similar):

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle.

Young (3 months) and old (20 months) male C57Bl/​6J mice were administered the senolytics dasatinib (5 mg/​kg) and quercetin (50 mg/​kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl2 or PBS 7-days or 28-days prior to euthanization.

Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice and increased similarly 7 days following injury in both age groups, with no effect of D+Q. Most SA β-Gal+ cells were also CD11b+ in young and old mice 7-days and 14-days following injury, suggesting they are infiltrating immune cells. By 14 days, SA β-Gal+/​CD11b+ cells from old mice expressed senescence genes, whereas those from young mice expressed higher levels of genes characteristic of anti-inflammatory macrophages. SA β-Gal+ cells remained elevated in old compared to young mice 28 days following injury, which were reduced by D+Q only in the old mice. In D+Q-treated old mice, muscle regenerated following injury to a greater extent compared to vehicle-treated old mice, having larger fiber cross-sectional area after 28 days. Conversely, D+Q blunted regeneration in young mice. In vitro experiments suggested D+Q directly improve myogenic progenitor cell proliferation.

Enhanced physical function and improved muscle regeneration demonstrate that senolytics have beneficial effects only in old mice.

“Energy Compensation and Metabolic Adaptation: The Biggest Loser Study Reinterpreted”, Hall 2021

2021-hall.pdf: “Energy compensation and metabolic adaptation: The Biggest Loser study reinterpreted”⁠, Kevin D. Hall (2021-11-23; similar):

The Biggest Loser weight-loss competition offered an unique opportunity to investigate human energy metabolism and body composition before, during, and after an extreme lifestyle intervention. Here, I reinterpret the results of The Biggest Loser study in the context of a constrained model of human energy expenditure.

Specifically, The Biggest Loser contestants engaged in large, sustained increases in physical activity that may have caused compensatory metabolic adaptations to substantially decrease resting metabolic rate and thereby minimize changes in total energy expenditure. This interpretation helps explain why the magnitude of persistent metabolic adaptation was largest in contestants with the greatest increases in sustained physical activity and why weight-loss interventions involving lower levels of physical activity have not measured similarly large metabolic adaptations.

Additional longitudinal studies quantifying the interrelationships between various components of energy expenditure and energy intake are needed to better understand the dynamics of human body weight regulation.

“Meat and Mental Health: A Meta-analysis of Meat Consumption, Depression, and Anxiety”, Dobersek et al 2021

“Meat and mental health: A meta-analysis of meat consumption, depression, and anxiety”⁠, Urska Dobersek, Kelsey Teel, Sydney Altmeyer, Joshua Adkins, Gabrielle Wy, Jackson Peak (2021-10-06; similar):

In this meta-analysis⁠, we examined the quantitative relation between meat consumption or avoidance, depression, and anxiety.

In June 2020, we searched 5 online databases for primary studies examining differences in depression and anxiety between meat abstainers and meat consumers that offered a clear (dichotomous) distinction between these groups. 20 studies met the selection criteria representing 171,802 participants with 157,778 meat consumers and 13,259 meat abstainers. We calculated the magnitude of the effect between meat consumers and meat abstainers with bias correction (Hedges’s g effect size) where higher and positive scores reflect better outcomes for meat consumers.

Meat consumption was associated with lower depression (Hedges’s g = 0.216, 95% CI [0.14 to 0.30], p < 0.001) and lower anxiety (g = 0.17, 95% CI [0.03 to 0.31], p = 0.02) compared to meat abstention. Compared to vegans, meat consumers experienced both lower depression (g = 0.26, 95% CI [0.01 to 0.51], p = 0.041) and anxiety (g = 0.15, 95% CI [−0.40 to 0.69], p = 0.598). Sex did not modify these relations. Study quality explained 58% and 76% of between-studies heterogeneity in depression and anxiety, respectively. The analysis also showed that the more rigorous the study, the more positive and consistent the relation between meat consumption and better mental health.

The current body of evidence precludes causal and temporal inferences.

[Keywords: anxiety, depression, meat, mental health, vegan, vegetarianism, sex]

“Major Depressive Disorder and Lifestyle: Correlated Genetic Effects in Extended Twin Pedigrees”, Huider et al 2021

“Major Depressive Disorder and Lifestyle: Correlated Genetic Effects in Extended Twin Pedigrees”⁠, Floris Huider, Yuri Milaneschi, Matthijs D. van der Zee, Eco J. C. de Geus, Quinta Helmer, Brenda W. J. H. Penninx et al (2021-09-26; ; similar):

In recent years, evidence has accumulated with regard to the ubiquity of pleiotropy across the genome, and shared genetic etiology is thought to play a large role in the widespread comorbidity among psychiatric disorders and risk factors.

Recent methods investigate pleiotropy by estimating genetic correlation from genome-wide association summary statistics. More comprehensive estimates can be derived from the known relatedness between genetic relatives. Analysis of extended twin pedigree data allows for the estimation of genetic correlation for additive and non-additive genetic effects, as well as a shared household effect.

Here we conduct a series of bivariate genetic analyses in extended twin pedigree data on lifetime major depressive disorder (MDD) and 3 indicators of lifestyle, namely smoking behavior, physical inactivity, and obesity, decomposing phenotypic variance and covariance into genetic and environmental components. We analyze lifetime MDD and lifestyle data in a large multigenerational dataset of 19,496 individuals by variance component analysis in the ‘Mendel’ software.

We find genetic correlations for MDD and smoking behavior (rg = 0.249), physical inactivity (rg = 0.161), body-mass index (rg = 0.081), and obesity (rg = 0.155), which were primarily driven by additive genetic effects.

These outcomes provide evidence in favor of a shared genetic etiology between MDD and the lifestyle factors.

[Keywords: major depressive disorder, lifestyle, extended twin pedigree, variance decomposition, Mendel, genetic correlation, pleiotropy]

“Energy Compensation and Adiposity in Humans”, Careau et al 2021

“Energy compensation and adiposity in humans”⁠, Vincent Careau, Lewis G. Halsey, Herman Pontzer, Philip N. Ainslie, Lene F. Andersen, Liam J. Anderson et al (2021-08-27; ⁠, ; similar):

  • Energy compensation in humans was analyzed from daily and basal energy expenditure
  • Reduced BEE results in energy compensation of 28%
  • Degree of energy compensation varied between people of different body composition

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures. This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response—energy compensation.

We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult.

Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

[Keywords: activity, basal metabolic rate, daily energy expenditure, energy management models, exercise, Homo sapiens, trade-offs, weight loss, energy compensation]

Figure 2: Energy compensation in humans. (A) Total energy expenditure (TEE; MJ∙d−1) and (B) activity energy expenditure (AEE; MJ∙d−1) as a function of basal energy expenditure (BEE; MJ∙d−1) in 1,754 subjects included in this study, controlling for sex, age, and body composition. (A) illustrates how the slope of the TEE-BEE relationship is <1 (compared to the 1:1 dotted line), whereas (B) illustrates the negative relationship between AEE and BEE.

…To further illustrate the compensation occurring at the within-individual level, we ran a second bivariate mixed model with AEE and BEE as the dependent variables. In this model, the within-individual covariance was statistically-significantly negative (Table S2B). The within-individual correlation (±SE) between AEE and BEE was r = −0.58 ± 0.08 (Figure 4B). Hence, during extended periods when the studied cohort expended more energy on activity, they compensated by reducing energy expended on basal processes (but individuals with higher-than-average AEE do not necessarily have a lower-than-average BEE). The within-individual slope in these people indicates particularly strong energy compensation between AEE and BEE (Figure 4B). That is, in this sample of people, the calories they burn during bouts of activity are almost entirely compensated for by reducing energy expended on other processes such that variation in activity had little impact on TEE.

Figure 4: Energy trade-offs within individuals. Residual (A) total energy expenditure (TEE; MJ∙d−1) and (B) activity energy expenditure (AEE; MJ∙d−1) as a function of basal energy expenditure (BEE; MJ∙d−1) in elderly men and women (n = 68) with 2 pairs of TEE-BEE measures each. Within-individual slopes are illustrated by the thin black lines connecting the 2 residual values (gray dots; extracted from the bivariate mixed model; Table S2) for each individual.

“Exercise-Induced Orgasm and Its Association With Sleep Orgasms and Orgasms During Partnered Sex: Findings From a U.S. Probability Survey”, Herbenick et al 2021

2021-herbenick.pdf: “Exercise-Induced Orgasm and Its Association with Sleep Orgasms and Orgasms During Partnered Sex: Findings From a U.S. Probability Survey”⁠, Debby Herbenick, Tsung-chieh Fu, Callie Patterson, J. Dennis Fortenberry (2021-08-24; ; similar):

Prior research has described women’s experiences with exercise-induced orgasm (EIO). However, little is known about men’s experiences with EIO, the population prevalence of EIO, or the association of EIO with other kinds of orgasm. Using U.S. probability survey data, the objectives of the present research were to:

  1. describe the lifetime prevalence of exercise-induced orgasm (EIO) and sleep orgasm;
  2. assess respondents’ age at first experience of EIO as well as the type of exercise connected with their first EIO;
  3. examine associations between lifetime EIO experience and orgasm at respondents’ most recent partnered sexual event; and
  4. examine associations between lifetime EIO experience and sleep orgasms.

Data were from the 2014 National Survey of Sexual Health and Behavior (1,012 men and 1,083 women, ages 14 years and older).

About 9% of respondents reported having ever experienced exercise-induced orgasm. More men than women reported having experienced orgasm during sleep at least once in their lifetime (66.3% men, 41.8% women). The mean age for women’s first EIO was statistically-significantly older than men (22.8 years women, 16.8 years men). Respondents described a wide range of exercises as associated with their first EIO (ie. climbing ropes, abdominal exercise, yoga). Lifetime EIO experience was associated with lifetime sleep orgasms but not with event-level orgasm during partnered sex.

Implications related to understanding orgasm and recommendations for clinicians and sex educators are discussed.

Exercise-Induced Orgasm: In their reports of interviews with thousands of people living in the United States, Kinsey et al (1948, 1953) ventured that about 5% of people had experienced orgasms from physical exercise or muscular tension. However, questions about orgasms during exercise were not standardized in their interviews, and thus their estimate was based largely on information volunteered by respondents.

To our knowledge, there has been only one systematic study of exercise-induced orgasm (EIO) (Herbenick & Fortenberry, 2011). That study used an online convenience survey that specifically recruited women who had prior experience with sexual arousal or orgasm from exercise. Thus, the study design was not situated to estimate a population-based prevalence of EIO. Also, the researchers surveyed only women, leaving men’s experience with exercise orgasms unexamined. In their convenience survey, Herbenick and Fortenberry found that women reported an average age of 19 years at first EIO experience and that the kinds of exercise participants recalled as most often associated with their first EIO were traditional abdominal exercises (eg. sit-ups, crunches, Roman’s chair leg raises), climbing ropes or poles, and lifting weights—all of which engage the core musculature as part of strength training or stabilization (eg. Oliva-Lozano & Muyor, 2020). This finding was consistent with descriptions of EIO in popular media, where the term “coregasm” was first coined by editors at Men’s Health magazine to reflect correspondence they had received from their readers about unexpectedly experiencing orgasms during exercises that engage core abdominal musculature, whether for strength or for stability (Men’s Health, 2007).

Most women in the Herbenick and Fortenberry (2011) survey indicated that they didn’t fantasize sexually in connection with experiencing EIO; also, most generally felt happy about their experience. However, the survey did not assess any aspects of respondents’ orgasm experiences outside of the exercise context, even though doing so might have helped to situate EIO within broader experiences of genital response and orgasm. For example, it is not known to what extent EIO is an idiosyncratic experience—a bodily quirk, even—or if it reflects something larger about how a person’s body and orgasmic response are organized. The present research extends the limited literature on EIO by—in a U.S. nationally representative sample—assessing participants’ age at first EIO experience, examining EIO among men as well as adolescents, and exploring relationships between EIO and other kinds or orgasm, including orgasms that occur during sleep.

[Keywords: exercise-induced orgasm, orgasm, sleep orgasm, nocturnal emission, probability sample]

“Healthy Weight Loss Maintenance With Exercise, Liraglutide, or Both Combined”, Lundgren et al 2021

2021-lundgren.pdf: “Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined”⁠, Julie R. Lundgren, Charlotte Janus, Simon B.K. Jensen, Christian R. Juhl, Lisa M. Olsen, Rasmus M. Christensen et al (2021-05-06; ; similar):

Background: Weight regain after weight loss is a major problem in the treatment of persons with obesity.

Methods: In a randomized, head-to-head, placebo-controlled trial⁠, we enrolled adults with obesity (body mass index [the weight in kilograms divided by the square of the height in meters], 32 to 43) who did not have diabetes. After an 8-week low-calorie diet, participants were randomly assigned for 1 year to one of 4 strategies: a moderate-to-vigorous—tensity exercise program plus placebo (exercise group); treatment with liraglutide (3.0 mg per day) plus usual activity (liraglutide group); exercise program plus liraglutide therapy (combination group); or placebo plus usual activity (placebo group). End points with prespecified hypotheses were the change in body weight (primary end point) and the change in body-fat percentage (secondary end point) from randomization to the end of the treatment period in the intention-to-treat population. Prespecified metabolic health-related end points and safety were also assessed.

Results: After the 8-week low-calorie diet, 195 participants had a mean decrease in body weight of 13.1 kg. At 1 year, all the active-treatment strategies led to greater weight loss than placebo: difference in the exercise group, −4.1 kg (95% confidence interval⁠, −7.8 to −0.4; p = 0.03); in the liraglutide group, −6.8 kg (95% CI⁠, −10.4 to −3.1; p < 0.001); and in the combination group, −9.5 kg (95% CI, −13.1 to −5.9; p < 0.001). The combination strategy led to greater weight loss than exercise (difference, −5.4 kg; 95% CI, −9.0 to −1.7; p = 0.004) but not liraglutide (−2.7 kg; 95% CI, −6.3 to 0.8; p = 0.13). The combination strategy decreased body-fat percentage by 3.9 percentage points, which was approximately twice the decrease in the exercise group (−1.7 percentage points; 95% CI, −3.2 to −0.2; p = 0.02) and the liraglutide group (−1.9 percentage points; 95% CI, −3.3 to −0.5; p = 0.009). Only the combination strategy was associated with improvements in the glycated hemoglobin level, insulin sensitivity⁠, and cardiorespiratory fitness. Increased heart rate and cholelithiasis were observed more often in the liraglutide group than in the combination group.

Conclusions: A strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone. (Funded by the Novo Nordisk Foundation and others; EudraCT number, 2015–005585–32⁠; number, NCT04122716⁠.)

See Also:

“Does the Combination of Resistance Training and a Nutritional Intervention Have a Synergistic Effect on Muscle Mass, Strength, and Physical Function in Older Adults? A Systematic Review and Meta-analysis”, Choi et al 2021

“Does the combination of resistance training and a nutritional intervention have a synergistic effect on muscle mass, strength, and physical function in older adults? A systematic review and meta-analysis”⁠, MoonKi Choi, Hayeon Kim, Juyeon Bae (2021; ; similar):

Background: Health-promoting interventions are important for preventing frailty and sarcopenia in older adults. However, there is limited evidence that nutritional interventions yield additional effects when combined with resistance training. This systematic review and meta-analysis aimed to compare the effectiveness of nutritional interventions with resistance training and that of resistance training alone.

Methods: Randomized controlled trials published in peer-reviewed journals prior to July 2020 were retrieved from databases and other sources. The articles were screened according to the inclusion and exclusion criteria. The methodological quality of the included studies was assessed using Cochrane’s risk of bias tool 2. A meta-analysis was performed using the RevMan 5.4 program and STATA 16 program.

Results: A total of 22 studies were included in the meta-analysis. The results of the meta-analysis showed no statistically-significant differences between groups in muscle mass, muscle strength, or physical functional performance. In the subgroup analysis regarding the types of nutritional interventions, creatine showed statistically-significant effects on lean body mass (n = 4, MD 2.61, 95% CI 0.51 to 4.72). Regarding the other subgroup analyses, there were no statistically-significant differences in appendicular skeletal muscle mass (p = .43), hand grip strength (p = .73), knee extension strength (p = .09), chair stand test results (p = .31), or timed up-and-go test results (p = .31). In the meta-regression, moderators such as the mean age of subjects and duration of interventions were not associated with outcome variables.

Conclusions: This meta-analysis showed that nutritional interventions with resistance training have no additional effect on body composition, muscle strength, or physical function. Only creatine showed synergistic effects with resistance training on muscle mass.

Trial Registration: CRD42021224843 .

“Evidence for Shared Genetics between Physical Activity, Sedentary Behaviour and Adiposity-related Traits”, Schnurr et al 2020

2020-schnurr.pdf: “Evidence for shared genetics between physical activity, sedentary behaviour and adiposity-related traits”⁠, Theresia M. Schnurr, Bente M. Stallknecht, Thorkild I.A. Sørensen, Tuomas O. Kilpeläinen, Torben Hansen et al (2020-12-22; ; similar):

Observational, cross-sectional and longitudinal studies showed that physical activity and sedentary behaviour are associated with adiposity-related traits, apparently in a bidirectional manner. Physical activity is also suggested to suppress the genetic risk of adiposity.

Since phenotypic associations with genetic variants are not subject to reverse causation or confounding⁠, they may be used as tools to shed light on cause and effect in this complex interdependency. We review the evidence for shared genetics of physical activity and adiposity-related traits and for gene-by-physical activity interactions on adiposity-related traits in human studies. We outline limitations, challenges and opportunities in studying and understanding of these relationships.

In summary, physical activity and sedentary behaviour are genetically correlated with body mass index and fat percentage but may not be correlated with lean body mass. Mendelian randomisation analyses show that physical activity and sedentary behaviour have bidirectional relationships with adiposity. Several studies suggest that physical activity suppresses genetic risk of adiposity. No studies have yet tested whether adiposity enhances genetic predisposition to sedentariness.

The complexity of the comprehensive causal model makes the assessment of the single or combined components challenging. Substantial progress in this field may need long-term intervention studies.

[Keywords: adiposity, genetic determinants, physical activity, sedentary behaviour]

“A Genetic Perspective on the Association between Exercise and Mental Health in the Era of Genome-wide Association Studies”, Geus 2020

“A genetic perspective on the association between exercise and mental health in the era of genome-wide association studies”⁠, Eco J. C. de Geus (2020-12-14; ; backlinks; similar):

  • Triangulation across the results from genetically informative designs supports the existence of causal effects of exercise on mental health as well as residual confounding by genetic factors that independently influence participation in regular exercise and mental health outcomes.
  • A model explaining the heritability of voluntary exercise behaviour in terms of genetic moderation of its positive mental health effects can explain how causal effects co-exist with genetic pleiotropy.
  • The model calls for further research with strategies that use genomic information to improve the success of interventions on regular exercise behaviour.

Regular exercise is associated with mental health throughout the life course but the chain-of-causality underlying this association remains contested. I review results from genetically informative designs that examine causality, including the discordant monozygotic twin design, multivariate genetic models, Mendelian Randomization⁠, and stratification on polygenic risk scores⁠. Triangulation across the results from these and the standard designs for causal inference (RCT, prospective studies) in the extant literature supports the existence of causal effects of exercise on mental health as well as residual confounding by genetic factors that independently influence participation in regular exercise and mental health outcomes. I present an update of our earlier model for the genetic determinants of voluntary exercise behaviour. The model allows causal effects of regular exercise on mental health to co-exist with genetic pleiotropy through differences in the genetic sensitivity to the mental health benefits of exercise. The model encourages research on strategies that use genomic information to improve the success of interventions on regular exercise behaviour.

[Keywords: twin study, Mendelian randomization⁠, polygenic risk score, exercise psychology, personalized medicine]

Figure 3: Genetic correlation between exercise behaviour and mental health. Note: The higher order latent genetic factor in the oval on the left contains all sets of genetic variants that explain the heritability of regular voluntary exercise behaviour. The sets of variants that are relevant for the model (G1 through G8) are repeated in the figure close to the traits where they apply. By influencing the causal mechanisms through which exercise influences mental health, these genetic variants create a genetic correlation between exercise and mental health. This genetic pleiotropy is indicated by the large dashed arrows.

“Effect of Vitamin D Supplementation, Omega–3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial”, Bischoff-Ferrari et al 2020

2020-bischoffferrari.pdf: “Effect of Vitamin D Supplementation, Omega–3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial”⁠, Heike A. Bischoff-Ferrari, Bruno Vellas, René Rizzoli, Reto W. Kressig, José A. P. da Silva, Michael Blauth et al (2020-11-10; ; similar):

Key Points:

Question: Do vitamin D, omega-3, and a strength-training exercise program alone or in combination prevent 6 health outcomes among relatively healthy adults aged 70 years or older?

Findings: In this randomized trial that included 2157 adults aged 70 years or older, 3-year treatment with vitamin D3 (2000 IU/​d), with omega-3 fatty acids (1 g/​d), or with a strength-training exercise program did not result in statistically-significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rate, or cognition.

Meaning: These findings do not support the use of vitamin D, omega-3, or a strength-training exercise program for these clinical outcomes among relatively healthy older adults. Abstract

Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.

Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.

Design, Setting, and Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.

Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/​d of vitamin D3, 1 g/​d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).

Main Outcomes and Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and p < 0.01 was required for statistical-significance.

Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically-significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both −0.8 (99% CI, –2.1 to 0.5) mm Hg, with p < 0.13 and p < 0.11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was –0.5 (99% CI, –1.2 to 0.2) mm Hg; p = 0.06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was –0.13 (99% CI, –0.23 to –0.03), with an IR ratio of 0.89 (99% CI, 0.78–1.01; p = 0.02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.

Table 1: Summary results.

Conclusions and Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically-significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.

Trial Registration: Identifier: NCT01745263

“An Exposure-Wide and Mendelian Randomization Approach to Identifying Modifiable Factors for the Prevention of Depression”, Choi et al 2020

2020-choi.pdf: “An Exposure-Wide and Mendelian Randomization Approach to Identifying Modifiable Factors for the Prevention of Depression”⁠, Karmel W. Choi, Murray B. Stein, Kristen M. Nishimi, Tian Ge, Jonathan R. I. Coleman, Chia-Yen Chen, Andrew Ratanatharathorn et al (2020-08-14; ⁠, ; similar):

Objective:: Efforts to prevent depression, the leading cause of disability worldwide, have focused on a limited number of candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank participants, the authors sought to systematically screen and validate a wide range of potential modifiable factors for depression.

Methods:: Baseline data were extracted for 106 modifiable factors, including lifestyle (eg. exercise, sleep, media, diet), social (eg. support, engagement), and environmental (eg. green space, pollution) variables. Incident depression was defined as minimal depressive symptoms at baseline and clinically-significant depression at follow-up. At-risk individuals for incident depression were identified by polygenic risk scores or by reported traumatic life events. An exposure-wide association scan was conducted to identify factors associated with incident depression in the full sample and among at-risk individuals. Two-sample Mendelian randomization was then used to validate potentially causal relationships between identified factors and depression.

Results:: Numerous factors across social, sleep, media, dietary, and exercise-related domains were prospectively associated with depression, even among at-risk individuals. However, only a subset of factors was supported by Mendelian randomization evidence, including confiding in others (odds ratio = 0.76, 95% CI = 0.67, 0.86), television watching time (odds ratio = 1.09, 95% CI = 1.05–1.13), and daytime napping (odds ratio = 1.34, 95% CI = 1.17–1.53).

Conclusions:: Using a two-stage approach, this study validates several actionable targets for preventing depression. It also demonstrates that not all factors associated with depression in observational research may translate into robust targets for prevention. A large-scale exposure-wide approach combined with genetically informed methods for causal inference may help prioritize strategies for multimodal prevention in psychiatry.

“Reversal of Epigenetic Age With Diet and Lifestyle in a Pilot Randomized Clinical Trial”, Fitzgerald et al 2020

“Reversal of Epigenetic Age with Diet and Lifestyle in a Pilot Randomized Clinical Trial”⁠, Kara Fitzgerald, Romilly Hodges, Douglas Hanes, Emily Stack, David Cheishvili, Moshe Szyf, Janine Henkel et al (2020-07-14; ; backlinks; similar):

Manipulations to set back biological age and extend lifespan in animal models are well established, and translation to humans has begun. The length of human life makes it impractical to evaluate results by plotting mortality curves, so surrogate markers of age have been suggested and, at present, the best established surrogates are DNA methylation clocks. Herein we report on a randomized, controlled clinical trial designed to be a first step in evaluating the effect of a diet and lifestyle intervention on biological age. Compared to participants in the control group (n = 20), participants in the treatment group tested an average 3.23 years younger at the end of the eight-week program according to the Horvath DNAmAge clock (p = 0.018). Those in the treatment group (n = 18) tested an average 1.96 years younger at the end of the program compared to the same individuals at the beginning with a strong trend towards statistical-significance (p = 0.066 for within group change). This is the first such trial to demonstrate a potential reversal of biological age. In this study, the intervention was confined to diet and lifestyle changes previously identified as safe to use. The prescribed program included multiple components with documented mechanistic activity on epigenetic pathways, including moderate exercise, breathing exercises for stress, and a diet rich in methyl donor nutrients and polyphenols.

“Increased Weight Loading Reduces Body Weight and Body Fat in Obese Subjects—A Proof of Concept Randomized Clinical Trial”, Ohlsson et al 2020

“Increased weight loading reduces body weight and body fat in obese subjects—A proof of concept randomized clinical trial”⁠, Claes Ohlsson, Edwin Gidestrand, Jacob Bellman, Christel Larsson, Vilborg Palsdottir, Daniel Hägg, Per-Anders Jansson et al (2020-04-30; similar):

Background: Recently we provided evidence for a leptin-independent homeostatic regulation, the gravitostat, of body weight in rodents. The aim of the present translational proof of concept study was to test the gravitostat hypothesis in humans.

Methods: We conducted a randomized controlled single center trial ( number, NCT03672903), to evaluate the efficacy of artificially increased weight loading on body weight in subjects with mild obesity (BMI 30–35 kg/​m2). Subjects were either treated with a heavy ( = high load; 11% of body weight) or light ( = low load; 1% of body weight) weight vest for eight hours per day for three weeks. The primary outcome was change in body weight. Secondary outcomes included change in body fat mass and fat-free mass as measured using bioelectrical impedance analysis.

Findings: In total 72 participants underwent randomization and 69 (36 high load and 33 low load) completed the study for the primary outcome. High load treatment resulted in a more pronounced relative body weight loss compared to low load treatment (mean difference −1.37%, 95% confidence interval (CI), −1.96 to −0.79; p = 1.5 × 10−5). High load treatment reduced fat mass (−4.04%, 95% CI, −6,53 to −1.55; p = 1.9 × 10−3) but not fat free mass (0.43%, 95% CI, −1.47 to 2.34; p = 0.65) compared to low load treatment.

Interpretation: Increased weight loading reduces body weight and fat mass in obese subjects in a similar way as previously shown in obese rodents. These findings demonstrate that there is weight loading dependent homeostatic regulation of body weight, the gravitostat, also in humans.

“The Psychophysiological Effects of Different Tempo Music on Endurance Versus High-Intensity Performances”, Patania et al 2020

“The Psychophysiological Effects of Different Tempo Music on Endurance Versus High-Intensity Performances”⁠, Vittoria Maria Patania, Johnny Padulo, Enzo Iuliano, Luca Paolo Ardigò, Dražen Čular, Alen Miletić, Andrea De Giorgio et al (2020-02-05; ; backlinks; similar):

The use of music during training represents a special paradigm for trainers to stimulate people undertaking different types of exercise. However, the relationship between the tempo of music and perception of effort during different metabolic demands is still unclear. Therefore, the aim of this research was to determine whether high intensity exercise is more sensitive to the beneficial effects of music than endurance exercise. This study assessed 19 active women (age 26.4 ± 2.6 years) during endurance (walking for 10′ at 6.5 km/​h on a treadmill) and high intensity (80% on 1-RM) exercise under four different randomly assigned conditions: no music (NM), with music at 90–110 bpm (LOW), with music at 130–150 bpm (MED), and with music at 170–190 bpm (HIGH). During each trial, heart rate (HR) and the rating of perceived exertion (RPE) were assessed. Repeated analysis of variance measures was used to detect any differences between the four conditions during high intensity and low intensity exercise. RPE showed more substantial changes during the endurance exercises (11%), than during high intensity exercise (6.5%), between HIGH and NM conditions. The metabolic demand during the walking exercise increased between NM and HIGH bpm conditions. This study indicates the benefits of music under stress conditions as well as during endurance and high intensity training. The results demonstrate that the beneficial effects of music are more likely to be seen in endurance exercise. Consequently, music may be considered an important tool to stimulate people engaging in low intensity physical exercise.

“Physical Activity and Weight following Car Ownership in Beijing, China: Quasi-experimental Cross Sectional Study”, Anderson & Yang 2019

“Physical activity and weight following car ownership in Beijing, China: quasi-experimental cross sectional study”⁠, Michael L. Anderson, Fangwen Lu Jun Yang (2019-12-18; similar):

Objective: To determine the implications of car ownership for physical activity and weight in a global city.

Design: Quasi-experimental cross sectional study.

Setting: Beijing, China, 2011-15.

Participants: People aged 18 and older from a random sample of households who had entered a permit lottery to purchase a vehicle between January 2011 and November 2015.

Interventions: Permit allowing purchase of a vehicle within six months of permit issuance.

Main outcome measures: Transit use (number of subway and bus rides each week), physical activity (minutes of walking or bicycling each day), and weight, measured once in early 2016.

Results: Of 937 people analysed in total, 180 had won a permit to purchase a new vehicle. Winning the permit lottery resulted in the purchase of an additional vehicle 91% of the time (95% confidence interval 89% to 94%; p < 0.001). About 5 years after winning, winners took statistically-significantly fewer weekly transit rides (−2.9 rides (−5.1 to −0.7); p = 0.01) and walked and cycled statistically-significantly less (−24.2 minutes (−40.3 to −8.1); p = 0.003) than those who did not win the lottery. Average weight did not change statistically-significantly between lottery winners and losers. Among those aged 50 and older, however, winners’ weight had increased relative to that of losers (10.3 kg (0.5 to 20.2); p = 0.04) 5.1 years after winning.

Conclusions: These data indicate that vehicle ownership in a rapidly growing global city led to long term reductions in physical activity and increase in weight. Continuing increases in car use and ownership in developing and middle income countries could adversely affect physical health and obesity rates.

“Exercise Conditioned Plasma Dampens Inflammation via Clusterin and Boosts Memory”, Miguel et al 2019

“Exercise conditioned plasma dampens inflammation via clusterin and boosts memory”⁠, Zurine De Miguel, Michael J. Betley, Drew Willoughby, Benoit Lehallier, Niclas Olsson, Liana Bonanno et al (2019-09-19; ; similar):

Physical exercise seems universally beneficial to human and animal health, slowing cognitive aging and neurodegeneration. Cognitive benefits are tied to increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms mediating these effects. We discovered “runner” plasma, collected from voluntarily running mice, infused into sedentary mice recapitulates the cellular and functional benefits of exercise on the brain. Importantly, runner plasma reduces baseline neuroinflammatory gene expression and prominently suppresses experimentally induced brain inflammation. Plasma proteomic analysis shows a striking increase in complement cascade inhibitors including clusterin, which is necessary for the anti-inflammatory effects of runner plasma. Cognitively impaired patients participating in structured exercise for 6 months showed higher plasma clusterin levels, which correlated positively with improvements in endurance and aerobic capacity. These findings demonstrate the existence of anti-inflammatory “exercise factors” that are transferable, benefit the brain, and are present in humans engaging in exercise.

“Metformin and Aging: A Review”, Glossmann & Lutz 2019

“Metformin and Aging: A Review”⁠, Hartmut H. Glossmann, O. M. Lutz (2019-09-13; ; backlinks; similar):

Metformin is sometimes proposed to be an “anti-aging” drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has “frailty” as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed. Concerns exist not only for vitamin B12 and B6 deficiencies, but also about whether there are adverse effects of metformin on individuals who try to remain healthy by maintaining cardiovascular fitness via exercise.

Conclusions, Recommendations, and Perspectives: The rationale for the ongoing or planned metformin trials is almost exclusively based on observations (associations) of potential benefits in a diabetic (or prediabetic) population. Its efficacy even in an at-risk cohort of aged people has not yet been proven. Metformin is associated with a higher risk of vitamin B12 and vitamin B6 deficiency, which may result in an increased risk of cognitive dysfunction98. Supplementation is strongly recommended to metformin users.

Of greater concern are the results of small trials in which the effects of metformin on metabolic responses to exercise or on cardiorespiratory fitness were tested. In a placebo-controlled, double-blind, crossover trial with healthy young subjects, metformin caused a small but statistically-significant decline in maximal aerobic capacity99. A double-blind, placebo-controlled landmark trial with older adults with one risk factor for T2D investigated the effects of metformin and 12 weeks of aerobic exercise 100. Contrary to expectations—namely, that the effects of exercise and the drug would be additive–“metformin attenuated the increase in whole-body insulin sensitivity and abrogated the exercise-mediated increase in skeletal muscle mitochondrial respiration.” The results of the (repurposing) MASTERS trial (NCT02308228; Metformin to Augment Strength Training Effective Response in Seniors)100 will be instructive. MASTERS is testing the hypothesis that older individuals’ long-term treatment with metformin augments the effects of resistance exercise, especially in the “nonresponder” aging population.

“Precision Exercise Medicine: Understanding Exercise Response Variability”, Ross et al 2019

“Precision exercise medicine: understanding exercise response variability”⁠, Robert Ross, Bret H. Goodpaster, Lauren G. Koch, Mark A. Sarzynski, Wendy M. Kohrt, Neil M. Johannsen et al (2019-09; similar):

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.

In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorizing exercise response levels-a topic that is of particular interest for personalized exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.

Figure 1: Preclinical animal model evidence for variation in training response: (A) frequency distribution for the change in running capacity (ΔDIST) for 152 genetically heterogeneous N/​NIH rats shown in ascending order (males and females combined). The lowest and highest 10th percentile animals were used as founders to start low response trainer (LRT) and high response trainer (HRT) selected lines. Dotted line indicates the population mean change in running capacity with training. (B) Percentile rank score for the change in running capacity (ΔDIST) for LRT rats from generation 15 of selection arranged from lowest to highest. (C) Percentile rank score for the ΔDIST for HRT rats from generation 15 of selection arranged from lowest to highest. Dotted lines indicate the mean change in running capacity for the LRT and HRT selected lines. Adapted from Koch et al 2013.

Human studies designed to investigate CRF response variability: The vast majority of studies on the effects of chronic exercise on CRF focus on main effects and group differences and ignore interindividual CRF response variability. Studies specifically designed to determine the variability of response to exercise report an extraordinary heterogeneity in CRF response. There is variability in improvement to a standardised dose of exercise ranging from no gain in VO2max to about 1 L improvement of O2 uptake.

Here we summarise the findings of selected studies that examined individual variability in CRF (VO2max) response to endurance-type exercise training. The selection criteria used to identify suitable trials included: (1) recruitment of previously sedentary adults, (2) exercise interventions were standardised and supervised, (3) intervention duration was 12 weeks or greater, (4) study examined variability in CRF response and (5) included aerobic/​endurance-type exercise. Combination (endurance and resistance) and resistance-only exercise were not considered. 8 studies met the inclusion criteria, with all but 2 having sample sizes of at least 30 participants (range 18–720). Table 1 provides a description of the study designs, exercise programmes, study population and mean change in CRF.

“The Chinese National Twin Registry: a “gold Mine” for Scientific Research”, Gao et al 2019

“The Chinese National Twin Registry: a “gold mine” for scientific research”⁠, W. Gao, W. Cao, J. Lv, C. Yu, T. Wu, S. Wang, L. Meng, D. Wang, Z. Wang, Z. Pang, M. Yu, H. Wang, X. Wu et al (2019-07-04; ; backlinks; similar):

The Chinese National Twin Registry (CNTR) currently includes data from 61 566 twin pair from 11 provinces or cities in China. Of these, 31 705, 15 060 and 13 531 pairs are monozygotic, same-sex dizygotic and opposite-sex dizygotic pairs, respectively, determined by opposite sex or intrapair similarity. Since its establishment in 2001, the CNTR has provided an important resource for analysing genetic and environmental influences on chronic diseases especially cardiovascular diseases. Recently, the CNTR has focused on collecting biologic specimens from disease-concordant or disease-discordant twin pairs or from twin pairs reared apart. More than 8,000 pairs of these twins have been registered, and blood samples have been collected from more than 1500 pairs.

In this review, we summarize the main findings from univariate and multivariate genetic effects analyses, gene-environment interaction studies, omics studies exploring DNA methylation and metabolomic markers associated with phenotypes. There remains further scope for CNTR research and data mining. The plan for future development of the CNTR is described. The CNTR welcomes worldwide collaboration.

“Interactions Between the Gravitostat and the Fibroblast Growth Factor System for the Regulation of Body Weight”, Palsdottir et al 2019

“Interactions Between the Gravitostat and the Fibroblast Growth Factor System for the Regulation of Body Weight”⁠, Vilborg Palsdottir, Sara H. Windahl, Daniel A Hägg, Hanna Keantar, Jakob Bellman, Andrew Buchanan, Tristan J. Vaughan et al (2019-03-19; similar):

Both fibroblast growth factors (FGFs), by binding to FGF receptors (FGFRs), and activation of the gravitostat, by artificial loading, decrease the body weight (BW). Previous studies demonstrate that both the FGF system and loading have the capacity to regulate BW independently of leptin. The aim of the current study was to determine the possible interactions between the effect of increased loading and the FGF system for the regulation of BW. We observed that the BW-reducing effect of increased loading was abolished in mice treated with a monoclonal antibody directed against FGFR1c, suggesting interactions between the two systems. As serum levels of endocrine FGF21 and hepatic FGF21 mRNA were increased in the loaded mice compared with the control mice, we first evaluated the loading response in FGF21 over expressing mice with constant high FGF21 levels. Leptin treatment, but not increased loading, decreased the BW in the FGF21-overexpressing mice, demonstrating that specifically the loading effect is attenuated in the presence of high activity in the FGF system. However, as FGF21 knockout mice displayed a normal loading response on BW, FGF21 is neither mediating nor essential for the loading response. In conclusion, the BW-reducing effect of increased loading but not of leptin treatment is blocked by high activity in the FGF system. We propose that both the gravitostat and the FGF system regulate BW independently of leptin and that pharmacologically enhanced activity in the FGF system reduces the sensitivity of the gravitostat.

“A Twin Study on the Correlates of Voluntary Exercise Behavior in Adolescence”, Schutte et al 2019

2018-schutte.pdf: “A twin study on the correlates of voluntary exercise behavior in adolescence”⁠, Nienke M. Schutte, Ineke Nederend, Meike Bartels, Eco J. C. de Geus (2019-01; ⁠, ; backlinks; similar):

  • The heritability of exercise behavior (EB) in young adults is substantial (60%–81%).
  • Several parameters measured in adolescence were correlated with adult EB.
  • These correlates showed statistically-significant genetic associations with adult EB.
  • A large part of the covariation between EB and the correlates was due to genetic causes.

Objectives: To improve the success of interventions aimed to increase moderate to vigorous physical activity, we need to better understand the correlates of the extensive individual differences in voluntary exercise activities. Starting in adolescence, genetic effects become a dominant factor in explaining individual differences in voluntary exercise behavior. Here we aim to establish the prospective contribution of potential correlates of voluntary exercise behavior to its heritability.

Design: In a sample of adolescent and young adult twins, data on potential correlates of exercise behavior were collected using surveys (time point 1, n = 373) and a laboratory study (time point 2, n = 499). Information on personality, perceived barriers & benefits, subjective and objective exercise ability and the affective response to exercise were collected in a set of healthy adolescent twin pairs (16–18y) and their non-twin siblings (12–25y). Almost 3 years later, the subjects were sent an online follow-up survey on their current exercise status (time point 3, n = 423).

Methods: In bivariate models, the phenotypic (co)variance in these correlates and exercise behavior at all time points were decomposed in sources of genetic (co)variance and environmental (co)variance. The correlates that were statistically-significant associated with exercise behavior at time point 1 or 2 and showed statistically-significant genetic correlations to exercise behavior at time point 3 were used in 2 further analyses: Multiple regression analysis to predict exercise behavior at time point 3, and a genetic analysis in a common 2-factor model, that tested the overlap in genetic factors influencing these correlates and exercise behavior.

Results: Personality (Extraversion), perceived benefits and barriers, exercise-induced affective response (Energy measured after the cycling test), and subjective and objective exercise ability (VO2max) showed statistically-significant phenotypic and genetic association with exercise behavior at time point 3. The genetic correlation between the 2 latent factors in the common 2-factor model was 0.51, indicating that part of the heritability in exercise behavior derives from genetic variants that also influence these correlates.

Conclusions: Given their shared genetic basis and predictive power we assert that individual differences in extraversion, perceived benefits and barriers, exercise-induced feelings of energy, and subjective and objective exercise ability can be used to develop stratified interventions for adolescent and young adult exercise behavior. In addition, our results provide the first clues on ‘where to look’ for specific genetic variants for voluntary exercise behavior.

[Keywords: exercise behavior, heritability, personality, exercise ability, perceived benefits/​barriers, affective response]

“Do High School Sports Build or Reveal Character? Bounding Causal Estimates of Sports Participation”, Ransom & Ransom 2018

2018-ransom.pdf: “Do high school sports build or reveal character? Bounding causal estimates of sports participation”⁠, Michael R. Ransom, Tyler Ransom (2018-06-01; ⁠, ; similar):

  • Many studies have documented that high school athletes attain higher levels of education and earn higher wages in the labor market as adults.
  • An important policy question is whether sports participation builds skills or if it instead reveals existing skill levels.
  • We separately analyze 3 longitudinal data sets from the United States.
  • We utilize newly developed econometric methods to put bounds on the causal effects of sports.
  • For most outcomes, we find no evidence of a causal effect of high school sports on educational and labor market outcomes.

We examine the extent to which participation in high school athletics in the United States has beneficial effects on future education, labor market, and health outcomes.

Due to the absence of plausible instruments in observational data, we use recently developed methods that relate selection on observables with selection on unobservables to estimate bounds on the causal effect of athletics participation…The econometric method we utilize in our analysis is developed by Krauth 2016 and allows researchers to empirically test the extent of deviations from exogeneity in a linear model with univariate treatment. Specifically, this method puts bounds on the correlation between the policy variable and the unobservable characteristics relative to the correlation between the policy variable and observable characteristics. We implement the method as a sensitivity analysis to include the case where sports participation is correlated with the error term in the outcome equation.

We do not find consistent evidence of individual education or labor market benefits. However, we do find that male (but not female) athletes are more likely to exercise regularly as adults, but are no less likely to be obese.

[Keywords: human capital, high school sports, selection]

…Athletic participation is strongly positively correlated with a number of outcomes—including high school graduation, college attendance, college graduation, wages, exercise habits, and absence of obesity—but we find that this correlation is almost completely due to selection. For most of the outcomes that we consider, we find that even if the correlation between athletic participation and unobservable characteristics is a small fraction of the correlation between athletic participation and observable characteristics, then there is no effect of sports. Across several different outcomes and different samples, we find no consistent benefit from high school sports. However, in a few cases that we discuss below, we do find statistically-significant effects from sports participation that are arguably causal.

We analyze 3 separate nationally representative longitudinal surveys that link athletic participation in high school with future individual outcomes such as post-secondary education, labor market earnings, health, and propensity to engage in risky behaviors. The 3 surveys are the National Longitudinal Survey of Youth 1979 (NLSY79); the National Education Longitudinal Study of 1988 (NELS:88); and the National Longitudinal Study of Adolescent to Adult Health (Add Health). Each of these studies has been used previously by researchers to analyze effects of high school sports, but no study has jointly analyzed all 3.

…We divide the variables into 3 categories: background characteristics, school characteristics, and outcomes.

  1. Background: Athletes tend to have higher cognitive test scores, be disproportionately white, have parents with higher levels of education, be more likely to co-reside with parents, and come from homes with higher incomes. In the NLSY79, athletes also score lower on the Rotter Locus of Control Scale, which indicates that athletes more strongly believe that their outcomes are the result of personal effort, as opposed to luck. In short, our basic summary statistics reveal that athletes are strongly positively selected on personal and family background traits.
  2. School: On the school side, athletes are less likely to be absent from school, more likely to be found in private schools and schools with smaller student bodies, more likely to be found in rural schools, and more likely to attend schools that are more racially segregated.8 These results hold for both men and women and are in line with existing literature and theory. Namely, overwhelmingly white, private, and rural schools provide more opportunities for student athletes, for a variety of reasons. Possible explanations include differences in school funding, or that it is statistically easier to make the team at a school with a smaller student body.
  3. Outcomes: In addition to observing that athletes have different background and school contexts, we also observe that athletes have very different adult outcomes. They attain higher levels of education, measured either by grades completed or degrees attained. Athletes also earn more as adults: about 15% higher wages for men and about 12% higher wages for women. Athletes are much more likely to report exercising regularly. Male athletes are neither more nor less likely to be obese as adults, while female athletes are much less likely to be obese. Athletes of both genders report a higher frequency of alcohol abuse as adults.

The results in Table 1 and Table 2 are striking in that the different surveys exhibit not only the same sign of sports effects, but also many of the same magnitudes, in spite of the fact that athletic participation is measured quite differently across the 3 surveys

“The Gravitostat Regulates Fat Mass in Obese Male Mice While Leptin Regulates Fat Mass in Lean Male Mice”, Ohlsson et al 2018

“The Gravitostat Regulates Fat Mass in Obese Male Mice While Leptin Regulates Fat Mass in Lean Male Mice”⁠, Claes Ohlsson, Daniel A. Hägg, Fredrik Hammarhjelm, Adrià Dalmau Gasull, Jakob Bellman, Sara H. Windahl et al (2018-05-23; similar):

Leptin has been the only known homeostatic regulator of fat mass, but we recently found evidence for a second one, named the gravitostat. In the current study, we compared the effects of leptin and increased loading (gravitostat stimulation) on fat mass in mice with different levels of body weight (lean, overweight, and obese).

Leptin infusion suppressed body weight and fat mass in lean mice given normal chow but not in overweight or obese mice given a high-fat diet for 4 and 8 weeks, respectively. The maximum effect of leptin on body weight and fat mass was obtained already at <44 ng/​mL of serum leptin. Increased loading using intraperitoneal capsules with different weights decreased body weight in overweight and obese mice. Although the implantation of an empty capsule reduced the body weight in lean mice, only a nonsignificant tendency of a specific effect of increased loading was observed in the lean mice.

These findings demonstrate that the gravitostat regulates fat mass in obese mice, whereas leptin regulates fat mass only in lean mice with low endogenous serum leptin levels. We propose that activation of the gravitostat primarily protects against obesity, whereas low levels of leptin protect against undernutrition.

“‘Vegan Bodybuilder’: How YouTube Attacker, Nasim Aghdam, Went Viral in Iran”, Wakabayashi et al 2018

“‘Vegan Bodybuilder’: How YouTube Attacker, Nasim Aghdam, Went Viral in Iran”⁠, Daisuke Wakabayashi, Thomas Erdbrink, Matthew Haag (2018-04-04; ⁠, ; backlinks; similar):

In Iran, she was known as Green Nasim⁠, a social media star with followings on YouTube, on Instagram and elsewhere. · In the United States, she cast a very different profile, a proponent of vegan diets, animal rights and home exercise who had increasingly become agitated by one of the tech companies that helped give her a platform… · The police said Ms. Aghdam’s anger over what she believed to be unfair treatment by YouTube had set her on a 500-mile drive from her home near San Diego to YouTube’s offices on the northern edge of Silicon Valley. · “People like me are not good for big business, like for animal business, medicine business and for many other businesses. That’s why they are discriminating and censoring us”, she said in a video posted online last year criticizing YouTube. “This is what they are doing to vegan activists and many other people who try to promote healthy, humane and smart living.”

…Ms. Aghdam was in her late 30s. In several of her videos, she said she was born in Iran, in the city of Urmia, where most people also speak Turkish, as she does in some of her videos. Ms. Aghdam had YouTube pages in Persian, Turkish and English. She explained that she and her family were members of the Baha’i faith, which faces persecution in Iran, a country with a Muslim majority. · Several of her colorful—and sometimes bizarre—videos had gone viral in Iran. Her website, which said it was quoting Western news outlets, identified her as “the first Persian female vegan bodybuilder.” · “Now the media will be faced with a new type of Iranian female which does not fit within any of their usual categorizations”, a Twitter user named Katayoon said Wednesday. · “This was shocking and saddening”, one Iranian, Bahare, wrote on Twitter of Ms. Aghdam. “We laughed so much but now it turns out all those videos were so serious for herself.” · Ms. Aghdam became especially famous for one clip in which she wears a revealing purple dress, showing cleavage, and begins to slowly strip off her clothes to reveal a pair of fake plastic breasts. “Don’t trust your eyes”, read a caption in English on the clip.

…Her personal website and videos posted to YouTube and elsewhere were filled with complaints about YouTube. “When searching for my website in google, at top of link they add ‘an error occurred’ but there is no error!” a website under Ms. Aghdam’s name,, said in February 2016. “They add it to keep you from my visiting my site.” · Life in the United States had not been good, she said in one video from March 30. “There they kill you by ax”, she said of Iran. “Here they kill you with cotton”, referring to an Iranian expression meaning dying by something that you do not know is dangerous. · In another video, she responded to viewers who had begun to wonder if she was mentally ill: “I don’t have any special mental or physical disease, but I live on a planet filled with disease, disorders, perversions and injustices.” · The American dream appeared to be tarnished for her after she began to face hurdles in the United States. · “If you are superficial, you will think it is heaven here, that you can go naked outside and have sex left and right like other animals without any morality”, she said in one video in Persian. “But if you enter the system, you will see that it is worse than Iran”, she said. “Those who want to inform people against the system and big companies get censored.”

“Nature vs. Nurture: Have Performance Gaps Between Men and Women Reached an Asymptote?”, Millard-Stafford et al 2018

2018-millardstafford.pdf: “Nature vs. Nurture: Have Performance Gaps Between Men and Women Reached an Asymptote?”⁠, Mindy Millard-Stafford, Ann E. Swanson, Matthew T. Wittbrodt (2018-04; ⁠, ; similar):

Men outperform women in sports requiring muscular strength and/​or endurance, but the relative influence of “nurture” versus “nature” remains difficult to quantify. Performance gaps between elite men and women are well documented using world records in second, centimeter, or kilogram sports. However, this approach is biased by global disparity in reward structures and opportunities for women.

Despite policies enhancing female participation (Title IX legislation), US women only closed performance gaps by 2% and 5% in Olympic Trial swimming and running, respectively, from 1972 to 1980 (with no change thereafter through 2016). Performance gaps of 13% in elite mid-distance running and 8% in swimming (~4-min duration) remain, the 5% differential between sports indicative of load carriage disadvantages of higher female body fatness in running. Conversely, sprint swimming exhibits a greater sex difference than sprint running, suggesting anthropometric/​power advantages unique to swim-block starts.

The ~40-y plateau in the performance gap suggests a persistent dominance of biological influences (eg. longer limb levers, greater muscle mass, greater aerobic capacity, and lower fat mass) on performance.

Current evidence suggests that women will not swim or run as fast as men in Olympic events, which speaks against eliminating sex segregation in these individual sports. Whether hormone reassignment sufficiently levels the playing field in Olympic sports for transgender females (born and socialized male) remains an issue to be tackled by sport-governing bodies.

“Where Does the Gravitostat Fit In?”, Ohlssona & Jansson 2018

“Where does the gravitostat fit in?”⁠, Claes Ohlssona, John-Olov Jansson (2018-02-13; similar):

[Rebuttal letter: the gravitostat is supported by hypergravity; astronaut microgravity experiments are only weak counterevidence because microgravity and space travel badly damages health in many ways, hiding any potential weight gain. The gravitostat may fit in the two-systems model of weight, in which case a testable prediction is that it should have different effects in rodents with different weight/​leptin combinations.]

“Body Weight Homeostat That Regulates Fat Mass Independently of Leptin in Rats and Mice”, Jansson et al 2018

“Body weight homeostat that regulates fat mass independently of leptin in rats and mice”⁠, John-Olov Jansson, Vilborg Palsdottir, Daniel A. Hägg, Erik Schéle, Suzanne L. Dickson, Fredrik Anesten et al (2018-01-09; similar):

Significance: The only known homeostatic regulator of fat mass is the leptin system. We hypothesized that there is a second homeostat regulating body weight with an impact on fat mass. In this study we have added and removed weight loads from experimental animals and measured the effects on the biological body weight. The results demonstrate that there is a body weight homeostat that regulates fat mass independently of leptin. As the body weight-reducing effect of increased loading was dependent on osteocytes, we propose that there is a sensor for body weight in the long bones of the lower extremities acting as “body scales.” This is part of a body weight homeostat, “gravitostat”, that keeps body weight and body fat mass constant.

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass.

[Keywords: diet-induced obesity, weight loss, osteocytes, glucose metabolism]

“Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials”, Association 2018

2018-gordon.pdf: “Association of Efficacy of Resistance Exercise Training With Depressive Symptoms: Meta-analysis and Meta-regression Analysis of Randomized Clinical Trials”⁠, American Medical Association (2018-01-01; )

“Percutaneous Coronary Intervention in Stable Angina (ORBITA): a Double-blind, Randomised Controlled Trial”, Al-Lamee et al 2017

2017-allamee.pdf: “Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial”⁠, Rasha Al-Lamee, David Thompson, Hakim-Moulay Dehbi, Sayan Sen, Kare Tang, John Davies, Thomas Keeble et al (2017-11-02; ⁠, ; backlinks; similar):

Background: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy.

Methods: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with, number NCT02062593.

Findings: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84.4% (SD 10.2), fractional flow reserve of 0.69 (0.16), and instantaneous wave-free ratio of 0.76 (0.22). There was no statistically-significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16.6 s, 95% CI −8.9 to 42.0, p = 0.200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group.

Interpretation: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.

“Genome-wide Meta-analysis Associates HLA-DQA1/DRB1 and LPA and Lifestyle Factors With Human Longevity”, Joshi et al 2017

“Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity”⁠, Peter K. Joshi, Nicola Pirastu, Katherine A. Kentistou, Krista Fischer, Edith Hofer, Katharina E. Schraut et al (2017-10-13; ⁠, ⁠, ⁠, ; backlinks; similar):

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents’ survival, we discover two regions associated with longevity (HLA-DQA1/​DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/​5, CDKN2A/​B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.

“Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank”, Tikkanen et al 2017

“Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank”⁠, Emmi Tikkanen, Stefan Gustafsson, David Amar, Anna Shcherbina, Daryl Waggott, Euan A. Ashley, Erik Ingelsson et al (2017-10-10; ; similar):

Background: Hand grip strength, a simple indicator of muscular strength, has been associated with a range of health conditions, including fractures, disability, cardiovascular disease and premature death risk. Twin studies have suggested a high (50-60%) heritability, but genetic determinants are largely unknown.


In this study, our aim was to study genetic variation associated with muscular strength in a large sample of 334,925 individuals of European descent from the UK Biobank, and to evaluate shared genetic aetiology with and causal effects of grip strength on physical and cognitive health.

Methods and Results

In our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength at genome-wide statistical-significance (P<5×10−8). Of these, 64 were associated (P<0.01 and consistent direction) also in the replication dataset (n = 111,610). Many of the lead SNPs were located in or near genes known to have a function in developmental disorders (FTO, SLC39A8, TFAP2B, TGFA, CELF1, TCF4, BDNF, FOXP1, KIF1B, ANTXR2), and one of the most significant genes based on a gene-based analysis (ATP2A1) encodes SERCA1, the critical enzyme in calcium uptake to the sarcoplasmic reticulum, which plays a major role in muscle contraction and relaxation. Further, we demonstrated a significant enrichment of gene expression in brain-related transcripts among grip strength associations. Finally, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents’ age of death and education; and showed that grip strength was causally related to fitness, physical activity and other indicators of frailty, including cognitive performance scores.

Conclusion: In our study of over 330,000 individuals from the general population, the genetic findings for hand grip strength suggest an important role of the central nervous system in strength performance. Further, our results indicate that maintaining good muscular strength is important for physical and cognitive performance and healthy aging.

“The Sense of Smell Impacts Metabolic Health and Obesity”, Riera et al 2017

“The Sense of Smell Impacts Metabolic Health and Obesity”⁠, Celine E. Riera, Eva Tsaousidou, Jonathan Halloran, Patricia Follett, Oliver Hahn, Mafalda M. A. Pereira et al (2017-07-05; ; similar):

  • Loss of adult olfactory neurons protects against diet-induced obesity
  • Loss of smell after obesity also reduces fat mass and insulin resistance
  • Loss of IGF1 receptors in olfactory sensory neurons (OSNs) improves olfaction
  • Loss of IGF1R in OSNs increases adiposity and insulin resistance

Olfactory inputs help coordinate food appreciation and selection, but their role in systemic physiology and energy balance is poorly understood. Here we demonstrate that mice upon conditional ablation of mature olfactory sensory neurons (OSNs) are resistant to diet-induced obesity accompanied by increased thermogenesis in brown and inguinal fat depots. Acute loss of smell perception after obesity onset not only abrogated further weight gain but also improved fat mass and insulin resistance. Reduced olfactory input stimulates sympathetic nerve activity, resulting in activation of β-adrenergic receptors on white and brown adipocytes to promote lipolysis. Conversely, conditional ablation of the IGF1 receptor in OSNs enhances olfactory performance in mice and leads to increased adiposity and insulin resistance. These findings unravel a new bidirectional function for the olfactory system in controlling energy homeostasis in response to sensory and hormonal signals.

[Keywords: olfactory sensory neuron, hyposmia, hyperosmia, diet-induced obesity, energy balance, thermogenesis, lipolysis, insulin-like growth factor 1 receptor, insulin resistance]

Our sense of smell is key to the enjoyment of food, so it may be no surprise that in experiments at the University of California, Berkeley, obese mice who lost their sense of smell also lost weight.

What’s weird, however, is that these slimmed-down but smell-deficient mice ate the same amount of fatty food as mice that retained their sense of smell and ballooned to twice their normal weight.

In addition, mice with a boosted sense of smell—super-smellers—got even fatter on a high-fat diet than did mice with normal smell.

The findings suggest that the odor of what we eat may play an important role in how the body deals with calories. If you can’t smell your food, you may burn it rather than store it.

These results point to a key connection between the olfactory or smell system and regions of the brain that regulate metabolism, in particular the hypothalamus, though the neural circuits are still unknown.

“This paper is one of the first studies that really shows if we manipulate olfactory inputs we can actually alter how the brain perceives energy balance, and how the brain regulates energy balance”, said Céline Riera, a former UC Berkeley postdoctoral fellow now at Cedars-Sinai Medical Center in Los Angeles.

…“Sensory systems play a role in metabolism. Weight gain isn’t purely a measure of the calories taken in; it’s also related to how those calories are perceived”, said senior author Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research, professor of molecular and cell biology and Howard Hughes Medical Institute Investigator. “If we can validate this in humans, perhaps we can actually make a drug that doesn’t interfere with smell but still blocks that metabolic circuitry. That would be amazing.”

“Chimpanzee Super Strength and Human Skeletal Muscle Evolution”, O’Neill et al 2017

“Chimpanzee super strength and human skeletal muscle evolution”⁠, Matthew C. O’Neill, Brian R. Umberger, Nicholas B. Holowka, Susan G. Larson, Peter J. Reiser (2017-06-26; backlinks; similar):

Significance: Chimpanzee “super strength” has been widely reported since the 1920s although a critical review of the available data suggests that the chimpanzee-human muscular performance differential is only ~1.5×. Some hypothesize that this differential reflects underlying differences in muscle mechanics. Here, we present direct measurements of chimpanzee skeletal muscle properties in comparison with those of humans and other terrestrial mammals. Our results show that chimpanzee muscle exceeds human muscle in maximum dynamic force and power output by ~1.35×. This is primarily due to the chimpanzee’s higher fast-twitch fiber content, rather than exceptional maximum isometric force or maximum shortening velocities. We suggest that muscular performance capabilities declined during hominin evolution in response to selection for repetitive, low-cost contractile behavior.

Since at least the 1920s, it has been reported that common chimpanzees (Pan troglodytes) differ from humans in being capable of exceptional feats of “super strength”, both in the wild and in captive environments. A mix of anecdotal and more controlled studies provides some support for this view; however, a critical review of available data suggests that chimpanzee mass-specific muscular performance is a more modest 1.5× greater than humans on average. Hypotheses for the muscular basis of this performance differential have included greater isometric force-generating capabilities, faster maximum shortening velocities, and/​or a difference in myosin heavy chain (MHC) isoform content in chimpanzee relative to human skeletal muscle. Here, we show that chimpanzee muscle is similar to human muscle in its single-fiber contractile properties, but exhibits a much higher fraction of MHC II isoforms. Unlike humans, chimpanzee muscle is composed of ~67% fast-twitch fibers (MHC IIa+IId). Computer simulations of species-specific whole-muscle models indicate that maximum dynamic force and power output is 1.35 times higher in a chimpanzee muscle than a human muscle of similar size. Thus, the superior mass-specific muscular performance of chimpanzees does not stem from differences in isometric force-generating capabilities or maximum shortening velocities—as has long been suggested—but rather is due in part to differences in MHC isoform content and fiber length. We propose that the hominin lineage experienced a decline in maximum dynamic force and power output during the past 7–8 million years in response to selection for repetitive, low-cost contractile behavior.

[Keywords: chimpanzee, human, muscle, myosin heavy chain, muscle modeling]

“Fitness, Physical Activity, and Cardiovascular Disease: Longitudinal and Genetic Analyses in the UK Biobank Study”, Tikkanen et al 2017

“Fitness, Physical Activity, and Cardiovascular Disease: Longitudinal and Genetic Analyses in the UK Biobank Study”⁠, Emmi Tikkanen, Stefan Gustafsson, Erik Ingelsson (2017-05-12; similar):

Background: Exercise is inversely related with cardiovascular disease (CVD), but large-scale studies of incident CVD events are lacking. Moreover, little is known about genetic determinants of fitness and physical activity, and modifiable effects of exercise in individuals with elevated genetic risk of CVD. Finally, causal analyses of exercise traits are limited.

Methods: We estimated associations of grip strength, physical activity, and cardiorespiratory fitness with CVD and all-cause death in up to 502,635 individuals from the UK Biobank. We also examined these associations in individuals with different genetic burden on coronary heart disease (CHD) and atrial fibrillation (AF). Finally, we performed genome-wide association study (GWAS) of grip strength and physical activity, as well as Mendelian randomization analysis to assess the causal role of grip strength in CHD.


Grip strength, physical activity, and cardiorespiratory fitness showed strong inverse associations with incident cardiovascular events and all-cause death (for composite CVD; HR, 0.78, 95% CI, 0.77–0.80; HR, 0.94, 95% CI, 0.93–0.95, and HR, 0.67, 95% CI, 0.63–0.71, per SD change, respectively). We observed stronger associations of grip strength with CHD and AF for individuals in the lowest tertile of genetic risk (p interaction = 0.006, p interaction = 0.03, respectively), but the inverse associations were present in each category of genetic risk. We report 27 novel genetic loci associated with grip strength and 2 loci with physical activity, with the strongest associations in FTO (rs56094641, p = 3.8×10−24) and SMIM2 (rs9316077, p = 1.4×10−8), respectively. By use of Mendelian randomization, we provide evidence that grip strength is causally related to CHD.


Maintaining physical strength is likely to prevent future cardiovascular events, also in individuals with elevated genetic risk for CVD.


National Institutes of Health (1 R01 HL135313–01), Knut and Alice Wallenberg Foundation (2013.0126), and the Finnish Cultural Foundation.

“Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology”, Schnurr et al 2016

“Genetic Correlation between Body Fat Percentage and Cardiorespiratory Fitness Suggests Common Genetic Etiology”⁠, Theresia M. Schnurr, Anette P. Gjesing, Camilla H. Sandholt, Anna Jonsson, Yuvaraj Mahendran, Christian T. Have et al (2016-11-02; similar):


It has long been discussed whether fitness or fatness is a more important determinant of health status. If the same genetic factors that promote body fat percentage (body fat%) are related to cardiorespiratory fitness (CRF), part of the concurrent associations with health outcomes could reflect a common genetic origin. In this study we aimed to (1) examine genetic correlations between body fat% and CRF; (2) determine whether CRF can be attributed to a genetic risk score (GRS) based on known body fat% increasing loci; and (3) examine whether the fat mass and obesity associated (FTO) locus associates with CRF.


Genetic correlations based on pedigree information were examined in a family based cohort (n = 230 from 55 families). For the genetic association analyses, we examined two Danish population-based cohorts (ntotal = 3206). The body fat% GRS was created by summing the alleles of twelve independent risk variants known to associate with body fat%. We assessed CRF as maximal oxygen uptake expressed in milliliters of oxygen uptake per kg of body mass (VO2max), per kg fat-free mass (VO2maxFFM), or per kg fat mass (VO2maxFM). All analyses were adjusted for age and sex, and when relevant, for body composition.


We found a significant negative genetic correlation between VO2max and body fat% (ρG = −0.72 (SE ±0.13)). The body fat% GRS associated with decreased VO2max (β = −0.15 mL/​kg/​min per allele, p = 0.0034, age and sex adjusted). The body fat%-increasing FTO allele was associated with a 0.42 mL/​kg/​min unit decrease in VO2max per allele (p = 0.0092, age and sex adjusted). Both associations were abolished after additional adjustment for body fat%. The fat% increasing GRS and FTO risk allele were associated with decreased VO2maxFM but not with VO2maxFFM.


Our findings suggest a shared genetic etiology between whole body fat% and CRF.

“Time-restricted Feeding in Young Men Performing Resistance Training: A Randomized Controlled Trial”, Tinsley et al 2016

2016-tinsley.pdf: “Time-restricted feeding in young men performing resistance training: A randomized controlled trial”⁠, Grant M. Tinsley, Jeffrey S. Forsse, Natalie K. Butler, Antonio Paoli, Annie A. Bane, Paul M. La Bounty et al (2016-08-22; ; similar):

A randomized controlled trial was conducted to examine 8 weeks of resistance training (RT) with and without time-restricted feeding (TRF) in order to assess nutrient intake and changes in body composition and muscular strength in young recreationally active males.

The TRF programme consisted of consuming all calories within a 4-hour period of time for 4 days per week, but included no limitations on quantities or types of foods consumed. The RT programme was performed 3 days per week and consisted of alternating upper and lower body workouts. For each exercise, 4 sets leading to muscular failure between 8 and 12 repetitions were employed. Research visits were conducted at baseline, 4, and 8 weeks after study commencement. Measurements of total body composition by dual-energy X-ray absorptiometry and muscle cross-sectional area by ultrasound were obtained. Upper and lower body strength and endurance were assessed, and 4-day dietary records were collected.

TRF reduced energy intake by ~650 kcal per day of TRF, but did not affect total body composition within the duration of the study. Cross-sectional area of the biceps brachii and rectus femoris increased in both groups. Effect size data indicate a gain in lean soft tissue in the group that performed RT without TRF (+2.3 kg, d = 0.25). Upper and lower body strength and lower body muscular endurance increased in both groups, but effect sizes demonstrate greater improvements in the TRF group.

Overall, TRF reduced energy intake and did not adversely affect lean mass retention or muscular improvements with short-term RT in young males.

[Keywords: Intermittent fasting, time-restricted feeding, body composition, resistance training, muscular strength, energy intake]

“Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity”, Karvinen et al 2016

“Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity”⁠, Sira M. Karvinen, Mika Silvennoinen, Hongqiang Ma, Timo Törmäkangas, Timo Rantalainen, Rita Rinnankoski-Tuikka et al (2016-07-25; backlinks; similar):

The production of heat, ie. thermogenesis, is a substantial component of the metabolic rate, which in turn affects weight gain and health. Thermogenesis is linked to physical activity (PA) level. However, it is not known whether intrinsic exercise capacity, aging, and long-term voluntary running affect core body temperature.

Here we use rat models selectively bred to differ in maximal treadmill endurance running capacity (Low capacity runners, LCR and High capacity Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging, and metabolic disease risk to study the connection between PA and body temperature.

10 high capacity runner (HCR) and 10 low capacity runner (LCR) female rats were studied between 9 and 21 months of age. Rectal body temperature of HCR and LCR rats was measured before and after 1-year voluntary running/​control intervention to explore the effects of aging and PA. Also, we determined whether injected glucose and spontaneous activity affect the body temperature differently between LCR and HCR rats at 9 vs. 21 months of age. HCRs had on average 1.3°C higher body temperature than LCRs (p < 0.001). Aging decreased the body temperature level of HCRs to similar levels with LCRs. The opportunity to run voluntarily had a statistically-significant impact on the body temperature of HCRs (p < 0.001) allowing them to maintain body temperature at a similar level as when at younger age. Compared to LCRs, HCRs were spontaneously more active, had higher relative gastrocnemius muscle mass and higher UCP2, PGC-1α, cytochrome c, and OXPHOS levels in the skeletal muscle (p < 0.050).

These results suggest that higher PA level together with greater relative muscle mass and higher mitochondrial content/​function contribute to the accumulation of heat in the HCRs. Interestingly, neither aging nor voluntary training had a statistically-significant impact on core body temperature of LCRs. However, glucose injection resulted in a lowering of the body temperature of LCRs (p < 0.050), but not that of HCRs.

In conclusion, rats born with high intrinsic capacity for aerobic exercise and better health have higher body temperature compared to rats born with low exercise capacity and disease risk. Voluntary running allowed HCRs to maintain high body temperature during aging, which suggests that high PA level was crucial in maintaining the high body temperature of HCRs.

“Lifespan and Skeletal Muscle Properties: The Effects of Genetic Background, Physical Activity and Aging”, Karvinen 2016

2016-karvinen.pdf: “Lifespan and Skeletal Muscle Properties: The Effects of Genetic Background, Physical Activity and Aging”⁠, Sira Karvinen (2016-04-22; ; backlinks; similar):

Obesity and metabolic disorders have become a notable world-wide epidemic. The pathogenesis of metabolic diseases, such as metabolic syndrome and type 2 diabetes, has begun to negatively affect life expectancy of current generations. Low aerobic capacity has shown to be a strong predictor of mortality both in rodents and humans. Exercise is known to increase an individual’s aerobic capacity; interestingly, recent studies have suggested that genetic background may play a substantial role in the physical activity level of an individual. The purpose of this study was to investigate the role of genetic background and physical activity on skeletal muscle properties, metabolism and lifespan.

The study consisted of three parts:

  1. a cross-sectional voluntary running intervention in high-capacity runner (HCR) and low-capacity runner (LCR) rats,
  2. a longitudinal voluntary running intervention in HCR and LCR rats, and
  3. a long-term follow-up study with physical activity discordant human twins.

Our study showed that low intrinsic aerobic capacity is associated with fast muscular fatigue and slow metabolic recovery after maximal muscle contractions. At the whole-body level, low intrinsic aerobic capacity was linked to low body temperature, which may play a role in the onset of gaining extra weight and, thus, developing metabolic disorders. High intrinsic aerobic capacity in turn was associated with elevated SIRT3 protein level in skeletal muscle, which is possibly linked to increased lifespan. Nevertheless, vigorous physical activity commenced at adult age did not reduce mortality or increase lifespan in rodents. High long-term participation in vigorous leisure-time physical activity did predict statistically-significantly reduced mortality in dizygotic twins; however, there was no difference in the lifespan of monozygotic twins that are genetically identical. HCRs were more physically active both in control and voluntary running groups when compared to corresponding LCR groups. Also, the persistent discordances in participation of vigorous physical activity were statistically-significantly more common in dizygotic twin pairs than in monozygotic pairs stating that genes have an influence on the persistent voluntary participation in vigorous leisure-time physical activity.

Our results indicated that genetic predisposition plays a substantial role in exercise participation, hence, genetic pleiotropy may partly explain the associations observed previously between high physical activity and mortality.

  1. Torvinen et al 2012, “Rats bred for low aerobic capacity become promptly fatigued and have slow metabolic recovery after stimulated, maximal muscle contractions”
  2. Karvinen et al 2012, “Physical activity in adulthood: genes and mortality”
  3. Karvinen et al 2016, “Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins”
  4. Karvinen et al 2016, “Voluntary running aids to maintain high body temperature in rats bred for high aerobic capacity”

“A Thrifty Variant in CREBRF Strongly Influences Body Mass Index in Samoans”, Minster et al 2016

“A thrifty variant in CREBRF strongly influences body mass index in Samoans”⁠, Ryan L. Minster, Nicola L. Hawley, Chi-Ting Su, Guangyun Sun, Erin E. Kershaw, Hong Cheng, Olive D. Buhule et al (2016; ; similar):

Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity.

We conducted a genome-wide association study (GWAS) in 3,072 Samoans:

discovered a variant, rs12513649, strongly associated with body mass index (BMI) (p = 5.3 × 10−14), and replicated the association in 2,102 additional Samoans (p = 1.2 × 10−9). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta p = 1.4 × 10−20). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36–1.45 kg⁄m2 per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model.

These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a ‘thrifty’ variant hypothesis as a factor in human obesity.

“Physical Activity in Adulthood: Genes and Mortality”, Karvinen et al 2015

“Physical activity in adulthood: genes and mortality”⁠, Sira Karvinen, Katja Waller, Mika Silvennoinen, Lauren G. Koch, Steven L. Britton, Jaakko Kaprio, Heikki Kainulainen et al (2015-12-15; backlinks; similar):

Observational studies report a strong inverse relationship between leisure-time physical activity and all-cause mortality. Despite suggestive evidence from population-based associations, scientists have not been able to show a beneficial effect of physical activity on the risk of death in controlled intervention studies among individuals who have been healthy at baseline. On the other hand, high cardiorespiratory fitness is known to be a strong predictor of reduced mortality, even more robust than physical activity level itself.

Here, in both animals and/​or human twins, we show that the same genetic factors influence physical activity levels, cardiorespiratory fitness and risk of death. Previous observational follow-up studies in humans suggest that increasing fitness through physical activity levels could prolong life; however, our controlled interventional study with laboratory rats bred for low and high intrinsic fitness contrast with these findings. Also, we find no evidence for the suggested association using pairwise analysis among monozygotic twin pairs who are discordant in their physical activity levels.

Based on both our animal and human findings, we propose that genetic pleiotropy might partly explain the frequently observed associations between high baseline physical activity and later reduced mortality in humans.

[See also author’s later thesis, “Lifespan and Skeletal Muscle Properties: The Effects of Genetic Background, Physical Activity and Aging”⁠.]

“Physical Activity, Fitness, Glucose Homeostasis, and Brain Morphology in Twins”, Rottensteiner et al 2015

2015-rottensteiner.pdf: “Physical activity, fitness, glucose homeostasis, and brain morphology in twins”⁠, Mirva Rottensteiner, Tuija Leskinen, Eini Niskanen, Sari Aaltonen, Sara Mutikainen, Jan Wikgren, Kauko Heikkilä et al (2015; ; backlinks; similar):

Purpose: The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity.

Methods: From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32–36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses.

Results: According to pairwise analysis, the active twins had lower body fat percentage (p = 0.029) and homeostatic model assessment index (p = 0.031) and higher Matsuda index (p = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of p < 0.001.

Conclusions: Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

“Physical Attractiveness As a Phenotypic Marker of Health: an Assessment Using a Nationally Representative Sample of American Adults”, Nedelec & Beaver 2014

2014-nedelec.pdf: “Physical attractiveness as a phenotypic marker of health: an assessment using a nationally representative sample of American adults”⁠, Joseph L. Nedelec, Kevin M. Beaver (2014-11-01; ; similar):

Evolutionary explanations regarding the differential preference for particular traits hold that preferences arose due to traits’ association with increased potential for reproductive fitness. Assessments of physical attractiveness have been shown to be related to perceived and measured levels of health, an important fitness-related trait.

Despite the robust association between physical attractiveness and health observed in the extant literature, a number of theoretical and methodological concerns remain. Specifically, the research in this area possesses a lack of specificity in terms of measures of health, a reliance on artificial social interactions in assessing physical attractiveness, and a relatively infrequent use of non-student samples and leaves unaddressed the confounding effects of raters of attractiveness.

Using these concerns as a springboard, the current study employed data from the National Longitudinal Study for Adolescent Health (n ≈ 15,000; aged 25 to 34 years) to assess the relationship between physical attractiveness and various specific and overall measures of health. Logistic and OLS regression models illustrated a robust association between physical attractiveness and various measures of health, controlling for a variety of confounding factors.

In sum, the more attractive a respondent was rated, the less likely he or she was to report being diagnosed with a wide range of chronic diseases and neuropsychological disorders. Importantly, this finding was observed for both sexes. These analyses provide further support for physical attractiveness as a phenotypic marker of health.

The findings are discussed in reference to evolutionary theory, and the limitations of the study and future research suggestions are also addressed.

“The Cross Section Illusion”, Greer 2014

“The Cross Section Illusion”⁠, Tanner Greer (2014-06-07; similar):

If you are concerned with American obesity rates and turn to the cross sectional data to try and figure out what is going on, it is easy to reach a flawed conclusion. The correlation between education and obesity, for example, seems quite clear. The poorer and less educated an American is, the more likely he or she is to be obese. Looking at this data it seems reasonable to suggest that something about poverty is making people more obese—perhaps cruddy processed food is the only thing America’’s poor and less educated can afford to buy, or maybe the poor live in urban areas where people do not exercise. These hypotheses are plausible… until you look at the time series. It then becomes apparent that the rich and educated are gaining weight at the same rate as the poor. Poverty cannot explain this.

It is very difficult to make meaningful claims about causation—or even correlation!—on the basis of cross section data alone. Often times seemingly perfect, statistically-significant correlations disappear when the same variables are viewed over a longer stretch of time. In other cases—as in this one—time series data reveals that the real story isn’’t about variance between two groups at all, but about the rate at which each group is changing. It is all too easy to be fooled by the Cross Section Illusion.

“Vitamin C and E Supplementation Hampers Cellular Adaptation to Endurance Training in Humans: a Double-blind, Randomised, Controlled Trial”, Paulsen et al 2014

2014-paulsen.pdf: “Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial”⁠, Gøran Paulsen, Kristoffer T. Cumming, Geir Holden, Jostein Hallén, Bent Ronny Rønnestad, Ole Sveen, Arne Skaug et al (2014-03-03; ; backlinks; similar):

  • Recent studies have indicated that antioxidant supplementation may blunt adaptations to exercise, such as mitochondrial biogenesis induced by endurance training. However, studies in humans are sparse and results are conflicting.
  • Isolated vitamin C and E supplements are widely used, and unravelling the interference of these vitamins in cellular and physiological adaptations to exercise is of interest to those who exercise for health purposes and to athletes.
  • Our results show that vitamin C and E supplements blunted the endurance training-induced increase of mitochondrial proteins (COX4), which is important for improving muscular endurance.
  • Training-induced increases in VO2max and running performance were not detectably affected by the supplementation.
  • The present study contributes to understanding of how antioxidants may interfere with adaptations to exercise in humans, and the results indicate that high dosages of vitamins C and E should be used with caution.

In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4–6 × 4–6 min; >90% of maximal heart rate (HRmax)] and steady state continuous sessions (30–60 min; 70–90% of HRmax). Maximal oxygen uptake (VO2max), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased their VO2max (mean ± s.d.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± s.d.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: −13 ± 54%; PGC-1α: −13 ± 29%; p ≤ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (p ≤ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements in VO2max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

“A Twin-sibling Study on the Relationship between Exercise Attitudes and Exercise Behavior”, Huppertz et al 2014

“A twin-sibling study on the relationship between exercise attitudes and exercise behavior”⁠, Charlotte Huppertz, Meike Bartels, Iris E. Jansen, Dorret I. Boomsma, Gonneke Willemsen, Marleen H. M. de Moor et al (2014-01; backlinks; similar):

Social cognitive models of health behavior propose that individual differences in leisure time exercise behavior are influenced by the attitudes towards exercise. At the same time, large scale twin-family studies show a large influence of genetic factors on regular exercise behavior.

This twin-sibling study aimed to unite these findings by demonstrating that exercise attitudes can be heritable themselves. Secondly, the genetic and environmental cross-trait correlations and the monozygotic (MZ) twin intrapair differences model were used to test whether the association between exercise attitudes and exercise behavior can be causal. Survey data were obtained from 5,095 twins and siblings (18–50 years).

A genetic contribution was found for exercise behavior (50% in males, 43% in females) and for the 6 exercise attitude components derived from principal component analysis: perceived benefits (21, 27%), lack of skills, support and/​or resources (45, 48%), time constraints (25, 30%), lack of energy (34, 44%), lack of enjoyment (47, 44%), and embarrassment (42, 49%). These components were predictive of leisure time exercise behavior (R2 = 28%). Bivariate modeling further showed that all the genetic (0.36 < |rA| < 0.80) and all but 2 unique environmental (0.00 < |rE| < 0.27) correlations between exercise attitudes and exercise behavior were statistically-significantly different from zero, which is a necessary condition for the existence of a causal effect driving the association. The correlations between the MZ twins’ difference scores were in line with this finding.

It is concluded that exercise attitudes and exercise behavior are heritable, that attitudes and behavior are partly correlated through pleiotropic genetic effects, but that the data are compatible with a causal association between exercise attitudes and behavior.

[Keywords: twin-sibling design, twins, correlational approach, physical activity, heritability]

“Is Eating Behavior Manipulated by the Gastrointestinal Microbiota? Evolutionary Pressures and Potential Mechanisms”, Alcock et al 2014

“Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms”⁠, Joe Alcock, Carlo C. Maley, C. Athena Aktipis (2014; ; similar):

Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (1) generating cravings for foods that they specialize on or foods that suppress their competitors, or (2) inducing dysphoria until we eat foods that enhance their fitness.

We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior.

Because microbiota are easily manipulable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.

“Greek Combat Sports and Their Transmission to Central and East Asia”, Christopoulos 2013

2013-christopoulos.pdf: “Greek Combat Sports and Their Transmission to Central and East Asia”⁠, Lucas Christopoulos (2013-03; ; similar):

After the conquests of Alexander the Great and during the reign of his numerous successors, the tradition of combat sports games became institutionalized by the elite of an Hellenized warlike aristocracy in Asia. The heroic cult of the Greeks was perpetuated as far as Central Asia, improving the local traditions by building a gymnasium in every new city of the colonies. The various technical aspects of ancient Greek combat sports were transmitted as well in order to improve effectiveness in close-combat fighting.

To trace back these technical features, a detailed description of wrestling⁠, boxing and pankration as developed in ancient Greece are compared together with their East-Asian counterparts.

…Eurydamas from Cyrene is said to have lost his teeth during his fight and swallowed them so as not to give satisfaction to his adversary, according to the Roman author Aelian⁠.52 The boxers used head protection and leather bands, called imantes or sphaira, around their fists in the place of gloves.53 In Roman times, boxers also wore iron rings called caestus54 on their fists, for the amusement of the Roman spectators during gladiatorial contests. Philostratus⁠, a Greek living in the Roman Empire in the third century A.D., describes clearly how the bands of leather were tightened around the boxers’ fists and why pigskin was prohibited in boxing competitions.55 Unlike modern boxing, pygmachia also used various open-hand strikes, as indicated by various sources. In Homer’s verses, Apollo came down to earth to kill Patroclus with an “open-palm strike to his back”56 and Damoxenos pierced the internal organs of Kreugas with a finger strike (plate 2).57 Vase paintings also depicted ancient boxing practices, as in the case of the pseudo-Panathenaic amphora from Exarchos in Locrid by the painter Eucharides (~500 B.C.), which shows a palm strike and a forearm block (plate 3).

The painting of Eucharides also shows the unusual “distended” abdomen of the athletes, as if filled with air, a characteristic that is seen today in China among the adepts of traditional combat sports. The use of the principles of pneuma together with other concepts from Greek medicine led to training in various breathing techniques that were later lost in the West because of the mind/​body split introduced by the Catholic Church. Indeed there is no trace of this practice in the Western world today. The explanation of Pausanias concerning the fight of Damoxenos, that “with the sharpness of his nails and the force of blow he drove his hand into his adversary, caught his bowels, and tore them out”,58 is incomplete in my opinion.

Pausanias⁠, a second-century A.D. traveler and geographer, must have had a superficial understanding of what he heard, since he had no practical knowledge of ancient pygmachia training. To pierce the human body with one’s bare hands requires strengthening of the fingers together with explosive power developed through breathing exercises, allowing one to apply the muscular strength of one’s whole body instantaneously when striking (plate 4). Standing without changing position, and breathing techniques such as those used by Melankomas or those described by Oreibasius,59 were an integral part of a boxer’s training to fill his body with pneuma. Today in China, the best traditional boxers60 are those who apply the notion of an inner vital breath or energy. Oreibasius called this type of exercise “side therapy” or apotherapia, techniques which developed the athlete’s strength through inner breathing exercises or massage to activate the pneuma within their bodies. He advised combat-sports athletes to breathe from the lower abdomen, and to push the pneuma down using other types of breathing exercises, and also to speak with a deep voice, in order to open and fill the “empty spaces of the body.”

…Pythagoras himself is said to have been crowned in boxing, according to Eusebios of Cesarea (A.D. 265–339). During the 48h Olympiad (588 B.C.), Glycon of Croton won the stadion race. Pythagoras of Samos was excluded from boxing in the junior category because of his effeminate appearance, but he was still able to participate in the adult contest and beat all his adversaries.70 Diogenes Laerce also writes that, having been expelled from the junior category, Pythagoras went on to participate in the adult contest and beat all his adversaries.71

Some of the boxers had such excellent technique that they were never hit by their opponents. They were called “the untouchables” (atravmatisti), and included famous boxers such as Kleoxenos of Alexandria (240 B.C.; one-hundred thirty-fifth Olympiad), Melankomas of Caria,72 and Hippomachos. Hippomachos, son of Moschion, sustained no blows or injuries from his 3 successive opponents in the games.73 Julius Africanus (A.D. ~200) wrote that Kleoxenos had never been injured in any of his fights, and that he won all the Panhellenic games without being hurt. Melankomas was particularly well versed in standing positions, which are practiced today in China,74 but have been lost to the Western world.75 He could remain standing for 2 days with his 2 hands raised,76 a practice far removed from modern boxing. Being so skilful at his art, he was never beaten by his opponents and neither did he hurt them. He just let them exhaust themselves. Dio Chrysostom (A.D. 30–117) wrote that he had perfect control over his mind and body:

The most fantastic thing is that he was not only undefeated by his adversaries, but also by hard training in the heat, avoiding hunger, and sexual desires. The men who wish to be superior to their adversaries should not be defeated by these things. If Melankomas did not have control of himself (enkrateo),77 I doubt that he would be superior in strength, even if he was naturally strong.78

“Fatigue Is a Brain-derived Emotion That Regulates the Exercise Behavior to Ensure the Protection of Whole Body Homeostasis”, Noakes 2012

“Fatigue is a brain-derived emotion that regulates the exercise behavior to ensure the protection of whole body homeostasis”⁠, Timothy David Noakes (2012-04-12; backlinks; similar):

An influential book written by A. Mosso in the late 19th century proposed that fatigue that “at first sight might appear an imperfection of our body, is on the contrary one of its most marvelous perfections. The fatigue increasing more rapidly than the amount of work done saves us from the injury which lesser sensibility would involve for the organism” so that “muscular fatigue also is at bottom an exhaustion of the nervous system.” It has taken more than a century to confirm Mosso’s idea that both the brain and the muscles alter their function during exercise and that fatigue is predominantly an emotion, part of a complex regulation, the goal of which is to protect the body from harm. Mosso’s ideas were supplanted in the English literature by those of A. V. Hill who believed that fatigue was the result of biochemical changes in the exercising limb muscles–“peripheral fatigue”–to which the central nervous system makes no contribution. The past decade has witnessed the growing realization that this brainless model cannot explain exercise performance. This article traces the evolution of our modern understanding of how the CNS regulates exercise specifically to insure that each exercise bout terminates whilst homeostasis is retained in all bodily systems. The brain uses the symptoms of fatigue as key regulators to insure that the exercise is completed before harm develops. These sensations of fatigue are unique to each individual and are illusory since their generation is largely independent of the real biological state of the athlete at the time they develop. The model predicts that attempts to understand fatigue and to explain superior human athletic performance purely on the basis of the body’s known physiological and metabolic responses to exercise must fail since subconscious and conscious mental decisions made by winners and losers, in both training and competition, are the ultimate determinants of both fatigue and athletic performance.

“Effect of Shared Environmental Factors on Exercise Behavior from Age 7 to 12 Years”, Huppertz et al 2012

“Effect of shared environmental factors on exercise behavior from age 7 to 12 years”⁠, Charlotte Huppertz, Meike Bartels, Catherina E. M Van Beijsterveldt, Dorret I. Boomsma, James J. Hudziak et al (2012; backlinks; similar):

Introduction: The aim of this study was to investigate the relative influence of genetic and environmental factors on children’s leisure time exercise behavior through the classic twin design.

Methods: Data were taken from The Netherlands Twin Register. The twins were 7 (n = 3966 subjects), 10 (n = 3562), and 12-yr-olds (n = 8687), with longitudinal data for 27% of the sample. Parents were asked to indicate the children’s regular participation in leisure time exercise activities, including frequency and duration. Resemblance between monozygotic and dizygotic twins for weekly MET-hours spent on exercise activities was analyzed as a function of their genetic relatedness.

Results: Average weekly MET-hours increased with age for both boys (age 7 yr: 14.0 (SD = 11.8); age 10 yr: 22.6 (SD = 18.7); age 12 yr: 28.4 (SD = 24.9)) and girls (age 7 yr: 9.7 (SD = 9.5); age 10 yr: 15.3 (SD = 15.1); age 12 yr: 19.3 (SD = 19.8)). Around 13% of boys and girls across all age groups did not participate in any regular leisure time exercise activities. Tracking of exercise behavior from age 7 to 12 yr was modest (0.168 < r < 0.534). For boys, genetic effects accounted for 24% (confidence interval, 18%–30%) of the variance at age 7 yr, 66% (53%–81%) at age 10 yr, and 38% (32%–46%) at age 12 yr. For girls, this was 22% (15%–30%), 16% (9%–24%), and 36% (30%–43%), respectively. Environmental influences shared by children from the same family explained 71%, 25%, and 50% of the variance in boys (age 7, 10, and 12 yr) and 67%, 72%, and 53% in girls. The shared environment influencing exercise behavior was partially different between boys and girls.

Conclusion: Our results stress the important role of shared environment for exercise behavior in young children.

“Music in the Exercise Domain: a Review and Synthesis (Part I)”, Karageorghis & Priest 2012

“Music in the exercise domain: a review and synthesis (Part I)”⁠, Costas I. Karageorghis, David-Lee Priest (2012; ; backlinks; similar):

Since a 1997 review by Karageorghis and Terry, which highlighted the state of knowledge and methodological weaknesses, the number of studies investigating musical reactivity in relation to exercise has swelled considerably. In this two-part review paper, the development of conceptual approaches and mechanisms underlying the effects of music are explicated (Part I), followed by a critical review and synthesis of empirical work (spread over Parts I and II).

Pre-task music has been shown to optimize arousal, facilitate task-relevant imagery and improve performance in simple motoric tasks. During repetitive, endurance-type activities, self-selected, motivational and stimulative music has been shown to enhance affect, reduce ratings of perceived exertion, improve energy efficiency and lead to increased work output. There is evidence to suggest that carefully selected music can promote ergogenic and psychological benefits during high-intensity exercise, although it appears to be ineffective in reducing perceptions of exertion beyond the anaerobic threshold. The effects of music appear to be at their most potent when it is used to accompany self-paced exercise or in externally valid conditions. When selected according to its motivational qualities, the positive impact of music on both psychological state and performance is magnified. Guidelines are provided for future research and exercise practitioners.

“Music in the Exercise Domain: a Review and Synthesis (Part II)”, Karageorghis & Priest 2012

“Music in the exercise domain: a review and synthesis (Part II)”⁠, Costas I. Karageorghis, David-Lee Priest (2012; ; backlinks; similar):

Since a 1997 review by Karageorghis and Terry, which highlighted the state of knowledge and methodological weaknesses, the number of studies investigating musical reactivity in relation to exercise has swelled considerably. In this two-part review paper, the development of conceptual approaches and mechanisms underlying the effects of music are explicated (Part I), followed by a critical review and synthesis of empirical work (spread over Parts I and II).

Pre-task music has been shown to optimize arousal, facilitate task-relevant imagery and improve performance in simple motoric tasks. During repetitive, endurance-type activities, self-selected, motivational and stimulative music has been shown to enhance affect, reduce ratings of perceived exertion, improve energy efficiency and lead to increased work output. There is evidence to suggest that carefully selected music can promote ergogenic and psychological benefits during high-intensity exercise, although it appears to be ineffective in reducing perceptions of exertion beyond the anaerobic threshold. The effects of music appear to be at their most potent when it is used to accompany self-paced exercise or in externally valid conditions. When selected according to its motivational qualities, the positive impact of music on both psychological state and performance is magnified. Guidelines are provided for future research and exercise practitioners.

“The Activity-Based Anorexia Mouse Model”, Klenotich & Dulawa 2012

2012-klenotich.pdf: “The Activity-Based Anorexia Mouse Model”⁠, Stephanie J. Klenotich, Stephanie C. Dulawa (2012; ⁠, ; similar):

Animals housed with running wheels and subjected to daily food restriction show paradoxical reductions in food intake and increases in running wheel activity.

This phenomenon, known as activity-based anorexia (ABA), leads to marked reductions in body weight that can ultimately lead to death. Recently, ABA has been proposed as a model of anorexia nervosa (AN). AN affects about 8 per 100,000 females and has the highest mortality rate among all psychiatric illnesses. Given the reductions in quality of life, high mortality rate, and the lack of pharmacological treatments for AN, a better understanding of the mechanisms underlying AN-like behavior is greatly needed.

This chapter provides basic guidelines for conducting ABA experiments using mice. The ABA mouse model provides an important tool for investigating the neurobiological underpinnings of AN-like behavior and identifying novel treatments.

[Keywords: activity-based anorexia, hyperactivity, anorexia nervosa, animal model, mice, food restriction]

“Canaries in the Coal Mine: a Cross-species Analysis of the Plurality of Obesity Epidemics”, Klimentidis et al 2011

“Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics”⁠, Yann C. Klimentidis, T. Mark Beasley, Hui-Yi Lin, Giulianna Murati, Gregory E. Glass, Marcus Guyton, Wendy Newton et al (2011; ; backlinks; similar):

[not observed 2000–2020?] A dramatic rise in obesity has occurred among humans within the last several decades. Little is known about whether similar increases in obesity have occurred in animals inhabiting human-influenced environments.

We examined samples collectively consisting of over 20 000 animals from 24 populations (12 divided separately into males and females) of animals representing eight species living with or around humans in industrialized societies.

In all populations, the estimated coefficient for the trend of body weight over time was positive (ie. increasing). The probability of all trends being in the same direction by chance is 1.2 × 10−7. Surprisingly, we find that over the past several decades, average mid-life body weights have risen among primates and rodents living in research colonies, as well as among feral rodents and domestic dogs and cats⁠.

The consistency of these findings among animals living in varying environments, suggests the intriguing possibility that the aetiology of increasing body weight may involve several as-of-yet unidentified and/​or poorly understood factors (eg. viral pathogens, epigenetic factors). This finding may eventually enhance the discovery and fuller elucidation of other factors that have contributed to the recent rise in obesity rates.

“Exercise Participation in Adolescents and Their Parents: Evidence for Genetic and Generation Specific Environmental Effects”, Moor et al 2011

2011-demoor.pdf: “Exercise Participation in Adolescents and Their Parents: Evidence for Genetic and Generation Specific Environmental Effects”⁠, M.H.M. de Moor, G. Willemsen, I. Rebollo Mesa, J. H. Stubbe, E.J.C. de Geus, D. I. Boomsma (2011; ; backlinks; similar):

Individual differences in adolescent exercise behavior are to a large extent explained by shared environmental factors. The aim of this study was to explore to what extent this shared environment represents effects of cultural transmission of parents to their offspring, generation specific environmental effects or assortative mating. Survey data on leisure-time exercise behavior were available from 3,525 adolescent twins and their siblings (13–18 years) and 3,138 parents from 1,736 families registered at the Netherlands Twin Registry. Data were also available from 5,471 adult twins, their siblings and spouses similar in age to the parents. Exercise participation (No/​Yes, using a cut-off criterion of 4 metabolic equivalents and 60 min weekly) was based on questions on type, frequency and duration of exercise. A model to analyze dichotomous data from twins, siblings and parents including differences in variance decomposition across sex and generation was developed. Data from adult twins and their spouses were used to investigate the causes of assortative mating (correlation between spouses = 0.41, due to phenotypic assortment). The heritability of exercise in the adult generation was estimated at 42%. The shared environment for exercise behavior in adolescents mainly represents generation specific shared environmental influences that seem somewhat more important in explaining familial clustering in girls than in boys (52 versus 41%). A small effect of vertical cultural transmission was found for boys only (3%). The remaining familial clustering for exercise behavior was explained by additive genetic factors (42% in boys and 36% in girls). Future studies on adolescent exercise behavior should focus on identification of the generation specific environmental factors.

“Environmental Influences on Children's Physical Activity: Quantitative Estimates Using a Twin Design”, Fisher et al 2010

“Environmental Influences on Children's Physical Activity: Quantitative Estimates Using a Twin Design”⁠, Abigail Fisher, Cornelia H. M. van Jaarsveld, Clare H. Llewellyn, Jane Wardle (2010-04-21; backlinks; similar):

Background: Twin studies offer a ‘natural experiment’ that can estimate the magnitude of environmental and genetic effects on a target phenotype. We hypothesised that fidgetiness and enjoyment of activity would be heritable but that objectively-measured daily activity would show a strong shared environmental effect.

Methodology/​Principal Findings: In a sample of 9–12 year-old same-sex twin pairs (234 individuals; 57 MZ, 60 DZ pairs) we assessed three dimensions of physical activity: (1) objectively-measured physical activity using accelerometry, (2) ‘fidgetiness’ using a standard psychometric scale, and (3) enjoyment of physical activity from both parent ratings and children’s self-reports. Shared environment effects explained the majority (73%) of the variance in objectively-measured total physical activity (95% confidence intervals (CI): 0.63–0.81) with a smaller unshared environmental effect (27%; CI: 0.19–0.37) and no statistically-significant genetic effect. In contrast, fidgetiness was primarily under genetic control, with additive genetic effects explaining 75% (CI: 62–84%) of the variance, as was parent’s report of children’s enjoyment of low 74% (CI: 61–82%), medium 80% (CI: 71–86%), and high impact activity (85%; CI: 78–90%), and children’s expressed activity preferences (60%, CI: 42–72%).

Conclusions: Consistent with our hypothesis, the shared environment was the dominant influence on children’s day-to-day activity levels. This finding gives a strong impetus to research into the specific environmental characteristics influencing children’s activity, and supports the value of interventions focused on home or school environments.

“A Longitudinal Study on Genetic and Environmental Influences on Leisure Time Physical Activity in the Finnish Twin Cohort”, Aaltonen et al 2010

2010-aaltonen.pdf: “A longitudinal study on genetic and environmental influences on leisure time physical activity in the Finnish Twin Cohort”⁠, Sari Aaltonen, Alfredo Ortega-Alonso, Urho M. Kujala, Jaakko Kaprio (2010; ; backlinks; similar):

The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18–54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (rg = 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (re = 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (rg = 0.79) than women (rg = 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62% and women 69%. The environmental correlations between the two time points were similar for men (re = 0.21) and for women (re = 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.

“Genetics of Exercise Behavior”, Stubbe & Geus 2009

2009-stubbe.pdf: “Genetics of Exercise Behavior”⁠, Janine H. Stubbe, Eco J. C. de Geus (2009-01-01; ; backlinks)

“Unique Environmental Effects on Physical Activity Participation: A Twin Study”, Duncan et al 2008

“Unique Environmental Effects on Physical Activity Participation: A Twin Study”⁠, Glen E. Duncan, Jack Goldberg, Carolyn Noonan, Anne Vernez Moudon, Philip Hurvitz, Dedra Buchwald (2008-04-16; backlinks; similar):

Background: The health benefits of regular physical activity are well established. However, the relative contribution of heritable and environmental factors to physical activity participation remains controversial. Using a cut-point of 60 minutes of total activity per week, data from the GenomEUtwin project revealed consistent genetic influence on physical activity participation in 37,051 twin pairs from seven countries. We hypothesized that the heritability of physical activity participation would be attenuated using the CDC/​ACSM recommended minimum threshold of 150 minutes of moderate intensity activity per week.

Methods: Data were obtained from 1,389 twin pairs from the community-based University of Washington Twin Registry. Twin similarity in physical activity participation using both cut-points was analyzed using tetrachoric correlations and structural equation modeling in all same-sex pairs.

Results: Correlations were higher in monozygotic (rMZ = 0.43, 95% CI = 0.33–0.54) than dizygotic pairs (rDZ = 0.30, 95% CI = 0.12–0.47) using the 60 minute cut-point. However, differences were attenuated using the 150 minute standard (rMZ = 0.30, 95% CI = 0.20–0.40; rDZ = 0.25, 95% CI = 0.07–0.42). Using the lower cut-point, the best fitting model of twin resemblance only included additive genetics and unique environment, with a heritability of 45%. In contrast, using the higher threshold, the best fitting model included the common and unique environment, with the unique environment contributing 72% of the variance.

Conclusion: Unique environment factors provide the strongest influence on physical activity participation at levels recommended for health benefits.

“Genetic Influences on Exercise Participation in 37.051 Twin Pairs from Seven Countries”, Stubbe et al 2006

“Genetic Influences on Exercise Participation in 37.051 Twin Pairs from Seven Countries”⁠, Janine H. Stubbe, Dorret I. Boomsma, Jacqueline M. Vink, Belinda K. Cornes, Nicholas G. Martin, Axel Skytthe et al (2006-12-20; backlinks; similar):

Background: A sedentary lifestyle remains a major threat to health in contemporary societies. To get more insight in the relative contribution of genetic and environmental influences on individual differences in exercise participation, twin samples from seven countries participating in the GenomEUtwin project were used.

Methodology: Self-reported data on leisure time exercise behavior from Australia, Denmark, Finland, Norway, the Netherlands, Sweden and United Kingdom were used to create a comparable index of exercise participation in each country (60 minutes weekly at a minimum intensity of four metabolic equivalents).

Principal Findings: Modest geographical variation in exercise participation was revealed in 85,198 subjects, aged 19–40 years. Modeling of monozygotic and dizygotic twin resemblance showed that genetic effects play an important role in explaining individual differences in exercise participation in each country. Shared environmental effects played no role except for Norwegian males. Heritability of exercise participation in males and females was similar and ranged from 48% to 71% (excluding Norwegian males).

Conclusions: Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality. This collaborative study suggests that attempts to find genes influencing exercise participation can pool exercise data across multiple countries and different instruments.

“Marital Status Changes and Body Weight Changes: a US Longitudinal Analysis”, Sobal et al 2003

2003-sobal.pdf: “Marital status changes and body weight changes: a US longitudinal analysis”⁠, Jeffery Sobal, Barbara Rauschenbach, Edward A. Frongillo (2003-04-01; ; similar):

The role of spouse is associated with better health. The dynamics of spousal roles can be represented by marital trajectories that may remain stable or may change by entry into marriage, dissolution of marriage, or death of a spouse. Body weight is an important health-related characteristic that has been found to have mixed relationships with marital status.

This analysis examined changes in marital status and body weight in 9,043 adults in the US National Health and Nutrition Epidemiological Follow-up Survey (NHEFS), a longitudinal national study that interviewed and measured adults in a baseline assessment and reassessed them again in a follow-up ~10 years later.

Men’s and women’s weights were differently associated with marital changes. Women who were unmarried at baseline and married at follow-up had greater weight change than those who were married at both times. Analysis of weight loss and weight gain separately revealed that sociodemographic variables, including marital change, were more predictive of variation in weight loss than weight gain. Unmarried women who married gained more weight than women married at both times. Men who remained divorced/​separated and men who became widowed lost more weight than men married at both baseline and follow-up.

These findings suggest that changes in social roles, such as entering or leaving marriage, influence physical characteristics such as body weight.

“A Randomized, Controlled Trial of Quadriceps Resistance Exercise and Vitamin D in Frail Older People: The Frailty Interventions Trial in Elderly Subjects (FITNESS)”, Latham et al 2003

2003-latham.pdf: “A Randomized, Controlled Trial of Quadriceps Resistance Exercise and Vitamin D in Frail Older People: The Frailty Interventions Trial in Elderly Subjects (FITNESS)”⁠, Nancy K. Latham, Craig S. Anderson, Arier Lee, Derrick A. Bennett, Anne Moseley, Ian D. Cameron, For The Fitness Collaborative Group et al (2003-02-20; ; backlinks; similar):

Objectives: To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge.

Design: Multicenter, randomized, controlled trial with a factorial design.

Setting: Five hospitals in Auckland, New Zealand, and Sydney, Australia.

Participants: Two hundred forty-three frail older people.

Interventions: Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits.

Measurements: The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants’ homes at 3 and 6 months after randomization and were performed by blinded assessors.

Results: There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5–8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/​mL) at baseline.

Conclusion: Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.

“Genetic Factors in Physical Activity Levels: A Twin Study”, Maia et al 2002

2002-maia.pdf: “Genetic factors in physical activity levels: A Twin Study”⁠, José A. R. Maia, Martine Thomis, Gaston Beunen (2002-08-01; ; backlinks; similar):

Background: Substantial interindividual variation is observed in sports participation and physical activity levels in youth. This study aimed to (1) estimate the relative contribution of genes, along with shared and nonshared environmental factors, to variation in sports participation index (SPI) and leisure-time physical activity (LTPA); and (2) test differences in those factors in males and females.

Methods: The sample was comprised of 411 Portuguese twin pairs of different zygosity aged 12 to 25 years. The SPI and LTPA were assessed with the Baecke questionnaire. Quantitative genetic modeling was used to test alternative models for the presence of additive gene effects (a2), common or shared environment within the family (c2), and unique environmental factors (e2).

Results: The best-fitting models showed sex-specific effects for the two phenotypes. Variance components for SPI in males were a2 = 68.4%, c2 = 20%, and e2 = 11.6%; and in females, a2 = 39.8%, c2 = 28.4%, and e2 = 31.8%. For variation in LTPA, genetic factors in males explained 63%, common environment was not statistically-significant, and unique environment explained 37%. In females, contributing factors were a2 = 32%, c2 = 38%, and e2 = 30%.

Conclusions: Genetic effects explained a considerable amount of variation in SPI and LTPA, which were greater in males than in females. The relevance of shared environmental factors (family and peers) and nonshared environmental factors in SPI and LTPA is particularly evident in females.

[Keywords: exercise, genetics, physical fitness, twins]

“Shorter, More Frequent Mechanical Loading Sessions Enhance Bone Mass”, Robling et al 2002

2002-robling.pdf: “Shorter, more frequent mechanical loading sessions enhance bone mass”⁠, Alexander G. Robling, Felicia M. Hinant, David B. Burr, Charles H. Turner (2002-02-01; ; similar):

Purpose: The beneficial effects of exercise on bone mass and strength can be attributed to the sensitivity of bone cells to mechanical stimuli. However, bone cells lose mechanosensitivity soon after they are stimulated. We investigated whether the osteogenic response to a simulated high-impact exercise program lasting 4 months could be enhanced by dividing the daily protocol into brief sessions of loading, separated by recovery periods.

Methods: The right forelimbs of adult rats were subjected to 360 load cycles · d-1, 3 d·wk-1, for 16 wk. On each loading day, one group received all 360 cycles in a single, uninterrupted bout (360×1); the other group received 4 bouts of 90 cycles/​bout (90×4), with each bout separated by 3 h. After sacrifice, bone mineral content (BMC), and areal bone mineral density (aBMD) were measured in the loaded (right) and non-loaded control (left) ulnae using DXA. Volumetric BMD (vBMD) and cross-sectional area (CSA) were measured at midshaft and the olecranon by using pQCT. Maximum and minimum second moments of area (IMAX and IMIN) were measured from the midshaft tomographs.

Results: After 16 wk of loading, BMC, aBMD, vBMD, midshaft CSA, IMAX, and IMIN were statistically-significantly greater in right (loaded) ulnae compared with left (non-loaded) ulnae in the 2 loaded groups. When the daily loading regimen was broken into 4 sessions per day (90×4), BMC, aBMD, midshaft CSA, and I(MIN) improved statistically-significantly over the loading schedule that applied the daily stimulus in a single, uninterrupted session (360×1).

Conclusion: Human exercise programs aimed at maintaining or improving bone mass might achieve greater success if the daily exercise regime is broken down into smaller sessions separated by recovery periods.

[Keywords: mechanical loading, bone adaptation, recovery, exercise, osteoporosis, BMD]

“Individual Differences in Response to Regular Physical Activity”, Bouchard & Rankinen 2001

2001-bouchard.pdf: “Individual differences in response to regular physical activity”⁠, Claude Bouchard, Tuomo Rankinen (2001-06-01; ; similar):

Purpose: The purpose of this review was to address the question of interindividual variation in responsiveness to regular exercise training and to define the contributions of age, sex, race, and pretraining phenotype level to this variability.

Methods: A literature review was conducted of the studies reporting interindividual variation in responsiveness to standardized and controlled exercise-training programs, and included an analysis of the contribution of age, sex, race, and initial phenotype values to the heterogeneity in VO2max, high-density lipoprotein (HDL)-C and submaximal exercise, heart rate (HR), and systolic blood pressure (SBP) training responses in subjects from the HERITAGE Family Study.

Results: Several studies have shown marked individual differences in responsiveness to exercise training. For example, VO2max responses to standardized training programs have ranged from almost no gain up to 100% increase in large groups of sedentary individuals. A similar pattern of heterogeneity has been observed for other phenotypes. Data from the HERITAGE Family Study show that age, sex, and race have little impact on interindividual differences in training responses. On the other hand, the initial level of a phenotype is a major determinant of training response for some traits, such as submaximal exercise heart rate and blood pressure (BP) but has only a minor effect on others (eg. VO2max, HDL-C). The contribution of familial factors (shared environment and genetic factors) is supported by data on substantial familial aggregation of training response phenotypes.

Conclusions: There is strong evidence for considerable heterogeneity in the responsiveness to regular physical activity. Age, sex, and ethnic origin are not major determinants of human responses to regular physical activity, whereas the pretraining level of a phenotype has a considerable impact in some cases. Familial factors also contribute substantially to variability in training response.

“Smoking and Sports Participation”, Koopmans et al 1994

1994-koopmans.pdf: “Smoking and Sports Participation”⁠, Judith R. Koopmans, Lorenz J. P. van Doornen, Dorret I. Boomsma (1994; ; backlinks; similar):

It has long been recognized that both smoking and sports participation tend to cluster in families. In this chapter, we first describe the current status of smoking and sports participation as cardiovascular risk factors. After an outline of the principles of the quantitative genetic approaches to the analysis of individual differences in behaviour, we will review the literature on genetic and environmental determinants of smoking and sports participation. In the second half of this chapter, results from the Dutch Twin/​Family Study of Health-Related Behavior are presented.

“Cigarette Smoking, Use of Alcohol, and Leisure-time Physical Activity among Same-sexed Adult Male Twins”, Kaprio et al 1981

1981-kaprio.pdf: “Cigarette smoking, use of alcohol, and leisure-time physical activity among same-sexed adult male twins”⁠, Jaako Kaprio, Markku Koskenvuo, Seppo Sarna (1981-01-01; ; backlinks)



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