Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies

The combination of obesity by BMI and low handgrip strength is not associated with cardiovascular disease.

“an association that was not observed with cardiovascular disease221”

• cites [221] Atkins, J. L. et al. Sarcopenic obesity and risk of cardiovascular disease and mortality: a population-based cohort study of older men. J. Am. Geriatr. Soc. 62, 253–260 (2014). sourceDisputed

  The Discussion (WC and MAMC Measurements; page unavailable) says sarcopenic obesity defined using grip strength predicted greater risk of CVD events—the opposite of the claimed lack of association. This paper's own null finding concerned obesity and low muscle mass defined using waist and midarm measurements, not BMI and handgrip strength (Methods, Anthropometric Measurements and Sarcopenic Obesity Definition; page unavailable). (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

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Aerobic exercise and resistance training are safe, even in patients at high risk of falling.

“Aerobic exercise and resistance training are safe, even in patients who are at a high risk of falling275.”

• cites [275] Gillespie, L. D. et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst. Rev. 9, CD007146 (2012). sourceDisputed

  The Results (page not specified) report significantly more musculoskeletal injuries with resistance training than with control (18 versus 5), contrary to the unqualified claim that it is safe. The review reports no trials of endurance training alone, so it also does not establish the safety of aerobic exercise, including for people at high risk of falling. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

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Reductions in TNF and IL-6 in older men with hypogonadism can be reversed by testosterone treatment.

“However, reductions in TNF and IL-6 observed in older men with hypogonadism can be reversed following testosterone treatment406.”

• cites [406] Corrales, J. J. et al. Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency. J. Endocrinol. 189, 595–604 (2006). sourceDisputed

  The Discussion says acute hypogonadism in elderly men increased circulating TNF and IL-6, rather than reducing them; subsequent testosterone treatment reduced TNF but not IL-6. The Results report that testosterone treatment suppressed spontaneous ex vivo production of both cytokines in the paper’s older diabetic men, not that it reversed reductions in them. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Individuals with sarcopenia have elevated levels of myostatin, a negative regulator of skeletal muscle growth and development.

“Individuals with sarcopenia have elevated levels of myostatin443, a negative regulator of skeletal muscle growth development444.”

• cites [443] Bergen, H. R. III et al. Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay. Skelet. Muscle 5, 21 (2015). sourceDisputed

  The citation is attached to the claim that people with sarcopenia have elevated myostatin. The Discussion reports no meaningful difference in myostatin concentrations between older subjects with and without sarcopenia in either sex. The Results also report that sarcopenic older women had absolute levels comparable to younger women, while sarcopenic older men had lower levels than younger men. The separate citation for myostatin’s regulatory role is not assessed here. (LLM, conf=0.89)

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• cites [444] McPherron, A. C., Lawler, A. M. & Lee, S. J. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387, 83–90 (1997). sourceNot checked — no full text of the source

Possible mechanisms for reduced muscle mass and strength in sarcopenic obesity include type II fibre atrophy, motor neuron loss, collagen deposition and fibre necrosis.

“A number of mechanisms might explain the reduction of muscle mass and strength in sarcopenic obesity, including type II muscle fibre atrophy, reduction in motor neurons, collagen deposition and fibre necrosis67–70.”

• cites [67] Thomas, D. R. Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. Clin. Nutr. 26, 389–399 (2007). sourceNot checked — no full text of the source
• cites [68] Nilwik, R. et al. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Exp. Gerontol. 48, 492–498 (2013). sourceNot checked — no full text of the source
• cites [69] Delbono, O. Neural control of aging skeletal muscle. Aging Cell 2, 21–29 (2003). sourcePartly supported

  The Introduction links age-related muscle-mass loss to fibre atrophy, and ‘Neural influences on aging skeletal muscle’ describes motor-unit loss and denervation of fast fibres. The Conclusions also discuss possible motor-neurone loss and reduced muscle force. These passages concern aging muscle, not specifically sarcopenic obesity; they do not establish type II fibre atrophy, collagen deposition, or fibre necrosis. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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• cites [70] Stenholm, S. et al. Sarcopenic obesity: definition, cause and consequences. Curr. Opin. Clin. Nutr. Metab. Care 11, 693–700 (2008). sourcePartly supported

  In “Searching for a definition based on pathophysiology and associated risk” (page unavailable), the paper identifies reduced fibre size and number, increased collagen, and motor-unit changes as contributors to declining muscle quality. “Age-related changes in body composition” (page unavailable) also names loss of alpha-motor units. It does not specify type II fibre atrophy or identify fibre necrosis as a mechanism. (LLM, conf=0.88)

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Muscle injury activates satellite cells to regenerate muscle by releasing IGF1, fibroblast growth factor and mechano growth factor, which stimulate satellite cell differentiation and proliferation.

“Muscle injury activates satellite cells to regenerate muscle by releasing IGF1, fibroblast growth factor and mechano growth factor, all of which stimulate the differentiation and proliferation of muscle satellite cells112,113.”

• cites [112] Kang, J. S. & Krauss, R. S. Muscle stem cells in developmental and regenerative myogenesis. Curr. Opin. Clin. Nutr. Metab. Care 13, 243–248 (2010). sourcePartly supported

  The Satellite cell heterogeneity section (page unavailable) says muscle injury activates satellite cells to proliferate and differentiate during regeneration. It does not say injury releases IGF1, fibroblast growth factor, or mechano growth factor to stimulate those cells; its discussion of FGF concerns embryonic progenitors instead. (LLM, conf=0.88)

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• cites [113] Thornell, L. E. Sarcopenic obesity: satellite cells in the aging muscle. Curr. Opin. Clin. Nutr. Metab. Care 14, 22–27 (2011). sourceNot checked — no full text of the source

Individuals with obesity are at risk of inflammation that can lead to preferential mobilization of muscle rather than fat.

“In sum, individuals with obesity are at risk of inflammation, which can lead to the preferential mobilization of muscle instead of fat91.”

• cites [91] Srikanthan, P., Hevener, A. L. & Karlamangla, A. S. Sarcopenia exacerbates obesity-associated insulin resistance and dysglycemia: findings from the National Health and Nutrition Examination Survey III. PLoS ONE 5, e10805 (2010). sourcePartly supported

  The Introduction (page not specified) says inflammation occurs in obesity and may accelerate muscle protein degradation. It does not say that inflammation causes muscle to be mobilized preferentially over fat; that comparison is unsupported. (LLM, conf=0.85)

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Adults aged 65 and older are at risk of anabolic resistance because of lower post-prandial amino acid availability, reduced muscle perfusion and reduced digestive capacity from splanchnic amino acid sequestration.

“Older adults (those ≥65 years) are at risk of developing anabolic resistance owing to reduced post-prandial amino acid availability, reduced muscle perfusion and a reduced digestive capacity resulting from splanchnic sequestration of amino acids71.”

• cites [71] Bauer, J. et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J. Am. Med. Dir. Assoc. 14, 542–559 (2013). This is a position paper from the PROT-Age study group that recommends an average daily intake of at least 1.0–1.2 g protein per kg body weight per day. sourcePartly supported

  The “Benefits of Higher Protein Intake for Older Adults” section (page unavailable) describes an impaired muscle anabolic response to meals in older adults and calls this anabolic resistance. It does not establish the claimed combination of reduced postprandial amino acid availability and reduced muscle perfusion as its causes. The “Protein DigestibilityeCorrected Amino Acid Score” section (page unavailable) says age-related gastrointestinal changes do not substantially impair amino acid availability from food, contrary to the claimed reduction in digestive capacity. (LLM, conf=0.88)

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Aerobic exercise, resistance training and their combination raise muscle protein synthesis in older adults despite age-related declines in anabolic signalling.

“Aerobic exercise101, resistance training102–104 and their combination105 increase muscle protein synthesis in older adults despite age-related decreases in anabolic signalling106–109.”

• cites [101] Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N. & Nair, K. S. Age and aerobic exercise training effects on whole body and muscle protein metabolism. Am. J. Physiol. Endocrinol. Metab. 286, E92–E101 (2004). sourceNot checked — no full text of the source
• cites [102] Yarasheski, K. E., Zachwieja, J. J. & Bier, D. M. Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women. Am. J. Physiol. 265, E210–E214 (1993). sourceNot checked — no full text of the source
• cites [103] Yarasheski, K. E. et al. Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men >/=76 yr old. Am. J. Physiol. 277, E118–E125 (1999). sourceNot checked — no full text of the source
• cites [104] Hasten, D. L., Pak-Loduca, J., Obert, K. A. & Yarasheski, K. E. Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78–84 and 23–32 yr olds. Am. J. Physiol. Endocrinol. Metab. 278, E620–E626 (2000). sourceNot checked — no full text of the source
• cites [105] Villareal, D. T., Smith, G. I., Sinacore, D. R., Shah, K. & Mittendorfer, B. Regular multicomponent exercise increases physical fitness and muscle protein anabolism in frail, obese, older adults. Obesity (Silver Spring) 19, 312–318 (2011). This study demonstrates that a multicomponent exercise programme consisting of strength, endurance, flexibility and balance increases the basal rate of muscle protein synthesis without affecting the magnitude of the muscle protein anabolic response to feeding. sourceSupported

Whether bioelectrical impedance prediction equations are valid across different ethnic groups is unclear.

“Further, whether the bioelectrical impedance prediction equations are valid when applied to different ethnic groups is unclear170, despite specific adaptations and adjustments171–173.”

• cites [170] Chumlea, W. C. et al. Body composition estimates from NHANES III bioelectrical impedance data. Int. J. Obes. Relat. Metab. Disord. 26, 1596–1609 (2002). This study presents normative bioelectrical impedance analysis equations validated using a population-based cohort of American adults. sourceNot checked — no full text of the source
• cites [171] Janssen, I., Heymsfield, S. B., Baumgartner, R. N. & Ross, R. Estimation of skeletal muscle mass by bioelectrical impedance analysis. J. Appl. Physiol. (1985) 89, 465–471 (2000). sourceNot checked — no full text of the source
• cites [172] Mally, K., Trentmann, J., Heller, M. & Dittmar, M. Reliability and accuracy of segmental bioelectrical impedance analysis for assessing muscle and fat mass in older Europeans: a comparison with dual-energy X-ray absorptiometry. Eur. J. Appl. Physiol. (1985) 111, 1879–1887 (2011). sourceNot checked — no full text of the source
• cites [173] Yu, S. C., Powell, A., Khow, K. S. & Visvanathan, R. The performance of five bioelectrical impedance analysis prediction equations against dual x-ray absorptiometry in estimating appendicular skeletal muscle mass in an adult Australian population. Nutrients 8, 189 (2016). sourceSupported

Muscle fascicle length and muscle tendon stiffness reportedly increased after 14 weeks of strength training (leg press and extension) in men and women over 65 years.

“Muscle fascicle length and muscle tendon stiffness reportedly increased after strength training (leg press and extension) over 14 weeks in a cohort of men and women aged over 65 years140.”

• cites [140] Reeves, N. D., Maganaris, C. N. & Narici, M. V. Effect of strength training on human patella tendon mechanical properties of older individuals. J. Physiol. 548, 971–981 (2003). sourcePartly supported

  The Abstract and Results report increased patella tendon stiffness after 14 weeks of leg press and leg extension training; Methods identifies the training group as five women and four men, with a mean age of 74.3 years. The paper does not report an increase in muscle fascicle length: its Discussion mentions fascicle length in connection with another study, not as a measured outcome here. (LLM, conf=0.89)

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In a pre-frail and frail population, a strategy combining physical training and nutritional intervention was more likely to produce stable or reduced IL-6 levels in individuals with improved physical performance than in those with lower physical performance.

“In a pre-frail and frail population, a strategy combining physical training and nutritional intervention was more likely to result in stable or reduced IL-6 levels in individuals who demonstrated improved physical performance than in those with lower physical performance149.”

• cites [149] Haider, S. et al. Change in inflammatory parameters in prefrail and frail persons obtaining physical training and nutritional support provided by lay volunteers: a randomized controlled trial. PLoS ONE 12, e0185879 (2017). sourcePartly supported

  The Abstract and Results (Table 4; page not available) report that prefrail and frail participants whose physical performance improved were more likely to have stable or reduced IL-6 than participants whose performance did not improve. The comparison was based on improvement over time, not on having higher versus lower physical performance levels. (LLM, conf=0.84)

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Variable hydration status affects the accuracy of bioelectrical impedance.

“Variable hydration status also impacts its accuracy167.”

• cites [167] Bosy-Westphal, A. et al. Quantification of whole-body and segmental skeletal muscle mass using phase-sensitive 8-electrode medical bioelectrical impedance devices. Eur. J. Clin. Nutr. 71, 1061–1067 (2017). sourceSupported

Muscle protein synthesis is also improved by nutrient-stimulated vasodilation and nutrient transport to local muscle myofibrils.

“Muscle protein synthesis is also improved by nutrient-stimulated vasodilation and nutrient transport to local muscle myofibrils112,124.”

• cites [112] Kang, J. S. & Krauss, R. S. Muscle stem cells in developmental and regenerative myogenesis. Curr. Opin. Clin. Nutr. Metab. Care 13, 243–248 (2010). sourceCould not verify

  The Introduction and Conclusion describe muscle stem cells, development, and regeneration. A passage in “Satellite cell heterogeneity” discusses signaling between nearby cells and satellite cells, but not nutrient-stimulated vasodilation, nutrient transport to myofibrils, or muscle protein synthesis. Searches for those terms found no passage addressing the claimed mechanism; page numbers were not available in our copy. (LLM, conf=0.76)

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• cites [124] Marzetti, E. et al. Physical activity and exercise as countermeasures to physical frailty and sarcopenia. Aging Clin. Exp. Res. 29, 35–42 (2017). This study provides an overview of the interplay between physical activity, exercise and sarcopenia. sourceNot checked — no full text of the source

With ageing, fat preferentially accumulates viscerally and ectopically rather than as abdominal subcutaneous fat.

“With ageing, fat preferentially accumulates both viscerally and ectopically rather than as abdominal subcutaneous fat.”

• cites [186] Villareal, D. T. et al. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am. J. Clin. Nutr. 82, 923–934 (2005). This study highlights current guidelines for the management of older adults with obesity. sourcePartly supported

  The 'Changes in body weight and body composition with aging' section says intraabdominal fat increases more, in relative terms, than subcutaneous fat. It also reports increases in intramuscular and intrahepatic fat, but does not say those ectopic depots increase preferentially over abdominal subcutaneous fat; the 'Definition of obesity' section says abdominal subcutaneous fat also increases with aging. Page numbers were not available in our copy. (LLM, conf=0.86)

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Sarcopenic obesity defined by FNIH criteria with elevated body fat is associated with increased risk of instrumental activity of daily living disability (OR 1.36, 95% CI 1.05-1.76).

“instrumental activity of daily living disability (OR 1.36, 95% CI 1.05–1.76)”

• cites [204] Hirani, V. et al. Longitudinal associations between body composition, sarcopenic obesity and outcomes of frailty, disability, institutionalisation and mortality in community-dwelling older men: The Concord Health and Ageing in Men Project. Age Ageing 46, 413–420 (2017). sourceSupported

Rapid intra-abdominal fat accumulation is worsened by physical inactivity, hormonal changes, reduced responsiveness to thyroid hormone and leptin resistance.

“Rapid accumulation of intra-abdominal fat is exacerbated by physical inactivity, hormonal changes, reduced responsiveness to thyroid hormone and leptin resistance186.”

• cites [186] Villareal, D. T. et al. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am. J. Clin. Nutr. 82, 923–934 (2005). This study highlights current guidelines for the management of older adults with obesity. sourcePartly supported

  The Pathogenesis section links declining physical activity and age-related hormonal changes, including reduced thyroid-hormone responsiveness and leptin resistance, to increasing body fat. The Changes in Body Weight and Body Composition with Aging section reports a greater relative increase in intra-abdominal fat. The paper does not specifically establish that each listed factor worsens intra-abdominal fat accumulation, and it describes the overall increase in body fat as gradual, not rapid. (LLM, conf=0.86)

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High BMI and low grip strength are associated with reduced long-term physical activity in the UK Biobank study.

“data from the UK Biobank study found an association between high BMI, low grip strength and reduced long-term physical activity211”

• cites [211] Kim, Y. et al. Adiposity and grip strength as long-term predictors of objectively measured physical activity in 93 015 adults: the UK Biobank study. Int. J. Obes. (Lond.) 41, 1361–1368 (2017). This study analyses data from the UK Biobank study and shows that advanced obesity and poor strength at baseline independently predict lower activities at follow-up. sourceSupported

In 120 predominantly female adults aged 46.9 ± 11.0 years with BMI ≥35 kg/m2, prevalence of sarcopenic obesity using DXA-defined body fat ranged from 0-84.5% in women to 0-100% in males depending on the definition applied.

“In another study, the authors identified individuals with a BMI ≥35 kg/m2 and evaluated the prevalence of sarcopenic obesity using DXA-defined body fat in 120 predominantly female adults (46.9 ± 11.0 years). The investigators reported rates that ranged from 0–84.5% in women to 0–100% in males depending upon the definition applied197.”

• cites [197] Johnson Stoklossa, C. A. et al. Prevalence of sarcopenic obesity in adults with class II/III obesity using different diagnostic criteria. J. Nutr. Metab. 2017, 7307618 (2017). sourcePartly supported

  The Results report 120 participants (85.8% female) and sarcopenic-obesity prevalence of 0–84.5% in females and 0–100% in males across definitions. However, the reported mean age is 46.9 ± 11.1 years, not ± 11.0. The Results also describe the cohort’s obesity as BMI-defined; the Methods say DXA supplied body-composition measures, not that body fat defined obesity for every prevalence estimate. (LLM, conf=0.88)

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Sarcopenic obesity defined by FNIH criteria with elevated body fat is associated with increased risk of activity of daily living disability (OR 1.58, 95% CI 1.12-2.24).

“activity of daily living disability (OR 1.58, 95% CI 1.12–2.24)”

• cites [204] Hirani, V. et al. Longitudinal associations between body composition, sarcopenic obesity and outcomes of frailty, disability, institutionalisation and mortality in community-dwelling older men: The Concord Health and Ageing in Men Project. Age Ageing 46, 413–420 (2017). sourceSupported

High BMI and low muscle strength are related to limitation in mobility at 2-year follow-up (OR 3.88, 95% CI 1.08-13.91).

“High BMI and low muscle strength were related to limitation in mobility at 2-year follow-up (OR 3.88, 95% CI 1.08–13.91)212.”

• cites [212] Jung, S. et al. Obesity and muscle weakness as risk factors for mobility limitation in community-dwelling older Japanese women: a two-year follow-up investigation. J. Nutr. Health Aging 20, 28–34 (2016). sourceSupported

Obesity defined by percentage of body fat combined with low muscle mass is associated with higher odds of difficulty ascending and descending stairs (OR 2.60 and 2.35, respectively).

“a combination of obesity, as defined by percentage of body fat, with low muscle mass represented odds ratios of difficulty ascending and descending stairs that were 2.60 and 2.35 higher, respectively”

• cites [203] Rolland, Y. et al. Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l’OSteoporose) Study. Am. J. Clin. Nutr. 89, 1895–1900 (2009). sourceSupported

Body fat has better predictive validity for the development of metabolic syndrome and cardiovascular disease risk than BMI.

“Body fat has better predictive validity on the development of the metabolic syndrome192 and cardiovascular disease risk193 than BMI.”

• cites [192] Fox, C. S. et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116, 39–48 (2007). sourcePartly supported

  The Discussion reports that visceral adipose tissue (VAT), but not subcutaneous adipose tissue, provided information about cardiometabolic risk factors beyond BMI. This supports a narrower comparison than the claim: the study assessed associations cross-sectionally, not whether body fat generally predicts future cardiovascular disease better than BMI. The Conclusions call for prospective studies of MetS and CVD incidence. (LLM, conf=0.86)

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• cites [193] Despres, J. P. Body fat distribution and risk of cardiovascular disease: an update. Circulation 126, 1301–1313 (2012). sourceNot checked — no full text of the source

Ethnic-specific differences lead to inaccurate prevalence estimates.

“Ethnic-specific differences result in inaccurate prevalence estimates184.”

• cites [184] Cruz-Jentoft, A. J. et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing 43, 748–759 (2014). sourcePartly supported

  The Discussion > Prevalence passage says ethnicity may affect prevalence estimates, especially when the reference and study populations do not match. It does not establish that ethnic differences necessarily result in inaccurate estimates; the citing sentence states that possibility as a definite outcome. Page information is unavailable in our copy. (LLM, conf=0.86)

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Sarcopenic obesity defined by FNIH criteria with elevated body fat is associated with increased risk of frailty (OR 2.00, 95% CI 1.42-2.82).

“sarcopenic obesity resulted in an increased risk of frailty (OR 2.00, 95% CI 1.42–2.82)”

• cites [204] Hirani, V. et al. Longitudinal associations between body composition, sarcopenic obesity and outcomes of frailty, disability, institutionalisation and mortality in community-dwelling older men: The Concord Health and Ageing in Men Project. Age Ageing 46, 413–420 (2017). sourceSupported

In the InCHIANTI study, mobility disability trajectories and gait speed over 6 years were steepest in individuals with obesity defined by BMI and low muscle strength.

“mobility disability trajectories and gait speed over 6 years were steepest in individuals with obesity as defined by BMI and low muscle strength200”

• cites [200] Stenholm, S. et al. The effect of obesity combined with low muscle strength on decline in mobility in older persons: results from the InCHIANTI study. Int. J. Obes. (Lond.) 33, 635–644 (2009). This study details data from the InCHIANTI study that prove that obesity combined with low muscle strength increases the risk of mobility disability with age. sourcePartly supported

  The Results (Change over time in walking speed) report the most prominent six-year decline in walking speed among participants aged 65–80 with obesity and low muscle strength. The Results (Risk of mobility disability) report a higher rate of new disability at six years, but do not describe disability trajectories as steepest; the walking-speed finding is also qualified by age. (LLM, conf=0.85)

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Data from the InCHIANTI study noted rates of 3.2-8.7% using low knee extensor strength with either high BMI or waist circumference.

“Data from the InCHIANTI study noted rates of 3.2–8.7% using the low knee extensor strength with either high BMI or waist circumferrence200.”

• cites [200] Stenholm, S. et al. The effect of obesity combined with low muscle strength on decline in mobility in older persons: results from the InCHIANTI study. Int. J. Obes. (Lond.) 33, 635–644 (2009). This study details data from the InCHIANTI study that prove that obesity combined with low muscle strength increases the risk of mobility disability with age. sourcePartly supported

  The Methods (Measurement of muscle strength; page not provided) define low strength using knee extensor strength, and the Results (Risk of mobility disability; page not provided) describe analyses using BMI or waist circumference to define obesity. The passages in our copy do not report the claimed 3.2–8.7% rates, so the numerical range is unsupported. (LLM, conf=0.84)

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In a population-based cohort using NHANES data and FNIH criteria for appendicular lean mass, sarcopenic obesity rates were 12.6% in men and 33.5% in women.

“In a population-based cohort using National Health and Nutrition Examination Survey (NHANES) data that applied the aforementioned FNIH criteria for appendicular lean mass, rates of sarcopenic obesity were 12.6% in men and 33.5% in women.”

• cites [198] Batsis, J. A., Mackenzie, T. A., Emeny, R. T., Lopez-Jimenez, F. & Bartels, S. J. Low lean mass with and without obesity, and mortality: results from the 1999–2004 National Health and Nutrition Examination Survey. J. Gerontol. A Biol. Sci. Med. Sci. 72, 1445–1451 (2017). This report details the definition of low lean mass determined by the Foundation of the National Institutes of Health, as well as the adverse association between low lean mass and mortality. sourceSupported

Low knee extensor strength combined with high BMI is associated with reduced gait speed and reduced Late-Life Function and Disability Index and Short Form-12 scores.

“a combination of low knee extensor strength with high BMI was associated with reduced gait speed and reduced Late-Life Function and Disability Index and Short Form-12 scores207”

• cites [207] Batsis, J. A., Zbehlik, A. J., Pidgeon, D. & Bartels, S. J. Dynapenic obesity and the effect on long-term physical function and quality of life: data from the osteoarthritis initiative. BMC Geriatr. 15, 118 (2015). sourcePartly supported

  The Results report lower gait speed, LLFDI limitations-subscale scores, and SF-12 physical-component scores in the dynapenic obesity group compared with those with neither condition. The claim is broader than those findings: the Results report no difference in SF-12 mental-component scores, and do not establish reductions across all LLFDI components. (LLM, conf=0.86)

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FNIH data classified 4.1% of men and 14.0% of women as having sarcopenic obesity using high BMI and low grip strength as measures of obesity and low muscle strength, respectively.

“while data from FNIH classified 4.1% of men and 14.0% of women as having sarcopenic obesity using high BMI and low grip strength as measures of obesity and low muscle strength, respectively202.”

• cites [202] Alley, D. E. et al. Grip strength cutpoints for the identification of clinically relevant weakness. J. Gerontol. A Biol. Sci. Med. Sci. 69, 559–566 (2014). sourcePartly supported

  Table 1 in the Results reports that 4.1% of obese men had weak grip strength, and the Results state that 14% of obese women were classified as weak. These percentages are among obese participants, not among all men and women; the paper also does not classify them as having “sarcopenic obesity.” (LLM, conf=0.90)

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In patients with sarcopenic obesity as defined by obesity with evidence of physical frailty, a combination of weight loss and regular exercise improved physical function and ameliorated frailty more than either intervention alone.

“a combination of weight loss and regular exercise improved physical function and ameliorated frailty more than either intervention alone246”

• cites [246] Villareal, D. T. et al. Weight loss, exercise, or both and physical function in obese older adults. N. Engl. J. Med. 364, 1218–1229 (2011). This is a randomized trial of older adults with frailty and obesity that compares diet, exercise type and controls and demonstrates that physical function improves and muscle and bone loss is mitigated with concomitant exercise therapy. sourceSupported

Reduced leg isometric strength and increased waist circumference are associated with increased mortality (HR 2.46, 95% CI 1.34-4.52).

“reduced leg isometric strength and increased waist circumference were associated with increased mortality232 (HR 2.46, 95% CI 1.34–4.52)”

• cites [232] Rossi, A. P. et al. Dynapenic abdominal obesity as predictor of mortality and disability worsening in older adults: a 10-year prospective study. Clin. Nutr. 35, 199–204 (2016). sourceSupported

Higher protein doses have recently demonstrated no changes in lean mass.

“higher doses have recently demonstrated no changes in lean mass273”

• cites [273] Bhasin, S. et al. Effect of protein intake on lean body mass in functionally limited older men: a randomized clinical trial. JAMA Intern. Med. 178, 530–541 (2018). sourceSupported

A meta-analysis of randomized trials of adults with obesity aged ≥55 years with follow-up ≥4 years reported a 16% reduction in mortality (95% CI 0.71-0.99).

“investigators reported a 16% reduction in mortality (95% CI 0.71–0.99)243”

• cites [243] Kritchevsky, S. B. et al. Intentional weight loss and all-cause mortality: a meta-analysis of randomized clinical trials. PLoS ONE 10, e0121993 (2015). This is an important meta-analysis that evaluates randomized controlled trials of weight loss interventions in older adults and their impact on mortality. sourcePartly supported

  The Results section (‘Sub-analyses: modifying effects of age, follow up duration, and magnitude of weight loss’) reports a 16% lower mortality estimate (RR 0.84; 95% CI 0.71–0.99) for trials with a mean participant age ≥55 years. Follow-up ≥4 years was a separate subgroup, with a different estimate (RR 0.85; 95% CI 0.72–1.00). The cited result therefore does not establish the claimed combined age-and-follow-up subgroup. (LLM, conf=0.90)

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Early pilot studies demonstrate that meals enhanced with protein and coupled with a weight loss intervention improve physical function.

“Early pilot studies demonstrate that meals enhanced with protein and coupled with a weight loss intervention improve physical function263.”

• cites [263] Porter Starr, K. N. et al. Improved function with enhanced protein intake per meal: a pilot study of weight reduction in frail, obese older adults. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1369–1375 (2016). sourceSupported

Cutoffs specific to individuals from South Korea predicted higher mortality risk than the FNIH cut-off.

“Cutoffs specific to individuals from South Korea predicted higher mortality risk than the FNIH cut-off233.”

• cites [233] Moon, J. H. et al. Predictive values of the new sarcopenia index by the Foundation for the National Institutes of Health sarcopenia project for mortality among older Korean adults. PLoS ONE 11, e0166344 (2016). sourcePartly supported

  The Discussion reports that lowest-quintile cutoffs specific to the Korean study population predicted mortality more accurately than FNIH cutoffs. It also says these associations were observed only in men, not women, so the claim is broader than the finding. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

A high-protein diet in conjunction with resistance training preserved appendicular lean mass during weight loss.

“a high- protein diet in conjunction with resistance training preserved appendicular lean mass during weight loss264”

• cites [264] Verreijen, A. M. et al. Effect of a high protein diet and/or resistance exercise on the preservation of fat free mass during weight loss in overweight and obese older adults: a randomized controlled trial. Nutr. J. 16, 10 (2017). sourcePartly supported

  The Discussion reports that only the combined high-protein and resistance-exercise group significantly increased fat-free mass during weight loss, while finding no significant interaction between the interventions. The Methods describe measurement of whole-body fat-free mass, not appendicular lean mass, so the cited paper does not establish preservation of that specific outcome. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Elevated BMI is associated with admission to a nursing home.

“an elevated BMI is associated with admission to a nursing home240”

• cites [240] Zizza, C. A., Herring, A., Stevens, J. & Popkin, B. M. Obesity affects nursing-care facility admission among whites but not blacks. Obes. Res. 10, 816–823 (2002). sourcePartly supported

  The Results section reports increased nursing-home admission risk for white adults with BMI of 30 or higher, but not for those with BMI of 25 to under 30. It reports no significant increased risk among Black adults. The claim omits these limits and therefore overgeneralizes the association. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

Acute calorie restriction can downregulate muscle protein synthesis and increase proteolysis, contributing to reduced muscle mass.

“Energy deficits created by acute calorie restriction could downregulate muscle protein synthesis and increase proteolysis, which contributes to reduced muscle mass247,253,254”

• cites [247] Villareal, D. T. et al. Aerobic or resistance exercise, or both in dieting obese older adults. N. Engl. J. Med. 376, 1943–1955 (2017). This is a randomized trial of older adults with obesity and frailty demonstrating that weight loss coupled with both aerobic and resistance activities is associated with improved physical function. sourcePartly supported

  The Results (Body Composition; page not available in our copy) report decreased lean mass during the six-month weight-loss intervention, supporting the reduced-mass portion of the claim. The Methods describe a sustained dietary energy deficit, but the paper does not report whether acute calorie restriction downregulates muscle protein synthesis or increases proteolysis. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [253] Areta, J. L. et al. Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit. Am. J. Physiol. Endocrinol. Metab. 306, E989–E997 (2014). sourceNot checked — no full text of the source
• cites [254] Pasiakos, S. M. et al. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 27, 3837–3847 (2013). sourceNot checked — no full text of the source

Generally, 25.0-30.0 g of protein containing 2.5-2.8 g of leucine can slow frailty.

“Generally, 25.0–30.0 g of protein containing 2.5–2.8 g of leucine can slow frailty261,262.”

• cites [261] Beasley, J. M. et al. Protein intake and incident frailty in the Women’s Health Initiative observational study. J. Am. Geriatr. Soc. 58, 1063–1071 (2010). sourcePartly supported

  The Results and Discussion report that higher protein intake was associated with lower incidence of frailty in older women. Our copy gives no 25.0–30.0 g protein or 2.5–2.8 g leucine recommendation (searched those amounts and leucine), and this observational association does not establish that such an intake slows frailty. (LLM, conf=0.89)

  Experimental — accuracy not yet measured
• cites [262] Tieland, M. et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J. Am. Med. Dir. Assoc. 13, 720–726 (2012). sourcePartly supported

  The indexed title reports that protein supplementation improved physical performance in frail elderly people. The retrieved passages do not establish that 25.0–30.0 g of protein containing 2.5–2.8 g of leucine slows frailty; searches for the amounts and for frailty progression found no supporting passage. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

In a pilot study, participants with sarcopenic obesity undergoing a weight loss programme augmented by a high-protein diet showed improvements in muscle strength and Short Form-36 scores.

“participants with sarcopenic obesity undergoing a weight loss programme augmented by a high-protein diet showed improvements in muscle strength and Short Form-36 scores (REF265)”

• cites [265] Sammarco, R. et al. Evaluation of hypocaloric diet with protein supplementation in middle-aged sarcopenic obese women: a pilot study. Obes. Facts 10, 160–167 (2017). sourcePartly supported

  The Results (p. 5) report significantly improved muscle strength in the high-protein group. They report a significant improvement in only the general-health score of the SF-36; the other SF-36 categories did not change significantly, so the claim is too broad about SF-36 scores. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Depression rate is highest in patients with sarcopenic obesity defined as low handgrip strength and obesity by BMI (OR 1.79, 95% CI 1.10-2.89) over 4 years compared with non-obese individuals in the highest tertile of grip strength.

“The rate of depression has been reported as being highest in patients with sarcopenic obesity (defined as low handgrip strength and obesity defined by BMI) (OR 1.79, 95% CI 1.10–2.89) over 4 years222”

• cites [222] Hamer, M., Batty, G. D. & Kivimaki, M. Sarcopenic obesity and risk of new onset depressive symptoms in older adults: English Longitudinal Study of Ageing. Int. J. Obes. (Lond.) 39, 1717–1720 (2015). This study includes longitudinal data that suggest an association between sarcopenic obesity and depression. sourcePartly supported

  The Results report an adjusted OR of 1.79 (95% CI 1.10–2.89) for new-onset depressive symptoms in obese adults with low grip strength versus non-obese adults with high grip strength. However, the outcome was assessed at six-year follow-up; four years refers to the interval over which grip-strength change was measured in a separate analysis. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

No differences in Short Form-36 scores were found between individuals with obesity and low handgrip strength and individuals with normal indices.

“Another study reported no differences in Short Form-36 scores, which provide a measure of quality of life235, between individuals with obesity and low handgrip strength and individuals with normal indices236.”

• cites [236] Silva Neto, L. S., Karnikowiski, M. G., Tavares, A. B. & Lima, R. M. Association between sarcopenia, sarcopenic obesity, muscle strength and quality of life variables in elderly women. Rev. Bras. Fisioter. 16, 360–367 (2012). sourcePartly supported

  The Results (Table 3; page not available in our copy) report no statistically significant differences in SF-36 domains between older women classified with and without sarcopenic obesity. But classification was based on body-composition measures, not low handgrip strength; the comparison group was women without sarcopenic obesity, not necessarily women with normal indices. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Weight loss plus combined aerobic and resistance exercise is the most effective method for improving functional status of adults aged 65 years and older with obesity.

“weight loss plus combined aerobic and resistance exercise was the most effective method for improving functional status of adults aged 65 years and older with obesity247”

• cites [247] Villareal, D. T. et al. Aerobic or resistance exercise, or both in dieting obese older adults. N. Engl. J. Med. 376, 1943–1955 (2017). This is a randomized trial of older adults with obesity and frailty demonstrating that weight loss coupled with both aerobic and resistance activities is associated with improved physical function. sourceSupported

Obesity defined by BMI combined with low handgrip strength is associated with increased risk of type 2 diabetes mellitus (OR 3.57, 95% CI 2.04-6.24).

“the combination of obesity as defined by BMI and low handgrip strength suggested an increased risk of type 2 diabetes mellitus (OR 3.57, 95% CI 2.04–6.24)”

• cites [221] Atkins, J. L. et al. Sarcopenic obesity and risk of cardiovascular disease and mortality: a population-based cohort study of older men. J. Am. Geriatr. Soc. 62, 253–260 (2014). sourceCould not verify

  The Methods define obesity by waist circumference and sarcopenia by midarm muscle circumference, not BMI and handgrip strength. The Results report cardiovascular events and mortality; a search for type 2 diabetes and the stated OR and confidence interval found no matching result in our copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Risk of falling is highest in individuals with low muscle mass and/or strength with obesity defined by percentage of body fat.

“risk of falling was highest in individuals with low muscle mass and/or strength with obesity as defined by percentage of body fat219”

• cites [219] Scott, D. et al. Sarcopenic obesity and dynapenic obesity: 5-year associations with falls risk in middle-aged and older adults. Obesity (Silver Spring) 22, 1568–1574 (2014). sourcePartly supported

  The Discussion reports that obesity combined with low muscle strength, but not low muscle mass, predicted an increased falls-risk score over five years in community-dwelling middle-aged and older adults. The Operational definitions section defines obesity by high DXA-assessed total or trunk fat mass, not percentage body fat; the study measured a risk score rather than observed falls. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

EuroQOL score was dependent on cardiovascular fitness rather than sarcopenic obesity.

“The EuroQOL score was dependent on cardiovascular fitness rather than sarcopenic obesity237.”

• cites [237] Pedrero-Chamizo, R. et al. Higher levels of physical fitness are associated with a reduced risk of suffering sarcopenic obesity and better perceived health among the elderly: the EXERNET multi-center study. J. Nutr. Health Aging 19, 211–217 (2015). sourcePartly supported

  The Results (page unavailable) associate better EuroQol-rated perceived health with higher aerobic fitness, supporting the cardiovascular-fitness part of the claim. But Table 2 and the Statistical analysis section also report differences in health-related quality of life across sarcopenic-obesity groups; the paper does not establish that the score depends on fitness rather than sarcopenic obesity. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

High protein intake (1.2 g/kg/day) during weight loss might eliminate the beneficial effect of weight loss on insulin sensitivity in skeletal muscle.

“High protein intake (1.2 g of protein per kg per day) during weight loss might eliminate the beneficial effect of weight loss on insulin sensitivity in skeletal muscle258.”

• cites [258] Smith, G. I. et al. High-protein intake during weight loss therapy eliminates the weight-loss-induced improvement in insulin action in obese postmenopausal women. Cell Rep. 17, 849–861 (2016). sourceSupported

Strategies that optimize protein anabolism during weight loss, such as consumption before exercise or spreading out protein during the day, can prevent weight loss-induced sarcopenia.

“Strategies that optimize protein anabolism during weight loss, such as consumption before exercise or spreading out of protein during the day, can prevent weight loss-induced sarcopenia247,250.”

• cites [247] Villareal, D. T. et al. Aerobic or resistance exercise, or both in dieting obese older adults. N. Engl. J. Med. 376, 1943–1955 (2017). This is a randomized trial of older adults with obesity and frailty demonstrating that weight loss coupled with both aerobic and resistance activities is associated with improved physical function. sourcePartly supported

  The Discussion (page not provided) suggests improving the efficiency of protein intake as a possible future strategy to preserve lean mass during weight loss. It does not mention protein consumption before exercise or distributing protein across the day, and reports that lean-mass loss was attenuated, not prevented. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [250] Batsis, J. A. et al. Weight loss interventions in older adults with obesity: a systematic review of randomized controlled trials since 2005. J. Am. Geriatr. Soc. 65, 257–268 (2017). This is a comprehensive systematic review of randomized trials in older adults with obesity highlighting the importance of the improvement in physical function through diet and exercise. sourcePartly supported

  The Discussion (page not provided) says that caloric reduction with appropriate protein supplementation and resistance exercise may prevent sarcopenia in older adults with obesity. It does not address consuming protein before exercise or spreading intake throughout the day, and its conclusion is more cautious than the claim’s “can prevent.” (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Reduced muscle strength is associated with increased mortality (HR 1.30, 95% CI 1.09-1.54) in the MiniFinland Health Examination Study.

“reduced muscle strength is associated with increased mortality (HR 1.30, 95% CI 1.09–1.54)228”

• cites [228] Stenholm, S. et al. Obesity and muscle strength as long-term determinants of all-cause mortality — a 33-year follow-up of the Mini-Finland Health Examination Survey. Int. J. Obes. (Lond.) 38, 1126–1132 (2014). sourcePartly supported

  The Abstract Results report HR 1.30 (95% CI 1.09–1.54), but specifically for participants aged 70 or older with normal weight and low handgrip strength, compared with normal-weight participants with high handgrip strength. The citing sentence omits those age, weight, and comparator qualifications and presents the estimate as applying to reduced strength generally. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Increased dietary protein stimulates muscle protein synthesis.

“Increased dietary protein stimulates muscle protein synthesis71,256.”

• cites [71] Bauer, J. et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J. Am. Med. Dir. Assoc. 14, 542–559 (2013). This is a position paper from the PROT-Age study group that recommends an average daily intake of at least 1.0–1.2 g protein per kg body weight per day. sourceSupported
• cites [256] Wolfe, R. R., Miller, S. L. & Miller, K. B. Optimal protein intake in the elderly. Clin. Nutr. 27, 675–684 (2008). sourceNot checked — no full text of the source

A Cochrane review identified 33 trials showing progressive resistance exercises significantly improved physical abilities (SMD 0.14, 95% CI 0.05-0.22) in 2,172 participants.

“identified 33 trials that significantly improved physical abilities (standardized mean difference 0.14, 95% CI 0.05–0.22) in 2,172 participants”

• cites [281] Liu, C. J. & Latham, N. K. Progressive resistance strength training for improving physical function in older adults. Cochrane Database Syst. Rev. 3, CD002759 (2009). This is a systematic Cochrane review of randomized controlled trials reporting physical outcomes of progressive resistance therapy that demonstrates improved strength and performance. sourceSupported

Obesity may increase fracture risk through bone quality or frailty independently of bone mineral density.

“Obesity is inversely related to BMD and fractures313 but might increase the fracture risk through bone quality314,315 or frailty132,316 independent of BMD.”

• cites [314] Nielson, C. M. et al. BMI and fracture risk in older men: the osteoporotic fractures in men study (MrOS). J. Bone Miner. Res. 26, 496–502 (2011). sourceSupported
• cites [315] Compston, J. E. et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am. J. Med. 124, 1043–1050 (2011). sourcePartly supported

  The Discussion reports more falls and several markers of frailty among obese women with fractures, and suggests these may help explain their fracture risk. It also cautions that higher BMD may not confer greater bone strength, but it does not establish that frailty increases fracture risk independently of BMD. The bone-quality portion of the citing sentence has separate citations. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [132] Villareal, D. T., Banks, M., Siener, C., Sinacore, D. R. & Klein, S. Physical frailty and body composition in obese elderly men and women. Obes. Res. 12, 913–920 (2004). sourcePartly supported

  The Results report that 96% of the obese elderly subjects met the study’s frailty criteria, and the Discussion associates obesity with physical frailty despite greater bone mass than in the nonobese groups. The paper does not establish that frailty increases fracture risk independently of BMD; it says the implications of the greater bone mass for fracture risk are unknown. Bone quality is not the part of the citing sentence attributed to this source. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [316] Ensrud, K. E. et al. A comparison of frailty indexes for the prediction of falls, disability, fractures, and mortality in older men. J. Am. Geriatr. Soc. 57, 492–498 (2009). sourcePartly supported

  The Results report that frail older men had higher age-adjusted nonspine fracture risk, and the multivariable prediction models included femoral-neck BMD. The paper does not show that obesity increases fracture risk through frailty, or establish frailty as a causal pathway independent of BMD; bone quality is associated with other citations in the citing sentence. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

In postmenopausal women with overweight or obesity, adding aerobic activity to calorie restriction increased serum concentrations of adiponectin (6.9 μg/ml without aerobic activity versus 8.5 μg/ml with aerobic activity, P < 0.001).

“adding aerobic activity to calorie restriction increased serum concentrations of adiponectin (6.9 μg/ml for individuals in the group without aerobic activity versus 8.5 μg/ml for individuals in the group with aerobic activity (P < 0.001))305”

• cites [305] Wang, X., You, T., Murphy, K., Lyles, M. F. & Nicklas, B. J. Addition of exercise increases plasma adiponectin and release from adipose tissue. Med. Sci. Sports Exerc. 47, 2450–2455 (2015). sourcePartly supported

  The Methods and Results describe overweight or obese postmenopausal women and support an increase in circulating adiponectin when aerobic exercise was added to caloric restriction. The Results report post-intervention plasma concentrations of 5.2 μg/ml without exercise and 7.6 μg/ml with exercise, not the claimed 6.9 and 8.5 μg/ml; the group-by-time interaction had P = 0.014, while the increase within the exercise group had P = 0.0001. The paper measured plasma, rather than serum, adiponectin. (LLM, conf=0.91)

  Experimental — accuracy not yet measured

In a secondary subset analysis of the LIFE pilot study, the short physical performance battery of patients with sarcopenia improved from 7.4 to 8.7 compared with the successful ageing group.

“the short physical performance battery — an objective assessment tool for the evaluation of lower extremity function (higher score equals better function)284 — of patients with sarcopenia improved from 7.4 to 8.7 when compared with the successful ageing group285”

• cites [285] Liu, C. K. et al. The impact of sarcopenia on a physical activity intervention: the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). J. Nutr. Health Aging 18, 59–64 (2014). sourcePartly supported

  The Results section, “Analysis of SPPB” (page unavailable), reports a 12-month SPPB score of 8.7 for sarcopenic participants in the physical-activity group and compares that group with the successful-aging group. Our copy does not establish the claimed starting score of 7.4. The reported difference between groups at 12 months was not statistically significant. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Adipose tissue has an adverse effect on bone microstructure.

“Adipose tissue has been shown to be inversely associated with bone material strength and positively associated with cortical porosity, indicating an adverse effect of adipose tissue on bone microstructure317.”

• cites [317] Sundh, D. et al. A high amount of local adipose tissue is associated with high cortical porosity and low bone material strength in older women. J. Bone Miner. Res. 31, 749–757 (2016). sourcePartly supported

  The Discussion (page not provided) reports that local tibial adipose tissue was inversely associated with bone material strength and positively associated with cortical porosity in older women. It describes a negative effect on cortical microstructure as possible, rather than establishing that adipose tissue has an adverse effect generally. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Unopposed diet therapy without exercise in older frail adults ≥65 years with obesity (BMI ≥30 kg/m2) led to a marked loss of lean mass at 6 months and 1 year (−3.5 kg and −3.2 kg, respectively) compared with the diet and exercise group, where the loss of lean mass was partially mitigated (−1.7 kg and −1.8 kg, respectively).

“Unopposed diet therapy without exercise in older frail adults ≥65 years with obesity (BMI ≥30 kg/m2) led to a marked loss of lean mass at 6 months and 1 year (−3.5 kg and −3.2 kg, respectively) compared with the diet and exercise group, where the loss of lean mass was partially mitigated (−1.7 kg and −1.8 kg, respectively)246.”

• cites [246] Villareal, D. T. et al. Weight loss, exercise, or both and physical function in obese older adults. N. Engl. J. Med. 364, 1218–1229 (2011). This is a randomized trial of older adults with frailty and obesity that compares diet, exercise type and controls and demonstrates that physical function improves and muscle and bone loss is mitigated with concomitant exercise therapy. sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Aquatic exercises are as effective as land-based exercises (SMD 0.39, 95% CI 0.12-0.66).

“aquatic exercises are as effective as land-based exercises (standardized mean difference 0.39, 95% CI 0.12–0.66)”

• cites [294] Waller, B. et al. The effect of aquatic exercise on physical functioning in the older adult: a systematic review with meta-analysis. Age Ageing 45, 593–601 (2016). sourceSupported

A meta-analysis of 18 trials (n = 3,824) including participants >65 years who participated in tai chi for a minimum of 4 weeks (range 1-12 months) 1-3 times per week demonstrated a reduction in falls of 20% (RR 0.8, 95% CI 0.72-0.88).

“A meta-analysis of 18 trials (n = 3,824), including study participants greater than 65 years who participated in tai chi for a minimum of 4 weeks (range 1–12 months) 1–3 times per week, demonstrated a reduction in falls of 20% (relative risk (RR) 0.8, 95% CI 0.72–0.88)292.”

• cites [292] Huang, Z. G., Feng, Y. H., Li, Y. H. & Lv, C. S. Systematic review and meta-analysis: Tai Chi for preventing falls in older adults. BMJ Open 7, e013661 (2017). sourcePartly supported

  The Abstract Results report 18 trials with 3,824 participants and RR 0.80 (95% CI 0.72–0.88), but the Results section specifies that this estimate for the number of fallers came from 16 studies with 3,539 participants. The Methods allowed participants over 60, or trials with an average age over 65, rather than requiring every participant to be over 65. The study-characteristics table also includes Tai Chi schedules longer than 12 months and more frequent than three times weekly, so the stated duration and frequency ranges do not describe all included trials. (LLM, conf=0.91)

  Experimental — accuracy not yet measured

In the Look AHEAD trial, total skeletal mass decreased in both intensive lifestyle groups and in the diabetes support and education group (−1.4 kg; P < 0.001).

“In the Look AHEAD trial, total skeletal mass decreased in both of the intensive lifestyle groups and in the diabetes support and education group (−1.4 kg; P < 0.001).”

• cites [310] Gallagher, D. et al. Changes in skeletal muscle and organ size after a weight-loss intervention in overweight and obese type 2 diabetic patients. Am. J. Clin. Nutr. 105, 78–84 (2017). sourcePartly supported

  The Abstract reports that total skeletal muscle decreased by 1.4 kg in both groups during year 1 (P < 0.001), and the SM section identifies those groups as ILI and DSE. The claim incorrectly describes two intensive lifestyle groups; the study reports one ILI group and one DSE group. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The LIFE study demonstrated reduced persistent mobility disability (HR 0.72, 95% CI 0.57-0.91) compared with a health education programme.

“demonstrated reduced persistent mobility disability (HR 0.72, 95% CI 0.57–0.91) compared with a health education programme”

• cites [282] Pahor, M. et al. Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 311, 2387–2396 (2014). This study reports on a gold standard, structured, long-term physical activity intervention, consisting of 3–4 times of aerobic, resistance and flexibility training per week, that demonstrates improvements in mobility disability over a 2.6-year follow-up. sourceSupported

A Cochrane review identified 73 trials showing progressive resistance exercises improved muscle strength (SMD 0.84, 95% CI 0.67-1.00) in 3,059 participants.

“improvements in muscle strength (standardized mean difference 0.84, 95% CI 0.67–1.00) in 73 trials281 (3,059 participants)”

• cites [281] Liu, C. J. & Latham, N. K. Progressive resistance strength training for improving physical function in older adults. Cochrane Database Syst. Rev. 3, CD002759 (2009). This is a systematic Cochrane review of randomized controlled trials reporting physical outcomes of progressive resistance therapy that demonstrates improved strength and performance. sourceSupported

The addition of weight loss of 0.3 kg per week for 6 months to physical activity in older community-dwelling adults with obesity or overweight results in a greater reduction in serum levels of leptin and IL-6 than either physical activity alone or a successful ageing health education intervention.

“The addition of weight loss of 0.3 kg per week for 6 months to physical activity in older community-dwelling adults with obesity or overweight results in a greater reduction in serum levels of leptin and IL-6 than either physical activity alone or a successful ageing health education intervention308.”

• cites [308] Beavers, K. M., Ambrosius, W. T., Nicklas, B. J. & Rejeski, W. J. Independent and combined effects of physical activity and weight loss on inflammatory biomarkers in overweight and obese older adults. J. Am. Geriatr. Soc. 61, 1089–1094 (2013). sourceSupported

A meta-analysis of 28 studies demonstrated a positive effect of aquatic exercises on physical functioning (RR 0.70, 95% CI 0.48-0.92) compared with no training.

“A meta-analysis of 28 studies demonstrated a positive effect of aquatic exercises on physical functioning (RR 0.70, 95% CI 0.48–0.92) compared with no training (control group)294.”

• cites [294] Waller, B. et al. The effect of aquatic exercise on physical functioning in the older adult: a systematic review with meta-analysis. Age Ageing 45, 593–601 (2016). sourcePartly supported

  The Abstract (p. 1) reports a positive effect of aquatic exercise versus control of 0.70 (95% CI 0.48–0.92), also reported in Results under “Aquatic exercise compared to control.” However, 28 studies were included in the systematic review, only 24 in the meta-analysis, and the effect measure was a standardised mean difference, not a risk ratio (RR). (LLM, conf=0.94)

  Experimental — accuracy not yet measured

Two versus three training sessions per week for 12 weeks of high-speed resistance training were equally effective for improving physical performance and quality of life.

“two versus three training sessions per week for 12 weeks of high-speed resistance training were equally effective for improving physical performance and quality of life288”

• cites [288] Ramirez-Campillo, R. et al. Effects of different doses of high-speed resistance training on physical performance and quality of life in older women: a randomized controlled trial. Clin. Interv. Aging 11, 1797–1804 (2016). sourcePartly supported

  The Discussion states that two and three HSRT sessions per week were equally effective for physical performance and quality of life, and the Methods specify a 12-week intervention. The Conclusion limits that finding to older women when training volume and intensity were equated; the citing sentence omits those conditions and reads more broadly. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

The positive effects on circulating cytokines, adiponectin and TNF were due to diet and not exercise.

“the positive effects on circulating cytokines, adiponectin and TNF were due to diet and not exercise301”

• cites [301] Bouchonville, M. et al. Weight loss, exercise or both and cardiometabolic risk factors in obese older adults: results of a randomized controlled trial. Int. J. Obes. (Lond.) 38, 423–431 (2014). sourceSupported

In response to a 6-month randomized diet and exercise intervention, levels of C-reactive protein and IL-6 decreased in older adults (age ≥65 years) with obesity (BMI ≥30 kg/m2) compared with controls (−2.5 versus 0.8 mg/l (P < 0.05) and −2.4 versus 1.6 pg/ml (P < 0.05), respectively).

“levels of C-reactive protein and IL-6 decreased in older adults (age ≥65 years) with obesity (BMI ≥30 kg/m2) compared with controls (−2.5 versus 0.8 mg/l (P < 0.05) and −2.4 versus 1.6 pg/ml (P < 0.05), respectively)300”

• cites [300] Villareal, D. T. et al. Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am. J. Clin. Nutr. 84, 1317–1323 (2006). sourceSupported

Adding testosterone supplementation to progressive resistance training improved body composition, including reduced fat mass and improved lean mass.

“The addition of pharmacotherapy, such as testosterone supplementation, to progressive resistance training augmented the improvements in body composition, including reduced fat mass and improved lean mass357.”

• cites [357] Hildreth, K. L. et al. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J. Clin. Endocrinol. Metab. 98, 1891–1900 (2013). sourceSupported

The summative effects of combining whole-body vibration therapy with resistance exercises or with vitamin D are mixed.

“Summative effects of the combination of whole body vibration therapy and resistance exercises374–377 or of whole-body vibration therapy and vitamin D367 are mixed.”

• cites [374] Bemben, D. A., Palmer, I. J., Bemben, M. G. & Knehans, A. W. Effects of combined whole-body vibration and resistance training on muscular strength and bone metabolism in postmenopausal women. Bone 47, 650–656 (2010). sourceNot checked — no full text of the source
• cites [375] Fjeldstad, C., Palmer, I. J., Bemben, M. G. & Bemben, D. A. Whole-body vibration augments resistance training effects on body composition in postmenopausal women. Maturitas 63, 79–83 (2009). sourceNot checked — no full text of the source
• cites [376] Machado, A., Garcia-Lopez, D., Gonzalez-Gallego, J. & Garatachea, N. Whole-body vibration training increases muscle strength and mass in older women: a randomized-controlled trial. Scand. J. Med. Sci. Sports 20, 200–207 (2010). sourceNot checked — no full text of the source
• cites [377] von Stengel, S., Kemmler, W., Engelke, K. & Kalender, W. A. Effect of whole-body vibration on neuromuscular performance and body composition for females 65 years and older: a randomized-controlled trial. Scand. J. Med. Sci. Sports 22, 119–127 (2012). sourceNot checked — no full text of the source
• cites [367] Verschueren, S. M. et al. The effects of whole-body vibration training and vitamin D supplementation on muscle strength, muscle mass, and bone density in institutionalized elderly women: a 6-month randomized, controlled trial. J. Bone Miner. Res. 26, 42–49 (2011). sourcePartly supported

  The Interaction effects section (page unavailable) reports no evidence of an interactive effect between whole-body vibration and vitamin D for any outcome. This supports a lack of additional benefit from the combination in this trial, but the paper does not itself report mixed effects of that combination. The resistance-exercise clause is attributed to other citations, not this source. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Exercise training during calorie restriction prevents increases in bone turnover and serum sclerostin, thereby minimizing bone loss.

“Studies emphasize exercise training during calorie restriction to prevent an increase in bone turn-over327 and an increase in serum levels of sclerostin328, thus minimizing bone loss.”

• cites [327] Shah, K. et al. Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip bone mineral density induced by weight loss despite decline in bone-active hormones. J. Bone Miner. Res. 26, 2851–2859 (2011). sourceSupported
• cites [328] Armamento-Villareal, R. et al. Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training. J. Bone Miner. Res. 27, 1215–1221 (2012). sourceSupported

After long-term calorie restriction, bone mineral density and bone turnover markers show larger changes in patients than in healthy controls advised to continue their current diet.

“These findings suggest that BMD and markers of bone turnover following long-term calorie restriction show larger changes in patients than in healthy control participants advised to continue their current diet322.”

• cites [322] Villareal, D. T. et al. Effect of two-year caloric restriction on bone metabolism and bone mineral density in non-obese younger adults: a randomized clinical trial. J. Bone Miner. Res. 31, 40–51 (2016). This is a 2-year randomized trial of caloric restriction, which had been previously shown to lead to bone loss at important sites of osteoporotic fractures as represented by reductions in BMD. sourcePartly supported

  The Abstract reports greater BMD changes after 24 months of calorie restriction than with an ad libitum diet, and greater changes in several bone-turnover markers at 12 months; at 24 months, only BSAP differed between groups. The Methods (Participants and Study Design; page unavailable) say both groups were healthy volunteers and the controls were advised to continue their current diets, so describing the restriction group as “patients” is misleading. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Calorie restriction has protective effects on bone quality.

“Furthermore, trabecular geometry, cortical geometry and strength were no different in individuals undergoing intentional weight loss through calorie restriction or weight maintenance for 6 months324, which suggests that calorie restriction has protective effects on bone quality.”

• cites [324] Pop, L. C. et al. Moderate weight loss in obese and overweight men preserves bone quality. Am. J. Clin. Nutr. 101, 659–667 (2015). sourceSupported

Trabecular bone microarchitecture did not differ between calorie-restricted participants and middle-aged individuals eating a Western diet.

“In one study, the authors reported that trabecular bone microarchitecture was no different in calorie- restricted participants (~35% less calories than controls) than in middle-aged individuals eating a Western diet323.”

• cites [323] Villareal, D. T. et al. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Aging Cell 10, 96–102 (2011). sourceSupported

Periodized resistance training in older adults had equal efficacy for physical function and physiological outcomes compared with non-periodized resistance training.

“Periodized resistance training in older adults demonstrated equal efficacy in physical function and physiological outcomes when compared with non-periodized resistance training360.”

• cites [360] Conlon, J. A. et al. Periodization strategies in older adults: impact on physical function and health. Med. Sci. Sports Exerc. 48, 2426–2436 (2016). sourceSupported

Vitamin D supplementation in patients with sarcopenic obesity can potentially improve muscle function and proximal muscle weakness through vitamin D metabolites.

“Supplementing vitamin D in patients with sarcopenic obesity can potentially influence and improve muscle function331 and proximal muscle weakness332 through the actions ofvitamin D metabolites333.”

• cites [331] Hassan-Smith, Z. K. et al. 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression. PLoS ONE 12, e0170665 (2017). sourcePartly supported

  The Discussion (page unavailable) links vitamin D metabolites to muscle function and gene expression, supporting the mechanism attributed to this source. But the study was cross-sectional in healthy volunteers; it did not test supplementation in patients with sarcopenic obesity or establish that supplementation improves muscle function or proximal weakness. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [332] Beaudart, C. et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J. Clin. Endocrinol. Metab. 99, 4336–4345 (2014). sourceNot checked — no full text of the source
• cites [333] Malafarina, V., Uriz-Otano, F., Malafarina, C., Martinez, J. A. & Zulet, M. A. Effectiveness of nutritional supplementation on sarcopenia and recovery in hip fracture patients. A multi-centre randomized trial. Maturitas 101, 42–50 (2017). sourceNot checked — no full text of the source

Older adults often receive gold-standard imaging that can accurately ascertain muscle and fat content for indications other than sarcopenic obesity, such as abdominal pain or back pain.

“Older adults often receive gold standard imaging, which can accurately ascertain muscle and fat content, for indications other than sarcopenic obesity, such as abdominal pain or back pain342,343.”

• cites [342] Maddalo, M. et al. Validation of a free software for unsupervised assessment of abdominal fat in MRI. Phys. Med. 37, 24–31 (2017). sourceNot checked — no full text of the source
• cites [343] van Vugt, J. L. A. et al. A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients. J. Cachexia Sarcopenia Muscle 8, 285–297 (2017). sourcePartly supported

  The Materials and Methods (Patients; page unavailable) say the abdominal CT scans were routinely obtained for rectal-cancer workup or treatment assessment, not for body-composition assessment. The Abstract (Conclusions; page unavailable) reports excellent agreement in muscle and fat measurements across software and observers. The paper does not establish that older adults often receive such imaging for abdominal or back pain, or that it is a gold-standard measure of accuracy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Whole-body vibration therapy transmits mechanical stimuli through the body to activate primary endings of muscle spindles, leading to neuromuscular activation.

“Whole-body vibration therapy uses the transmission of mechanical stimuli through the person’s body365,366 to activate the primary ends of muscle spindles, which leads to neuromuscular activation367–369.”

• cites [365] Rogan, S., Hilfiker, R., Herren, K., Radlinger, L. & de Bruin, E. D. Effects of whole-body vibration on postural control in elderly: a systematic review and meta-analysis. BMC Geriatr. 11, 72 (2011). sourcePartly supported

  The Discussion says vibration delivers energy to the body and identifies reflex muscle contraction during WBV as a possible stimulus to the muscle–nerve system. It does not identify activation of the primary endings of muscle spindles as the mechanism; the passages have no page numbers. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [366] Rogan, S. et al. Feasibility and effects of applying stochastic resonance whole-body vibration on untrained elderly: a randomized crossover pilot study. BMC Geriatr. 15, 25 (2015). sourcePartly supported

  The Background and Methods > Protocol describe participants standing on vibrating platforms and receiving whole-body vibration, supporting the mechanical-stimulation part of the claim. The cited paper does not describe activation of muscle-spindle primary endings or establish that mechanism for neuromuscular activation; the citing sentence places separate citations after that clause. No page numbers are available in our copy. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [367] Verschueren, S. M. et al. The effects of whole-body vibration training and vitamin D supplementation on muscle strength, muscle mass, and bone density in institutionalized elderly women: a 6-month randomized, controlled trial. J. Bone Miner. Res. 26, 42–49 (2011). sourceSupported
• cites [368] Cardim, A. B. et al. Does whole-body vibration improve the functional exercise capacity of subjects with COPD? A meta-analysis. Respir. Care 61, 1552–1559 (2016). sourceSupported
• cites [369] Burke, D. & Schiller, H. H. Discharge pattern of single motor units in the tonic vibration reflex of human triceps surae. J. Neurol. Neurosurg. Psychiatry 39, 729–741 (1976). sourceSupported

In older adults with obesity, bone mineral density loss appears to continue during long-term lifestyle change in the opposite direction to weight changes.

“Loss of BMD in older adults with obesity seems to continue during long-term lifestyle change in the opposite direction to the weight changes321.”

• cites [321] Waters, D. L. et al. Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults. J. Nutr. Health Aging 17, 3–7 (2013). sourceSupported

In the Look AHEAD trial, long-term intentional weight loss was associated with a 39% increased risk of fragility fractures.

“However, 2017 data from the Look AHEAD trial showed that long-term intentional weight loss was associated with a 39% increased risk of fragility fractures325.”

• cites [325] Johnson, K. C. et al. The effect of intentional weight loss on fracture risk in persons with diabetes: results from the Look AHEAD randomized clinical trial. J. Bone Miner. Res. 32, 2278–2287 (2017). sourcePartly supported

  The Results report a 39% higher risk of frailty fracture in the intensive lifestyle intervention group than in the diabetes support and education group. The Methods define that endpoint by fracture site—hip, pelvis, upper arm, or shoulder—not as fragility fractures, so the cited figure does not establish the claim for fragility fractures. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Leucine-rich protein can activate metabolic pathways involved in testosterone and IGF1 homeostasis.

“For instance, leucine-rich protein can activate metabolic pathways involved in testosterone and IGF1 homeostasis348–351.”

• cites [348] Witard, O. C., McGlory, C., Hamilton, D. L. & Phillips, S. M. Growing older with health and vitality: a nexus of physical activity, exercise and nutrition. Biogerontology 17, 529–546 (2016). sourcePartly supported

  The section “Optimizing the quality and utilization of protein intake on a per meal basis” (page unavailable) says leucine-rich protein can activate mTOR signaling involved in muscle protein synthesis. It does not link that activation to testosterone or IGF1 homeostasis; its separate mention of testosterone concerns pharmaceutical therapy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [349] Garatachea, N. et al. Exercise attenuates the major hallmarks of aging. Rejuvenation Res. 18, 57–89 (2015). sourceCould not verify

  The Introduction (page unavailable) says resistance exercise acutely raises testosterone and IGF-1 and activates amino-acid-sensing pathways. Searches for “leucine-rich protein,” leucine, and testosterone found no passage saying that leucine-rich protein activates pathways involved in homeostasis of those hormones. The exercise findings do not establish the protein-specific claim. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [350] Emmelot-Vonk, M. H. et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 299, 39–52 (2008). sourceNot checked — no full text of the source
• cites [351] Travison, T. G. et al. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J. Gerontol. A Biol. Sci. Med. Sci. 66, 1090–1099 (2011). sourceNot checked — no full text of the source

In patients with sarcopenic obesity defined by handgrip strength and BMI, a 10-week periodization strategy of strength and endurance training with concentric and eccentric movements produced no differences in strength, power or short physical performance battery.

“In patients with sarcopenic obesity (defined using handgrip strength and BMI), no differences were observed in strength, power or short performance physical battery following a 10-week periodization strategy of strength and endurance training with concentric and eccentric movements290.”

• cites [290] Vasconcelos, K. S. et al. Effects of a progressive resistance exercise program with high-speed component on the physical function of older women with sarcopenic obesity: a randomized controlled trial. Braz. J. Phys. Ther. 20, 432–440 (2016). sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Trabecular geometry, cortical geometry and strength did not differ between individuals undergoing intentional weight loss by calorie restriction and those on weight maintenance for six months.

“Furthermore, trabecular geometry, cortical geometry and strength were no different in individuals undergoing intentional weight loss through calorie restriction or weight maintenance for 6 months324, which suggests that calorie restriction has protective effects on bone quality.”

• cites [324] Pop, L. C. et al. Moderate weight loss in obese and overweight men preserves bone quality. Am. J. Clin. Nutr. 101, 659–667 (2015). sourceSupported

At 12 months, the disposition index improved more in the diet-exercise group than in the diet-only group.

“increased differences were reported in the disposition index (an index of insulin secretion after correction for insulin resistance) in the diet–exercise group (92.4 ± 11.4%) compared with the diet-only group (61.9 ± 15.3%) at 12 months320.”

• cites [320] Colleluori, G., Napoli, N., Phadnis, U., Armamento-Villareal, R. & Villareal, D. T. Effect of weight loss, exercise, or both on undercarboxylated osteocalcin and insulin secretion in frail, obese older adults. Oxid. Med. Cell. Longev. 2017, 4807046 (2017). sourceSupported

Periodization has emerged as a potential strategy to improve muscle performance.

“Periodization, which is a systematic variation in physical training specificity, intensity and volume within periods, has emerged as a potential strategy to improve muscle performance358.”

• cites [358] Strohacker, K., Fazzino, D., Breslin, W. L. & Xu, X. The use of periodization in exercise prescriptions for inactive adults: a systematic review. Prev. Med. Rep. 2, 385–396 (2015). sourceSupported

In the Testosterone Trials, testosterone treatment improved 6-minute walk test results versus placebo (20.5% versus 12.6%; P=0.003).

“In the ‘Testosterone Trials’, treatment with testosterone improved participants’ results in the 6 min walk test compared with placebo (20.5% versus 12.6%; P = 0.003)53.”

• cites [53] Snyder, P. J. et al. Effects of testosterone treatment in older men. N. Engl. J. Med. 374, 611–624 (2016). This is a randomized trial of testosterone therapy in symptomatic older men that demonstrates no benefit in vitality or walking distance following supplementation. sourcePartly supported

  The Results > Efficacy section reports improved 6-minute walking outcomes with testosterone versus placebo among participants across all three Testosterone Trials, including P = 0.003 for the proportion whose walking distance increased by at least 50 m. Our copy does not give the cited 20.5% versus 12.6% figures. It also reports no significant difference for that outcome among participants in the Physical Function Trial alone. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

In men over 60 years with low testosterone, testosterone supplementation increased lean mass by 1.6 to 6.20 kg.

“in men over 60 years with low testosterone, gains in lean mass following testosterone supplementation ranged from 1.6 kg to 6.20 kg (REF407).”

• cites [407] Neto, W. K. et al. Effects of testosterone on lean mass gain in elderly men: systematic review with meta-analysis of controlled and randomized studies. Age (Dordr.) 37, 9742 (2015). This is a meta-analysis demonstrating that testosterone supplementation in elderly men leads to increases in lean mass and potentially reductions in fat mass. sourceSupported

Testosterone-associated increases in lean mass were accompanied by improvements in handgrip strength, knee extension, leg press and chest press.

“Elsewhere, testosterone-associated increases in lean mass were accompanied by improvements in handgrip strength, knee extension and leg press and chest press exercises415,416.”

• cites [415] Srinivas-Shankar, U. et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 95, 639–650 (2010). sourceNot checked — no full text of the source
• cites [416] Page, S. T. et al. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J. Clin. Endocrinol. Metab. 90, 1502–1510 (2005). sourcePartly supported

  The Strength section (p. 3) reports improved handgrip strength with testosterone, and the paper reports increased lean body mass. But knee strength did not differ significantly from placebo; the paper does not report improvements in leg-press or chest-press exercises. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Improvements in lean mass do not directly result in improved function after testosterone therapy.

“Improvements in lean mass do not directly result in improved function after testosterone therapy409.”

• cites [409] Schroeder, E. T. et al. Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation. Eur. J. Appl. Physiol. 112, 1123–1131 (2012). sourcePartly supported

  The Discussion reports that large lean-mass gains at week 8 were not accompanied by large improvements in muscle function, supporting the point that the gains did not immediately translate into functional improvement. But it also reports more substantial strength and muscle-performance gains by week 17, so the claim is too broad without a timing qualifier. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Orlistat promotes weight loss through fat and visceral adipose tissue loss but minimally changes lean mass.

“Orlistat promotes the weight loss via fat and visceral adipose tissue loss but minimally changes lean mass389–391.”

• cites [389] Kujawska-Luczak, M. et al. The effect of orlistat versus metformin on body composition and insulin resistance in obese premenopausal women: 3-month randomized prospective open-label study. Arch. Med. Sci. 13, 725–731 (2017). sourcePartly supported

  The Results (Body composition measurements, Table II; page unavailable) report weight and total-fat loss with orlistat. They do not report lean-mass changes, and orlistat's absolute android fat change was small; the Methods describe regional fat measurements rather than a direct measurement of visceral adipose tissue. Thus, this paper supports weight and fat loss, but not the specific claims of visceral adipose tissue loss and minimal lean-mass change. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [390] Smith, S. R. et al. Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial. Obesity (Silver Spring) 19, 1796–1803 (2011). sourceNot checked — no full text of the source
• cites [391] Smith, T. J. et al. Efficacy of orlistat 60 mg on weight loss and body fat mass in US Army soldiers. J. Acad. Nutr. Diet. 112, 533–540 (2012). sourceNot checked — no full text of the source

Data on the effect of testosterone supplementation on muscle strength and function are conflicting.

“There are conflicting data on the effect of testosterone supplementation on muscle strength and function50,51,357,414.”

• cites [50] Urban, R. J. et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am. J. Physiol. 269, E820–E826 (1995). sourceNot checked — no full text of the source
• cites [51] Snyder, P. J. et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J. Clin. Endocrinol. Metab. 84, 2647–2653 (1999).Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [357] Hildreth, K. L. et al. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J. Clin. Endocrinol. Metab. 98, 1891–1900 (2013). sourceSupported
• cites [414] Bhasin, S. et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J. Clin. Endocrinol. Metab. 90, 678–688 (2005). This is a randomized trial of dose-dependent testosterone supplementation that demonstrates that older men are as responsive as young men to the anabolic effects of testosterone; however, older men have lower testosterone clearance rates, higher increments in haemoglobin and a higher frequency of adverse effects. sourceNot checked — no full text of the source

In select older men over 60 years with testosterone deficiency and frailty, body composition and quality of life improved after testosterone supplementation.

“In select older men over the age of 60 years with testosterone deficiency and frailty, body composition and quality of life improved following supplementation with testosterone409–411.”

• cites [409] Schroeder, E. T. et al. Value of measuring muscle performance to assess changes in lean mass with testosterone and growth hormone supplementation. Eur. J. Appl. Physiol. 112, 1123–1131 (2012). sourcePartly supported

  The Results (‘Changes in body composition’; page not provided) report increased lean mass in older men receiving testosterone, supporting the body-composition portion. The Methods (‘Study participants’; page not provided) specify men aged 65–90 with testosterone in the lower portion of the adult range, but do not establish that they were frail or testosterone-deficient. The paper does not report an improvement in quality of life. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [410] Hyde, Z. et al. Low free testosterone predicts frailty in older men: the health in men study. J. Clin. Endocrinol. Metab. 95, 3165–3172 (2010). sourceNot checked — no full text of the source
• cites [411] Krasnoff, J. B. et al. Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J. Clin. Endocrinol. Metab. 95, 2790–2799 (2010). sourcePartly supported

  The Discussion (page unavailable in our copy) says testosterone administration is associated with increased skeletal muscle mass, supporting the body-composition part of the claim. It does not report improved quality of life after supplementation in men over 60 with both testosterone deficiency and frailty; it notes that most earlier trials enrolled healthy older men without functional limitations. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

To date, the American Association of Clinical Endocrinologists, the Endocrine Society and the Obesity Society have not recommended testosterone supplementation as a treatment for sarcopenia or obesity.

“To date, the American Association of Clinical Endocrinologists187, the Endocrine Society425 and the Obesity Society186 have not recommended testosterone supplementation as a treatment for sarcopenia or obesity.”

• cites [187] Garvey, W. T. et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr. Pract. 22 (Suppl. 3), 1–203 (2016). Guidelines for the management of obesity by the AACE/ACE. sourceNot checked — no full text of the source
• cites [425] Bhasin, S. et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 95, 2536–2559 (2010). sourceNot checked — no full text of the source
• cites [186] Villareal, D. T. et al. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am. J. Clin. Nutr. 82, 923–934 (2005). This study highlights current guidelines for the management of older adults with obesity. sourceCould not verify

  The Treatment options and Pharmacotherapy sections discuss obesity treatments, and the Future Research Directions section discusses sarcopenic obesity. None states whether the Obesity Society recommends testosterone supplementation for sarcopenia or obesity. A treatment list that omits testosterone does not establish the claimed non-recommendation. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

Selective androgen receptor modulators indirectly affect nonmuscle androgen receptor pathways mediated by muscle fibroblasts.

“SARMs indirectly affect nonmuscle androgen receptor pathways mediated by muscle fibroblasts426.”

• cites [426] Dubois, V., Laurent, M., Boonen, S., Vanderschueren, D. & Claessens, F. Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions. Cell. Mol. Life Sci. 69, 1651–1667 (2012). sourcePartly supported

  The Introduction describes SARMs as tissue-selective androgen receptor ligands and says non-genomic pathways may play a role in their action. It does not establish that SARMs indirectly affect nonmuscle androgen receptor pathways through muscle fibroblasts; the Introduction instead treats indirect androgen action through other cells as an open question. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Enobosarm significantly increased lean mass from baseline (1.0 kg, 95% CI −4.8 to 11.5; P=0.046) versus controls (0.02 kg, 95% CI −5.8 to 6.7; P=0.88).

“Enobosarm significantly increased lean mass compared with baseline (1.0 kg, 95% CI −4.8 to 11.5; P = 0.046) versus controls (0.02 kg, 95% CI −5.8 to 6.7; P = 0.88).”

• cites [429] Dalton, J. T. et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J. Cachexia Sarcopenia Muscle 2, 153–161 (2011). sourcePartly supported

  The Results (Table 2; page unavailable) support an increase in lean body mass with enobosarm, but not the quoted estimates, confidence intervals, or P values. The 3-mg group gained 1.246 kg from baseline, versus a 0.073-kg decrease with placebo; the reported P value for the treatment-versus-placebo comparison is <0.001. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

An early human study suggests mesenchymal stem cells have a role in managing frailty.

“An early human study suggests a role for mesenchymal stem cells in managing frailty468.”

• cites [468] Tompkins, B. A. et al. Allogeneic mesenchymal stem cells ameliorate aging frailty: a phase ii randomized, double-blind, placebo-controlled clinical trial. J. Gerontol. A Biol. Sci. Med. Sci. 72, 1513–1522 (2017). sourceSupported

Vitamin K deficiency is associated with increased risk of fragility fractures, particularly in malnourished patients.

“Its deficiency has been associated with increased risk of fragility fractures452–455, particularly in patients who are malnourished456,457.”

• cites [452] Hart, J. P. et al. Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J. Clin. Endocrinol. Metab. 60, 1268–1269 (1985). sourceNot checked — no full text of the source
• cites [453] Bitensky, L. et al. Circulating vitamin K levels in patients with fractures. J. Bone Joint Surg. Br. 70, 663–664 (1988). sourceNot checked — no full text of the source
• cites [454] Hodges, S. J., Akesson, K., Vergnaud, P., Obrant, K. & Delmas, P. D. Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture. J. Bone Miner. Res. 8, 1241–1245 (1993). sourceNot checked — no full text of the source
• cites [455] Hodges, S. J. et al. Depressed levels of circulating menaquinones in patients with osteoporotic fractures of the spine and femoral neck. Bone 12, 387–389 (1991). sourceNot checked — no full text of the source
• cites [456] Binkley, N. et al. Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J. Bone Miner. Res. 24, 983–991 (2009). sourcePartly supported

  The Introduction and Discussion report associations between low vitamin K status and increased hip fracture risk. But the Discussion (p. 989) does not establish a stronger association specifically in malnourished patients; it suggests that general undernutrition or frailty, rather than vitamin K inadequacy itself, may explain the observed fracture risk. The study did not evaluate fractures as an endpoint. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [457] Binkley, N. C. & Suttie, J. W. Vitamin K nutrition and osteoporosis. J. Nutr. 125, 1812–1821 (1995). sourceNot checked — no full text of the source

Lack of functional improvements with anamorelin was also observed in patients with unresectable non-small-cell lung cancer.

“Lack of functional improvements were also observed in patients with unresectable non-small-cell lung cancer442.”

• cites [442] Katakami, N. et al. Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: results from a randomized, double-blind, placebo-controlled, multicenter study of Japanese patients (ONO-7643-04). Cancer 124, 606–616 (2018). sourceSupported

Selective androgen receptor modulator treatment in older women with low lean mass, self-reported mobility disability and a short physical performance battery score between 4 and 9 improved muscle mass without improving strength.

“SARM treatment in older women with low lean mass, a self-reported mobility disability and a short physical performance battery score between 4 and 9 provided improvements in muscle mass without benefits of improved strength430.”

• cites [430] Papanicolaou, D. A. et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J. Nutr. Health Aging 17, 533–543 (2013). sourceSupported

Other studies showed selective androgen receptor modulators increased lean mass without improving strength or physical performance in patients with sarcopenia.

“Other studies showed increases in lean mass without improvements in strength or physical performance in patients with sarcopenia428,430.”

• cites [428] Dobs, A. S. et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 14, 335–345 (2013). sourcePartly supported

  The Results report increased lean body mass and no significant improvement in hand-grip strength, supporting those parts of the claim. But the Results and Discussion report significant improvements in stair-climb power, a measure of physical function—the opposite of the claimed lack of improvement. The trial studied patients with cancer-induced muscle wasting, not a general sarcopenia population. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [430] Papanicolaou, D. A. et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J. Nutr. Health Aging 17, 533–543 (2013). sourceSupported

Early data suggest myostatin inhibitors improve physical function in patients with non-small-cell lung cancer.

“Early data suggest improved physical function in patients with non-small-cell lung cancer427.”

• cites [427] Crawford, J. et al. Study design and rationale for the phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the prevention and treatment of muscle wasting in cancer patients (POWER Trials). Curr. Oncol. Rep. 18, 37 (2016). sourcePartly supported

  The Design of the POWER Trials section reports that enobosarm improved physical function in a preceding phase 2b trial involving patients with non-small-cell lung cancer. But the Novel Drug: Enobosarm section identifies it as a selective androgen receptor modulator, not a myostatin inhibitor. The verbatim citing sentence is supported; the supplied paraphrase adds an unsupported drug classification. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The prevalence of obesity together with sarcopenia is rising among adults aged 65 years and older.

“The prevalence of obesity in combination with sarcopenia (the age-related loss of muscle mass and strength or physical function) is increasing in adults aged 65 years and older.”

A substantial proportion of adults over 65 are classified as having sarcopenic obesity.

“A major subset of adults over the age of 65 is now classified as having sarcopenic obesity, a high-risk geriatric syndrome predominantly observed in an ageing population that is at risk of synergistic complications from both sarcopenia and obesity.”

Lower IGF1 together with age-related testosterone decline raises the likelihood of incident frailty.

“This reduction in IGF1, along with the age-related reductions in testosterone, increases the likelihood of incident frailty62.”

• cites [62] Yeap, B. B. et al. Associations of insulin-like growth factor-I and its binding proteins and testosterone with frailty in older men. Clin. Endocrinol. (Oxf.) 78, 752–759 (2013). sourceNot checked — no full text of the source

Pro-inflammatory lipids release paracrine hormones and cytokines that create a feedforward cycle by producing intramyocellular lipids.

“Pro-inflammatory lipids also secrete paracrine hormones and cytokines that promote a feedforward cycle by producing intramyocellular lipids.”

Ageing reduces cardiopulmonary status because of inefficient oxygen extraction and a simultaneous reduction in metabolically active muscle mass.

“Ageing leads to reduced cardiopulmonary status owing to inefficient oxygen extraction and a concomitant reduction in metabolically active muscle mass128.”

• cites [128] Lambert, C. P. & Evans, W. J. Adaptations to aerobic and resistance exercise in the elderly. Rev. Endocr. Metab. Disord. 6, 137–143 (2005). sourceNot checked — no full text of the source

Physical activity can prevent myocyte apoptosis.

“Myocyte apoptosis can be abrogated by physical activity125,126, while mechanisms of cellular quality control, including autophagy, mitophagy and mitochondriogenesis127, contribute to the development of sarcopenic obesity and could be potential targets for therapy.”

• cites [125] Hood, D. A. Mechanisms of exercise-induced mitochondrial biogenesis in skeletal muscle. Appl. Physiol. Nutr. Metab. 34, 465–472 (2009). sourceNot checked — no full text of the source
• cites [126] Mooren, F. C. & Kruger, K. Exercise, autophagy, and apoptosis. Prog. Mol. Biol. Transl Sci. 135, 407–422 (2015). sourceNot checked — no full text of the source

Physical activity recruits muscle satellite cells located between myofibres and their basal lamina into existing muscle fibres.

“Muscle satellite cells located between myofibres and their surrounding basal lamina are recruited into existing muscle fibres by physical activity110,111.”

• cites [110] Dreyer, H. C., Blanco, C. E., Sattler, F. R., Schroeder, E. T. & Wiswell, R. A. Satellite cell numbers in young and older men 24 hours after eccentric exercise. Muscle Nerve 33, 242–253 (2006). sourceNot checked — no full text of the source
• cites [111] Petrella, J. K., Kim, J. S., Mayhew, D. L., Cross, J. M. & Bamman, M. M. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J. Appl. Physiol. (1985) 104, 1736–1742 (2008). sourceNot checked — no full text of the source

Resistance training reduces levels of cytokines such as resistin, leptin and IL-6.

“Resistance training has also been shown to reduce levels of cytokines, such as resistin, leptin and IL-6 (REF142).”

• cites REF142Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Crosstalk with biologically active muscle tissue creates a negative feedback cycle that promotes progressive fat mass gain and loss of lean mass and muscle strength.

“In tandem, crosstalk with biologically active muscle tissue leads to a negative feedback cycle that promotes progressive gain in fat mass and loss of lean mass and muscle strength.”

The core biological factors underlying sarcopenic obesity are age-related changes in metabolism and body composition together with concurrent environmental obesogenic factors and physical illnesses that develop with ageing.

“The core biological factors that underlie sarcopenic obesity are age-related changes in metabolism and body composition and the presence of concurrent environmental obesogenic factors and physical illnesses that develop with the ageing process.”

In a study of eight young adults aged 18-29 and seven older adults aged 67-81, isometric knee extension at varying maximal voluntary contraction levels followed by a 6-week resistance programme produced early increases in isometric knee extensor maximal force and motor unit discharge rates.

“In a study of eight young adults (aged 18–29 years) and seven older adults (aged 67–81 years), isometric knee extension at varying degrees of maximal voluntary contraction followed by a 6-week resistance programme demonstrated early increases of isometric knee extensor maximal force (which is a marker of voluntary muscle contraction) and increases in motor unit discharge rates (which is a magn”

• cites [141] Kamen, G. & Knight, C. A. Training-related adaptations in motor unit discharge rate in young and older adults. J. Gerontol. A Biol. Sci. Med. Sci. 59, 1334–1338 (2004). sourceNot checked — no full text of the source

Gold standard body composition methods including CT and MRI allow clinicians to accurately analyse adipose tissue and muscle mass.

“Gold standard methods to assess body composition, including CT and MRI, allow clinicians to accurately analyse adipose tissue and muscle mass150 (FIG. 2).”

• cites [150] Woodrow, G. Body composition analysis techniques in the aged adult: indications and limitations. Curr. Opin. Clin. Nutr. Metab. Care 12, 8–14 (2009). sourceNot checked — no full text of the source

Overestimation of total body water and extracellular fluid leads to aberrant bioelectrical impedance values.

“Thus, an overestimation of the total volume of water and extracellular fluid in the body leads to aberrant values.”

• AssumptionThe authors state this as an assumption: For bioelectrical impedance to be valid, tissue hydration must be constant and the body must be cylindrical.

Resistance exercises increased TNF mRNA and protein in skeletal muscle biopsy samples from frail adults.

“Separately, resistance exercises resulted in increased TNF mRNA and protein from skeletal muscle biopsy samples in frail adults134.”

• cites [134] Greiwe, J. S., Cheng, B., Rubin, D. C., Yarasheski, K. E. & Semenkovich, C. F. Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J. 15, 475–482 (2001). sourceNot checked — no full text of the source

Without a consistent definition of sarcopenia, investigators are limited in identifying participants for interventional research.

“Without a consistent definition of sarcopenia, investigators are limited in their ability to identify participants for interventional research.”

Others applied mathematical body fat thresholds from reference populations to provide sufficient power that might not be based on distal outcomes.

“Others applied mathematical body fat thresholds of reference populations to provide sufficient power that might not be based on distal outcomes190,191.”

• cites [190] Baumgartner, R. N. et al. Epidemiology of sarcopenia among the elderly in New Mexico. Am. J. Epidemiol. 147, 755–763 (1998). This is a landmark study that demonstrates the prevalence of sarcopenia in a cohort of older adults in the New Mexico Elder Health Survey. sourceNot checked — no full text of the source
• cites [191] Baumgartner, R. N. et al. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes. Res. 12, 1995–2004 (2004). This study highlights the synergistic problems of sarcopenia and obesity that lead to impairments in instrumental activities of daily living. sourceNot checked — no full text of the source

Abdominal visceral fat and quadriceps muscle area are associated with postural instability.

“abdominal visceral fat and quadriceps muscle area served as markers for central obesity and sarcopenia, respectively, and were associated with postural instability213”

• cites [213] Ochi, M. et al. Quadriceps sarcopenia and visceral obesity are risk factors for postural instability in the middle-aged to elderly population. Geriatr. Gerontol. Int. 10, 233–243 (2010). sourceNot checked — no full text of the source

Sarcopenic obesity defined by muscle mass and BMI ≥25 kg/m2 is associated with increased risk of dyslipidaemia (OR 2.82, 95% CI 1.76-4.51).

“individuals with sarcopenic obesity were at an increased risk of dyslipidaemia (OR 2.82, 95% CI 1.76–4.51)214”

• cites [214] Baek, S. J. et al. Sarcopenia and sarcopenic obesity and their association with dyslipidemia in Korean elderly men: the 2008–2010 Korea National Health and Nutrition Examination Survey. J. Endocrinol. Invest. 37, 247–260 (2014). sourceNot checked — no full text of the source

An earlier cross-sectional study found no differences in disability between sarcopenic obesity defined by low muscle mass and elevated body fat and controls.

“did not demonstrate differences in disability compared with controls205”

• cites [205] Zoico, E. et al. Physical disability and muscular strength in relation to obesity and different body composition indexes in a sample of healthy elderly women. Int. J. Obes. Relat. Metab. Disord. 28, 234–241 (2004). sourceNot checked — no full text of the source

Overlap using different diagnostic criteria for sarcopenic obesity is limited but ranges from 2.1% to 4.1%.

“Overlap using different diagnostic criteria of sarcopenic obesity is limited183 but ranges from 2.1% to 4.1%.”

• cites [183] Kemmler, W. et al. Prevalence of sarcopenia and sarcopenic obesity in older German men using recognized definitions: high accordance but low overlap! Osteoporos. Int. 28, 1881–1891 (2017). sourceNot checked — no full text of the source

A comparison of sarcopenic obesity rates using bioelectrical impedance to define sarcopenia and percentage body fat to define obesity showed increasing rates with age.

“A comparison of the rates of sarcopenic obesity using bioelectrical impedance to define sarcopenia and percentage of body fat to define obesity showed increasing rates with age196.”

• cites [196] Kemmler, W., von Stengel, S., Engelke, K., Sieber, C. & Freiberger, E. Prevalence of sarcopenic obesity in Germany using established definitions: baseline data of the FORMOsA study. Osteoporos. Int. 27, 275–281 (2016). sourceNot checked — no full text of the source

Low muscle strength and abdominal obesity are associated with increased mobility disability and risk of hospitalization (OR 2.10, 95% CI 1.14-3.88) in an 11-year follow-up study.

“An increase in mobility disability and risk of hospitalization (OR 2.10, 95% CI 1.14–3.88) was associated with low muscle strength and abdominal obesity in an 11-year follow-up study”

A shortcoming in ascertaining accurate prevalence rates for sarcopenic obesity is the lack of a consistent definition for either sarcopenia or obesity.

“A shortcoming in ascertaining accurate prevalence rates for sarcopenic obesity is the lack of a consistent definition for either sarcopenia or obesity.”

Low handgrip strength and elevated BMI are strongly associated with increased risk of functional decline.

“Low handgrip strength and elevated BMI were strongly associated with an increased risk of functional decline210.”

• cites [210] Yang, M., Jiang, J., Hao, Q., Luo, L. & Dong, B. Dynapenic obesity and lower extremity function in elderly adults. J. Am. Med. Dir. Assoc. 16, 31–36 (2015). sourceNot checked — no full text of the source

Muscle strength is a stronger predictor of long-term functional decline than muscle mass.

“Muscle strength is a stronger predictor of long-term functional decline than muscle mass206.”

• cites [206] Schaap, L. A., Koster, A. & Visser, M. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons. Epidemiol. Rev. 35, 51–65 (2013). This is a meta-analysis that proves the longitudinal impact of BMI on incident loss of muscle mass and muscle strength. sourceNot checked — no full text of the source

These findings are also observed when evaluating overlap of sarcopenia-only definitions, which is less than 50%.

“These findings are also observed when evaluating the overlap of sarcopenia-only definitions, which is less than 50%183.”

• cites [183] Kemmler, W. et al. Prevalence of sarcopenia and sarcopenic obesity in older German men using recognized definitions: high accordance but low overlap! Osteoporos. Int. 28, 1881–1891 (2017). sourceNot checked — no full text of the source

A review of eight definitions for sarcopenic obesity found a 19-fold to 26-fold variation in sex-specific rates.

“A review of eight definitions for sarcopenic obesity noted a 19-fold to 26-fold variation in sex-specific rates178.”

• cites [178] Batsis, J. A. et al. Variation in the prevalence of sarcopenia and sarcopenic obesity in older adults associated with different research definitions: dual-energy X-ray absorptiometry data from the National Health and Nutrition Examination Survey 1999–2004. J. Am. Geriatr. Soc. 61, 974–980 (2013). This study applies multiple definitions of sarcopenic obesity on a cohort of American adults and emphasizes the varied prevalences of this disorder. sourceNot checked — no full text of the source

Feasible anthropometric indices used as surrogates for adiposity, including BMI and waist circumference, have poor sensitivity.

“Feasible anthropometric indices as surrogates for adiposity, including BMI and waist circumference, have poor sensitivity.”

The analysis showed that definitions for sarcopenia were highly dependent on mathematical thresholds, reference populations and muscle mass definitions.

“The analysis showed that definitions for sarcopenia were highly dependent on mathematical thresholds, reference populations and muscle mass definitions.”

• cites [178] Batsis, J. A. et al. Variation in the prevalence of sarcopenia and sarcopenic obesity in older adults associated with different research definitions: dual-energy X-ray absorptiometry data from the National Health and Nutrition Examination Survey 1999–2004. J. Am. Geriatr. Soc. 61, 974–980 (2013). This study applies multiple definitions of sarcopenic obesity on a cohort of American adults and emphasizes the varied prevalences of this disorder. sourceNot checked — no full text of the source

Sarcopenic obesity is associated with an increased risk of incident disability over 8 years compared with healthy body composition (RR 2.63, 95% CI 1.19-5.85).

“sarcopenic obesity was associated with a relative risk of incident disability over 8 years that was 2.63 (95% CI 1.19–5.85)”

• cites [191] Baumgartner, R. N. et al. Sarcopenic obesity predicts instrumental activities of daily living disability in the elderly. Obes. Res. 12, 1995–2004 (2004). This study highlights the synergistic problems of sarcopenia and obesity that lead to impairments in instrumental activities of daily living. sourceNot checked — no full text of the source

Low muscle strength defined by FNIH criteria with elevated BMI is not associated with differences in metabolic components among postmenopausal women aged 55-75 years.

“low muscle strength (as defined by the FNIH criteria) with an elevated BMI was not associated with differences in metabolic components among groups of postmenopausal women aged 55–75 years217”

• cites [217] Aubertin-Leheudre, M., Lord, C., Goulet, E. D., Khalil, A. & Dionne, I. J. Effect of sarcopenia on cardiovascular disease risk factors in obese postmenopausal women. Obesity (Silver Spring) 14, 2277–2283 (2006). sourceNot checked — no full text of the source

Sarcopenic obesity defined by low appendicular lean mass normalized for height2 and increased BMI is associated with unfavourable scores on the Medical Outcomes Survey.

“Sarcopenic obesity (as defined by low appendicular lean mass normalized for height2 and increased BMI) was associated with unfavourable scores on the Medical Outcomes Survey234.”

• cites [234] Messier, V. et al. Metabolic profile and quality of life in class I sarcopenic overweight and obese postmenopausal women: a MONET study. Appl. Physiol. Nutr. Metab. 34, 18–24 (2009). sourceNot checked — no full text of the source

Mortality is significantly elevated in people with sarcopenic obesity defined using muscle strength with waist circumference (HR 1.23, 95% CI 1.09-1.38).

“muscle strength with waist circumference (HR 1.23, 95% CI 1.09–1.38)230”

• cites [230] Tian, S. & Xu, Y. Association of sarcopenic obesity with the risk of all-cause mortality: a meta-analysis of prospective cohort studies. Geriatr. Gerontol. Int. 16, 155–166 (2016). sourceNot checked — no full text of the source

A recent meta-analysis found that mortality was highest in patients with sarcopenic obesity (HR 1.24, 95% CI 1.12-1.37) compared with healthy individuals.

“a recent meta-analysis found that mortality was highest in patients with sarcopenic obesity (HR 1.24, 95% CI 1.12–1.37) compared with healthy individuals”

• cites [230] Tian, S. & Xu, Y. Association of sarcopenic obesity with the risk of all-cause mortality: a meta-analysis of prospective cohort studies. Geriatr. Gerontol. Int. 16, 155–166 (2016). sourceNot checked — no full text of the source

Sarcopenic obesity defined by muscle mass and BMI ≥25 kg/m2 has significant positive associations with insulin resistance as defined by HOMA scores and triglycerides.

“had significant positive associations with insulin resistance as defined by HOMA scores and triglycerides215”

• cites [215] Chung, J. Y., Kang, H. T., Lee, D. C., Lee, H. R. & Lee, Y. J. Body composition and its association with cardiometabolic risk factors in the elderly: a focus on sarcopenic obesity. Arch. Gerontol. Geriatr. 56, 270–278 (2013). sourceNot checked — no full text of the source

Spine and total BMD are lower in individuals who are sarcopenic obese and dynapenic obese than in individuals with obesity alone.

“spine and total BMD were lower in individuals who were sarcopenic obese and dynapenic obese than in individuals with obesity alone220”

• cites [220] Scott, D. et al. Associations of sarcopenic obesity and dynapenic obesity with bone mineral density and incident fractures over 5–10 years in community-dwelling older adults. Calcif. Tissue Int. 99, 30–42 (2016). sourceNot checked — no full text of the source

Sarcopenic obesity defined by muscle mass assessed by bioelectrical impedance and percentage of body fat is associated with increased mortality (HR 1.29, 95% CI 1.03-1.60).

“Sarcopenic obesity (defined by muscle mass assessed by bioelectrical impedance and percentage of body fat) was associated with an increased mortality (HR 1.29, 95% CI 1.03–1.60)230.”

• cites [230] Tian, S. & Xu, Y. Association of sarcopenic obesity with the risk of all-cause mortality: a meta-analysis of prospective cohort studies. Geriatr. Gerontol. Int. 16, 155–166 (2016). sourceNot checked — no full text of the source

Sarcopenic obesity is associated with higher risk of radiographic knee osteoarthritis (OR 3.51, 95% CI 2.15-5.75) than non-sarcopenic obesity.

“Individuals with sarcopenic obesity have a higher risk (OR 3.51, 95% CI 2.15–5.75) of radiographic knee osteoarthritis218 than individuals in the non-sarcopenic obesity group.”

• cites [218] Lee, S., Kim, T. N. & Kim, S. H. Sarcopenic obesity is more closely associated with knee osteoarthritis than is nonsarcopenic obesity: a cross-sectional study. Arthritis Rheum. 64, 3947–3954 (2012). sourceNot checked — no full text of the source

Mortality is significantly elevated in people with sarcopenic obesity defined using mid-arm circumference (HR 1.46, 95% CI 1.23-1.73).

“mortality was significantly elevated in people with sarcopenic obesity, which was defined using mid-arm circumference (HR 1.46, 95% CI 1.23–1.73)”

• cites [230] Tian, S. & Xu, Y. Association of sarcopenic obesity with the risk of all-cause mortality: a meta-analysis of prospective cohort studies. Geriatr. Gerontol. Int. 16, 155–166 (2016). sourceNot checked — no full text of the source

Low quadriceps strength is associated with increased mortality.

“low quadriceps strength was associated with increased mortality231”

• cites [231] Newman, A. B. et al. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J. Gerontol. A Biol. Sci. Med. Sci. 61, 72–77 (2006). This study demonstrates the importance of muscle strength as opposed to muscle mass as a key determinant of mortality. sourceNot checked — no full text of the source

Low handgrip strength with high waist circumference and/or BMI is significantly associated with elevated levels of IL-6, C-reactive protein and IL-1.

“low handgrip strength and high waist circumference and/or BMI were significantly associated with elevated levels of IL-6, C-reactive protein and IL-1 (REF57)”

• cites [57] Schrager, M. A. et al. Sarcopenic obesity and inflammation in the InCHIANTI study. J. Appl. Physiol. (1985) 102, 919–925 (2007). This is an epidemiological study that shows that obesity directly affects inflammation and negatively affects muscle strength. sourceNot checked — no full text of the source

Among individuals with sarcopenic obesity, resistance training produced the greatest improvements in strength compared with aerobic, combined aerobic and resistance, and control.

“individuals in the resistance training group had the greatest improvements in strength”

• cites [248] Chen, H. T., Chung, Y. C., Chen, Y. J., Ho, S. Y. & Wu, H. J. Effects of different types of exercise on body composition, muscle strength, and IGF-1 in the elderly with sarcopenic obesity. J. Am. Geriatr. Soc. 65, 827–832 (2017). sourceNot checked — no full text of the source

Sarcopenia defined using EWGSOP criteria is associated with increased incidence of long-term care certification.

“A population-based cohort study that defined sarcopenia using the EWGSOP criteria found an increased incidence of long-term care certification in patients with sarcopenia239.”

• cites [239] Akune, T. et al. Incidence of certified need of care in the long-term care insurance system and its risk factors in the elderly of Japanese population-based cohorts: the ROAD study. Geriatr. Gerontol. Int. 14, 695–701 (2014). sourceNot checked — no full text of the source

In a pilot study of patients with sarcopenic obesity, high-speed circuit training was associated with nonsignificant improvements between groups in short performance physical battery (mean difference 1.1, 95% CI -0.1 to 2.4; P = 0.08).

“High-speed circuit training was associated with nonsignificant improvements between groups in short performance physical battery (mean difference 1.1, 95% CI–0.1 to 2.4; P = 0.08)”

• cites [289] Balachandran, A., Krawczyk, S. N., Potiaumpai, M. & Signorile, J. F. High-speed circuit training versus hypertrophy training to improve physical function in sarcopenic obese adults: a randomized controlled trial. Exp. Gerontol. 60, 64–71 (2014). sourceNot checked — no full text of the source

In a pilot study of patients with sarcopenic obesity, high-speed circuit training was associated with improvements in power (mean difference 158 W, 95% CI 2-315; P = 0.01).

“power (mean difference 158 W, 95% CI 2–315; P = 0.01)”

• cites [289] Balachandran, A., Krawczyk, S. N., Potiaumpai, M. & Signorile, J. F. High-speed circuit training versus hypertrophy training to improve physical function in sarcopenic obese adults: a randomized controlled trial. Exp. Gerontol. 60, 64–71 (2014). sourceNot checked — no full text of the source

Improved insulin sensitivity is due, in part, to the distribution of adiponectin across various tissues and an upregulation in the expression of its receptor.

“These data suggest that improved insulin sensitivity is due, in part, to the distribution of adiponectin across various tissues and an upregulation in the expression of its receptor.”

High-intensity resistance training combined with short resting intervals improves body composition, muscle and functional performance in men aged 68 ± 4.1 years.

“High-intensity resistance training combined with short resting intervals improves body composition, muscle and functional performance in men aged 68 ± 4.1 years286.”

• cites [286] Villanueva, M. G., Lane, C. J. & Schroeder, E. T. Short rest interval lengths between sets optimally enhance body composition and performance with 8 weeks of strength resistance training in older men. Eur. J. Appl. Physiol. 115, 295–308 (2015). sourceNot checked — no full text of the source

Increased muscle mass and reduced total and visceral fat over an 8-week intervention were observed in predominantly female individuals, mean age 69 years, with sarcopenic obesity engaged in resistance training.

“Increased muscle mass and reduced total and visceral fat over an 8-week intervention were observed in predominantly female individuals, whose mean age was 69 years, with sarcopenic obesity engaged in resistance training248.”

• cites [248] Chen, H. T., Chung, Y. C., Chen, Y. J., Ho, S. Y. & Wu, H. J. Effects of different types of exercise on body composition, muscle strength, and IGF-1 in the elderly with sarcopenic obesity. J. Am. Geriatr. Soc. 65, 827–832 (2017). sourceNot checked — no full text of the source

High-speed resistance training over 12 weeks induced greater improvements in muscle power and functional capacity than low-speed training.

“High-speed resistance training over 12 weeks induced greater improvements in muscle power and functional capacity than low-speed training287.”

• cites [287] Ramirez-Campillo, R. et al. High-speed resistance training is more effective than low-speed resistance training to increase functional capacity and muscle performance in older women. Exp. Gerontol. 58, 51–57 (2014). sourceNot checked — no full text of the source

A low-fat diet without exercise has a detrimental effect on appendicular lean mass.

“Percent weight loss from appendicular lean mass dropped markedly more in the low-fat and no exercise group than in the other groups, suggesting that this intervention has a detrimental effect on appendicular lean mass312.”

• cites [312] Wood, R. J. et al. Preservation of fat-free mass after two distinct weight loss diets with and without progressive resistance exercise. Metab. Syndr. Relat. Disord. 10, 167–174 (2012). sourceNot checked — no full text of the source

Calorie restriction alters bone metabolism and causes hip bone mineral density loss without lumbar spine effects, even after four months of restriction.

“Calorie restriction alters bone metabolism, resulting in the loss of BMD in the hip without effects on lumbar spine318, even after a 4-month restriction319.”

• cites [318] Zibellini, J. et al. Does diet-induced weight loss lead to bone loss in overweight or obese adults? A systematic review and meta-analysis of clinical trials. J. Bone Miner. Res. 30, 2168–2178 (2015). sourceNot checked — no full text of the source
• cites [319] Soltani, S., Hunter, G. R., Kazemi, A. & Shab-Bidar, S. The effects of weight loss approaches on bone mineral density in adults: a systematic review and meta-analysis of randomized controlled trials. Osteoporos. Int. 27, 2655–2671 (2016). sourceNot checked — no full text of the source

Levels of adiponectin were elevated following a multicomponent, randomized lifestyle intervention study that investigated the mRNA expression of adiponectin and its receptor in skeletal muscle in adults with impaired glucose tolerance aged ≥60 years with BMI 30-40 kg/m2.

“Levels of adiponectin were also elevated following a multicomponent, randomized lifestyle intervention study that investigated the mRNA expression of adiponectin and its receptor in skeletal muscle in adults with impaired glucose tolerance who were aged ≥60 years and had a BMI of 30–40 kg/m2 (REF306).”

• cites [306] O’Leary, V. B. et al. Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults. Am. J. Physiol. Endocrinol. Metab. 293, E421–E427 (2007). sourceNot checked — no full text of the source

A review of 52 studies reported that loss of fat-free mass as a proportion of overall weight was attenuated after combining exercise with calorie restriction.

“A review of 52 studies reported that loss of fat-free mass as a proportion of overall weight was attenuated after combining exercise with calorie restriction298.”

• cites [298] Weinheimer, E. M., Sands, L. P. & Campbell, W. W. A systematic review of the separate and combined effects of energy restriction and exercise on fat-free mass in middle-aged and older adults: implications for sarcopenic obesity. Nutr. Rev. 68, 375–388 (2010). This is a systematic review assessing the effects of energy restriction and exercise on fat-free mass and suggests that exercise is an effective tool in combating sarcopenia-induced weight loss. sourceNot checked — no full text of the source

A meta-analysis showed that aerobic exercise and resistance were useful tools to preserve fat-free mass in adults aged ≥50 years who were engaged in a moderate energy restriction-induced weight loss programme.

“A meta-analysis showed that aerobic exercise and resistance were useful tools to preserve fat-free mass in adults aged ≥50 years who were engaged in a moderate energy restriction-induced weight loss programme298.”

• cites [298] Weinheimer, E. M., Sands, L. P. & Campbell, W. W. A systematic review of the separate and combined effects of energy restriction and exercise on fat-free mass in middle-aged and older adults: implications for sarcopenic obesity. Nutr. Rev. 68, 375–388 (2010). This is a systematic review assessing the effects of energy restriction and exercise on fat-free mass and suggests that exercise is an effective tool in combating sarcopenia-induced weight loss. sourceNot checked — no full text of the source

In men with metabolic syndrome and a mean age of 59 years, a low-fat diet without progressive resistance exercise produced greater appendicular lean mass loss than other diet and exercise groups.

“Percent weight loss from appendicular lean mass dropped markedly more in the low-fat and no exercise group than in the other groups, suggesting that this intervention has a detrimental effect on appendicular lean mass312.”

• cites [312] Wood, R. J. et al. Preservation of fat-free mass after two distinct weight loss diets with and without progressive resistance exercise. Metab. Syndr. Relat. Disord. 10, 167–174 (2012). sourceNot checked — no full text of the source

Yoga has been shown to improve mobility in participants 60 years of age and older, with no restriction on their characteristics, whose follow-up ranged from 8 to 24 weeks.

“yoga has been shown to improve mobility in participants 60 years of age and older, with no restriction on their characteristics, whose follow-up ranged from 8 to 24 weeks (total duration 8–36 hours of yoga)293”

• cites [293] Youkhana, S., Dean, C. M., Wolff, M., Sherrington, C. & Tiedemann, A. Yoga-based exercise improves balance and mobility in people aged 60 and over: a systematic review and meta-analysis. Age Ageing 45, 21–29 (2016). sourceNot checked — no full text of the source

In patients with knee osteoarthritis, weight training combined with walking three times a week for 1 hour does not have any significant effect on levels of TNF, IL-6 or C-reactive protein.

“in patients with knee osteoarthritis, weight training combined with walking three times a week for 1 hour does not have any significant effect on levels of TNF, IL-6 or C-reactive protein307”

• cites [307] Nicklas, B. J. et al. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am. J. Clin. Nutr. 79, 544–551 (2004). This is an early trial suggesting that resistance training is important for improving body composition and muscle strength in elderly individuals who are obese, an effect which is improved with caloric restriction. sourceNot checked — no full text of the source

Up to 1,200 mg supplemental calcium per day and 800-1,000 IU per day of vitamin D3 are needed to minimize weight loss-induced bone mineral density reduction.

“Conventional strategies to minimize the effect of weight loss on bone metabolism, including up to 1,200 mg supplemental calcium per day and 800–1,000 international units (IU) per day of vitamin D3, are needed to minimize the risk of weight loss-induced BMD reduction329.”

• cites [329] Moyer, V. A. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 158, 691–696 (2013). sourceNot checked — no full text of the source

Three years of testosterone administration in patients with low testosterone increased lean mass by 0.9 kg (95% CI 0.5-1.4; P<0.001).

“Three years of testosterone administration in patients with low levels of testosterone resulted in an increase in lean mass (0.9 kg, 95% CI 0.5–1.4; P < 0.001)412.”

• cites [412] Storer, T. W. et al. Effects of testosterone supplementation for 3 years on muscle performance and physical function in older men. J. Clin. Endocrinol. Metab. 102, 583–593 (2017). sourceNot checked — no full text of the source

Augmenting squatting exercises with whole-body vibration therapy failed to improve muscle mass in younger men aged 18-30 years.

“Augmenting existing squatting exercises with whole-body vibration therapy failed to improve muscle mass in younger men aged 18–30 years379.”

• cites [379] Lamont, H. S. et al. Effects of a 6-week periodized squat training with or without whole-body vibration upon short-term adaptations in squat strength and body composition. J. Strength Cond. Res. 25, 1839–1848 (2011). sourceNot checked — no full text of the source

Testosterone supplementation promotes IGF1 mRNA and protein expression, increasing lean mass through increased muscle protein synthesis.

“Supplementation with testosterone promotes IGF1 mRNA and protein expression, leading to increased lean mass through increased muscle protein synthesis52.”

• cites [52] Ferrando, A. A. et al. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am. J. Physiol. Endocrinol. Metab. 282, E601–E607 (2002). sourceNot checked — no full text of the source

The safety and efficacy of bariatric surgery in sarcopenic obesity is unknown apart from one study of gastric bypass and sleeve gastrectomy.

“Its safety and efficacy in sarcopenic obesity is unknown other than one study that evaluated the influence of sarcopenic obesity on gastric bypass and sleeve gastrectomy results393.”

• cites [393] Mastino, D. et al. Bariatric surgery outcomes in sarcopenic obesity. Obes. Surg. 26, 2355–2362 (2016). sourceNot checked — no full text of the source

Phentermine minimally alters lean mass.

“Phentermine minimally alters lean mass386.”

• cites [386] Cordero-MacIntyre, Z. R. et al. Effect of a weight-reduction program on total and regional body composition in obese postmenopausal women. Ann. NY Acad. Sci. 904, 526–535 (2000). sourceNot checked — no full text of the source

Another trial found testosterone treatment improved stair-climbing power and strength.

“Another trial of testosterone treatment found improved stair-climbing power and strength351.”

• cites [351] Travison, T. G. et al. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J. Gerontol. A Biol. Sci. Med. Sci. 66, 1090–1099 (2011). sourceNot checked — no full text of the source

Healthy men with reduced testosterone had no improvements in muscle strength or mobility after six months of supplementation.

“Healthy men with reduced levels of testosterone had no improvements in muscle strength or mobility after 6 months of supplementation350.”

• cites [350] Emmelot-Vonk, M. H. et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 299, 39–52 (2008). sourceNot checked — no full text of the source

Androgen therapy reduces fat mass by 1.78%.

“Androgen therapy also reduces fat mass (−1.78%).”

With ageing, muscle strength often drops before muscle mass.

“With ageing, muscle strength often drops before muscle mass73.”

• cites [73] Goodpaster, B. H. et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J. Gerontol. A Biol. Sci. Med. Sci. 61, 1059–1064 (2006). This study shows that loss of strength with ageing is much more rapid than the concomitant loss of muscle mass, suggesting a decline in muscle quality. sourceNot checked — no full text of the source

Compared with controls, patients treated with lorcaserin had greater fat mass loss than lean mass loss.

“When compared with controls, patients treated with lorcaserin had greater fat mass loss than lean mass loss382.”

• cites [382] Apovian, C., Palmer, K., Fain, R., Perdomo, C. & Rubino, D. Effects of lorcaserin on fat and lean mass loss in obese and overweight patients without and with type 2 diabetes mellitus: the BLOSSOM and BLOOM-DM studies. Diabetes Obes. Metab. 18, 945–948 (2016). sourceNot checked — no full text of the source

Testosterone potentially augments diet-induced fat mass loss in individuals with BMI ≥30 kg/m2 and low testosterone.

“Testosterone potentially augments diet-induced loss of fat mass in individuals with BMI ≥30 kg/m2 and low testosterone levels.”

Testosterone plus growth hormone in older men aged 65-80 years with normal testosterone levels produced greater lean mass improvements than either treatment alone.

“Therapy with testosterone and GH in older men aged 65–80 years with normal testosterone levels resulted in greater improvements in lean mass with both treatments than with either alone56,408.”

• cites [56] Giannoulis, M. G., Martin, F. C., Nair, K. S., Umpleby, A. M. & Sonksen, P. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocr. Rev. 33, 314–377 (2012). sourceNot checked — no full text of the source
• cites [408] Giannoulis, M. G. et al. The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. J. Clin. Endocrinol. Metab. 91, 477–484 (2006). sourceNot checked — no full text of the source

The nonlinear relationship between mass and function suggests that hypertrophy rather than muscle fibre hyperplasia occurs without neuronal plasticity.

“The nonlinear relationship between mass and function suggests that hypertrophy rather than muscle fibre hyperplasia materializes without neuronal plasticity.”

Testosterone deficiency can impair muscle adaptation to exercise through reduced IGF1 expression and increased inflammatory cytokines.

“Testosterone deficiency can impair muscle adaptation to exercise owing to reduced expression of IGF1 and increased inflammatory cytokines.”

Anamorelin, an oral ghrelin analogue, is effective for improving appetite in patients with cancer cachexia.

“Anamorelin, an oral ghrelin analogue, is effective for improving appetite in patients with cancer cachexia and might hold promise in patients with sarcopenic obesity.”

Adverse effects of anamorelin are no different from placebo.

“Adverse effects are no different than with placebo.”

Vitamin K might mitigate bone loss after intentional weight loss by inhibiting bone resorption and osteoclast formation.

“Vitamin K might have a role in mitigating bone loss following intentional weight loss by inhibiting bone resorption450 and osteoclast formation451.”

• cites [450] Sato, Y., Honda, Y., Kuno, H. & Oizumi, K. Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D− and K-deficient stroke patients. Bone 23, 291–296 (1998). sourceNot checked — no full text of the source
• cites [451] Schurgers, L. J. & Vermeer, C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis 30, 298–307 (2000). sourceNot checked — no full text of the source