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Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.
Deng, N, Reyes-Uribe, L, Fahrmann, JF, Thoman, WS, Munsell, MF, Dennison, JB, Murage, E, Wu, R, Hawk, ET, Thirumurthi, S, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;29(21):4361-4372
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Lynch syndrome (LS) is a genetic disorder conferring a 60% lifetime risk of developing colorectal cancer (CRC). Exercise is associated with a reduction in CRC risk in the general population, potentially mediated via modulation of inflammation. The aim of this non-randomised, controlled trial was to test whether an intervention consisting of 3 x 45-minute cycling classes per week for 12 months affects inflammatory factors (prostaglandin E2, PGE2) in the colorectal mucosa and blood and whether this intervention is feasible in LS carriers. The control group received usual care with one session of exercise counselling. Of 60 patients invited to join the study, 21 (35%) agreed to take part. Of the 11 participants in the intervention group, 9 (81.2%) completed the study with an average adherence to the intervention of 51.3%, compared to 7/10 completing in the control group. VO2 peak (maximal aerobic capacity) increased significantly in the intervention group, compared to the control group over the 12 months. Patients in the intervention group also had a significant reduction in colonic and systemic PGE2 levels compared to controls following intervention. Changes in gene expression which may reflect an increased immune surveillance of the colon were also observed in the intervention group. The authors concluded that the study confirmed that exercise may modulate inflammation in the colonic mucosa in patients at high risk of CRC and that further randomised studies are necessary to confirm the potential benefits of exercise for patients with LS.
Abstract
PURPOSE Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.
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Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
Gómez-Pérez, AM, Ruiz-Limón, P, Salas-Salvadó, J, Vioque, J, Corella, D, Fitó, M, Vidal, J, Atzeni, A, Torres-Collado, L, Álvarez-Sala, A, et al
Gut microbes. 2023;15(1):2223339
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. The aim of this study was to evaluate the changes in the microbiota associated with changes in biochemical markers of NAFLD/NASH after an intervention. This substudy was conducted in the frame of the PREDIMED-Plus study, a 6-year, multicentre, randomised clinical trial for primary prevention of cardiovascular disease (CVD) conducted in men aged 55–75 years and women aged 60–75 years with overweight or obesity and metabolic syndrome. Results showed a relationship between liver disease biochemical indexes changes and gut microbiota changes within a context of a Mediterranean lifestyle. In fact, two noninvasive scores for liver steatosis and liver fibrosis, usually used in clinical practice, could differentiate gut microbiota populations. Authors conclude that their findings highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
Abstract
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.
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An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.
Konieczna, J, Ruiz-Canela, M, Galmes-Panades, AM, Abete, I, Babio, N, Fiol, M, Martín-Sánchez, V, Estruch, R, Vidal, J, Buil-Cosiales, P, et al
JAMA network open. 2023;6(10):e2337994
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The Mediterranean diet (MedDiet), which focuses on whole grains, lean meat, fruits, vegetables, and low amounts of minimally processed foods has been shown in previous research to improve body composition and decrease fat storage around the middle. This randomised control trial of 1556 older adults aimed to determine the effects of combining a 30% lower energy version of the MedDiet in combination with physical exercise on body composition. After 3 years, the results showed that compared to a normal MedDiet without exercise, the lower energy version in combination with exercise improved body composition by decreasing total fat, and the fat stored around the organs and increasing muscle mass. However, benefits were more pronounced after 1 year and decreased slightly at 3 years. It was concluded that a low energy MedDiet in combination with physical activity may be able to improve the body composition of overweight and older adults with obesity. This study could be used by healthcare professionals to recommend a low energy MedDiet to older adults to promote weight loss, whilst attenuating muscle loss associated with ageing.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The addition of exercise to an energy-reduced diet, which focuses on whole grains, healthy fats, lean protein, and fruits and vegetables can emphasise positive effects on body composition in older adults.
- However, there is a loss of lean mass associated with this type of diet (contrary to author conclusions) and measures should be taken to monitor and increase protein intake to prevent or limit this loss.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study aimed to determine the long-term effects of an energy reduced MedDiet in combination with physical activity on body composition.
Methods
- This is a predetermined 3-year interim analysis of a 6-year single-blind, randomised control trial of 1556 individuals aged 55-75 who are overweight or obese with metabolic syndrome.
- 760 individuals on 30% energy reduced MedDiet with limited processed foods, plus 45 minutes walking 6 days per week and behavioural and motivational support. [Intervention group]
- 761 on standard MedDiet without physical activity. [Control]
Results
Within group comparisons showed that individuals in the intervention group lost (P value represents baseline vs year 3):
- Total fat mass percentage (1-year vs baseline, −1.14%; 95% CI, −1.32% to −0.96%; 3-year vs baseline, −0.52%; 95% CI, −0.71% to −0.33% P=<0.001)
- Absolute visceral fat (1-year vs baseline, −154 g; 95% CI, −191 to −116 g; 3-year vs baseline, −75.1 g, 95% CI, −115 to −35.3 g P=<0.001)
- Absolute total fat after 1 year (mean change at 1 year vs baseline, −1677 g; 95% CI, −1930 to −1424 g) but regained some at year 3 (mean change at 3 years vs baseline, −1018 g; 95% CI, −1280 to −756 g P=<0.001)
- Absolute lean mass (mean change at 1 year vs baseline −300 g; 95% CI, −439 to −162 g) with further losses at year 3 (−626 g; 95% CI, −770 to −483 g P=0.001).
Within group comparisons also showed significantly increased:
- Total lean mass percentage, which was greater at year 1 than year 3 (1-year vs baseline, 1.07%; 95%CI, 0.90%-1.25%; 3-year vs baseline, 0.47%; 95% CI, 0.29%-0.65% P=<0.001).
As a result of total fat loss and some lean mass in the intervention group, the lean:fat mass ratio improved and was unchanged in the control group (between group differences (P=<0.001).
Compared to women, men may find the MedDiet + exercise more beneficial as it was shown that body composition changes were slightly more pronounced in men.
Conclusion
An energy-reduced MedDiet plus exercise emphasised positive changes to body composition compared to standard MedDiet in older adults who are overweight or have obesity.
Clinical practice applications:
- The recommendation of a reduced energy MedDiet in combination with physical activity to older people who are overweight or obese may improve body composition.
- Although lean mass loss slowed between years 1 and 3, other practices should be employed to attenuate the loss of lean mass associated with an energy-reduced MedDiet and ageing.
Considerations for future research:
- The research has not yet concluded but when it does, it will address the incidence of cardiovascular disease along with body composition changes.
- It will also look at long-term effects of the diet to determine longevity.
- Future research could focus on how to limit lean mass loss through the possibility of changing the type of exercise that accompanies the MedDiet.
Abstract
IMPORTANCE Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN89898870.
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Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.
Scheffers, LE, Vos, IK, Utens, EMWJ, Dieleman, GC, Walet, S, Escher, JC, van den Berg, LEM
Journal of pediatric gastroenterology and nutrition. 2023;77(2):214-221
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Inflammatory bowel disease (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory diseases of the gastrointestinal tract, characterised by periods of remission and relapse of symptoms. The aim of this study was to assess the effects of a tailored lifestyle intervention on physical fitness (maximal and submaximal exercise capacity, strength, and core stability), the patient-reported outcomes (quality of life, fatigue, and fear), clinical disease activity, and nutritional status. This study was a prospective single-centre randomised semi-crossover-controlled trial. Children were randomized into group A (start exercise) or group B (start control period). Results showed improved physical fitness, quality of life, and parent-reported fatigue. Additionally, a combination of lower clinical disease activity scores accompanied by fewer IBD symptoms suggests positive effects on intestinal inflammation. Authors concluded that based on the findings of their study, children and adolescents with IBD should be motivated and supported to acquire and maintain a healthy lifestyle.
Expert Review
Conflicts of interest:
None
Take Home Message:
- IBD is a chronic inflammatory disease of the gastrointestinal tract, characterised by periods of abdominal pain, severe diarrhoea, and fatigue
- This clinical trial suggests that a 12-week program of physical training plus personalised healthy dietary advice may improve physical fitness, quality of life, and fatigue in children with IBD.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomised semi-crossover controlled trial was conducted to investigate the impact of a 12-week lifestyle program (3 physical training sessions per week plus personalised healthy dietary advice) in children with Inflammatory Bowel Disease (IBD).
Method
- Sixteen children with a median age of 15 [IQR: 12–16]) that were diagnosed with IBD (CD, UC, or IBD-unclassified) were randomized to group A (start exercise) or group B (start control period). Group A started the intervention immediately after the first assessment and did not have a control period. Group B started after a control period (this was planned to last for 6 weeks but due to the COVID-19 lockdown extended to 6 months)
- The lifestyle intervention lasted 12 weeks and consisted of 3 physiotherapist-supervised training sessions per week, lasting 60 minutes each. In addition, all participants received a recommended caloric intake per day based on measured rest energy expenditure and a brochure regarding healthy diet in children
- Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (faecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition)
- A total of 15 out of 16 participants (93%) completed the program, one patient dropped out after one training session due to motivational problems.
Results
The primary findings of this study were as follows:
- While medical treatment remained unchanged, Paediatric Crohn's Disease Activity Index decreased versus the control period (15 [3–25] vs 2.5 [0–5], P = 0.012)
- The number of patients in clinical remission increased from 5 to 12 (P < 0.001), compared to the control period
- Quality of life (IMPACT-III) improved on 4 out of 6 domains and the total score (+13 points) versus the control period including a large improvement in bowel-related symptoms, P= 0.029)
- Fecal calprotectin decreased, but not compared to the control period, mainly due to relatively large intra-patient fluctuations (400 μg/g [57.1–1662.7] vs 128 μg/g [23.8–642.3], P = 0.016)
- Parents reported an improvement in the quality of life versus the control period on the child health questionnaire and total fatigue score (PedsQoL • Multidimensional Fatigue Scale) (+14 points, P = 0.048)
- Walking distance improved after the 12-week program, compared to the control period (P = 0.001).
Conclusion
This study revealed that a 12-week physical training program and personalised dietary advice improved bowel symptoms, quality of life, and fatigue in children with IBD.
Clinical practice applications:
- The mechanism behind the anti-inflammatory effects of exercise has not been clarified
- Multiple theories have been suggested in previously published studies such as a reduced release of adipokines due to less visceral fat, increased secretion of anti-inflammatory cytokines such as interleukin (IL)-6, and reduced transient stool time
- This clinical trial demonstrated that a 12-week program of physical training sessions plus personalised healthy dietary advice resulted in improved physical fitness, quality of life, and parent-reported fatigue.
Considerations for future research:
- A sample size calculation was not provided in the study report and it is therefore assumed that the sample size of 16 children in this trial was too small to draw a definite conclusion. A larger study over a longer period is therefore needed across diverse age and ethnic population groups to draw better conclusions
- This study did not measure mucosal inflammation before and after the intervention due to the invasive nature of the procedure. It would however be useful that future research investigate this to gain more insight into the effect of lifestyle interventions on IBD.
Abstract
OBJECTIVES Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.
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Are inflammatory markers associated with sarcopenia-related traits in older adults with sarcopenia? - A cross-sectional analysis of the ENHANce study.
Dupont, J, Vercauteren, L, Amini, N, Lapauw, L, De Schaepdryver, M, Poesen, K, Dedeyne, L, Verschueren, S, Tournoy, J, Koppo, K, et al
Experimental gerontology. 2023;178:112196
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Sarcopenia is a muscle disease, characterised by loss of muscle mass and function, leading to ‘muscle failure’. Primary sarcopenia is age-driven and one of the major mechanisms behind the onset and progression of sarcopenia is the chronic low grade inflammatory state related with ageing, the so-called ‘Inflammageing’. The aim of this study was to explore the levels of inflammatory markers (CRP, albumin, IL-1β, IL-6, IL-8 and TNF-α) in older adults with sarcopenia. This study was an exploratory, secondary, cross-sectional analysis. In total, 40 older adults (15 men and 25 women) with probable, confirmed, or severe sarcopenia were included. Results showed subclinical low levels of inflammatory markers in older adults suffering from sarcopenia, compatible with age-related Inflammageing. Positive associations were found between the examined inflammatory markers and sarcopenia-related traits. Furthermore, gender had a significant influence on the associations between these inflammatory markers and sarcopenia-related traits. Authors concluded that their findings stress the complexity of the inflammageing-sarcopenia interplay and the importance of not only looking at muscle mass or the sarcopenia construct when researching sarcopenia, but also considering other sarcopenia-related traits and gender in future research.
Abstract
AIMS: To explore the relationship between inflammatory markers and sarcopenia-related traits in sarcopenic older adults. METHODS Baseline data of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study were used for a secondary, exploratory, cross-sectional analysis. ENHANce is a 5-armed triple blinded randomized controlled trial, in older adults (>65y) with sarcopenia defined according to the revised criteria of the European Working Group of Sarcopenia in Older People (EWGSOP2) aiming to assess the effect of combined anabolic interventions (protein supplement, omega-3 supplement and physical exercise) on physical performance, compared to single/placebo interventions. Inflammatory markers C-reactive protein (hs-CRP), albumin, interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α) were assessed at baseline. Spearman's rho (ρ) correlation coefficients were calculated to associate these inflammatory markers with baseline sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass [aLM], gait speed, Short Physical Performance Battery), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS We included 40 sarcopenic subjects (15 men/25 women, age 77.1 ± 6.8 years). Contrary to expectations, the pro-inflammatory IL-1β correlated positively with handgrip strength (ρ: 0.376; p = 0.024) and IL-6 with aLM (ρ: 0.334; p = 0.0433). IL-6 inversely correlated with step count (ρ:-0.358; p = 0.048). Subgroup analysis revealed important gender differences. IL-8 inversely correlated with handgrip strength in women (ρ: -0.425; p = 0.034) but not in men. In contrast, pro-inflammatory cytokines CRP (ρ: -0.615; p = 0.019), IL-6 (ρ: -0.604; p = 0.029) and TNF-α (ρ: -0.615; p = 0.025) inversely correlated with the SF-36 physical component score in men but not in women. CONCLUSION Although Inflammageing might play a role in sarcopenia-related traits, this exploratory study highlights an important role of gender. Future research should take this into account when elucidating the Inflammageing-sarcopenia interplay.
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The influence of vitamin D supplementation and strength training on health biomarkers and chromosomal damage in community-dwelling older adults.
Draxler, A, Franzke, B, Kelecevic, S, Maier, A, Pantic, J, Srienc, S, Cellnigg, K, Solomon, SM, Zötsch, C, Aschauer, R, et al
Redox biology. 2023;61:102640
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Aging is associated with a decline in physiological and physical function resulting in reduced physical activity, all of which are driving factors to the onset of chronic diseases and physical impairment. Older adults are often deficient in micronutrients, specifically vitamin D, which has been shown to have detrimental effects on the immune system, inflammatory and healing processes of fractured bones and also cardiovascular health beyond other musculoskeletal effects. The aim of this study was to investigate the effect of different vitamin D regimens in older individuals during an ongoing strength training period of 10 weeks while receiving vitamin D supplementation at the recommended level of 800 IU per day vs. a single dose of 50.000 IU per month. The data presented in this paper are part of the NutriAging Vitamin D study. The study was a randomised placebo-controlled double-blind trial which recruited one hundred community-dwelling women and men (aged 65–85 years). Participants were randomly allocated into three intervention groups, either the control group, the vitamin D daily (VDD) or the vitamin D monthly group (VDM). Results showed that oxidative stress might have played a role in the detrimental progress on chromosomal stability parameters since the protective effect of GSH (reduced glutathione) was reduced in all study groups at the end of the intervention, but the least reduction occurred in the VDD group. Authors concluded that a supplementation with the recommended dose of 800 IU vitamin D per day might be more advantageous when it comes to chromosomal stability parameters in older, formerly untrained participants undergoing demanding resistance exercise for 10 weeks.
Abstract
Older adults lack of proper physical activity which is often accompanied by vitamin D deficiency. Those factors are known to contribute to health issues in the later years of life. The main goal of this intervention study was to investigate the effect of different vitamin D supplementation strategies for 4 weeks solely or combined with a 10-week strength training program on chromosomal stability in peripheral blood mononuclear cells in community-dwelling older people. One hundred women and men (65-85 years) received either vitamin D3 daily (800 IU), a monthly dose (50.000 IU) or placebo for 17 weeks. All groups received 400 mg calcium daily. The fitness status of the study participants was measured using the 30- second chair stand test, the handgrip strength test and the 6-min walk test. The cytokinesis block micronucleus cytome (CBMN) assay was applied to analyze chromosomal anomalies, including cytotoxic and genotoxic parameters. Changes in antioxidant markers were measured in plasma. Walking distance and chair stand performance improved significantly. Increased levels of the parameters of the CBMN assay were detected for all intervention groups at study end. At baseline micronuclei (MNi) frequency correlated significantly with BMI in both sexes (females: r = 0.369, p = 0.034; males: r = 0.265, p = 0.035), but not with vitamin D serum levels. In females, body fat (r = 0.372, p < 0.001) and functional parameter using the 30-s chair stand test (r = 0.311, p = 0.002) correlated significantly with MNi frequency. Interestingly, not vitamin D supplementation but 10 weeks of resistance training increased MNi frequency indicating elevated chromosomal instability and also adverse effects on antioxidant markers including glutathione and FRAP were detected in the group of community-dwelling older adults.
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The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity.
Levakov, G, Kaplan, A, Yaskolka Meir, A, Rinott, E, Tsaban, G, Zelicha, H, Blüher, M, Ceglarek, U, Stumvoll, M, Shelef, I, et al
eLife. 2023;12
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Obesity is linked to premature brain ageing and subsequent development of diseases such as dementia and Alzheimer’s disease. Weight loss through lifestyle modifications may be able to attenuate brain ageing. This sub-study of 102 individuals from a randomised control trial known as the Dietary Intervention Randomised Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), aimed to determine the effect of 18 months lifestyle modifications and weight loss on brain age. The results showed that a decrease in BMI attenuated brain ageing and that 1% body weight loss reduced brain ageing by 8.9 months. Reduced brain age was also associated with decreased waist circumference and fat mass. Interestingly, reduced consumption of processed foods was also associated with reduced brain age. It was concluded that weight loss can be of benefit to brain health. This study could be used by healthcare professionals to understand that people with obesity are at a higher risk of brain related diseases, and that weight loss may be an effective way to prevent their development.
Abstract
BACKGROUND Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention. METHODS In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age. RESULTS To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months' attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age. CONCLUSIONS Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging. FUNDING The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai). Obesity is linked with the brain aging faster than would normally be expected. Researchers are able to capture this process by calculating a person’s ‘brain age’ – how old their brain appears on detailed scans, regardless of chronological age. This approach also helps to monitor how certain factors, such as lifestyle, can influence brain aging over relatively short time scales. It is not clear whether lifestyle interventions that promote weight loss can help to slow obesity-driven brain aging. To answer this question, Levakov et al. studied 102 individuals who met the criteria for obesity and took part in a lifestyle intervention aimed to improve diet and physical activity levels over 18 months. The participants received a brain scan at the beginning and the end of the program; additional tests and measurements were also conducted at these times to capture other biological processes impacted by obesity, such as liver health. Levakov et al. used the brain scans taken at the start and end of the study to examine the impact of the lifestyle intervention on the aging trajectory. The results revealed that a reduction in body weight of 1% led to the participants’ brain age being nearly 9 months younger than the expected brain age after 18 months. This attenuated aging was associated with changes in other biological measures, such as decreased liver fat and liver enzymes. Increases in liver fat and production of specific liver enzymes were previously shown to negatively impact brain health in Alzheimer’s disease. Finally, examining more closely the food consumption reports completed by participants showed that reduced consumption of processed food, sweets and beverages were linked to attenuated brain aging. The findings show that lifestyle interventions which promote weight loss can have a beneficial impact on the aging trajectory of the brain observed with obesity. The next steps will include determining whether slowing down obesity-driven brain aging results in better clinical outcomes for patients. In addition, the work by Levakov et al. demonstrates a potential strategy to evaluate the success of lifestyle changes on brain health. With global rates of obesity rising, identifying interventions that have a positive impact on brain health could have important clinical, educational and social impacts.
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Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3-5: a randomized controlled trial.
Yang, WC, Hsieh, HM, Chen, JP, Liu, LC, Chen, CH
BMC nephrology. 2023;24(1):372
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Chronic kidney disease (CKD) is a prevalent clinical issue often observed in older adults. Nutritional management has become essential for older adults with CKD. Recent nutritional guidelines have suggested that a low-protein diet (LPD) can be prescribed. The aim of this study was to compare the effects of a regular LPD alone or a 6% LPF combined with a regular LPD prescription on nutrition status, physical performance, and clinical parameter changes in older adults with CKD stages 3–5. This study was a single-centre, two-armed, open-label, parallel, randomised controlled clinical trial. Participants were allocated at a 1:1 ratio - (1) the control group, patients received a regular LPD prescription; (2) the intervention group, patients received a regular LPD prescription with 6% LPF. Results showed that an LPD plus a 6% LPF provided no changes in energy and protein intake while increasing fatty acid and specific micronutrient intake during the 3-month follow-up period. Furthermore, blood urea nitrogen (clinical parameter) was significantly reduced in the intervention group over three months. Authors concluded that an LPD prescription with a 6% LPF can delay physical performance deterioration and increase micronutrient intake in three months compared to LPD education alone in older adults with CKD stages 3–5.
Abstract
BACKGROUND Although combining a low-protein diet (LPD) with oral nutritional supplements increases treatment adherence and nutritional status in patients with chronic kidney disease (CKD), the effect of this combination approach in older adults remains unclear. This study examined the impact of a 6% low-protein formula (6% LPF) with diet counseling in older adults with stage 3-5 CKD. METHODS In this three-month randomized controlled study, 66 patients (eGFR < 60 mL/min/1.73 m2, non-dialysis, over 65 years of age) were randomly assigned to an intervention group (LPD plus a 6% LPF) or control group (LPD alone). The 6% LPF comprised 400 kcal, 6 g of protein, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and various micronutrients. All data were collected at baseline and after three months, including physical performance based on hand grip strength (HGS) and gait speed, nutritional status using Mini Nutritional Assessment-Short Form (MNA-SF) scores, body composition through bioelectrical impedance analysis, and dietary intake from 24-h dietary records. RESULTS This study incorporated 47 participants (median age, 73; median eGFR, 36 ml/min/1.73 m2; intervention group: 24; control group: 23). The intervention group exhibited significant differences in HGS and gait speed, and micronutrient analysis revealed significantly higher monounsaturated fatty acids (MUFA), EPA, DHA, calcium, iron, zinc, copper, thiamine, riboflavin, niacin, B6, B12, and folic acid intake than the control group. MNA-SF scores, macronutrient intake, and body composition did not differ significantly between the two groups. CONCLUSIONS Compared to LPD counseling alone, an LPD prescription with 6% LPF in older adults with CKD stages 3-5 helped relieve physical deterioration and increased micronutrient intake after three months. TRIAL REGISTRATION ClinicalTrials.gov NCT05318014 (retrospectively registered on 08/04/2022).
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Mediterranean Style Dietary Pattern with High Intensity Interval Training in Men with Prostate Cancer Treated with Androgen Deprivation Therapy: A Pilot Randomised Control Trial.
Baguley, BJ, Adlard, K, Jenkins, D, Wright, ORL, Skinner, TL
International journal of environmental research and public health. 2022;19(9)
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The use of androgen deprivation therapy (ADT) has coincided with improvements in disease control and improved overall survivorship in many men treated for prostate cancer. Exercise and nutrition interventions during and/or after ADT are strongly recommended to mitigate or improve body composition and reduce cardiometabolic side effects. The aim of this study was to examine the combined effects of a Mediterranean diet (MED-diet) and high intensity interval training (HIIT) on cardiorespiratory fitness, body composition and quality of life, compared to usual care, in men with prostate cancer treated with ADT. This study is a two-arm randomised controlled trial. Participants (n = 23) were randomly allocated to either an intervention or usual care group in a 1:1 ratio. Results show that for men with prostate cancer undergoing ADT, a MED-diet with HIIT compared to usual care at 20 weeks (i) significantly improved cardiorespiratory fitness relative; (ii) reduced body weight; (iii) maintained lean body mass despite achieving weight loss; (iv) significantly improved vitality and mental health composite, and clinical improvements were seen in prostate-cancer specific quality of life and cancer-related fatigue. Authors conclude that future larger-scale trials examining the MED-diet with HIIT on cardiorespiratory fitness, body composition and quality of life would help to extend the findings of their study.
Abstract
Background: Androgen deprivation therapy (ADT) in prostate cancer has been shown to deteriorate body composition (reduced lean mass and increased body and fat mass) and increase the risk of cardiovascular morbidity. The Mediterranean style dietary pattern (MED-diet) and high intensity interval training (HIIT) may synergistically alleviate these side effects and improve quality of life in men treated with ADT. Methods: Twenty-three men (65.9 ± 7.8 years; body mass index: 29.6 ± 2.7 kg/m2; ADT duration: 33.8 ± 35.6 months) receiving ADT for ≥3 months were randomly assigned (1:1) to 20 weeks of usual care or the MED-diet (10 nutrition consults) with HIIT (4 × 4 min 85−95% heart rate peak, 3× week, starting at 12 weeks). Results: The MED-diet with HIIT significantly improved cardiorespiratory fitness (+4.9 mL·kg−1·min, p < 0.001), and body mass (−3.3 kg, p < 0.001) compared to the usual care group at 20 weeks. Clinically meaningful (≥3 points) improvements were seen in quality of life and cancer-related fatigue after 20 weeks. Conclusions: The MED-diet with HIIT increased cardiorespiratory fitness and reduced body weight in men with prostate cancer treated with ADT. Larger trials determining whether the MED-diet with HIIT translates to cardiovascular benefits are warranted.
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Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial.
Mundell, NL, Owen, PJ, Dalla Via, J, Macpherson, H, Daly, RM, Livingston, PM, Rantalainen, T, Foulkes, S, Millar, J, Murphy, DG, et al
BMJ open. 2022;12(6):e060189
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Androgen deprivation therapy (ADT) for local and advanced prostate cancer (PCa) is effective at reducing androgens, and thus inhibiting tumour progression. However, testosterone reduces the production of a highly neurotoxic protein (amyloid beta peptide 40), which is linked with the development of dementia and Alzheimer’s disease. The aim of this study was to investigate the effects of a multi-component resistance-based exercise programme with daily protein, vitamin D and calcium supplementation on cognitive function compared with usual care in PCa survivors treated with ADT. This study is a secondary analysis of a 12-month single-blinded, two-arm randomised controlled trial. Participants (n = 70) were randomised (1:1 ratio) to either: (a) multi-component exercise intervention including progressive resistance training, body-weight impact and balance exercises, as well as a daily nutritional supplement containing whey protein, calcium and vitamin D, or (b) usual care control receiving 1000 IU vitamin D only. Results show that a multicomponent exercise training and nutritional supplementation intervention did not improve cognitive function in men treated with ADT for PCa compared with usual care. Authors conclude that cognitive decline associated with ADT may mechanistically differ to that of general age-related cognitive declines, thus it is important that future studies also examine other intervention modalities.
Abstract
OBJECTIVES The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT). DESIGN 12-month, two-arm, randomised controlled trial. SETTING University clinical exercise centre. PARTICIPANTS 70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36). INTERVENTION Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation. PRIMARY AND SECONDARY OUTCOME MEASURES Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%). RESULTS Sixty (86%) men completed the trial (Ex + Suppl, n=31; control, n=29). Five (7.1%) men were classified as having mild cognitive impairment at baseline. Median (IQR) adherence to the exercise and supplement was 56% (37%-82%) and 91% (66%-97%), respectively. Ex + Suppl had no effect on cognition at any time. CONCLUSIONS A 12-month multicomponent exercise training and supplementation intervention had no significant effect on cognition in men treated with ADT for prostate cancer compared with usual care. Exercise training adherence below recommended guidelines does not support cognitive health in men treated with ADT for prostate cancer. TRIAL REGISTRATION NUMBER Australian and New Zealand Clinical Trial Registry (ACTRN12614000317695, registered 25/03/2014) and acknowledged under the Therapeutic Goods Administration Clinical Trial Notification Scheme (CT-2015-CTN-03372-1 v1).