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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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Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.
Kviatkovsky, SA, Hickner, RC, Cabre, HE, Small, SD, Ormsbee, MJ
Journal of the International Society of Sports Nutrition. 2023;20(1):2243252
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As we age, collagen degrades, which can result in an increased risk for injuries and pain. Pain management largely focuses on drugs to control inflammation, which can result in side effects. Collagen is the predominant component of connective tissues and supplementation has been shown to have beneficial effects on joint pain and inflammation. This randomised control trial aimed to determine the effect of different doses of collagen over 3 different time periods on measures of pain, function, and mental and physical health in 86 active, middle-aged men and women. The results showed that daily activity was improved when individuals were given 10g/day collagen for at least 6 months. Pain was also improved with this dose for at least 6-months, but only in those who exercised more than 3 hours per week. Mental health improved with 10g/day when given for at least 3-9 months. Physical function was also improved with 20g/day collagen for at least 3-9 months, but only amongst women. It was concluded that 10-20g/day collagen supplementation for at least 6 months may improve pain, functionality, and mental health in healthy, middle-aged men and women. Women may particularly benefit from 20g/day collagen and enhanced effects may be seen when in combination with exercise. This study could be used by healthcare professionals to recommend collagen supplementation to improve joint pain and physical and mental health in combination with exercise.
Abstract
INTRODUCTION Chronic pain affects 19% of adults in the United States, with increasing prevalence in active and aging populations. Pain can limit physical activity and activities of daily living (ADLs), resulting in declined mental and social health. Nutritional interventions for pain currently target inflammation or joint health, but few influence both. Collagen, the most abundant protein in the human body and constituent of the extra cellular matrix, is such a nutraceutical. While there have been reports of reductions in pain with short-term collagen peptide (CP) supplementation, there are no long-term studies specifically in healthy middle-aged active adults. PURPOSE To determine the effects of daily CP consumption over 3, 6, and 9 months on survey measures of pain, function, and physical and mental health using The Knee Injury & Osteoarthritis Outcomes Score (KOOS) and Veterans Rand 12 (VR-12) in middle-aged active adults. METHODS This study was a double-blind randomized control trial with three treatment groups (Placebo, 10 g/d CP, and 20 g/d CP). RESULTS Improvements in ADLs (p = .031, ηp2 = .096) and pain (p = .037, ηp2 = .164) were observed with 10 g/d CP over 6 months, although pain only improved in high frequency exercisers (>180 min/week). Additionally, VR-12 mental component scores (MCS) improved with 10 g/d of CP over 3-9 months (p = .017, ηp2 = .309), while physical component scores (PCS) improved with 20 g/d of CP over 3-9 months, but only in females (p = .013, ηp2= .582). CONCLUSION These findings suggest 10 to 20 g/d of CP supplementation over 6 to 9 months may improve ADLs, pain, MCS, and PCS in middle-aged active adults.
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Predictive metabolites for incident myocardial infarction: a two-step meta-analysis of individual patient data from six cohorts comprising 7897 individuals from the COnsortium of METabolomics Studies.
Nogal, A, Alkis, T, Lee, Y, Kifer, D, Hu, J, Murphy, RA, Huang, Z, Wang-Sattler, R, Kastenmüler, G, Linkohr, B, et al
Cardiovascular research. 2023;119(17):2743-2754
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Heart disease is a major cause of death worldwide. Individuals at risk are usually identified by the presence of diseases such as obesity and diabetes, and lifestyle factors such as smoking. However, there is a new understanding that when the body converts food into energy it creates by-products which might play an important role in the development of heart disease. Better understanding of these may be able to aid the identification of individuals at risk. This analysis of 7897 participants from 6 different cohort studies aimed to determine biomarkers associated with a heart attack. The results showed there were 56 metabolites associated with heart attack, some of which were associated with an increased occurrence and some a decreased occurrence. Most of the identified metabolites were lipids. Metabolites involved in bile acid production and amino acids were also identified. It was concluded that these metabolites may act as an indicator for individuals who are at risk of heart attack, however further research is needed. This study could be used by healthcare professionals to understand that the science behind the use of metabolites to indicate risk for heart attack is developing but still in its infancy.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There are certain lipids and amino acids that are associated with the incidence of MI, but the use of these to identify people at risk of MI is still in its infancy
- Current proven strategies to identify those at risk should take precedence over the measurement, identification and use of metabolites. However, this area of research is of current interest.
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
Individuals at risk of cardiovascular disease are usually identified by the presence of comorbidities (e.g. obesity and diabetes), and lifestyle factors (e.g. smoking). However, there is a new understanding that certain metabolites may be associated with myocardial infarction (MI) and a better understanding of these may be able to aid the identification of individuals at risk. This meta-analysis aimed to determine metabolites associated with a MI.
Methods
- This meta-analysis of 6 cohort studies from the USA and Europe involved 7897 participants
- The primary outcome was the metabolites associated with incident MI
- The secondary outcome was the metabolites associated with prevalent MI
- A total of 1442 metabolites were measured.
Results
- There were 1373 MI cases from the studies
- The results showed that there were 56 metabolites associated with MI, 42 had a direct association and 14 had an inverse relationship
- Most of the identified metabolites were lipids (n=21) and amino acids (n=17)
- Of the lipids, 3-methyladipate and 1-palmitoyl-2-linoleoyl-glycerol (16:0/18:2) were associated with a higher risk of MI (HR estimates ranged from 1.28; 95% confidence interval (CI) = 1.13–1.44, P < 0.001 to 1.21; 95% CI = 1.08–1.35, P = <0.005 respectively)
- Of the amino acids, 4-hydroxyphenylacetate and cystathionine had the largest increase in risk (HR estimates 1.24; 95% CI = 1.11–1.38, P = <0.01 and 1.2; 95% CI = 1.07–1.35, P = <0.01 respectively)
- When the meta-analysis was stratified by race, it showed that out of the 56 metabolites identified, the majority were associated with white individuals (n=41), whereas only 18 were associated with black individuals. Of these, 3 were specific to individuals with an African ancestry.
Conclusion
- It was concluded that certain metabolites and their associated pathways may help to identify individuals at risk for MI before disease onset and lead to better prevention
Clinical practice applications:
- Research into metabolite association with increased risk of MI is still in its infancy and has little merit until we understand the mechanisms involved and the direction of causation
- It does however give an idea of the tools that may be developed in the future that will aid identification and help to develop prevention strategies
- The metabolites associated with MI may be racially specific and further understanding is needed on this. Hence the data should be interpreted with caution.
Considerations for future research:
- Whilst associations are indicative of relationships, they do not identify causation. Future research should focus on the pathways which may link the metabolites with MI
- Identifying these pathways will also help to develop prevention strategies pertinent to specific nutrients
- A better understanding of how metabolites may be racially distinct is also required.
Abstract
AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the COnsortium of METabolomics Studies. METHODS AND RESULTS We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient data meta-analysis. We first assessed the associations between circulating metabolites and incident MI for each cohort adjusting for traditional risk factors and then performed a fixed effect inverse variance meta-analysis to pull the results together. Finally, we conducted a pathway enrichment analysis to identify potential pathways linked to MI. On meta-analysis, 56 metabolites including 21 lipids and 17 amino acids were associated with incident MI after adjusting for multiple testing (false discovery rate < 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol/sorbitol {hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.26-1.56], P < 0.001}, whereas the largest decrease in risk was found for glutamine [HR (95% CI) = 0.74 (0.67-0.82), P < 0.001]. Moreover, the identified metabolites were significantly enriched (corrected P < 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis. CONCLUSIONS In the most comprehensive metabolomic study of incident MI to date, 10 novel metabolites were associated with MI. Metabolite profiles might help to identify high-risk individuals before disease onset. Further research is needed to fully understand the mechanisms of action and elaborate pathway findings.
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Curcumin Offers No Additional Benefit to Lifestyle Intervention on Cardiometabolic Status in Patients with Non-Alcoholic Fatty Liver Disease.
Naseri, K, Saadati, S, Yari, Z, Askari, B, Mafi, D, Hoseinian, P, Asbaghi, O, Hekmatdoost, A, de Courten, B
Nutrients. 2022;14(15)
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Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Individuals with NAFLD are at a significantly increased risk of heart disease and is the leading cause of death in these individuals. Lifestyle modification is the main therapy for NAFLD, namely increased exercise and diet alteration. In addition, natural therapies such as curcumin may also be of benefit as it has been shown to improve factors such as inflammation and oxidative stress, which contribute to NAFLD. This randomised control trial of 50 individuals with NAFLD aimed to determine the effect of adding curcumin to lifestyle modifications on NAFLD. After 12-weeks it was shown that there were no additional benefits of adding 1.5g of curcumin to lifestyle modifications on degree of fatty liver, insulin resistance, heart disease and body morphology. It was concluded that the addition of curcumin has no additional benefits to dietary modification and increased exercise for improving NAFLD. This study could be used by healthcare professionals to understand that lifestyle modifications are still the leading non-pharmacological treatment of NAFLD and individuals with the disease should be in consultation with a nutritionist and an exercise therapist.
Abstract
Cardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Curcumin has been shown to exert glucose-lowering and anti-atherosclerotic effects in type 2 diabetes. Hence, we investigated curcumin's effects on atherogenesis markers, fatty liver, insulin resistance, and adipose tissue-related indicators in patients with NAFLD. In this secondary analysis of a 12-week randomized controlled trial, fifty-two patients with NAFLD received lifestyle modification. In addition, they were randomly allocated to either the curcumin group (1.5 g/day) or the matching placebo. Outcome variables (assessed before and after the study) were: the fatty liver index (FLI), hepatic steatosis index (HSI), fatty liver score (FLS), BMI, age, ALT, TG score (BAAT), triglyceride glucose (TyG) index, Castelli risk index-I (CRI-I), Castelli risk index-II (CRI-II), TG/HDL-C ratio, atherogenic coefficient (AC), atherogenic index of plasma (AIP), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), lipid accumulation product (LAP), body adiposity index (BAI), visceral adiposity index (VAI), metabolic score for visceral fat (METS-VF), visceral adipose tissue (VAT), and waist-to-height ratio (WHtR) values. The TyG index decreased in the curcumin group and increased in the placebo group, with a significant difference between the groups (p = 0.029). However, a between-group change was not significant after adjustment for multiple testing. Other indices were not significantly different between the groups either before or after multiple test correction. After the intervention, there was a lower number of patients with severe fatty liver (FLI ≥ 60) and metabolic syndrome in the curcumin group compared to the placebo (p = 0.021 and p = 0.012, respectively). In conclusion, curcumin offers no additional cardiometabolic benefits to lifestyle intervention in patients with NAFLD.
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The Long Haul of COVID-19 Recovery: Immune Rejuvenation versus Immune Support.
Bland, JS
Integrative medicine (Encinitas, Calif.). 2020;19(6):18-22
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Following Covid-19 infection, sufferers have reported various residual symptoms, which have been likened to those experienced by chronic fatigue sufferers and those with Gulf War syndrome. This review paper aimed to assess whether the body has a similar immune response to these diseases during Covid-19, and if so, what therapies could be used. It also reviewed any diet and lifestyle factors that may be affecting the immune response. The paper stated that Covid-19 infection is associated with inflammation, which can damage immune cells and inflammation prior to Covid-19 infection may contribute to severity of the infection. Prior research in seemingly healthy individuals indicates that environment, diet, and lifestyle factors can all contribute to differing “immune identities” and eliminating immune cells which carry the imprint of memories should be a therapy focus in Covid-19 patients. Fasting, diets low in refined sugars and high in omega-3 and plant chemicals were discussed as ways for the body to clear out immune cells. It was concluded that personalising therapy strategies based on an individual’s immune identity to reduce inflammation could ultimately support the immune system. This paper could be used by healthcare professionals to understand the importance of diet and lifestyle changes to reduce inflammation and support the immune system.
Abstract
With the COVID-19 pandemic still affecting communities all over the world and "Long Haul" chronic health issues emerging, it is time for us to look back at past multi-symptom health conditions that required a different approach to their treatment, beyond just managing symptoms. It is important for us to consider how to apply what we have learned about immune rejuvenation and its impact on conditions associated with chronic immune dysfunction. We know more than we ever have before about how to reduce chronic inflammation at its source through the support of selective immune cell autophagy/mitophagy and improved immune cell mitochondrial activity, followed by remodeling of the immune epigenome, and-ultimately-a reset of immune function.
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Lifestyle changes for treating psoriasis.
Ko, SH, Chi, CC, Yeh, ML, Wang, SH, Tsai, YS, Hsu, MY
The Cochrane database of systematic reviews. 2019;7:CD011972
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Psoriasis is an inflammatory skin disease that results in patches of dry, scaly skin that can be itchy or sore. This Cochrane Database Systematic Review aimed to review and assess the effects of lifestyle factors such as diet, smoking, obesity, alcohol consumption and exercise on the severity of psoriasis. The study authors examined the research evidence up to July 2018. 10 randomised controlled trials (RCTs) with a total of 163 participants were included in the qualitative analysis, and 6 studies in the meta-analysis. Most of the studies included co-interventions such as medication or light therapy. The authors didn’t find any RCTs for smoking cessation or reduced alcohol consumption. Dietary interventions (low-calorie diets, based on the Ornish diet or South Beach diet) were likely to result in a 75% improvement in severity of psoriasis symptoms in obese people after 6 months. A combined low-calorie diet and exercise programme improved the severity of psoriasis compared to providing information on weight loss to improve psoriasis, although the difference wasn’t statistically significant. Participants generally adhered well to the lifestyle interventions assessed in the review. The authors concluded that the body of evidence regarding the effects of lifestyle changes for treating psoriasis is limited. More trials are needed on the effects of different dietary interventions such as vegetarian or ketogenic diets, different types of exercise programmes (e.g. yoga, walking, jogging) and whether other lifestyle changes such as reducing smoking and alcohol consumption, or stress management techniques are effective.
Abstract
BACKGROUND Psoriasis is an inflammatory skin disease that presents with itching, red, scaling plaques; its worsening has been associated with obesity, drinking, smoking, lack of sleep, and a sedentary lifestyle. Lifestyle changes may improve psoriasis. OBJECTIVES To assess the effects of lifestyle changes for psoriasis, including weight reduction, alcohol abstinence, smoking cessation, dietary modification, exercise, and other lifestyle change interventions. SEARCH METHODS We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched the China National Knowledge Infrastructure, the Airiti Library, and five trials registers up to July 2018. We checked the references of included trials for further relevant trials, and we asked the authors of the included trials if they were aware of any relevant unpublished data. SELECTION CRITERIA We included randomised controlled trials (RCTs) of lifestyle changes (either alone or in combination) for treating psoriasis in people diagnosed by a healthcare professional. Treatment had to be given for at least 12 weeks. Eligible comparisons were no lifestyle changes or another active intervention. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Severity of psoriasis' and 'Adherence to the intervention'. Secondary outcomes were 'Quality of life', 'Time to relapse', and 'Reduction in comorbidities'. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS We included 10 RCTs with 1163 participants (mean age: 43 to 61 years; 656 men and 478 women were reported). Six trials examined the effects of dietary intervention (low-calorie diet) in 499 obese participants (mean age: 44.3 to 61 years; where reported, 395 had moderate-to-severe psoriasis). One trial assessed a combined dietary intervention and exercise programme in 303 obese participants with moderate-to-severe psoriasis who had started a systemic therapy for psoriasis and had not achieved clearance after four weeks of continuous treatment (median age: 53 years). Another trial assessed a walking exercise and continuous health education in 200 participants (mean age: 43.1 years, severity not reported). Finally, two trials included education programmes promoting a healthy lifestyle in 161 participants (aged 18 to 78 years), with one trial on mild psoriasis and the other trial not reporting severity.Comparisons included information only; no intervention; medical therapy alone; and usual care (such as continuing healthy eating).All trials were conducted in hospitals and treated participants for between 12 weeks and three years. One trial did not report the treatment period. Seven trials measured the outcomes at the end of treatment and there was no additional follow-up. In two trials, there was follow-up after the treatment ended. Five trials had a high risk of performance bias, and four trials had a high risk of attrition bias.We found no trials assessing interventions for alcohol abstinence or smoking cessation. No trials assessed time to relapse. Only two trials assessed adverse events; in one trial these were caused by the add-on therapy ciclosporin (given in both groups). The trial comparing two dietary interventions to a no-treatment group observed no adverse events.The results presented in this abstract are based on trials of obese participants.Outcomes for dietary interventions versus usual care were measured 24 weeks to six months from baseline. Compared to usual care, dietary intervention (strict caloric restriction) may lead to 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.07 to 2.58; 2 trials, 323 participants; low-quality evidence). Adherence to the intervention may be greater with the dietary intervention than usual care, but the 95% CI indicates that the dietary intervention might also make little or no difference (RR 1.26, 95% CI 0.76 to 2.09; 2 trials, 105 participants; low-quality evidence). Dietary intervention probably achieves a greater improvement in dermatology quality-of-life index (DLQI) score compared to usual care (MD -12.20, 95% CI -13.92 to -10.48; 1 trial, 36 participants; moderate-quality evidence), and probably reduces the BMI compared to usual care (MD -4.65, 95% CI -5.93 to -3.36; 2 trials, 78 participants; moderate-quality evidence).Outcomes for dietary interventions plus exercise programme were measured 16 weeks from baseline and are based on one trial (303 participants). Compared to information only (on reducing weight to improve psoriasis), combined dietary intervention and exercise programme (dietetic plan and physical activities) probably improves psoriasis severity, but the 95% CI indicates that the intervention might make little or no difference (PASI 75: RR 1.28, 95% CI 0.83 to 1.98). This combined intervention probably results in a greater reduction in BMI (median change -1.10 kg/m², P = 0.002), but there is probably no difference in adherence (RR 0.95, 95% CI 0.89 to 1.01; 137/151 and 145/152 participants adhered in the treatment and control group, respectively). There were no data on quality of life. These outcomes are based on moderate-quality evidence. AUTHORS' CONCLUSIONS Dietary intervention may reduce the severity of psoriasis (low-quality evidence) and probably improves quality of life and reduces BMI (moderate-quality evidence) in obese people when compared with usual care, while combined dietary intervention and exercise programme probably improves psoriasis severity and BMI when compared with information only (moderate-quality evidence). None of the trials measured quality of life.We did not detect a clear difference in treatment adherence between those in the combined dietary intervention and exercise programme group and those given information only (moderate-quality evidence). Adherence may be improved through dietary intervention compared with usual care (low-quality evidence). Participants generally adhered well to the lifestyle interventions assessed in the review.No trials assessed the time to relapse. Trial limitations included unblinded participants and high dropout rate.Future trials should reduce dropouts and include comprehensive outcome measures; they should examine whether dietary intervention with or without an exercise programme is effective in non-obese people with psoriasis, whether an additional exercise programme is more effective than dietary intervention alone, whether the time to relapse prolongs in people who receive dietary intervention with or without exercise programme, and whether smoking cessation and alcohol abstinence are effective in treating psoriasis.
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Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention.
Dieli-Conwright, CM, Parmentier, JH, Sami, N, Lee, K, Spicer, D, Mack, WJ, Sattler, F, Mittelman, SD
Breast cancer research and treatment. 2018;168(1):147-157
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Obese breast cancer patients have double the mortality compared to non-obese patients. This is thought to be mediated by low grade inflammation of the adipose (fat) tissue. The main type of immune cells involved in the process are called adipose tissue macrophages (ATMs), of which there are two types: M1 and M2 ATMs, with the M2 ATMs having a mostly anti-inflammatory effect, whilst the M1 ATMs are more pro-inflammatory and are thought to promote cancer growth and recurrence. This 16-week randomised pilot study assessed whether exercise can positively influence adipose tissue inflammation in breast cancer survivors. Participants were randomised to either an exercise (EX) group, who had three supervised exercise sessions per week with a combination of aerobic and resistance exercise, or a control (CON) group. Outcome measures included body composition, blood biomarkers for systemic inflammation and adipose tissue biopsies which were analysed for tissue inflammatory markers, including M1 and M2 ATMs. The EX group had significant improvements in body weight and composition, as well as in metabolic blood parameters (including those for lipid and glucose metabolism) and inflammatory markers, whilst the CON group experienced a worsening of these parameters. The EX participants also had a decrease in the pro-inflammatory M1 ATMs and an increase in the anti-inflammatory M2 ATMs. The authors state that the results were not only statistically, but also clinically significant. The authors conclude that moderate-to-vigorous intensity resistance and aerobic exercise can improve adipose tissue inflammation in obese breast cancer survivors.
Abstract
PURPOSE Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors. METHODS Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period. RESULTS EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p < 0.03 vs. CON). Adipose tissue from EX participants showed a significant decrease in ATM M1 (p < 0.001), an increase in ATM M2 (p < 0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and TNF- α (all p < 0.055). CONCLUSIONS A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.
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Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative.
Stout, AC, Barbe, MF, Eaton, CB, Amin, M, Al-Eid, F, Price, LL, Lu, B, Lo, GH, Zhang, M, Pang, J, et al
BMC musculoskeletal disorders. 2018;19(1):1
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Individuals with osteoarthritis (OA) typically present with greater systemic inflammation and impaired glucose homeostasis. Currently it is unclear whether these factors are associated with early-stage OA, namely bone marrow lesions and swelling. The purpose of this cross-sectional study was to investigate the role of inflammation and glucose homeostasis in early-stage OA. Using baseline data from the Osteoarthritis Initiative, 343 participants were enrolled and tested for markers of inflammation and impaired glucose homeostasis. Bone marrow lesions and swelling were also assessed through imaging results. Results indicate that among individuals without OA, those with greater systemic inflammation were more likely to have bone marrow lesions and knee swelling. According to these results, the authors conclude that systemic inflammation and glucose homeostasis are related to structural features of osteoarthritis. Future studies should explore whether these factors are predictive of OA in order to identify therapeutic targets to prevent or delay the onset of knee OA.
Abstract
BACKGROUND Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA. METHODS We conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm3) and effusion (knee with an effusion volume > 7.5 cm3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores. RESULTS We included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML. CONCLUSIONS Among individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.