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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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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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Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.
Avorgbedor, F, Blumenthal, JA, Hinderliter, A, Ingle, K, Lin, PH, Craighead, L, Tyson, C, Kraus, W, Sherwood, A, Smith, PJ
Journal of clinical hypertension (Greenwich, Conn.). 2023;25(1):106-110
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Hypertension is one of the primary causes of cardiovascular disease, stroke, Alzheimer’s Disease, and Alzheimer’s Disease and related dementias (AD/ADRD). Among individuals with hypertension, those with resistant hypertension (RH) appear to have the greatest risk of cerebrovascular disease and associated cognitive impairment. The aim of this study was to investigate the potential influence of individual differences in pre-treatment inflammatory profiles on changes in cognition following lifestyle modification among RH participants in the TRIUMPH clinical trial. This study is a report based on the TRIUMPH study which was a randomised clinical trial. One hundred forty patients with RH were randomised with 2:1 allocation to either a 4-month Centre-based Lifestyle intervention or Standardized Education and Physician Advice. Results show that basal levels of elevated peripheral inflammation may represent an intermediate phenotype of risk for cognitive decline. In fact, individuals with higher levels of c-reactive protein at baseline demonstrated greater improvements in Executive Function/Learning following participation in an intensive lifestyle intervention. Authors conclude that their findings may help inform targeted treatments to reduce ADRD among middle-aged and older adults with cardiovascular disease risk factors.
Abstract
Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.
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Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.
Axelrod, CL, Fealy, CE, Erickson, ML, Davuluri, G, Fujioka, H, Dantas, WS, Huang, E, Pergola, K, Mey, JT, King, WT, et al
Metabolism: clinical and experimental. 2021;121:154803
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Insulin resistance is a key pathophysiological mechanism in the development and progression of type 2 diabetes. Abnormalities in lipid metabolism and ectopic lipid accumulation are known to directly contribute to the onset of insulin resistance. Authors hypothesised that lipid infusion would increase dynamin related protein 1 [a type of protein]-mediated mitochondrial fission in skeletal muscle independent of function and content, consequently reducing peripheral insulin sensitivity. The study included sedentary but otherwise healthy adults who were prospectively randomized to receive either lipid or saline infusion to isolate the direct contribution of fatty acids to skeletal muscle mitochondrial dynamics. Results show that mitochondrial fission and quality control networks are activated in response to lipid infusion which occurs independent of changes in mitochondrial content or capacity and contributes to the onset of insulin resistance in healthy humans. Authors conclude that treatments that limit lipid-induced activation of mitochondrial fission and/or quality control processes may have therapeutic value in the treatment of insulin resistance.
Abstract
BACKGROUND AND AIMS A diminution in skeletal muscle mitochondrial function due to ectopic lipid accumulation and excess nutrient intake is thought to contribute to insulin resistance and the development of type 2 diabetes. However, the functional integrity of mitochondria in insulin-resistant skeletal muscle remains highly controversial. METHODS 19 healthy adults (age:28.4 ± 1.7 years; BMI:22.7 ± 0.3 kg/m2) received an overnight intravenous infusion of lipid (20% Intralipid) or saline followed by a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity using a randomized crossover design. Skeletal muscle biopsies were obtained after the overnight lipid infusion to evaluate activation of mitochondrial dynamics proteins, ex-vivo mitochondrial membrane potential, ex-vivo oxidative phosphorylation and electron transfer capacity, and mitochondrial ultrastructure. RESULTS Overnight lipid infusion increased dynamin related protein 1 (DRP1) phosphorylation at serine 616 and PTEN-induced kinase 1 (PINK1) expression (P = 0.003 and P = 0.008, respectively) in skeletal muscle while reducing mitochondrial membrane potential (P = 0.042). The lipid infusion also increased mitochondrial-associated lipid droplet formation (P = 0.011), the number of dilated cristae, and the presence of autophagic vesicles without altering mitochondrial number or respiratory capacity. Additionally, lipid infusion suppressed peripheral glucose disposal (P = 0.004) and hepatic insulin sensitivity (P = 0.014). CONCLUSIONS These findings indicate that activation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. Targeting mitochondrial dynamics and quality control represents a promising new pharmacological approach for treating insulin resistance and type 2 diabetes. CLINICAL TRIAL REGISTRATION NCT02697201, ClinicalTrials.gov.
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The Weight Optimization Revamping Lifestyle using the Dietary Guidelines (WORLD) Study: Sustained Weight Loss Over 12 Months.
Psota, TL, Tindall, AM, Lohse, B, Miller, PE, Petersen, KS, Kris-Etherton, PM
Obesity (Silver Spring, Md.). 2020;28(7):1235-1244
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Effective long-term weight loss strategies to reduce the risk of death and diseases associated with being obese or overweight are required, as restrictive programmes are difficult to sustain, and weight loss may be heavily influenced by behavioural factors. This randomised control trial of 101 premenopausal women with obesity or overweight aimed to compare a lower-fat and moderate-fat diets, both with nutrition education for 12 months. The results showed that both treatment groups lost weight. Both groups consumed the same amount of fat but increased their diet quality. Diet quality and greater attendance at nutritional education sessions were associated with greater weight loss. Cholesterol was significantly lower in both groups, but blood pressure remained unchanged. Interestingly there were a large number of women who did not complete the trial. It was concluded that irrespective of the amount of fat consumed, nutrition education can help to achieve sustained weight loss, improve diet quality and decrease heart disease risk for at least 12 months. This study could be used by healthcare professionals to understand that recommending fat-based targets for weight loss may be ineffective and the importance of emotional and behavioural support for individuals on a weight loss regime to improve their risk for heart disease.
Abstract
OBJECTIVE This study aimed to compare two energy-restricted, nutrient-dense diets at the upper or lower ends of the dietary fat recommendation range (lower fat [20% energy from fat] versus moderate fat [35%]) on weight loss using behavioral theory-based nutrition education. METHODS A total of 101 premenopausal women with overweight or obesity were randomized to an energy-restricted lower-fat or moderate-fat diet for 1 year. Interventions included 28 behavioral theory-based nutrition education sessions plus weekly exercise sessions. RESULTS Both treatment groups experienced weight loss (-5.0 kg for lower fat and -4.3 kg for moderate fat; P < 0.0001), but there was no difference in weight loss or fat intake between groups. Total and low-density lipoprotein cholesterol decreased (-3. 4 mg/dL and -3.8 mg/dL; P < 0.05), and high-density lipoprotein cholesterol increased (1.9 mg/dL; P < 0.05) in both groups at 12 months. Diet quality, assessed by the Healthy Eating Index, increased significantly at 4 months versus baseline (70.8 [0.9] vs. 77.8 [1.0]) and was maintained through 12 months. Higher Healthy Eating Index scores were associated with greater weight loss at 4 months (r = -0.2; P < 0.05). CONCLUSIONS In the context of a well-resourced, free-living weight-loss intervention, total fat intake did not change; however, theory-based nutrition education underpinned by food-based recommendations resulted in caloric deficits, improvements in diet quality, and weight loss that was sustained for 1 year.
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The effects of intensive dietary weight loss and exercise on gait in overweight and obese adults with knee osteoarthritis. The Intensive Diet and Exercise for Arthritis (IDEA) trial.
Messier, SP, Beavers, DP, Mihalko, SL, Miller, GD, Lyles, MF, Hunter, DJ, Carr, JJ, Eckstein, F, Guermazi, A, Loeser, RF, et al
Journal of biomechanics. 2020;98:109477
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Obesity is a common contributor to knee joint arthritis. In a previous trial, called the Intensive Diet and Exercise for Arthritis (IDEA) trial, it was demonstrated that 18 months of weight loss via a combination of diet and exercise was superior to diet alone for improved clinical outcomes in 454 individuals with knee joint arthritis. This sub analysis of the original randomised control trial, aimed to determine if weight loss due to diet plus exercise was more beneficial than weight loss due to diet or exercise alone to the way a person walked with knee joint arthritis. The results showed that weight loss was greatest amongst the diet and exercise group, then the diet group, and finally the exercise group. The diet and exercise group walked faster than either the diet or exercise alone groups. Dietary weight loss resulted in improved pressure upon the hip, knee and ankle joints, which was attenuated with a combination of diet and exercise. It was concluded that dietary weight loss was more beneficial for knee joint arthritis, however dietary weight loss combined with exercise is still superior to exercise alone. This study could be used by healthcare professionals to recommend a dietary weight loss regime for individuals with knee arthritis in order to improve their ability to walk.
Abstract
The Intensive Diet and Exercise for Arthritis (IDEA) trial was an 18-month randomized controlled trial that enrolled 454 overweight and obese older adults with symptomatic and radiographic knee osteoarthritis (OA). Participants were randomized to either exercise (E), intensive diet-induced weight loss (D), or intensive diet-induced weight loss plus exercise (D + E) interventions. We previously reported that the clinical benefits of D + E were significantly greater than with either intervention alone (e.g., greater pain reduction, and better function, mobility, and health-related quality of life). We now test the hypothesis that D + E has greater overall benefit on gait mechanics compared to either intervention alone. Knee joint loading was analyzed using inverse dynamics and musculoskeletal modeling. Analysis of covariance determined the interventions' effects on gait. The D + E group walked significantly faster at 18-month follow-up (1.35 m s-1) than E (1.29 m s-1, p = 0.0004) and D (1.31 m s-1, p = 0.0007). Tibiofemoral compressive impulse was significantly lower (p = 0.0007) in D (1069 N s) and D + E (1054 N s) compared to E (1130 N s). D had significantly lower peak hip external rotation moment (p = 0.01), hip abduction moment (p = 0.0003), and peak hip power production (p = 0.016) compared with E. Peak ankle plantar flexion moment was significantly less (p < 0.0001) in the two diet groups compared with E. There also was a significant dose-response to weight loss; participants that lost >10% of baseline body weight had significantly (p = 0.0001) lower resultant knee forces and lower muscle (quadriceps, hamstring, and gastrocnemius) forces than participants that had less weight loss. Compared to E, D produces significant load reductions at the hip, knee, and ankle; combining D with E attenuates these reductions, but most remain significantly better than with E alone.
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Systematic review of the prospective association of daily step counts with risk of mortality, cardiovascular disease, and dysglycemia.
Hall, KS, Hyde, ET, Bassett, DR, Carlson, SA, Carnethon, MR, Ekelund, U, Evenson, KR, Galuska, DA, Kraus, WE, Lee, IM, et al
The international journal of behavioral nutrition and physical activity. 2020;17(1):78
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The health benefits of physical activity for people of all ages, fitness levels, and sociodemographic backgrounds are well-documented. The main aim of this study was to provide an updated description of the association between daily step counts and subsequent cardiovascular disease (CVD) morbidity or mortality, dysglycaemia, and all-cause mortality in adults and the patterns of these associations. This study is a systemic review of 17 studies from 13 different cohorts. Participants’ mean age ranged from 49.7 to 78.9 years with samples comprised of 46.9% female participants on average. Results showed that increasing steps per day is beneficial for health: taking more steps per day was associated with lower risk of all-cause mortality, and lower risk of CVD morbidity or mortality. These associations appear to hold across age, gender, and weight status. Authors conclude that this additional evidence will help guide meaningful volume targets that can be used for health care, education, and behavioural interventions, and potentially inform the development of public health guidelines for steps and health.
Abstract
BACKGROUND Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes. METHODS A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations. RESULTS Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics. CONCLUSIONS Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.
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Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study.
Li, ZH, Zhong, WF, Liu, S, Kraus, VB, Zhang, YJ, Gao, X, Lv, YB, Shen, D, Zhang, XR, Zhang, PD, et al
BMJ (Clinical research ed.). 2020;368:m456
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Fish oil is a rich source of long chain omega 3 fatty acids, a group of polyunsaturated fats that primarily include eicosapentaenoic acid and docosahexaenoic acid. The aim of this study was to investigate the associations of habitual use of fish oils with the risk of certain outcomes (the incidence of, and mortality from, cardiovascular disease (CVD) as well as all-cause mortality) and to explore modifying factors that might affect these associations. This study is a large-scale cohort study of 427 678 participants aged between 40 to 69 years. Results showed that a considerable proportion (31.2%) of all participants reported habitual use of fish oil supplements. Findings also indicate that habitual fish oil supplementation was associated with a significantly lower all-cause mortality and incidence of, and mortality from, CVD and myocardial infarction. Authors conclude that habitual use of fish oils is beneficial for CVD events in the general population, supporting their use for the prevention of mortality from all causes and CVD.
Abstract
OBJECTIVES To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort. DESIGN Population based, prospective cohort study. SETTING UK Biobank. PARTICIPANTS A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018. MAIN EXPOSURE All participants answered questions on the habitual use of supplements, including fish oil. MAIN OUTCOME MEASURES All cause mortality, CVD mortality, and CVD events. RESULTS At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005). CONCLUSIONS Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.
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Dietary fiber intake and glycemic control: coronary artery calcification in type 1 diabetes (CACTI) study.
Basu, A, Alman, AC, Snell-Bergeon, JK
Nutrition journal. 2019;18(1):23
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The incidence of type 1 diabetes and cardiovascular disease, the major vascular complication of diabetes, have been increasing wordwide. The aim of the study is to identify the associations of dietary fibre with glycaemic control. The study is a cross-sectional longitudinal study which enrolled 1257 individuals in the cross-sectional analysis and a total of 990 participants were included in the longitudinal analysis. The participants had no known history of coronary heart disease. Results indicate an inverse association between total fibre intake and the average blood glucose levels for the last two to three months in both diabetic and nondiabetic participants. Authors conclude that their study provides some evidence on the role dietary fibre intake plays on glycaemic control, which is important in the management of type 1 diabetes in patients at high risk of cardiovascular disease.
Abstract
BACKGROUND Dietary fiber has been recommended for glucose control, and typically low intakes are observed in the general population. The role of fiber in glycemic control in reported literature is inconsistent and few reports are available in populations with type 1 diabetes (T1D). METHODS Using data from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study [n = 1257; T1D: n = 568; non-diabetic controls: n = 689] collected between March 2000 and April 2002, we examined cross-sectional (baseline) and longitudinal (six-year follow-up in 2006-2008) associations of dietary fiber and HbA1c. Participants completed a validated food frequency questionnaire, and a physical examination and fasting biochemical analyses (12 h fast) at baseline visit and at the year 6 visit. We used a linear regression model stratified by diabetes status, and adjusted for age, sex and total calories, and diabetes duration in the T1D group. We also examined correlations of dietary fiber with HbA1c. RESULTS Baseline dietary fiber intake and serum HbA1c in the T1D group were 16 g [median (IQ): 11-22 g) and 7.9 ± 1.3% mean (SD), respectively, and in the non-diabetic controls were 15 g [median (IQ): 11-21 g) and 5.4 ± 0.4%, respectively. Pearson partial correlation coefficients revealed a significant but weak inverse association of total dietary fiber with HbA1c when adjusted for age, sex, diabetes status and total calories (r = - 0.07, p = 0.01). In the adjusted linear regression model at baseline, total dietary fiber revealed a significant inverse association with HbA1c in the T1D group [β ± SE = - 0.32 ± 0.15, p = 0.034], as well as in the non-diabetic controls [- 0.10 ± 0.04, p = 0.009]. However, these results were attenuated after adjustment for dietary carbohydrates, fats and proteins, or for cholesterol and triglycerides. No such significance was observed at the year 6 follow-up, and with the HbA1c changes over 6 years. CONCLUSION Thus, at observed levels of intake, total dietary fiber reveals modest inverse associations with poor glycemic control. Future studies must further investigate the role of overall dietary quality adjusting for fiber-rich foods in T1D management.
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Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.
Elhassan, YS, Kluckova, K, Fletcher, RS, Schmidt, MS, Garten, A, Doig, CL, Cartwright, DM, Oakey, L, Burley, CV, Jenkinson, N, et al
Cell reports. 2019;28(7):1717-1728.e6
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As the body ages, there is a decline in muscle mass and function, which can be combatted with diet, exercise, and supplementation. Nicotinamide riboside (NR) or vitamin B3 has been shown in animal studies to promote healthy muscle, however its effects in human muscle are unknown. This randomised control trial of overweight older men aimed to determine if NR can be used by muscle and whether it has any effect on muscle function. The results showed that NR supplementation (1 g/day) for 3 weeks can be used by the muscle but had no effect on muscle function as shown by the hand grip test. Supplementation also decreased energy production in muscle and had anti-inflammatory effects. It was concluded that NR is available to muscle and that it may have anti-inflammatory properties, which may be of benefit to older individuals.
Abstract
Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.