Obesity is a known risk factor for postmenopausal breast cancer and is associated with poorer prognosis for premenopausal and postmenopausal patients; however, the aetiological mechanisms are unknown. Preclinical studies support weight loss via caloric restriction and increased physical activity as a possible cancer control strategy, though few clinical studies have been conducted. We undertook a feasibility trial among women recently diagnosed with stage 0-II breast cancer hypothesising that presurgical weight loss would be feasible, safe and result in favourable changes in tumour markers and circulating biomarkers.A two-arm randomised controlled trial among 40 overweight or obese women, newly diagnosed with stage 0-II breast cancer and scheduled for surgery was planned. The attention control arm received upper body progressive resistance training and diet counselling to correct deficiencies in nutrient intake; the experimental arm received the same plus counselling on caloric restriction and aerobic exercise to achieve a weight loss of 0.68-0.919 kg/week. In addition to achieving feasibility benchmarks (accruing and retaining at least 80% of participants, and observing no serious adverse effects attributable to the intervention), we will explore the potential impact of an acute state of negative energy balance on tumour proliferation rates (Ki-67), as well as other tumour markers, serum biomarkers, gene expression, microbiome profiles and other clinical outcomes (eg, quality of life). Outcomes for the 2 study arms are compared using mixed models repeated-measures analyses.Ethics approval was received from the University of Alabama at Birmingham Institutional Review Board (Protocol number F130325009). Study findings will be disseminated through peer-reviewed publications. Given that this is one of the first studies to investigate the impact of negative energy balance directly on tumour biology in humans, larger trials will be pursued if results are favourable.NCT02224807; Pre-results.
ABSTRACT Resistance training (RT) alters skeletal muscle nuclear DNA methylation patterns (or the methylome). However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older untrained males (65±7 years old) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 hours following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Various biochemical assays were also performed, and older male data were compared to younger trained males (22±2 years old, n=7). RT increased whole-body lean tissue mass (p=0.017), VL thickness (p=0.012), and knee extensor torque (p=0.029) in older males. RT also profoundly affected the mtDNA methylome in older males, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p<0.05). Notably, several mtDNA sites presented a more “youthful” signature after RT in older males when comparisons were made to younger males. The 1.12 kilobase D-loop/control region on mtDNA, which regulates mtDNA replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and increases in mitochondrial complex III and IV protein levels were also observed (p<0.05). This is the first study to show RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT remarkably evokes mitochondrial methylome profiles to mimic a more youthful signature in older males.
In March 2020, the COVID-19 pandemic led to restricted vocational (Voc-PA) and recreational physical activity (Rec-PA) outside of the home. We conducted a nation-wide survey in the United States (US) during the mitigation peak of the pandemic (June 2020) to assess health-related changes from the previous year. A diet quality (DQ) assessment tool weighted the relative healthfulness of eating occasions from foods prepared-at-home (Home) and away-from-home (Away). Previously-validated instruments assessed PA and demographic variables; height/weight were self-reported to calculate body mass index (BMI). T-tests explored longitudinal, between-sex, and obesity status differences in DQ, PA, and BMI; Pearson correlations explored associations. Of 1648 respondents, 814 valid responses (56.8% female, 81.7% white) were analyzed. Overall and Home DQ was higher for females than males in 2020 (p < 0.001 for both). Respondents increased DQ from 2019 to 2020, primarily from Away (p < 0.001 for both sexes). Total Rec-PA and Voc-PA was higher in males (p = 0.002, p < 0.001) than females in 2020; females reported higher other PA (p = 0.001). Change in BMI was inversely associated with change in both DQ and PA (p < 0.001 for both). In this sample of US adults, early adaptations to the COVID-19 pandemic included improved DQ and BMI. Whether these short-term improvements were maintained warrant further investigation.
Importance Cancer survivors experience accelerated functional decline that threatens independence and quality of life. Previous studies have suggested that vegetable gardening may improve diet, physical activity, and physical function in this vulnerable population, which comprises more than 5% of the US population. Objective To assess whether diet, physical activity and functioning, and other outcomes improved in older cancer survivors assigned to a vegetable gardening intervention compared with a waitlist. Design, Setting, and Participants From May 11, 2016, to May 2, 2022, a 2-arm, assessor-blinded, crossover-designed, intent-to-treat, randomized clinical trial was conducted at cancer survivors’ homes across Alabama. Medicare-eligible survivors of cancers with 5-year survival of 60% or more were registry ascertained and screened for suboptimal vegetable and fruit consumption (&lt;5 servings per day), physical activity (&lt;150 moderate-to-vigorous minutes per week), and physical function (36-Item Short Form Health Survey [SF-36] subscale score ≤90). Consented participants underwent baseline assessments, were randomly assigned to intervention or waitlisted arms, and were reassessed at 1-year follow-up. Intervention One-year, home-based vegetable gardening intervention providing gardening supplies and mentorship by cooperative extension–certified master gardeners to plant and maintain spring, summer, and fall gardens. Waitlisted participants received the identical intervention after 12 months. Main Outcomes and Measures The main outcome was a composite index of improvements in self-reported vegetable and fruit consumption, physical activity, and physical function corroborated by plasma α-carotene levels, accelerometry, and physical performance assessments, respectively. Results Of 381 enrolled participants (mean [SD] age, 69.8 [6.4] years; range, 50-95 years; 263 [69.0%] female), 194 were assigned to the gardening intervention and 187 were waitlisted (attrition rates, 7.2% and 7.0%, respectively). Intent-to-treat analyses did not detect a significant improvement in the composite index of vegetable and fruit intake, moderate-vigorous physical activity, and physical function (intervention arm vs waitlisted arm, 4.5% vs 3.1%; P = .53) or between-arm differences in vegetable and fruit intake (mean difference, 0.3 [95% CI, −0.1 to 0.7] servings per day; P = .10). The intervention arm experienced a significant improvement in vegetable and fruit intake (mean increase, 0.3 [95% CI, 0.0-0.6] servings per day; P = .04). Significant improvements also were observed in the intervention arm vs waitlisted arm in physical performance (mean difference for 2-minute step test, 6.0 [95% CI, 0.8-11.2] steps; P = .03; for 30-second chair stand, 0.8 [95% CI, 0.1-1.5] repetitions; P = .02), perceived health (8.4 [95% CI, 3.0-13.9] points on a 100-point scale [higher scores indicate better health]; P = .003), and gut microbiome alpha diversity (84.1 [95% CI, 20.5-147.6] more observed species; P = .01). The COVID-19 pandemic significantly moderated effects (eg, odds of improvement in self-reported physical functioning were greater before vs during the pandemic: odds ratio, 2.17; 95% CI, 1.12-4.22; P = .02). Conclusions and Relevance In this randomized clinical trial including older cancer survivors, a vegetable gardening intervention did not significantly improve a composite index of diet, physical activity, and physical function; however, survivors assigned to the intervention had significantly increased vegetable and fruit consumption and, compared with waitlisted survivors, experienced significant improvements in perceived health and physical performance. Further study in broader populations and during pandemic-free periods is needed to determine definitive benefits. Trial Registration ClinicalTrials.gov Identifier: NCT02985411
Breast cancer is a hormonally-driven cancer, and various dietary factors are associated with estrogen metabolism, including dietary fiber. Several studies report associations between dietary fiber and breast cancer; however, research on whether fiber influences circulating estrogens through the gut microbiota is rare. The objective of this cross-sectional study among 29 newly-diagnosed (stage 0-II), post-menopausal breast cancer patients is to examine associations between dietary fiber and the gut microbiota that are linked with β-glucuronidase activity, and purportedly increase circulating estrogens. Spearman's and partial correlations controlling for body mass index and age were performed using dietary recall data, Illumina MiSeq generated microbiota relative abundance, and HPLC-mass spectrometry-derived estradiol and estrone levels.Major findings are: (1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30. doi:10.3322/caac.21442[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) total dietary fiber is inversely associated with Clostridium hathewayi (r= −0.419; p = 0.024); (2 American Cancer Society. Breast Cancer Facts & Figures 2018. Atlanta: American Cancer Society, 2018. [Google Scholar]) soluble fiber is inversely associated with Clostridium (r=-0.11; p = 0.02); (3 Munsell MF, Sprague BL, Berry DA, Chisholm G, Trentham-Dietz A. Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev. 2014;36(1):114–36. doi:10.1093/epirev/mxt010[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) insoluble fiber is positively associated with Bacteroides uniformis sp. (r = 0.382; p = 0.041); and (4 Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78. doi:10.1016/S0140-6736(08)60269-X[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) serum estradiol and estrone levels are not correlated with species/genera or dietary fiber, though there is a trend toward an inverse association between soluble fiber and estradiol levels (r= −0.30; p = 0.12). More studies are needed to understand the complex interaction between dietary fiber, intestinal microbiota, and hormonal levels in older females.
Resistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole-body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p < .05). Several mtDNA sites presented a more "youthful" signature in older males after RT in comparison to younger males. The 1.12 kilobase mtDNA D-loop/control region, which regulates replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and complex III/IV protein levels were also observed (p < .05). While limited to a shorter-term intervention, this is the first evidence showing that RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT evokes mitochondrial methylome profiles to mimic younger men. The significance of these findings relative to broader RT-induced epigenetic changes needs to be elucidated.
