Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study.

BACKGROUND: Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects. METHODS: This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a programme of comprehensive lifestyle changes (diet, activity, stress management, and social support), and the men in the control group underwent active surveillance alone. We took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes. FINDINGS: Relative telomere length increased from baseline by a median of 0·06 telomere to single-copy gene ratio (T/S)units (IQR-0·05 to 0·11) in the lifestyle intervention group, but decreased in the control group (-0·03 T/S units, -0·05 to 0·03, difference p=0·03). When data from the two groups were combined, adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up (for each percentage point increase in lifestyle adherence score, T/S units increased by 0·07, 95% CI 0·02-0·12, p=0·005). At 5 years, telomerase activity had decreased from baseline by 0·25 (-2·25 to 2·23) units in the lifestyle intervention group, and by 1·08 (-3·25 to 1·86) units in the control group (p=0·64), and was not associated with adherence to lifestyle changes (relative risk 0·93, 95% CI 0·72-1·20, p=0·57). INTERPRETATION: Our comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding. FUNDING: US Department of Defense, NIH/NCI, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, Prostate Cancer Foundation.

Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention.

Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer. However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood. We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression. Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe. Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts. Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention. Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05). Intensive nutrition and lifestyle changes may modulate gene expression in the prostate. Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.

Increased telomerase activity and comprehensive lifestyle changes: a pilot study.

BACKGROUND: Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). METHODS: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791. FINDINGS: PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047). INTERPRETATION: Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.

Comparison of coronary risk factors and quality of life in coronary artery disease patients with versus without diabetes mellitus.

It is unclear whether patients with coronary artery disease (CAD) and diabetes mellitus (DM) can make comprehensive lifestyle changes that produce similar changes in coronary risk factors and quality of life compared with patients with CAD and without DM. We examined medical characteristics, lifestyle, and quality of life by diabetic status and gender in the Multicenter Lifestyle Demonstration Project (MLDP), a study of 440 nonsmoking patients with CAD (347 men, 55 with DM; 15.9%; 93 women, 36 with DM; 38.7%). Patients met in groups to improve lifestyle (plant-based, low-fat diet; exercise; stress management) for 1 year. Follow-ups were conducted at 3 and 12 months. At baseline, body mass and systolic blood pressure were significantly higher among patients with DM. Men with DM had a worse medical history (e.g., hypertension, hyperlipidemia, and family history of CAD) than did those without DM. Patients with DM, especially women, reported poorer quality of life than did patients without DM. The 2 groups of patients were able to adhere to the recommended lifestyle, as demonstrated by significant improvements in weight (mean -5 kg), body fat, low-density lipoprotein cholesterol, exercise capacity, and quality of life. No significant changes in triglycerides and high-density lipoprotein cholesterol were noted. By the end of 12 months, improvements in glucose-lowering medications (i.e., discontinuation or a change from insulin to oral hypoglycemic agents) were noted for 19.8% (n = 18) of patients with DM. In conclusion, patients with CAD and DM are able to follow a comprehensive lifestyle change program and show similar improvements in coronary risk factors and quality of life as those without DM.

Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease.

Pomegranate juice contains antioxidants such as soluble polyphenols, tannins, and anthocyanins and may have antiatherosclerotic properties. However, no study has investigated the effects of pomegranate juice on patients who have ischemic coronary heart disease (CHD). We investigated whether daily consumption of pomegranate juice for 3 months would affect myocardial perfusion in 45 patients who had CHD and myocardial ischemia in a randomized, placebo-controlled, double-blind study. Patients were randomly assigned into 1 of 2 groups: a pomegranate juice group (240 ml/day) or a placebo group that drank a beverage of similar caloric content, amount, flavor, and color. Participants underwent electrocardiographic-gated myocardial perfusion single-photon emission computed tomographic technetium-99m tetrofosmin scintigraphy at rest and during stress at baseline and 3 months. Visual scoring of images using standardized segmentation and nomenclature (17 segments, scale 0 to 4) was performed by a blinded independent nuclear cardiologist. To assess the amount of inducible ischemia, the summed difference score (SDS) was calculated by subtracting the summed score at rest from the summed stress score. The experimental and control groups showed similar levels of stress-induced ischemia (SDS) at baseline (p >0.05). After 3 months, the extent of stress-induced ischemia decreased in the pomegranate group (SDS -0.8 +/- 2.7) but increased in the control group (SDS 1.2 +/- 3.1, p <0.05). This benefit was observed without changes in cardiac medications, blood sugar, hemoglobin A1c, weight, or blood pressure in either group. In conclusion, daily consumption of pomegranate juice may improve stress-induced myocardial ischemia in patients who have CHD.

Nutrient adequacy of a very low-fat vegan diet.

This study assessed the nutrient adequacy of a very low-fat vegan diet. Thirty-nine men (mean age=65 years) with early stage prostate cancer who chose the "watchful waiting" approach to disease management, were instructed by a registered dietitian and a chef on following a very low-fat (10%) vegan diet with the addition of a fortified soy protein powdered beverage. Three-day food diaries, excluding vitamin and mineral supplements, were analyzed and nutrient values were compared against Dietary Reference Intakes (DRI). Mean dietary intake met the recommended DRIs. On the basis of the Adequate Intake standard, a less than adequate intake was observed for vitamin D. This demonstrates that a very low-fat vegan diet with comprehensive nutrition education emphasizing nutrient-fortified plant foods is nutritionally adequate, with the exception of vitamin D. Vitamin D supplementation, especially for those with limited sun exposure, can help assure nutritional adequacy.

A qualitative analysis of interviews of men with early stage prostate cancer: the Prostate Cancer Lifestyle Trial.

We conducted interviews with a subsample of men (n = 26) participating in the Prostate Cancer Lifestyle Trial (PCLT), who had biopsy-proven prostate cancer (Gleason grade <7; prostate-specific antigen 4-10 ng/mL) and chose "watchful waiting" after diagnosis. The PCLT aimed at improving diet, exercise, stress management practices, and group support within a peer community setting. The aims of this study were to examine psychological, emotional, spiritual, and social reactions to (a) a diagnosis of early stage prostate cancer and (b) participation in the PCLT. Qualitative analyses were completed using MAXqda. Results indicated that the cancer diagnosis was met with anxiety, distress, and denial, or a "bump in the road" attitude. There was some indication that conflict with partners was exacerbated by the diagnosis. A significant component of the lifestyle intervention was involvement in the peer community. This community provided opportunities to experience connections with others facing similar health difficulties. Men generally expressed positive attitudes (emotionally, physically, and spiritually) about the lifestyle change, and felt that their participation in the program contributed to feelings of hope, optimism, and fighting spirit. Additionally, participants frequently mentioned increased comfort with emotional expression.

Improvement in medical risk factors and quality of life in women and men with coronary artery disease in the Multicenter Lifestyle Demonstration Project.

This study examined medical and psychosocial characteristics of 440 patients (mean age 58 years, 21% women) with coronary artery disease at baseline and at 3-month and 12-month follow-ups. All patients were participants in the Multicenter Lifestyle Demonstration Project, aimed at improving diet (low fat, whole foods, plant-based), exercise, stress management, and social support. Spousal participation was encouraged. Both genders evidenced significant improvements in their diet, exercise, and stress management practices, which they maintained over the course of the study. Both women and men also showed significant medical (e.g., plasma lipids, blood pressure, body weight, exercise capacity) and psychosocial (e.g., quality of life) improvement. Despite their worse medical, psychosocial, and sociodemographic status at baseline, women's improvement was similar to that of men's. These results demonstrate that a multi-component lifestyle change program focusing on diet, exercise, stress management, and social support can be successfully implemented at hospitals in diverse regions of the United States. Furthermore, this program may be particularly beneficial for women with coronary artery disease who generally have higher mortality and morbidity than men after a heart attack, angioplasty, or bypass surgery.

Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.

OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.

Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial.

High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.

Lifestyle and health-related quality of life of men with prostate cancer managed with active surveillance.

OBJECTIVES: To assess the impact of lifestyle on health-related quality of life (HR-QOL), perceived stress, and self-reported sexual function in men with early-stage prostate cancer electing active surveillance. METHODS: A total of 44 intervention and 49 usual-care control participants were enrolled in a randomized clinical trial examining the effects of lifestyle changes on prostate cancer progression. The intervention consisted of a low-fat, vegan diet, exercise, and stress management. Participants completed the Medical Outcomes Study Short Form-36 Health Status Survey (a measure of mental and physical HR-QOL), the Perceived Stress Scale, the Sexual Function subscale of the University of California, Los Angeles, Prostate Cancer Index, and measures of lifestyle behaviors (to yield an overall lifestyle index) at baseline and 12 months. The data were analyzed using analysis of variance for repeated measures. The relationship between lifestyle and QOL was also analyzed using multiple linear regression analyses. RESULTS: Intervention participants had significantly improved their lifestyle compared with controls at 12 months. The quality-of-life scores were high across groups and time points. However, a healthier lifestyle was related to better QOL at baseline. Participants in both groups who reported a healthier lifestyle also reported better mental and physical HR-QOL and sexual function. Furthermore, participants whose lifestyle improved over time showed enhanced physical HR-QOL and decreased perceived stress. CONCLUSIONS: Men who choose active surveillance for early-stage prostate cancer are able to make comprehensive lifestyle changes. Although the average QOL was already high in this sample, individuals who improved their lifestyle enhanced their QOL further.

Intensive lifestyle changes may affect the progression of prostate cancer.

PURPOSE: Men with prostate cancer are often advised to make changes in diet and lifestyle, although the impact of these changes has not been well documented. Therefore, we evaluated the effects of comprehensive lifestyle changes on prostate specific antigen (PSA), treatment trends and serum stimulated LNCaP cell growth in men with early, biopsy proven prostate cancer after 1 year. MATERIALS AND METHODS: Patient recruitment was limited to men who had chosen not to undergo any conventional treatment, which provided an unusual opportunity to have a nonintervention randomized control group to avoid the confounding effects of interventions such as radiation, surgery or androgen deprivation therapy. A total of 93 volunteers with serum PSA 4 to 10 ng/ml and cancer Gleason scores less than 7 were randomly assigned to an experimental group that was asked to make comprehensive lifestyle changes or to a usual care control group. RESULTS: None of the experimental group patients but 6 control patients underwent conventional treatment due to an increase in PSA and/or progression of disease on magnetic resonance imaging. PSA decreased 4% in the experimental group but increased 6% in the control group (p = 0.016). The growth of LNCaP prostate cancer cells (American Type Culture Collection, Manassas, Virginia) was inhibited almost 8 times more by serum from the experimental than from the control group (70% vs 9%, p <0.001). Changes in serum PSA and also in LNCaP cell growth were significantly associated with the degree of change in diet and lifestyle. CONCLUSIONS: Intensive lifestyle changes may affect the progression of early, low grade prostate cancer in men. Further studies and longer term followup are warranted.