Experimental group patients were prescribed an intensive lifestyle program that included a vegan diet supplemented with soy (1 daily serving of tofu plus 58 gm of a fortified soy protein powdered beverage), fish oil (3 gm daily), vitamin E (400 IU daily), selenium (200 mcg daily) and vitamin C (2 gm daily), moderate aerobic exercise (walking 30 minutes 6 days weekly), stress management techniques (gentle yoga based stretching, breathing, meditation, imagery and progressive relaxation for a total of 60 minutes daily) and participation in a 1-hour support group once weekly to enhance adherence to the intervention.
The diet was predominantly fruits, vegetables, whole grains (complex carbohydrates), legumes and soy products, low in simple carbohydrates and with approximately 10% of calories from fat. The diet is intensive but palatable and practical. In earlier studies most patients were able to adhere to this diet for at least 5 years.
A registered dietitian was available for nutrition education and counseling. A nurse case manager contacted patients by telephone once weekly for the first 3 months and once monthly thereafter. Control group patients were asked to follow the advice of their physicians regarding lifestyle changes. All therapeutic decisions, including whether to undergo conventional treatment during the study course, were deferred to the personal physician of each patient. Serum PSA was measured twice at baseline and at 1 year.
Patients were counseled to avoid activities that might affect PSA for 3 days prior to testing, including sexual activity, exercise and digital rectal examination. Serum PSA was measured at Memorial Sloan-Kettering Cancer Center prospectively by a heterogeneous sandwich magnetic separation assay with the Immuno 1™ System. Testosterone was measured by a competitive immunoassay with an Immulite® automated analyzer.
LNCaP cells were grown in 75 cm2 flasks in RPMI-1640 medium without phenol red, as previously described in detail.12 Cells were collected using 0.25% Trypsin-
Dietary intake assessing the percent of calories from fat and mg cholesterol was measured with a semiquantitative food frequency questionnaire. Nutrient assessment was calculated elsewhere using United States Department of Agriculture food composition tables and other sources. The frequency and duration of exercise and of stress management techniques were assessed by self-reporting questionnaires. Attendance at group support sessions was recorded. The level of adherence to the recommended lifestyle change was based on a formula validated in previous studies.
A total score of 1 indicated 100% adherence to the program and 0 indicated no adherence. Eligible patients were randomly assigned to the control or the intervention group. Assessment of outcome measures were done while blinded to group assignment. Baseline equivalence of the 2 groups were analyzed using the independent sample t test in the case of continuous variables and the chi-square test of association in the case of categorical variables.
Between group differences in baseline to 12-month changes in clinical and behavioral outcomes were compared using ANCOVA with baseline values as covariates. Although control patients were not asked to make changes in diet and lifestyle, some did so in varying degrees, that is 18% to 137% (experimental group 58% to 316%). As a secondary analysis, we correlated the degree of lifestyle change with changes in serum PSA, LNCaP cell growth, LNCaP apoptosis, serum testosterone and CRP across the 2 groups regardless of group assignment with baseline values as a covariate. Natural log transformation achieved normality (ln-CRP).
All reported significance levels are 2-sided and p 0.05 was considered the required value for concluding tAt baseline there were no significant differences between the groups in demographic or clinical measures (table 1). Subject age, PSA and Gleason scores in those who were randomized into the study but refused to participate were not significantly different from values in those who participated. After 1 year adherence to the intervention was 95% in the experimental group and 45% in the control group. There were no adverse events attributable to the lifestyle intervention. Diet, exercise, stress management techniques and group support improved significantly more in the experimental group than in the control group (table 2).
Six control group patients withdrew before 12 months and underwent conventional treatment, including radical prostatectomy in 3, and androgen deprivation, external beam radiation and brachytherapy in 1 each. Four of these patients underwent conventional treatment due to an increase in PSA during the study and 2 underwent it due to progression of prostate cancer, as assessed by magnetic resonance imaging compared with earlier studies.
In contrast, no experimental group patients underwent conventional treatment during the study. Changes in serum PSA and LNCaP cell growth from baseline to 12 months were significantly different between the groups, showing more favorable changes in the experimental group.
Specifically serum PSA decreased an average of 0.25 ng/ml or 4% of the baseline average in the experimental group but it showed an average increase of 0.38 ng/ml or 6% of the baseline average in the control group (F 5.6, p 0.016, fig. 1). Serum from experimental group patients inhibited LNCaP cell growth by 70%, whereas serum from control group patients inhibited growth by only 9% (p 0.001, fig. 2). CRP decreased more in the experimental group (p 0.07). There were no significant differences between the groups in serum testosterone or in apoptosis (table 3). Pearson correlations between changes in serum PSA, LNCaP, apoptosis, testosterone and CRP, and following recommended lifestyle changes in the entire sample indicated that the extent to which participants made changes in diet and lifestyle was significantly related to decreases in PSA (r 0.23, p 0.035, fig. 3) and to LNCaP cell growth (r 0.37, p 0.001, fig. 4).
DEAN ORNISH, GERDI WEIDNER, WILLIAM R. FAIR, RUTH MARLIN, ELAINE B. PETTENGILL, CAREN J. RAISIN, STACEY DUNN-EMKE, LILA CRUTCHFIELD, F. NICHOLAS JACOBS, R. JAMES BARNARD, WILLIAM J. ARONSON, PATRICIA MCCORMAC, DAMIEN J. MCKNIGHT, JORDAN D. FEIN, ANN M. DNISTRIAN, JEANMAIRE WEINSTEIN, TUNG H. NGO, NANCY R. MENDELL AND PETER R. CARROLL‡ From the Departments of Urology (PRC) and Medicine (DO) and Preventive Medicine Research Institute (DO, RM, EBP, CJR, SDE, LC, PM, DJM, JDF, JW, GW), University of California-San Francisco, San Francisco and Departments of Physiological Science (RJB, THN) and Urology (WJA), University of California-Los Angeles, Los Angeles, California, Department of Urologic Oncology, Memorial SloanKettering Cancer Center (WRF and AMD), New York and Department of Statistics, State University of New York at Stony Brook (NRM), Stony Brook, New York, and Windber Research Institute (FNJ), Johnstown, Pennsylvania ABSTRACT