Feasibility of two levels of protein intake in patients with colorectal cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) randomized controlled pilot trial.

BACKGROUND: Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer. PATIENTS AND METHODS: Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test. RESULTS: Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m2; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: -0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (ß = 0.37; 95% confidence interval 0.08-0.67; P = 0.014). CONCLUSION: Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions.

Regulation of renal 25-hydroxyvitamin D-1-hydroxylase activity in the mouse after uninephrectomy.

Although renal hypertrophy occurs rapidly after uninephrectomy, restoring the majority of renal excretory function, it remains unknown whether similar compensatory mechanisms maintain 1,25-dihydroxyvitamin D production (and calcium homeostasis). To address this issue we compared plasma calcitriol levels and renal 25-hydroxyvitamin D (25OHD)-1-alpha-hydroxylase activity (in remnant kidneys) of mice at various times after uninephrectomy to similar observations obtained in sham-operated age- and sex-matched controls. At all times postoperatively, the uninephrectomized mice sustained plasma 1,25-dihydroxyvitamin D levels no different from those of shams. Maintenance of calcitriol production occurred secondary to a significant increment of renal 25OHD-1 alpha-hydroxylase activity (per mg DNA) 1-3 days after surgery when renal mass/function remained markedly depressed. In contrast, 10 and 21 days postoperatively, when hypertrophy was complete, enhanced enzyme function was no longer apparent. Throughout this period a significant inverse linear correlation existed between renal 25OHD-1 alpha-hydroxylase and the renal mass as well as glomerular filtration rate and renal blood flow. The variance in enzyme activity resulted in maintenance of a stable renal 25OHD-1 alpha-hydroxylase (per animal or total kidney mass) at all times investigated postuninephrectomy. Such compensatory regulation of vitamin D metabolism after unilateral kidney extirpation may be an important factor contributing to the low morbidity/mortality in the renal donor.