2 results
Loss of adipose tissue mass during chemotherapy predicts reduced survival in patients with colorectal cancer treated with palliative intent
- Erin Stella Sullivan, Louise E. Daly, Éadaoin B Ní Bhuachalla, Samantha J. Cushen, Derek G. Power, Aoife M Ryan
-
- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E149
-
- Article
-
- You have access Access
- Export citation
-
Obesity is an established risk factor for colorectal cancer (CRC), however little is known about changes in body composition during chemotherapy and its impact on survival. The aim of this study was to examine in patients with CRC: (1) The prevalence of abnormal body composition phenotypes, (2) The impact of baseline body composition on overall survival, (3) Changes in body composition throughout treatment and its impact on overall survival.
A prospective study of adult CRC patients undergoing chemotherapy between 2012–2016 was conducted. Longitudinal changes in body composition were examined using computed tomography (CT) images at two timepoints (interval 7 months, IQR: 5–9 months) using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-offs. Cox proportional-hazards models were used to estimate mortality hazard ratios, adjusted for known prognostic covariates – stage, age, sex, performance status & systemic inflammation.
In total, 268 patients were recruited (66% male, mean age 63 years) and 51% were undergoing chemotherapy with a palliative intent. At baseline, 4% were underweight (BMI < 20 kg/m2), 38% had a normal BMI, and 58% were overweight/obese. Despite this, 38% had cancer cachexia, 34% were sarcopenic and 43% had low MA. Neither sarcopenia, sarcopenic obesity nor cachexia at baseline predicted survival. Over 100 days, 68% were muscle stable (± 1 kg), while 25% lost > 1 kg and 7% gained > 1 kg. Fat mass remained stable ± 1 kg in 49%, while 28% lost > 1 kg and 23% gained > 1 kg. When adjusted for known prognostic covariates, baseline BMI (20–25 kg/m2) in those having palliative chemotherapy was independently associated with reduced survival compared to those with BMI indicating overweight (BMI 25–30 kg/m2) [HR: 1.80 (95% CI: 1.04–3.14), p = 0.037]. In those undergoing chemotherapy with palliative intent, a loss of > 6.4% subcutaneous fat (Q1 SAT) over 100 days was predictive of poor survival versus those with small losses, remaining stable or gaining SAT (Q2-4), independent of changes in muscle mass [HR: 2.22 (95% CI: 1.07–4.62), p = 0.033].
Patients with CRC, particularly those treated with a palliative intent, experience significant losses in muscle and fat mass during chemotherapy. Loss of SAT mass during palliative chemotherapy is prognostic of poor survival, independent of changes in muscle mass. Baseline BMI in the overweight range confers a survival advantage. Nutritional strategies to prevent or attenuate weight loss during chemotherapy are advisable especially in the context of advanced CRC.
A phase 1, single-blind, placebo-controlled, 3-arm cross-over trial assessing the appetite enhancing effects of potentially ghrelinergic dairy-derived peptides
- Samantha J. Cushen, Erin Stella Sullivan, Tracey Kelly, Louise E. Daly, Éadaoin B Ní Bhuachalla, Ken Howick, Harriët Schellekens, John F. Cryan, Brendan T. Griffin, Darren Dahly, Aoife M Ryan
-
- Journal:
- Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
- Published online by Cambridge University Press:
- 10 June 2020, E121
-
- Article
-
- You have access Access
- Export citation
-
Methods to stimulate appetite in the sick or elderly remains a challenge with few safe therapeutic options. Ghrelin is an orexigenic hormone, increasing appetite and subsequent food intake. It has received considerable attention as a therapeutic target to stimulate food intake in patients with anorexia. The identification of food-grade bioactives with proven orexigenic effects would mark significant progress in the treatment of disease-related malnutrition. This study therefore investigated the effects of two milk-derived ghrelinergic peptides on appetite and energy intake in healthy humans.
A single-blind, placebo-controlled, 3-arm (placebo, casein bioactive MF1145 and whey bioactive UL-2-141) cross-over trial was conducted in healthy male volunteers. Participants received 26 mg/kg of both the bioactives and placebo. The main outcome measures were energy & protein intake from a set breakfast and ad libitum lunch and subjective appetite sensations as assessed by visual analogue scale (VAS). Basal and postprandial levels of active ghrelin (AG) were measured. Dietary intakes were analysed using Nutritics software. Statistical analyses were performed in R.
Overall, 22 male participants (mean age 27 years) were included, average BMI was 24.6 kg/m2, (19.8 to 30.2 kg/m2). Mean energy and protein intakes at lunch when treated with placebo were 1343 kcal (95% CI: 1215–1471 kcal) and 74 g (95% CI: 66–81 g), respectively. Energy and protein intakes were not significantly different from placebo for either treatment (p = 0.918, p = 0.319 for UL-2-141 and p = 0.889, p = 0.959 for MF1145, respectively). Similarly, appetite, hunger and satiety responses on VAS were not significantly different from placebo for either treatment. AG peak post-lunch on placebo was 653 pg/ml (95% CI: 511–794 pg/ml). Treatment with UL-2-141 resulted in 139 pg/ml reduction in post-prandial AG compared to placebo and treatment with MF1145 resulted in 114 pg/ml reduction compared to placebo. This pattern was significant for both treatments (p = 0.021 and p = 0.045, respectively) however when controlling for fasting-AG, the pattern was no longer significant (p = 0.590 and p = 0.877 respectively). Pre-prandial AG peaks were not significantly different across treatments.
While these peptides have previously demonstrated ghrelinergic effects in rats, no effect on appetite or food intake in humans was identified by this study. This may be attributable to the small sample size or low dose. However, since healthy adults are often not in tune with their own physiological hunger, they may not respond strongly to simple physiological modulators and repeating the study in subjects with established anorexia may be prudent.