Combined Nutritional and Exercise Interventions for Cachexia in Chronic Diseases: A Systematic Review and...

Cachexia is a condition marked by weight loss and reduced skeletal muscle mass, with or without the loss of fat mass, commonly occurring in patients with chronic diseases such as cancer and heart failure, on a background of inflammation. Interventions that combine nutrition and exercise may offer greater benefits than either approach alone in mitigating cachexia-related impairments. Nevertheless, their overall impact remains unclear. The aim of this review was to evaluate the effectiveness of combined nutritional and exercise interventions for cachexia in patients with chronic diseases.

We conducted searches via PubMed, the Cochrane Library, Embase, CINAHL, PEDro, ICTRP, and ClinicalTrials.gov through to 3 December 2024. Eligible studies were intervention studies or observational studies comparing combined nutritional and exercise interventions with control conditions, which included usual care or unimodal interventions (nutrition or exercise alone), in patients diagnosed with cachexia according to the Evans or Fearon criteria. The assessed outcomes included body weight, body composition, mortality, activities of daily living, physical function, exercise tolerance, and quality of life.

Of 1926 identified records, five studies involving only patients with cancer met the inclusion criteria. There is significant uncertainty regarding how combined interventions impact mortality rates compared to control groups (two studies, 66 participants: odds ratio 1.15, 95% confidence interval 0.13-9.97; I² = 0%; evidence of very low certainty). Meta-analyses for other outcomes could not be performed because of sparse and heterogeneous data. We also identified 22 ongoing trials involving patients with cancer, chronic kidney disease, and AIDS, with results pending.

Current evidence regarding combined nutritional and exercise interventions for cachexia is of very low certainty, and no high-quality evidence currently exists to support their effectiveness. Findings across studies are inconsistent, and further rigorous, well-designed trials are urgently needed. The development and adoption of core outcome sets will be essential to enable future meta-analyses. Results from ongoing trials are awaited.