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Fish Oil Supplementation in Patients With Advanced Cancer

Edinburgh Cancer Center, Edinburgh, UK

To the Editor: Weight loss in cancer patients is multifactorial. In some patients, it appears to be related to secretion by the cancer of pro-inflammatory cytokines and tumor-specific cachectic factors. In other patients, reduced dietary intake as a consequence of nausea, vomiting, dysphagia, or anorexia may be more important.

The n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docasahexaenoic acid are immunomodulatory and have been shown to suppress endotoxin-induced production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor, from peripheral blood mononuclear cells.¹ EPA also has antitumor and anticachexia activity in the murine MAC16 colon adenocarcinoma model, used as a model of cancer cachexia.² Studies of EPA supplementation in weight-losing patients with pancreatic cancer have demonstrated stabilization of weight loss and improvement in performance status.^3,4

Bruera et al⁵ investigated the effect of fish oil supplementation on appetite in 60 weight-losing patients with advanced malignancy. The patients had a range of cancer diagnoses, and the etiology of weight loss in these patients was likely to be multifactorial. In addition to this, a number of patients were on agents that could modify appetite in their own right, including corticosteroids (eight patients), antineoplastic hormonal therapy (four patients), and chemotherapy (five patients). There was no baseline performance status requirement in the study, and the fact that 31% of patients dropped out during the 2-week duration of the study would suggest that patients were very frail. This may not be the most appropriate group for nutritional intervention.

The primary end point of the study was appetite. If EPA supplementation exerts its activity by immunological mechanisms, it may be possible to affect nutritional parameters without a direct effect on appetite. This is suggested by the fact that, despite the very small numbers of patients reported in the study, there was a trend toward weight gain in the group supplemented with EPA (0.49 kg ± 6.2 kg) but not in the placebo group (-0.55 kg ± 3.9 kg). This is surprising, given the short duration of treatment in the study.

Weight loss in patients with gastrointestinal cancers is associated with shorter survival time and reduced quality of life.⁶ In well chosen patient groups, nutritional intervention may enhance quality of life, response to antineoplastic therapies, and survival. Potentially useful agents should not be discarded on the basis of poorly controlled studies in disparate patient groups, such as this one.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Meydani SN, Lichtenstein AH, Cornwall S, et al: Immunological effects of National Educational Panel Step-2 diets with and without fish-derived n-3 fatty acid enrichment. J Clin Invest 92:105–113, 1993[Medline]

2. Beck SA, Smith KL, and Tisdale MJ: Anticachectic and antitumour effect of eicosapentaenoic acid and its effect on protein turnover. Cancer Res 51:6089–6093, 1991[Abstract/Free Full Text]

3. Barber MD, Ross JA, Voss A, et al: The effect of oral nutritional supplementation enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer 81:80–86, 2001

4. Fearon KCH, von Meyerfeldt M, Moses AGW, et al: An energy and protein dense, high n-3 fatty acid oral supplement promotes weight gain in cancer cachexia. Eur J Cancer 37:90, 2001 (suppl 6)[CrossRef]

5. Bruera E, Strasser F, Palmer L, et al: Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: A double blind, placebo-controlled study. J Clin Oncol 21:129–134, 2003[Abstract/Free Full Text]

6. Andreyer H, Norman A, Oates J, et al: Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinial malignancies? Eur J Cancer 34:503–509, 1998[CrossRef][Medline]

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