van der Meij BS, Langius JA, Spreeuwenberg MD, et al. Oral nutritional supplements containing n-3 polyunsaturated fatty acids affect quality of life and functional status in lung cancer patients during multimodality treatment: an RCT. Eur J Clin Nutr. Mar 2012;66(3):399-404.
Randomized, double-blind, placebo-controlled trial
40 patients (21 men, 19 women) with stage IIIa or IIIb non-small cell lung cancer (NSCLC) randomized to 2 groups. All participants were 18–80 years old with a prognosis >3 months. Exclusion criteria included surgery, chemotherapy, or radiotherapy for the month prior to enrollment. The study also excluded patients with edema, ascites, severe comorbidities, or high-dose corticosteroid use and those who had consumed fish oil supplements during the previous month. Due to a variety of causes for dropout, at the conclusion of the study only 33 participants (14 in the intervention group, 19 in the control group) were assessed.
Study Medication and Dosage
The intervention group received a liquid supplement (ProSure®) that contained omega-3 fatty acids (2.02 g eicosapentanoic acid and 0.92 docosapentanoic acid). The control group received an isocaloric equivalent (Ensure®). Patients were asked to drink 2 cans daily, but average daily intake was only 1 can.
Quality of life, Karnofsky Performance Status, and physical activity (assessed through wearing an accelerometer) were assessed at baseline and after 3 and 5 weeks. Handgrip strength was assessed weekly.
There was a statistically significant benefit to quality of life in the intervention group. Physical and cognitive function (P<0.01), global health status (P=0.04) and social function (P=0.04) were all higher in the intervention group at 5 weeks. The intervention group also tended to have higher physical activity (P=0.05). Handgrip strength did not differ between the groups. Karnofsky scores were higher at week 3 in the intervention group versus controls (P=0.04), but not at week 5.
Fish oil supplements have been shown to prevent cachexia and improve quality of life in many previous interventional studies.1,2,3 This abstract is yet another dataset corroborating the benefits of fish oil supplementation during conventional cancer treatment.
The combination of chemotherapy and radiation followed by surgery is often used with curative intent in those with stage III NSCLC. In practice, this generally means that greater toxicity is tolerated by the treatment team and the patient in the hope that the possibility of long-term survival is worth it. (This is in contrast with stage IV NSCLC, in which dose reduction of chemo or radiation might be chosen to preserve the patient’s quality of life.) The toxicities from treatment, however, can be life altering. Cachexia not only hampers quality of life but may worsen chemo-radiation toxicities and impact overall mortality.4 Therefore, preventing cachexia in patients undergoing treatment can have profound benefits for patients with NSCLC both during and after treatment.
To be clear, weight loss is not simply due to caloric deficits during conventional treatments; it results from a tumor induced catabolic state.5 In one study of 441 NSCLC patients, 46.7% had sarcopenia (skeletal muscle quantity <2 standard deviations of healthy adults) at the time of diagnosis, regardless of their body mass index (BMI).6 In a separate study of patients with lung cancer, those with sarcopenia before treatment commenced had significantly lower levels of EPA and DHA than non-sarcopenic patients.7 In addition, those with the greatest muscle loss over the course of chemo-radiation treatment had the lowest levels of EPA and DHA. This implies that repletion of fatty acids may be sufficient to confer benefit in patients. Indeed, the optimal anticachetic dose of fish oil has yet to be defined, and while studies often use an intervention of 2.0 gram EPA and 1.0 gram DHA daily, compliance is often only 50–75% of these amounts.
There appear to be many other reasons to use fish oil in our patients with NSCLC. In a small study published in 2011 (n=40), fish oil supplementation (2.5 g EPA + DHA/day) led to greater response to chemotherapy versus a control group (60.0% vs 25.8%, P=0.008).8 The same study also showed a trend toward greater survival at 1 year (60.0% vs 38.7%; P=0.15). Another study that looked at fish oil supplementation in 22 patients with lung cancer found improvements in appetite and fatigue and a lower C-reactive protein.9 Lastly, while preliminary, fish oil has been shown to directly inhibit the growth of lung cancer.10
Repletion of omega-3 fatty acids in patients with NSCLC should be a primary goal. According to the above study, EPA and DHA in amounts of approximately 1.0 g and 0.45 g respectively can affect the quality of life of patients undergoing treatment. There is little question that repletion, and perhaps increased levels of omega-3 fatty acids, confers benefits in patients with lung cancer.
This study sample size is small, and a larger trial is needed to verify these results. Poor compliance with the intended interventional amount of approximately 2.0 grams of EPA and 0.9 grams of DHA daily resulted in a approximately half of that dose.
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- Fearon KC, Von Meyenfeldt MF, Moses AG, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003;52(10):1479-1486.
- Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer. 2011;117(8):1775-1782.
- van der Meij BS, Langius JA, Smit EF, et al. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr. 2010;140(10):1774-1780.
- Ross PJ, Ashley S, Norton A, et al. Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers? Br J Cancer. 2004;90(10):1905-11.
- Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009;89(2):381-410.
- Baracos VE, Reiman T, Mourtzakis M, Gioulbasanis I, Antoun S. Body composition in patients with non–small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr. 2010;91(4):1133S-1137S.
- Murphy RA, Mourtzakis M, Chu QS, Reiman T, Mazurak VC. Skeletal muscle depletion is associated with reduced plasma (n-3) fatty acids in non-small cell lung cancer patients. J Nutr. 2010;140(9):1602-1606.
- Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117(16):3774-3780.
- Cerchietti LC, Navigante AH, Castro MA. Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Nutr Cancer. 2007;59(1):14-20
- Han S, Sun X, Ritzenthaler JD, Roman J. Fish oil inhibits human lung carcinoma cell growth by suppressing integrin-linked kinase. Mol Cancer Res. 2009;7(1):108-117.