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Journal of Clinical Oncology, Vol 25, No 10 (April 1), 2007: pp. 1285-1287 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.01.001
Wine for Appetite Loss: "How Do You Know?"
From the Oncology Division, Washington University, St Louis, MO; and the Department of Oncology, Mayo Clinic, Rochester, MN Address reprint requests to Aminah Jatoi, MD, Mayo Clinic, Department of Oncology, 200 First St SW, Rochester, MN 55905; e-mail: jatoi.aminah{at}mayo.edu INTRODUCTION Patients often ask me, "How do I protect myself from unfounded medical recommendations?" My advice to them is to respond to any opinion, from any healer, no matter how seemingly reliable, with, "How do you know?"1 Should recommendations for palliating loss of appetite in cancer patients be subject to this same degree of questioning? We contend the answer is "yes." Invariably, cancer patients list appetite loss as one of their five most common and distressing end-of-life symptoms.2 Two other points further underscore its negative impact. First, appetite loss carries far-reaching negative social ramifications. Strife can occur at mealtime because of it. McClement et al3 followed the course of 13 cancer patients, 23 bereaved family members, and 11 health care providers in an inpatient hospice service and concluded that this symptom was often the nidus for negative interactions between patients, family members, and health care providers. Second, appetite loss predicts an early demise. In a North Central Cancer Treatment Group study, Loprinzi et al4 studied 1,115 patients with colorectal and lung cancer. Evaluating patient-reported quality of life data, these investigators observed that poor food intake was a powerful, independent predictor of compromised survival. Thus, undeniably, appetite loss is a major end-of-life symptom. Recommending palliative strategies—strategies that meet rigorous, scientifically proven thresholds of efficacy—should apply to its palliation, as they do to any other aspect of cancer care. What do major cancer organizations recommend? If one surveys patient-directed nonprescription recommendations for palliating loss of appetite from major cancer organizations around the world, one recommendation appears over and over. Simply paraphrased, it reads as follows, "With your doctor's approval, enjoy a glass of wine before eating." This recommendation crops up on multiple patient-oriented Web sites, including those from the American Cancer Society, the National Cancer Institute, the Oncology Nursing Society, and the American Society of Clinical Oncology (Table 1). Surprisingly, despite the near ubiquitous nature of this recommendation, to our knowledge, there has never been a clinical trial that has examined the use of alcoholic beverages, such as wine, for the palliation of appetite loss in patients with cancer. More importantly, to claim that wine stimulates appetite in patients with cancer suffering from poor appetite just because it seems do so in healthy individuals with healthy appetites (as discussed herein) represents a giant leap of faith to what, we believe, is an unproven conclusion.
Admittedly, the hypothesis that wine boosts appetite among patients with cancer is not farfetched. First, for centuries, wine has been paired with food. Indeed, the French word "aperitif" refers to "appetite" and describes an alcoholic beverage that is thought to stimulate appetite at mealtime.5,6 Originally used for general medicinal purposes in the 1500s, many of these beverages became popular in the United States in the early 1900s and are now often served along with food, in part, because of their presumed orexigenic effects. This long cultural history that pairs the "aperitif" with food suggests that the former may in fact be valued for its original, less well-defined "medicinal purposes." Of note, however, a history of resorting to wine to palliate appetite loss in cancer patients appears less well documented. Second, a sizable epidemiologic literature describes a direct relationship between alcohol consumption and weight gain or between alcohol consumption and increased caloric intake. Comprising a robust compilation of literature, these studies do not focus on patients with active cancer. Instead, they focus on data from the Nurses' Health Study II, which included 49,324 women; the British Regional Heart Study, which included 7,735 men; the European Prospective Investigation into Cancer and Nutrition, which included 100,000 women; the National Health Interview Survey, which included 45,896 individuals; a Finnish study, which included 12,669 individuals; the Health Professionals Follow Up Study, which included 138,031 individuals; and the National Health and Nutrition Examination Survey, which included 10,428 individuals.7-13 Each of these studies shows that alcohol intake is associated with either increased caloric intake and/or weight gain in general populations. For example, the Health Professionals Follow Up Study found that average energy consumption was 7,575 kJ/d in abstainers, whereas it was 9,821 kJ/d in heavy alcohol users.12 Not all studies have consistently reported such positive findings, but negative studies might perhaps be explained by their failure to: (1) adjust for smoking, which is associated with decreased caloric intake and lower body mass index; (2) report frequency of alcohol consumption, instead of the average volume over time; or (3) capture gender differences which suggest that women might require more alcohol to induce weight gain. Once again, however, lacking are epidemiologic studies that show this same association between wine intake and weight gain specifically in cancer patients. Interestingly, the increased energy intake attributed to wine in individuals without cancer seems to represent more than an increased calorie source from the wine itself. Described as the "wine paradox," this phenomenon is well recognized and refers to the fact that individuals clearly do not eat less during a meal after having received wine before that meal.14 In other words, there is no compensatory reduction in caloric intake during a meal following alcohol ingestion. Individuals eat a full meal with "extra" calories coming from the alcohol. Third, several smaller studies in healthy case subjects have attempted to capture evidence of wine's orexigenic effects and to explore potential mechanisms to explain such observations. For example, in one often-cited study, Westerterp-Plantega et al15 examined 52 individuals and evaluated several types of pre-meal beverages, including a dry white wine that contained 10% alcohol (1 MJ) as well as nonalcoholic isocaloric drinks that contained fats, proteins, or carbohydrates. Also included in the study design was an option for just plain water and/or no premeal drink. These investigators observed that ad libitum food consumption was increased over a 24-hour period after the ingestion of the dry white wine as opposed to other nonalcoholic premeal beverages. With wine, energy intake was greater (3.5 MJ v 2.7 MJ), rate of eating was faster (44 g/min v 38 g/min), and meal duration was longer (14 minutes v 12 minutes). In addition, satiation occurred later (3.5 minutes v 1.5 minutes), and eating after satiation continued for a longer period (2.5 minutes v 0.6 minutes). This small study suggests that wine carries appetite-stimulatory effects that even override satiety. Thus, at least in healthy individuals, wine appears to whet the appetite. Once again, to our knowledge, for patients with advanced cancer, whose aberrant appetite is often commonplace, similar preliminary studies have not been reported. Furthermore, in exploring the mechanisms behind the orexigenic effect of wine, investigators have invoked leptin suppression and alterations in a variety of other neurotransmitters and hormones, including neuropeptide Y, serotonin, gamma aminobutyric acid, and glucagon-like peptide-1.16 Perhaps wine stimulates appetite as a result of its effects on such mediators. These mechanisms add further plausibility to the hypothesis that wine may help cancer patients. However, Davis et al17 have reviewed the hormonal mediation of appetite loss in cancer patients and have concluded that the hormonal milieu in cancer patients seems different from that observed in healthy individuals. This conclusion, that the hormonal environment of cancer patients with appetite loss may be at odds, further underscores the need to search among cancer patients themselves for such wine-induced hormonal changes that may possibly result in appetite improvement. Hence, how should we respond to patients who learn about this widespread recommendation to drink wine and then ask us, "How do you know?" Do we have rigorous accurate data to provide patients with a solid recommendation to rely on wine to palliate their appetite loss? We do not think so. Conspicuously lacking—amid all the cultural, epidemiologic, and pilot evidence—are parallel data in cancer patients. Conspicuously absent, to our knowledge, is even a single clinical trial that attempts to either prove or debunk the hypothesis that wine stimulates appetite in cancer patients. Conspicuously missing is any study that shows that wine is well tolerated in cancer patients and does not cause undue sedation, metabolic complications, or other unexpected adverse events. Finally, conspicuously unavailable are studies that demonstrate that wine works the same or better than other well-established orexigenic agents for cancer patients, such as progesterones or corticosteroids.18,19 In response to, "How do you know?," at this time, we can only say, "We don't." Yet, since 1974, when Moertel et al20 published the first placebo-controlled trial on appetite and weight loss in patients with advanced cancer, other researchers have conducted numerous highly rigorous studies to enable health care providers to offer recommendations to cancer patients for appetite stimulation based on hard, reliable, robust data.21-23 We may not have such data on wine now, but there is no question that it is within our grasp to acquire it. Finally, the quote at the beginning of this article represents a response to the charged scientific and ethical controversy from several years ago surrounding high-dose chemotherapy for the treatment of breast cancer.1 This emphasis on the need for circumspection, accuracy, and reliance on evidence-based medicine when advising patients remains forever timely and relevant, and is summarized toward the end of that article as follows: So, when our patients ask us, "How do you know?" we will answer with assurance that clinical trials have shown us the way ... .1 We owe our cancer patients just as much questioning, just as much exacting circumspection, and just as much scientific rigor in our approach to their end-of-life symptoms. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest.
NOTES Authors' disclosures of potential conflicts of interest are found at the end of this article. REFERENCES
1. Norton L: High-dose chemotherapy for breast cancer: "How do you know?" J Clin Oncol 19:2769-2770, 2001 2. Sarhill N, Mahmoud F, Walsh D, et al: Evaluation of nutritional status in advanced metastatic cancer. Support Care Cancer 11:652-659, 2003[CrossRef][Medline] 3. McClement SE, Degner LF, Harlos M: Family responses to declining intake in a terminally ill relative. J Palliat Care 20:93-100, 2004[Medline] 4. Loprinzi CL, Laurie JA, Wieand HS, et al: Prospective evaluation of prognostic variables from patient-completed questionnaires: North Central Cancer Treatment Group. J Clin Oncol 12:601-607, 1994[Abstract] 5. Grimes W: The aperitif moment: Sip or flinch. http://www.tedhaigh.com/Aperitif.pdf 6. Cocktail Times: The history of spirits: History of aperitif. http://www.cocktailtimes.com/history/aperitif.shtml 7. Wannamethee SG, Field AE, Colditz GA, et al: Alcohol intake and 9-year weight gain in women: A prospective study. Obes Res 12:1386-1396, 2004[Medline] 8. Wannamethee SG, Shaper AG: Alcohol, body weight, and weight gain in middle-aged men. Am J Clin Nutr 77:1312-1317, 2003 9. Kesse E, Clavel-Chapelon F, Slimani N, et al: Do eating habits differ according to alcohol consumption? Results of a study of the French cohort of the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 74:322-327, 2001 10. Breslow RA, Smothers BA: Drinking patterns and body mass index in never smokers. Am J Epidemiol 161:368-376, 2005 11. Rissan AM, Heliovaara M, Knekt P, et al: Determinants of weight gain and overweight in adult Finns. Eur J Clin Nutr 45:419-430, 1991[Medline] 12. Colditz GA, Giovannucci E, Rimm EB, et al: Alcohol intake in relation to diet and obesity in women and men. Am J Clin Nutr 54:49-55, 1991 13. Gruchow HW, Sobocinski KA, Barboriak JJ, et al: Alcohol consumption, nutrient intake and relative body weight among US adults. Am J Clin Nutr 42:289-295, 1985 14. Jequier E: Alcohol intake and body weight: A paradox. Am J Clin Nutr 69:173-174, 1999 15. Westerterp-Plantenga MS, Verwegen CRT: The appetizing effect of an aperitif in overweight and normal-weight humans. Am J Clin Nutr 69:205-212, 1999 16. Yeomans MR, Caton S, Hetherington MM: Alcohol and food intake. Curr Opin Clin Nutr Metab Care 6:639-644, 2003[Medline] 17. Davis MP, Dreicer R, Walsh D, et al: Appetite and cancer-associated anorexia: A review. J Clin Oncol 22:1510-1517, 2004 18. Loprinzi CL, Ellison NM, Schaid DJ, et al: Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. J Natl Cancer Inst 82:1127-1132, 1990 19. Loprinzi CL, Kugler JW, Sloan JA, et al: Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 17:3299-3306, 1999 20. Moertel CG, Schutt AJ, Reitemeier RJ, et al: Corticosteroid therapy of preterminal cancer. Cancer 33:1607-1609, 1974[CrossRef][Medline] 21. Fearon KC, Barber MD, Moses AG, et al: Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. J Clin Oncol 24:3401-3407, 2006 22. Strausser F, Luftner D, Possinger K, et al: Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multi-center, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia Study Group. J Clin Oncol 24:3394-3400, 2006 23. Bruera E, Strasser F, Palmer JL, 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 Submitted September 1, 2006; accepted September 11, 2006.
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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