Can Antioxidants Reduce Pain from Chronic Pancreatitis?
A randomized, placebo-controlled trial published in the September issue of Gastroenterology found that antioxidants do not reduce pain or improve quality of life in patients with chronic pancreatitis—at least for middle-aged patients with alcohol- or smoking-related disease.
Chronic pancreatitis is characterized by inflammation of the pancreas, with loss of normal pancreatic parenchymal architecture and varying degrees of fibrosis. It causes chronic unremitting and incapacitating abdominal pain, and there is no specific therapy.
One factor that could contribute to development of chronic pancreatitis is exposure of acinar cells to oxygen free radicals (oxidative stress), so antioxidants (such as selenium, vitamin C, and methionine) might reduce acinar injury and pain.
Ajith Siriwardena et al. tested the effects of antioxidants; they randomly assigned 92 patients (average age of 50) with chronic pancreatitis and pain to groups that were given mixture of antioxidants (a daily dose of 38.5 mg selenium yeast, 113.4 mg d-α-tocopherol, 126.3 mg ascorbic acid, 480 mg l-methionine, and 4.2 mg β-carotene) or placebo for 6 months.
They found that antioxidants did not reduce pain scores any more than placebo over the 6-month trial (see below figure); nor were there any differences in pain scores from patient diaries, quality of life, or need for analgesics or hospitalization.
Although serum levels of antioxidants (vitamin C and E, β-carotene, and selenium) increased significantly in the group given antioxidants, there were no differences in painful or painless days between groups.
These findings differed from those from a randomized trial reported in Gastroenterology in 2009 by Payal Bhardwaj et al., which found that antioxidants (a daily dose of 600 μg organic selenium, 0.54 g ascorbic acid, 9000 IU β-carotene, 270 IU α-tocopherol, and 2 g methionine) did reduce pain in patients with chronic pancreatitis. Bhardwaj et al. reported that patients given the antioxidants had 7.3 fewer painful days per month after they took the antioxidants, whereas patients given placebo had only 3.2 fewer painful days per month. However, this study population included younger patients (an average age of 30), and only 40 of the 147 subjects had alcohol-related disease—this differs from the older patients with alcohol-associated disease typically seen in Europe and the US.
In an editorial, Chris Forsmark and Rodger Liddle explain that antioxidants could be less effective for older patients with pancreatitis associated with alcohol use, and those who are not already undernourished (or perhaps already deficient in antioxidants). In support of this, the study of Bhardwaj et al. observed, in a subgroup analysis, that patients with chronic pancreatitis associated with alcohol use did not benefit from the antioxidants. The results from the 2 studies might also differ because the participants in each study were given different antioxidants.
Furthermore, in the study of Siriwardena et al., 80% of subjects were smokers, whereas smokers comprised only 28% of subjects in the study of Bhardwaj et al. Smoking is an important risk factor for chronic pancreatitis.
Forsmark and Liddle conclude that the routine use of antioxidants for chronic pancreatitis should be questioned—particularly for the typical middle-aged male patient with alcoholic or smoking-induced chronic pancreatitis.
More Information on Chronic Pancreatitis
- The National Library of Medicine Website on Chronic Pancreatitis
- The National Institutes of Health Medline Plus Website on Chronic Pancreatitis
Read the article online.
Siriwardena A, Mason JM, Sheen AJ, et al. Antioxidant therapy does not reduce pain in patients with chronic pancreatitis: the anticipate study. Gastroenterology 2012;143:655-663.e1.
Read the accompanying editorial.
Forsmark CE, Liddle RA. The challenging task of treating painful chronic pancreatitis. Gastroenterology 2012;143:533-535.
Read the 2009 paper by Payal Bhardwaj et al.
Bhardwaj P, Garg PK, Maulik SK, et al. A randomized controlled trial of antioxidant supplementation for pain relief in patients with chronic pancreatitis. Gastroenterology 2009;136:149-159.e2.