This podcast reviews the results of the observational study by Ladas and colleagues that found protective associations between dietary antioxidant intake and the occurrence of bacterial infections and mucositis.

TRANSCRIPT

This JCO podcast provides observations and commentary from the JCO article "The Protective Effects of Dietary Intake of Antioxidants and Treatment-Related Toxicity in Childhood Leukemia, A Report From the DALLT Cohort" by Ladas et al.

My name is Wendy Demark-Wahnefried, and I am Webb Endowed Chair and Professor of Nutrition Sciences at the University of Alabama at Birmingham, as well as the Associate Director for Cancer Prevention and Control at the O'Neal Comprehensive Cancer Center at UAB in Birmingham, Alabama in the United States. I do not have any relationships to disclose regarding these studies, and my review is grounded by the fact that I am a nutrition scientist with particular expertise in cancer survivorship.

The topic of nutrition and cancer generates a great deal of interest, especially once individuals are diagnosed with cancer. This is particularly germane with regard to antioxidants, since some scientists hypothesize that high levels of antioxidants may be beneficial for cancer control while others speculate that high levels may prevent apoptosis of cancer cells and actually impede the effectiveness of cancer therapy. However data are sparse, and there are very few studies of high quality, therefore the paper by Ladas and colleagues is both timely and important.

The study enrolled 794 children ages 1 through 18 who were diagnosed with acute lymphoblastic leukemia. These children were enrolled from 10 institutions across the continental United States, Puerto Rico, and Canada. The children or their guardians completed age appropriate food frequency questionnaires that assessed dietary intake over the previous month and did so at two time points, soon after diagnosis and after the induction phase of treatment, or roughly a month after the first questionnaire.

The nutrients that were studied were vitamins A, C, and E, as well as alpha, beta and total carotenoids-- these are the substances in plant foods that give the food its color-- and zinc. It should be noted that the antioxidant selenium was not studied.

Nutrient intake was statistically analyzed in relation to bacterial infection and higher grade mucositis or inflammation of the digestive tract resulting in mouth sores or ulceration of the esophagus. Nutrient intake also was studied in relation to disease-free survival and minimal residual disease. Children were followed for up to 10 years.

Of the 513 participants who completed the dietary surveys at both time points, 23% experienced a bacterial infection, and 16% experienced higher grade mucositis. Only 9% had higher levels of minimal residual disease, and 2% did not achieve complete remission.

Results showed that children having diets with higher levels of antioxidants had a significantly lower risk of bacterial infection, with risk lowered by 10% to 27%, depending upon the antioxidant. Similarly, children having diets with higher levels of antioxidants had a significantly lower risk of higher grade mucositis, with risk lowered by 17% to 67%, again, depending upon the antioxidant.

Importantly, evidence of protection was only observed for nutrients obtained through the diet and not nutritional supplements. In addition, no significant associations were observed between antioxidant intake, either through diet or supplements, and disease-free survival.

This study has several strengths, in that it involved the participation of a diverse and ample sample of several children and their parents across several sites. Furthermore, data were collected at two time points.

As always, there are limitations, and when relying on self-reported data there is always the risk of inaccurate reporting and misclassification. In addition, and thankfully, the number of children who had higher levels of minimal residual disease or who had not experienced complete remission was very small. And therefore, the study was likely under power to detect any associations between nutrient intake and these outcomes.

Finally, because these results emanate from an observational study, cause and effect cannot be inferred. Thus the title of this manuscript, which begins with "The Protective Effects" in quotations, may be a bit of an overstatement. So what are the implications of this study?

As noted previously, there are few data in this area, therefore more studies are needed to either confirm or refute these results. And such research is necessary in other cancer populations, such as among adults with other cancers who receive different therapies. Until such time, these data reinforce that a healthy diet may associate with lower risk of common treatment-related toxicities.

It is noteworthy that investigators were only able to detect protective associations from antioxidants from dietary sources and not from supplements. These data reinforce both the American Institute of Cancer Research and the American Cancer Society guidelines that recommend that nutrients be obtained from foods rather than from supplements.

As such, both clinicians and patients may have an interest in the dietary sources of antioxidants that were studied. Many people already know that citrus fruits are rich sources of vitamin C, but there are also other fruits and vegetables, such as strawberries, cantaloupe, and mangoes, as well as tomatoes, peppers and vegetables in the cabbage family, which also contain high levels of this nutrient. Foods that are high in vitamin E include plant oils, nuts, and seeds.

Dark green and orange vegetables, and fruits, such as spinach, broccoli, sweet potatoes, apricots, and peaches are rich sources of carotenoids, which ultimately can be converted to vitamin A. Alternatively, preformed vitamin A in the diet can be obtained from animal products such as dairy products and eggs. Finally, foods rich in zinc include shellfish, poultry, legumes-- meaning dried beans, peas, and peanuts-- and red meat.

In sum, these data reinforce current guidelines that encourage consumption of a well-balanced plant-based diet that has ample amounts of vegetables and fruit, at least 2 and 1/2 cups a day, as well as whole grains, nuts, seeds, and legumes. Such a diet may be beneficial in preventing common treatment-related toxicities, and larger studies may be able to discern potential associations with cancer-related outcomes such as disease-free survival. However, more study is required.

This concludes this JCO podcast. Thank you for listening.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

For more original research, editorials, and review articles, please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.

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