January 2018 Issue

Inflammation and Cancer Risk: Can Anti-Inflammatory Diets Help?
By Karen Collins, MS, RDN, CDN, FAND
Today's Dietitian
Vol. 20, No. 1, P. 12

What the research says may change the way some dietitians counsel patients.

"What are the best anti-inflammatory foods to help reduce my risk of cancer?"

As dietitians, you've probably heard this question from clients. Unfortunately, clients often read articles or see headlines based on single laboratory studies that don't directly translate to evidence-based actionable advice. However, it's the RD's job to help them view anti-inflammatory eating within the big picture of inflammation and cancer risk.

Chronic inflammation plays a role in the development of several chronic diseases. Studies link elevated biomarkers of inflammation to cancer and identify several mechanisms that may be responsible.

• Some cancers are associated with local inflammation. Examples include cancers of the stomach (Helicobacter pylori infection), liver (hepatitis B and C infections), esophagus (Barrett's esophagus and reflux esophagitis), and colon (ulcerative colitis and Crohn's disease).

• Chronic low-grade systemic inflammation also can promote cancer development. Inflammation can increase levels of reactive oxygen and nitrogen species (commonly called "free radicals") that can damage DNA, the first step in cancer development. In addition, inflammatory cytokines activate transcription factors that promote cancer progression through changes in signaling pathways that promote cell proliferation and resistance to cell death.1

What Makes Foods Anti-Inflammatory?
Many factors can lead to chronic low-grade inflammation, and diet offers multiple potential approaches to reduce it.

Nutrients and phytochemicals with potential antioxidant or anti-inflammatory effects are a clear starting point. Vitamins C and E, selenium, and carotenoids provide antioxidants that act in different body compartments to reduce development of reactive species that can initiate cancer development through direct DNA damage or inflammation. A wide range of plant compounds, including polyphenols in tea, berries, onions, nuts, grapes, and spices such as turmeric and ginger, often are referred to as antioxidant or anti-inflammatory. In laboratory studies, these activate antioxidant defenses and reduce inflammatory cell-signaling pathways.2

However, these phytochemicals are broken down into smaller more bioavailable compounds before they leave the digestive tract and circulate through the body. So laboratory tests using the intact phytochemical and even tests in animals that may digest and metabolize the phytochemicals differently from humans only show potential. Human studies are needed to clarify whether these foods or spices are truly anti-inflammatory. Human randomized controlled trials generally use isolates and extracts of compounds. Dose is an important issue in translating these studies into dietary advice. For example, translating amounts of curcumin (from turmeric) and ginger powder showing anti-inflammatory effects in trials to amounts of culinary spices translates to at least 8 tsp per day of turmeric or 1.6 tsp of dried ginger per day.3-7

Small effects from a wide range of vegetables, fruits, whole grains, legumes, nuts, tea, coffee, and spices could add up, and perhaps even act synergistically to provide anti-inflammatory benefits. But working from the perspective of evidence-based practice, dietitians must be clear that current evidence shows potential, not promises, from these foods commonly labeled "anti-inflammatory."

Foods that support health-protective gut bacteria provide other sources of anti-inflammatory cancer protection.8 According to Johanna Lampe, PhD, RD, of Fred Hutchinson Cancer Research Center in Seattle, prebiotics promote growth of gut microbes that may offer protective effects within the colon and perhaps with broader effects on cancer risk. Foods with inulin, inulin-type fructans, and other carbohydrates with demonstrated prebiotic effects include pulses (dried beans, dried peas, chickpeas, and lentils); onions, garlic, and leeks; and both Jerusalem and globe artichokes.

In addition, as gut microbes break down certain other carbohydrates, they produce butyrate and other short-chain fatty acids that nurture cells lining the colon. Butyrate is also a signaling molecule showing protective effects in cancer pathways.8 Foods with fermentable dietary fiber, resistant starch, and beta-glucans that microbes use to produce short-chain fatty acids include pulses, oats, barley, mushrooms, and sorbitol-containing fruits such as apples, pears, raisins, peaches, and plums.

Dietary fiber may act through anti-inflammatory and other mechanisms to reduce cancer risk. Lampe says dietary fiber that's more soluble and more easily fermented has been shown to reduce colon cancer development in animal models, though it's less clear whether this specific effect holds up in relation to colorectal cancer in humans.

Foods supplying omega-3 fatty acids, especially EPA and DHA, provide the starting point for production of anti-inflammatory eicosanoid compounds. Primary EPA and DHA sources are seafood—especially cold-water fish such as sardines, mackerel, herring, and albacore tuna—and algae. It's common for people to read or hear that omega-6 polyunsaturated fats (the major fat in many vegetable oils and nuts) are promoters of inflammation based on earlier laboratory studies, but current research doesn't support this view.9

Human studies haven't found a consistent link to higher fish or omega-3 intake as a strategy to lower cancer risk, but that may partly reflect methodological challenges in such studies. For overall health and potentially anti-inflammatory cancer protection, including more foods that supply omega-3 fat is recommended.9

Body Fat's Association
Excess body fat, especially visceral fat deep within the abdomen, is strongly linked with inflammation.10,11 Adipose tissue secretes proteins (such as interleukin-6 and tumor necrosis factor) that circulate throughout the body, promoting inflammation. And levels of adiponectin, an anti-inflammatory hormone, typically decrease as body fat increases.11

For people with overweight or obesity, even a 5% to 10% reduction in weight, especially when achieved through a combination of diet and exercise, is enough to reduce inflammation biomarkers.12,13 Moreover, emerging evidence suggests that anti-inflammatory effects may start with a change in the balance of calorie consumption compared with calories expended in activity. If substantiated, that would mean each day of more healthful habits could produce benefits even before resulting in weight loss.

Anti-Inflammatory Eating Patterns Over Superfoods
Just as for other aspects of health, overall dietary pattern is likely the best focus for messages about anti-inflammatory diets to reduce cancer risk. This encourages consuming an abundance of foods with potential protection and limiting foods that may have net proinflammatory effects. Studies suggest that excessive amounts of red and processed meats, refined grains, and sugar-sweetened beverages may act through a variety of mechanisms to increase inflammation.

The Dietary Inflammatory Index (DII) is a scoring system that provides one lens through which to view an eating pattern's link to inflammation. The DII is a score based on 45 different nutrients and compounds that research suggests may influence inflammation. Higher DII scores (more inflammatory) are associated with greater risk of elevated hsCRP (high-sensitivity C-reactive protein). More inflammation-promoting diets as identified by DII scores have been linked with greater risk of colorectal cancer especially and with greater overall cancer incidence and mortality.14

Eating patterns also have been studied with Empirical Dietary Inflammatory Pattern (EDIP) scores. This score is based on 18 different food groups, one-half expected to be inflammatory and one-half to be anti-inflammatory. Highest scores on the EDIP (more inflammatory) were associated with 38% to 60% higher levels of inflammation biomarker hsCRP compared with lowest EDIP scores, even after adjusting for other factors that affect inflammation.15 Higher EDIP scores were linked with greater risk of colorectal cancer in an analysis of two prospective cohort studies, with subtype analysis suggesting that the link may involve inflammation suppressing the normal antitumor immune response.16

Although metrics such as the DII and EDIP are valuable as ways to assess dietary questionnaires in research studies on inflammation and disease risk, they aren't practical tools intended for clinical use by dietitians. Studies suggest three important bottom-line talking points for messages about anti-inflammatory diets and lowering cancer risk.

• In virtually all studies, the association of diet quality and inflammation biomarkers becomes weaker when researchers adjust for weight (as BMI). This reflects the significant influence excess body fat has in promoting inflammation. Therefore, an eating pattern that emphasizes foods with anti-inflammatory potential will be most effective in reducing inflammation and lowering cancer risk when it also supports a healthy weight.

• Recommended eating patterns based on anti-inflammatory diet scores are similar to other ways of expressing diet quality. DII scores indicating a more anti-inflammatory diet are associated with healthier Healthy Eating Index-2010, Alternative Healthy Eating Index, and Dietary Approaches to Stop Hypertension Index scores.17 In a systematic review of diet and colorectal cancer risk, anti-inflammatory scores based on DII showed a similar but no stronger link to risk than other established diet quality scores.18

• Discussing anti-inflammatory foods and eating patterns may be useful to gain people's interest but should be viewed and shared within the context of the overall body of research on diet to lower cancer risk. This research reflects anti-inflammatory mechanisms, as well as how dietary choices act through insulin and steroid hormones, epigenetic changes in gene expression, and other cancer-protective roles. Scores based on the American Institute for Cancer Research recommendations for cancer prevention are associated equally or even more strongly with lower risk of cancer.19

— Karen Collins, MS, RDN, CDN, FAND, is a nutrition consultant specializing in cancer prevention and cardiometabolic health, and nutrition advisor to the American Institute for Cancer Research.

References
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2. Li W, Guo Y, Zhang C, et al. Dietary phytochemicals and cancer chemoprevention: a perspective on oxidative stress, inflammation, and epigenetics. Chem Res Toxicol. 2016;29(12):2071-2095.

3. Natural medicines. Therapeutic Research Center website. https://naturalmedicines.therapeuticresearch.com. Updated October 26, 2017. Accessed November 7, 2017.

4. Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL. Curcumin content of turmeric and curry powders. Nutr Cancer. 2006;55(2):126-131.

5. Gantait A, Barman T, Mukherjee PK. Validated method for estimation of curcumin in turmeric powder. Indian J Trad Knowledge. 2011;10(2):247-250.

6. US Department of Agriculture. National Nutrient Database for Standard Reference, Release 28. http://ndb.nal.usda.gov. Updated May 17, 2016. Accessed November 7, 2017.

7. Karimi N, Dabidi Roshan V, Fathi Bayatiyani Z. Individually and combined water-based exercise with ginger supplement, on systemic inflammation and metabolic syndrome indices, among the obese women with breast neoplasms. Iran J Cancer Prev. 2015;8(6):e3856.

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12. Imayama I, Ulrich CM, Alfano CM, et al. Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial. Cancer Res. 2012;72(9):2314-2326.

13. van Gemert WA, May AM, Schuit AJ, Oosterhof BY, Peeters PH, Monninkhof EM. Effect of weight loss with or without exercise on inflammatory markers and adipokines in postmenopausal women: the SHAPE-2 trial, a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2016;25:799-806.

14. Fowler ME, Akinyemiju TF. Meta-analysis of the association between dietary inflammatory index (DII) and cancer outcomes. Int J Cancer. 2017;141(11):2215-2227.

15. Tabung FK, Smith-Warner SA, Chavarro JE, et al. An empirical dietary inflammatory pattern score enhances prediction of circulating inflammatory biomarkers in adults. J Nutr. 2017;147(8):1567-1577.

16. Liu L, Nishihara R, Qian ZR, et al. Association between inflammatory diet pattern and risk of colorectal carcinoma subtypes classified by immune responses to tumor. Gastroenterology. 2017;153(6):1517-1530.e14.

17. Wirth MD, Hébert JR, Shivappa N, et al. Anti-inflammatory Dietary Inflammatory Index scores are associated with healthier scores on other dietary indices. Nutr Res. 2016;36(3):214-219.

18. Steck SE, Guinter M, Zheng J, Thomson CA. Index-based dietary patterns and colorectal cancer risk: a systematic review. Adv Nutr. 2015;6(6):763-773.

19. Romaguera D, Vergnaud AC, Peeters PH, et al. Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study. Am J Clin Nutr. 2012;96(1):150-163.

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