European Journal of Nutrition

, Volume 58, Issue 2, pp 797–805 | Cite as

Association between the Dietary Inflammatory Index (DII) and urinary enterolignans and C-reactive protein from the National Health and Nutrition Examination Survey-2003–2008

  • Nitin ShivappaEmail author
  • Michael D. Wirth
  • E. Angela Murphy
  • Thomas G. Hurley
  • James R. Hébert
Original Contribution



Enterolignans are important biomarkers of microbiota diversity, with higher levels indicating greater diversity. Diet and inflammation have been shown to play a role in maintaining microbiota diversity. This study examined whether inflammatory potential of diet, as measured by the Dietary Inflammatory Index (DII®) has an impact on levels of urinary enterolignans in the National Health and Nutrition Examination Survey (NHANES) 2003–2008. We also carried out construct validation of the DII with C-reactive protein (CRP).


Data came from NHANES 2003–2008. Enterolignans [enterodiol (END) and enterolactone (ENL)] and CRP were assayed from urine and serum specimens, respectively. Energy-adjusted DII (E-DII) scores were calculated from food intakes assessed using 24-h dietary recalls and expressed per 1000 calories consumed. Associations were examined using survey-based multivariable linear and logistic regression for enterolignans, and logistic regression for CRP.


After multivariable adjustment, higher E-DII scores (i.e., indicating a relatively more pro-inflammatory diet) were associated with lower levels of creatinine-normalized END [beta coefficient (b)DIIquartile4vs1 = − 1.22; 95% CI = − 0.69, − 1.74; Ptrend ≤ 0.001] and ENL (bDIIquartile4vs1 = − 7.80; 95% CI = − 5.33, − 10.26; Ptrend ≤ 0.001). A positive association was also observed when enterolignans were dichotomized based on the cut-off of the 75th percentile value. In this same sample, the E-DII also was associated with CRP ≥ 3 mg/l (ORDIIcontinuous = 1.12; 95% CI 1.05, 1.19).


In these NHANES data, there was an association between E-DII score and enterolignans. This study also provided construct validation of the E-DII using CRP in a nationally representative sample. The results indicate that dietary inflammatory potential is associated with urinary enterolignans, a potential marker for microbiota diversity. However, studies are required to understand the direct association between DII and microbiota.


Dietary inflammatory index Neterolignans Microbiota USA 


Author contribution

The authors’ contributions were as follows: NS calculated DII, carried out analyses and wrote the first draft of the manuscript, MW, AM, JRH and TH provided suggestions and revised the manuscript. All authors approved the final version of the manuscript.


Drs. Shivappa, Wirth and Hébert were supported by grant number R44DK103377 from the United States National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

Dr. James R. Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company planning to license the right to his invention of the dietary inflammatory index (DII) from the University of South Carolina in order to develop computer and smart phone applications for patient counseling and dietary intervention in clinical settings. Drs. Nitin Shivappa and Michael Wirth are employees of CHI.


  1. 1.
    Valsta LM, Kilkkinen A, Mazur W, Nurmi T, Lampi AM, Ovaskainen ML, Korhonen T, Adlercreutz H, Pietinen P (2003) Phyto-oestrogen database of foods and average intake in Finland. Br J Nutr 89:S31–S38. CrossRefGoogle Scholar
  2. 2.
    Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey A, Harper P (2006) Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. J Nutr 136(12):3046–3053CrossRefGoogle Scholar
  3. 3.
    Cotterchio M, Boucher B, Manno M, Gallinger S (2005) Dietary phytoestrogen intake is associated with reduced colorectal cancer risk. Am J Epidemiol 161(11):S10–S10Google Scholar
  4. 4.
    Lampe JW, Atkinson C, Hullar MAJ (2006) Assessing exposure to lignans and their metabolites in humans. J AOAC Int 89(4):1174–1181Google Scholar
  5. 5.
    Heinonen S, Nurmi T, Liukkonen K, Poutanen K, Wahala K, Deyama T, Nishibe S, Adlercreutz H (2001) In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agr Food Chem 49(7):3178–3186. CrossRefGoogle Scholar
  6. 6.
    Hullar MAJ, Lancaster SM, Li F, Tseng E, Beer K, Atkinson C, Wahala K, Copeland WK, Randolph TW, Newton KM, Lampe JW (2015) Enterolignan-producing phenotypes are associated with increased gut microbial diversity and altered composition in premenopausal women in the United States. Cancer Epidemiol Biomar 24(3):546–554. CrossRefGoogle Scholar
  7. 7.
    Rajagopala SV, Vashee S, Oldfield LM, Suzuki Y, Venter JC, Telenti A, Nelson KE (2017) The human microbiome and cancer. Cancer Prev Res 10(4):226–234. CrossRefGoogle Scholar
  8. 8.
    Hakansson A, Molin G (2011) Gut microbiota and inflammation. Nutrients 3(6):637–682. CrossRefGoogle Scholar
  9. 9.
    Lopetuso LR, Scaldaferri F, Petito V, Gasbarrini A (2013) Commensal clostridia: leading players in the maintenance of gut homeostasis. Gut Pathog. Google Scholar
  10. 10.
    Kedia S, Rampal R, Paul J, Ahuja V (2016) Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India. J Gastroenterol 51(7):660–671. CrossRefGoogle Scholar
  11. 11.
    Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, Abrouk M, Farahnik B, Nakamura M, Zhu TH, Bhutani T, Liao W (2017) Influence of diet on the gut microbiome and implications for human health. J Transl Med 15(1):73. CrossRefGoogle Scholar
  12. 12.
    Shivappa N, Steck SE, Hurley TG, Hussey JR, Hebert JR (2014) Designing and developing a literature-derived, population-based dietary inflammatory index. Public Health Nutr 17(8):1689–1696. CrossRefGoogle Scholar
  13. 13.
    Wirth MD, Shivappa N, Davis L, Hurley TG, Ortaglia A, Drayton R, Blair SN, Hebert JR (2017) Construct validation of the dietary inflammatory index among African Americans. J Nutr Health Aging 21(5):487–491. CrossRefGoogle Scholar
  14. 14.
    Boden S, Wennberg M, Van Guelpen B, Johansson I, Lindahl B, Andersson J, Shivappa N, Hebert JR, Nilsson LM (2017) Dietary inflammatory index and risk of first myocardial infarction; a prospective population-based study. Nutr J 16(1):21. CrossRefGoogle Scholar
  15. 15.
    Shivappa N, Steck SE, Hurley TG, Hussey JR, Ma Y, Ockene IS, Tabung F, Hebert JR (2014) A population-based dietary inflammatory index predicts levels of C-reactive protein in the seasonal variation of blood cholesterol study (SEASONS). Public Health Nutr 17(8):1825–1833. CrossRefGoogle Scholar
  16. 16.
    Shivappa N, Wirth MD, Hurley TG, Hebert JR (2017) Association between the dietary inflammatory index (DII) and telomere length and C-reactive protein from the National Health and Nutrition Examination Survey-1999–2002. Mol Nutr Food Res. Google Scholar
  17. 17.
    Vahid F, Shivappa N, Hekmatdoost A, Hebert JR, Davoodi SH, Sadeghi M (2017) Association between maternal dietary inflammatory index (DII) and abortion in Iranian women and validation of DII with serum concentration of inflammatory factors: case-control study. Appl Physiol Nutr Metab 42(5):511–516. CrossRefGoogle Scholar
  18. 18.
    Tabung FK, Steck SE, Zhang J, Ma Y, Liese AD, Agalliu I, Hingle M, Hou L, Hurley TG, Jiao L, Martin LW, Millen AE, Park HL, Rosal MC, Shikany JM, Shivappa N, Ockene JK, Hebert JR (2015) Construct validation of the dietary inflammatory index among postmenopausal women. Ann Epidemiol 25(6):398–405. CrossRefGoogle Scholar
  19. 19.
    Shivappa N, Hebert JR, Rietzschel ER, De Buyzere ML, Langlois M, Debruyne E, Marcos A, Huybrechts I (2015) Associations between dietary inflammatory index and inflammatory markers in the Asklepios study. Br J Nutr 113(4):665–671. CrossRefGoogle Scholar
  20. 20.
    Wood LG, Shivappa N, Berthon BS, Gibson PG, Hebert JR (2015) Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma. Clin Exp Allergy 45(1):177–183. CrossRefGoogle Scholar
  21. 21.
    Shivappa N, Prizment AE, Blair CK, Jacobs DR Jr, Steck SE, Hebert JR (2014) Dietary inflammatory index and risk of colorectal cancer in the Iowa women’s health study. Cancer Epidemiol Biomark Prev 23(11):2383–2392. CrossRefGoogle Scholar
  22. 22.
    Tabung FK, Steck SE, Ma Y, Liese AD, Zhang J, Caan B, Hou L, Johnson KC, Mossavar-Rahmani Y, Shivappa N, Wactawski-Wende J, Ockene JK, Hebert JR (2015) The association between dietary inflammatory index and risk of colorectal cancer among postmenopausal women: results from the women’s health initiative. Cancer Causes Control CCC 26(3):399–408. CrossRefGoogle Scholar
  23. 23.
    Zamora-Ros R, Shivappa N, Steck SE, Canzian F, Landi S, Alonso MH, Hebert JR, Moreno V (2015) Dietary inflammatory index and inflammatory gene interactions in relation to colorectal cancer risk in the Bellvitge colorectal cancer case-control study. Genes Nutr 10(1):447. CrossRefGoogle Scholar
  24. 24.
    Shivappa N, Godos J, Hebert JR, Wirth MD, Piuri G, Speciani AF, Grosso G (2017) Dietary inflammatory index and colorectal cancer risk—a meta-analysis. Nutrients. Google Scholar
  25. 25.
    Shivappa N, Hebert JR, Rashidkhani B (2015) Dietary inflammatory index and risk of esophageal squamous cell cancer in a case-control study from Iran. Nutr Cancer 67(8):1253–1259. CrossRefGoogle Scholar
  26. 26.
    Shivappa N, Zucchetto A, Serraino D, Rossi M, La Vecchia C, Hebert JR (2015) Dietary inflammatory index and risk of esophageal squamous cell cancer in a case-control study from Italy. Cancer Causes Control CCC 26(10):1439–1447. CrossRefGoogle Scholar
  27. 27.
    Tang L, Shivappa N, Hebert JR, Lee AH, Xu F, Binns CW (2018) Dietary inflammatory index and risk of oesophageal cancer in Xinjiang Uyghur autonomous region, China. Br J Nutr. Google Scholar
  28. 28.
    Shivappa N, Hebert JR, Anderson LA, Shrubsole MJ, Murray LJ, Getty LB, Coleman HG (2017) Dietary inflammatory index and risk of reflux oesophagitis, Barrett’s oesophagus and oesophageal adenocarcinoma: a population-based case-control study. Br J Nutr 117(9):1323–1331. CrossRefGoogle Scholar
  29. 29.
    Zheng J, Merchant AT, Wirth MD, Zhang J, Antwi SO, Shoaibi A, Shivappa N, Stolzenberg-Solomon RZ, Hebert JR, Steck SE (2018) Inflammatory potential of diet and risk of pancreatic cancer in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Int J Cancer. Google Scholar
  30. 30.
    Antwi SO, Oberg AL, Shivappa N, Bamlet WR, Chaffee KG, Steck SE, Hebert JR, Petersen GM (2016) Pancreatic cancer: associations of inflammatory potential of diet, cigarette smoking and long-standing diabetes. Carcinogenesis 37(5):481–490. CrossRefGoogle Scholar
  31. 31.
    Shivappa N, Bosetti C, Zucchetto A, Serraino D, La Vecchia C, Hebert JR (2015) Dietary inflammatory index and risk of pancreatic cancer in an Italian case-control study. Br J Nutr 113(2):292–298. CrossRefGoogle Scholar
  32. 32.
    Graffouillere L, Deschasaux M, Mariotti F, Neufcourt L, Shivappa N, Hebert JR, Wirth MD, Latino-Martel P, Hercberg S, Galan P, Julia C, Kesse-Guyot E, Touvier M (2016) The dietary inflammatory index is associated with prostate cancer risk in French middle-aged adults in a prospective study. J Nutr. Google Scholar
  33. 33.
    Shivappa N, Miao Q, Walker M, Hebert JR, Aronson KJ (2017) Association between a dietary inflammatory index and prostate cancer risk in Ontario, Canada. Nutr Cancer 69(6):825–832. CrossRefGoogle Scholar
  34. 34.
    Shivappa N, Hebert JR, Askari F, Kardoust Parizi M, Rashidkhani B (2017) Increased inflammatory potential of diet is associated with increased risk of prostate cancer in Iranian men. Int J Vitam Nutr Res. Google Scholar
  35. 35.
    Shivappa N, Jackson MD, Bennett F, Hebert JR (2015) Increased dietary inflammatory index (DII) is associated with increased risk of prostate cancer in Jamaican men. Nutr Cancer 67(6):941–948. CrossRefGoogle Scholar
  36. 36.
    Shivappa N, Jalilpiran JRH, Faghih Y S (2018) Association between dietary inflammatory index and prostate cancer in Shiraz province of Iran. Asian Pac J Cancer Prev APJCP 19(2):415–420. Google Scholar
  37. 37.
    Shivappa N, Bosetti C, Zucchetto A, Montella M, Serraino D, La Vecchia C, Hebert JR (2015) Association between dietary inflammatory index and prostate cancer among Italian men. Br J Nutr 113(2):278–283. CrossRefGoogle Scholar
  38. 38.
    Shivappa N, Godos J, Hebert JR, Wirth MD, Piuri G, Speciani AF, Grosso G (2018) Dietary inflammatory index and cardiovascular risk and mortality—a meta-analysis. Nutrients. Google Scholar
  39. 39.
    Shivappa N, Hebert JR, Kivimaki M, Akbaraly T (2017) Alternate Healthy Eating Index 2010, Dietary Inflammatory Index and risk of mortality: results from the Whitehall II cohort study and meta-analysis of previous Dietary Inflammatory Index and mortality studies. Br J Nutr 118(3):210–221. CrossRefGoogle Scholar
  40. 40.
    Bondonno NP, Lewis JR, Blekkenhorst LC, Shivappa N, Woodman RJ, Bondonno CP, Ward NC, Hebert JR, Thompson PL, Prince RL, Hodgson JM (2017) Dietary Inflammatory Index in relation to sub-clinical atherosclerosis and atherosclerotic vascular disease mortality in older women. Br J Nutr 117(11):1577–1586. CrossRefGoogle Scholar
  41. 41.
    Shivappa N, Schneider A, Hebert JR, Koenig W, Peters A, Thorand B (2018) Association between dietary inflammatory index, and cause-specific mortality in the MONICA/KORA Augsburg cohort study. Eur J Public Health 28(1):167–172. CrossRefGoogle Scholar
  42. 42.
    Zucchetto A, Gini A, Shivappa N, Hebert JR, Stocco C, Dal Maso L, Birri S, Serraino D, Polesel J (2016) Dietary Inflammatory Index and prostate cancer survival. Int J Cancer 139(11):2398–2404. CrossRefGoogle Scholar
  43. 43.
    Laboratory Procedure Manual (2017) Phytoestrogens in urine NHANES 2009–2010. Bioactive Dietary Compounds Laboratory (BDCL); Nutritional Biomarkers Branch (NBB); Division of Laboratory Sciences (DLS); National Center for Environmental Health (NCEH). Accessed 26 Sept 2017
  44. 44.
    Laboratory Procedure Manual (2017) Urinary creatinine. University of Minnesota, January 2011. Accessed 26 Sept 2017
  45. 45.
    Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO III, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107(3):499–511CrossRefGoogle Scholar
  46. 46.
    Oda E, Oohara K, Abe A, Veeraveedu PT, Watanabe K, Kato K, Aizawa Y (2006) The optimal cut-off point of C-reactive protein as an optional component of metabolic syndrome in Japan. Circ J 70(4):384–388CrossRefGoogle Scholar
  47. 47.
    Hennis A, Wu SY, Nemesure B, Leske MC, Barbados Eye Studies G (2004) Risk factors for incident cortical and posterior subcapsular lens opacities in the barbados eye studies. Arch Ophthalmol 122(4):525–530. CrossRefGoogle Scholar
  48. 48.
    Steele EM, Monteiro CA (2017) Association between dietary share of ultra-processed foods and urinary concentrations of phytoestrogens in the US. Nutrients. Google Scholar
  49. 49.
    Reger MK, Zollinger TW, Liu Z, Jones J, Zhang J (2016) Urinary phytoestrogens and cancer, cardiovascular, and all-cause mortality in the continuous National Health and Nutrition Examination Survey. Eur J Nutr 55(3):1029–1040. CrossRefGoogle Scholar
  50. 50.
    Neill AS, Ibiebele TI, Lahmann PH, Hughes MC, Nagle CM, Webb PM, Australian Ovarian Cancer Study G, Australian National Endometrial Cancer Study G (2014) Dietary phyto-oestrogens and the risk of ovarian and endometrial cancers: findings from two Australian case-control studies. Br J Nutr 111(8):1430–1440. CrossRefGoogle Scholar
  51. 51.
    Landete JM, Arques J, Medina M, Gaya P, de Las Rivas B, Munoz R (2016) Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food Sci Nutr 56(11):1826–1843. CrossRefGoogle Scholar
  52. 52.
    Wirth MD, Shivappa N, Hurley TG, Hebert JR (2016) Association between previously diagnosed circulatory conditions and a dietary inflammatory index. Nutr Res 36(3):227–233. CrossRefGoogle Scholar
  53. 53.
    Shivappa N, Steck SE, Hussey JR, Ma Y, Hebert JR (2017) Inflammatory potential of diet and all-cause, cardiovascular, and cancer mortality in National Health and Nutrition Examination Survey III study. Eur J Nutr 56(2):683–692. CrossRefGoogle Scholar
  54. 54.
    Wirth MD, Shivappa N, Burch JB, Hurley TG, Hebert JR (2017) The Dietary Inflammatory Index, shift work, and depression: results from NHANES. Health Psychol 36(8):760–769. CrossRefGoogle Scholar
  55. 55.
    Deng FE, Shivappa N, Tang Y, Mann JR, Hebert JR (2017) Association between diet-related inflammation, all-cause, all-cancer, and cardiovascular disease mortality, with special focus on prediabetics: findings from NHANES III. Eur J Nutr 56(3):1085–1093. CrossRefGoogle Scholar
  56. 56.
    Valentin-Blasini L, Blount BC, Caudill SP, Needham LL (2003) Urinary and serum concentrations of seven phytoestrogens in a human reference population subset. J Expo Anal Environ Epidemiol 13(4):276–282. CrossRefGoogle Scholar
  57. 57.
    French MR, Thompson LU, Hawker GA (2007) Validation of a phytoestrogen food frequency questionnaire with urinary concentrations of isoflavones and lignan metabolites in premenopausal women. J Am Coll Nutr 26(1):76–82CrossRefGoogle Scholar
  58. 58.
    Basiotis PP, Welsh SO, Cronin FJ, Kelsay JL, Mertz W (1987) Number of days of food-intake records required to estimate individual and group nutrient intakes with defined confidence. J Nutr 117(9):1638–1641CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cancer Prevention and Control ProgramUniversity of South CarolinaColumbiaUSA
  2. 2.Department of Epidemiology and BiostatisticsUniversity of South CarolinaColumbiaUSA
  3. 3.College of NursingUniversity of South CarolinaColumbiaUSA
  4. 4.Connecting Health Innovations, LLCColumbiaUSA
  5. 5.Department of Pathology, Microbiology, and ImmunologyUniversity of South Carolina School of MedicineColumbiaUSA

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