Skip to main content Accessibility help

Inverse association between serum antioxidant levels and inflammatory markers is moderated by adiposity: a report based on a large representative population sample of American adults

  • Mohsen Mazidi (a1), Andre Pascal Kengne (a2), Niki Katsiki (a3), Dimitri P. Mikhailidis (a4) and Maciej Banach (a5) (a6) (a7)...


We examined the association between plasma antioxidant levels and markers of inflammation, including C-reactive protein (CRP) and fibrinogen (FG) in US adults. National Health and Nutrition Examination Survey participants examined between 2001 and 2002 were included, if data on CRP or FG levels. Serum vitamins A and E, two retinyl esters, and six carotenoids were measured using HPLC with photodiode array detection. Multivariable-adjusted linear regression analyses accounted for the survey design and sample weights. A total of 784 eligible participants were included; 47·5 % (n 372) were men. In multivariable linear regression models, serum α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, combined lutein/zeaxanthin, trans-lycopene, retinyl palmitate, α-tocopherol, retinol and 25-hydroxy vitamin D were negatively associated with serum CRP (P<0·001 for all comparisons). Serum α-carotene, trans-β-carotene, cis-β-carotene, combined lutein/zeaxanthin, trans-lycopene, α-tocopherol, retinol and 25-hydroxy vitamin D were negatively associated with serum FG levels (P<0·001 for all comparisons). In the same model, the risk of CVD, defined as CRP levels >3 mg/l, decreased with increasing levels of antioxidants (α-carotene, trans-β-carotene, cis-β-carotene, vitamins A and E). Furthermore, we found a moderate impact of adiposity on the link between antioxidants and CRP. Our results suggest that the lower the antioxidants levels, the higher the inflammatory burden, based on CRP and FG levels. Adiposity moderately affects this association. Furthermore, an inverse relationship between CVD risk and antioxidant levels was observed. This finding suggests that reduced levels of vitamins with antioxidant properties may predispose to increased CVD risk.


Corresponding author

*Corresponding author: M. Mazidi, email


Hide All
1. Szmitko, PE, Wang, CH, Weisel, RD, et al. (2003) New markers of inflammation and endothelial cell activation: part I. Circulation 108, 19171923.
2. Pepys, MB & Hirschfield, GM (2003) C-reactive protein: a critical update. J Clin Invest 111, 18051812.
3. Mazidi, M, Heidari-Bakavoli, A, Khayyatzadeh, SS, et al. (2016) Serum hs-CRP varies with dietary cholesterol, but not dietary fatty acid intake in individuals free of any history of cardiovascular disease. Eur J Clin Nutr 70, 14541457.
4. Mazidi, M, Karimi, E, Rezaie, P, et al. (2017) Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. J Diabetes Complications 31, 12371242.
5. Mineo, C, Gormley, AK, Yuhanna, IS, et al. (2005) FcgammaRIIB mediates C-reactive protein inhibition of endothelial NO synthase. Circ Res 97, 11241131.
6. Stefanadi, E, Tousoulis, D, Papageorgiou, N, et al. (2010) Inflammatory biomarkers predicting events in atherosclerosis. Curr Med Chem 17, 16901707.
7. Danesh, J, Lewington, S, Thompson, SG, et al. (2005) Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 294, 17991809.
8. Espinola-Klein, C, Rupprecht, HJ, Bickel, C, et al. (2007) Inflammation, atherosclerotic burden and cardiovascular prognosis. Atherosclerosis 195, e126e134.
9. Becker, RC, Cannon, CP, Bovill, EG, et al. (1996) Prognostic value of plasma fibrinogen concentration in patients with unstable angina and non-Q-wave myocardial infarction (TIMI IIIB trial). Am J Cardiol 78, 142147.
10. Hermsdorff, HH, Zulet, MA, Puchau, B, et al. (2010) Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study. Nutr Metab (Lond) 7, 42.
11. Pellegrini, N, Salvatore, S, Valtuena, S, et al. (2007) Development and validation of a food frequency questionnaire for the assessment of dietary total antioxidant capacity. J Nutr 137, 9398.
12. Kaur, G, Rao, LV, Agrawal, A, et al. (2007) Effect of wine phenolics on cytokine-induced C-reactive protein expression. J Thromb Haemost 5, 13091317.
13. El-Mowafy, AM, El-Mesery, ME, Salem, HA, et al. (2010) Prominent chemopreventive and chemoenhancing effects for resveratrol: unraveling molecular targets and the role of C-reactive protein. Chemotherapy 56, 6065.
14. Suzuki, K, Inoue, T, Hashimoto, S, et al. (2010) Association of serum carotenoids with high molecular weight adiponectin and inflammation markers among Japanese subjects. Clin Chim Acta 411, 13301334.
15. Vivekananthan, DP, Penn, MS, Sapp, SK, et al. (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361, 20172023.
16. Kushi, LH, Folsom, AR, Prineas, RJ, et al. (1996) Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 334, 11561162.
17. Katsiki, N & Manes, C (2009) Is there a role for supplemented antioxidants in the prevention of atherosclerosis? Clin Nutr 28, 39.
18. Mazidi, M, Katsiki, N, Mikhailidis, DP, et al. (2018) The link between insulin resistance parameters and serum uric acid is mediated by adiposity. Atherosclerosis 270, 180186.
19. Mazidi, M, Shivappa, N, Wirth, MD, et al. (2018) Dietary inflammatory index and cardiometabolic risk in US adults. Atherosclerosis 276, 2327.
20. Centers for Disease Control and Prevention (2015) National Center for Health Statistics, National Health and Nutrition Survey. Survey E. (accessed October 2015).
21. Mazidi, M, Michos, ED & Banach, M (2017) The association of telomere length and serum 25-hydroxyvitamin D levels in US adults: the National Health and Nutrition Examination Survey. Arch Med Sci 13, 6165.
22. Mazidi, M, Penson, P & Banach, M (2017) Association between telomere length and complete blood count in US adults. Arch Med Sci 13, 601605.
23. Friedewald, WT, Levy, RI & Fredrickson, DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18, 499502.
24. Pearson, TA, Mensah, GA, Alexander, RW, et al. (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, 499511.
25. Mazidi, M, Shivappa, N, Wirth, MD, et al. (2017) The association between dietary inflammatory properties and bone mineral density and risk of fracture in US adults. Eur J Clin Nutr 71, 12731277.
26. Mazidi, M, Kengne, AP, Mikhailidis, DP, et al. (2017) Dietary food patterns and glucose/insulin homeostasis: a cross-sectional study involving 24,182 adult Americans. Lipids Health Dis 16, 192.
27. Slinker, BK & Glantz, SA (1985) Multiple regression for physiological data analysis: the problem of multicollinearity. Am J Physiol 249, R1R12.
28. Preacher, KJ & Hayes, AF (2008) Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 40, 879891.
29. Serafini, M & Peluso, I (2016) Functional foods for health: the interrelated antioxidant and anti-inflammatory role of fruits, vegetables, herbs, spices and cocoa in humans. Curr Pharm Des 22, 67016715.
30. Dagenais, GR, Marchioli, R, Yusuf, S, et al. (2000) Beta-carotene, vitamin C, and vitamin E and cardiovascular diseases. Curr Cardiol Rep 2, 293299.
31. Lee, IM, Cook, NR, Gaziano, JM, et al. (2005) Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA 294, 5665.
32. Sleight, P (2000) The HOPE Study (Heart Outcomes Prevention Evaluation). J Renin Angiotensin Aldosterone Syst 1, 1820.
33. Sesso, HD, Christen, WG, Bubes, V, et al. (2012) Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA 308, 17511760.
34. Ye, Y, Li, J & Yuan, Z (2013) Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. PLOS ONE 8, e56803.
35. Carr, BR, Khan, N, Adams-Huet, B, et al. (2006) Effect of vitamin E supplementation with and without hormone therapy on circulatory inflammatory markers in postmenopausal women. Fertil Steril 85, 667673.
36. Devaraj, S, Li, D & Jialal, I (1996) The effects of alpha tocopherol supplementation on monocyte function. Decreased lipid oxidation, interleukin 1 beta secretion, and monocyte adhesion to endothelium. J Clin Invest 98, 756763.
37. van Tits, LJ, Demacker, PN, de Graaf, J, et al. (2000) Alpha-tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals. Am J Clin Nutr 71, 458464.
38. Block, G, Jensen, C, Dietrich, M, et al. (2004) Plasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant supplementation. J Am Coll Nutr 23, 141147.
39. Bruunsgaard, H, Poulsen, HE, Pedersen, BK, et al. (2003) Long-term combined supplementations with alpha-tocopherol and vitamin C have no detectable anti-inflammatory effects in healthy men. J Nutr 133, 11701173.
40. Hartel, C, Strunk, T, Bucsky, P, et al. (2004) Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes. Cytokine 27, 101106.
41. Baeuerle, PA & Henkel, T (1994) Function and activation of NF-kappa B in the immune system. Ann Rev Immunol 12, 141179.
42. Bowie, AG & O’Neill, LA (2000) Vitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinase. J Immunol 165, 71807188.
43. Carcamo, JM, Pedraza, A, Borquez-Ojeda, O, et al. (2002) Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 41, 1299513002.
44. Perez-Cruz, I, Carcamo, JM & Golde, DW (2003) Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells. Blood 102, 336343.
45. Ribeiro Nogueira, C, Ramalho, A, Lameu, E, et al. (2009) Serum concentrations of vitamin A and oxidative stress in critically ill patients with sepsis. Nutr Hosp 24, 312317.
46. Britton, G (1995) Structure and properties of carotenoids in relation to function. FASEB J 9, 15511558.
47. Erlinger, TP, Guallar, E, Miller, ER 3rd, et al. (2001) Relationship between systemic markers of inflammation and serum beta-carotene levels. Arch Intern Med 161, 19031908.
48. Hu, P, Reuben, DB, Crimmins, EM, et al. (2004) The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci 59, 849854.
49. Gawron-Skarbek, A, Guligowska, A, Prymont-Przyminska, A, et al. (2017) Dietary vitamin C, E and beta-carotene intake does not significantly affect plasma or salivary antioxidant indices and salivary C-reactive protein in older subjects. Nutrients 9, E729.
50. Il’yasova, D, Ivanova, A, Morrow, JD, et al. (2008) Correlation between two markers of inflammation, serum C-reactive protein and interleukin 6, and indices of oxidative stress in patients with high risk of cardiovascular disease. Biomarkers 13, 4151.
51. McDonald, SL, Savy, M, Fulford, AJ, et al. (2014) A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: the Gambia protocol. BMC Pediatr 14, 92.
52. Kim, CH (2011) Retinoic acid, immunity, and inflammation. Vitam Horm 86, 83101.
53. Farhangi, MA, Keshavarz, SA, Eshraghian, M, et al. (2013) Vitamin A supplementation, serum lipids, liver enzymes and C-reactive protein concentrations in obese women of reproductive age. Ann Clin Biochem 50, 2530.
54. Filteau, SM, Morris, SS, Raynes, JG, et al. (1995) Vitamin A supplementation, morbidity, and serum acute-phase proteins in young Ghanaian children. Am J Clin Nutr 62, 434438.
55. Kritchevsky, SB, Bush, AJ, Pahor, M, et al. (2000) Serum carotenoids and markers of inflammation in nonsmokers. Am J Epidemiol 152, 10651071.
56. Khaw, KT & Woodhouse, P (1995) Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease. BMJ 310, 15591563.
57. Iribarren, C, Folsom, A, Jacobs, DR Jr, et al. (1997) Patterns of covariation of serum β-carotene and α-tocopherol in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Nutr Metab Cardiovasc Dis 7, 445458.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed