Research Article| Volume 26, ISSUE 3, P194-200, March 2016

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Reduced dietary intake of pro-inflammatory Toll-like receptor stimulants favourably modifies markers of cardiometabolic risk in healthy men

Published:December 18, 2015DOI:


      • Pro-inflammatory TLR-stimulants are abundant in some processed foods.
      • A 7 day low TLR-stimulant diet in healthy men reduced white cell count and LDL-C.
      • A 4 day high TLR-stimulant diet reversed these effects.
      • Processed foods may impact on cardiometabolic risk via dietary TLR-stimulants.


      Background and aims

      Because pro-inflammatory stimulants of Toll-like receptor-2 and TLR4 (pathogen-associated molecular patterns, PAMPs), are abundant in some processed foods, we explored the effects of diets enriched or depleted in these molecules on markers of cardiometabolic risk in man.

      Methods and results

      Adherence to a low PAMP diet for 7 days reduced LDL-cholesterol (−0.69 mM, P = 0.024) and abdominal circumference (−1.6 cm, P = 0.001) in 11 habitual consumers of high PAMP foodstuffs, and these markers, together with leukocyte counts (+14%, P = 0.017) increased significantly after 4 days consuming predominantly high PAMP foods. Change in LDL-cholesterol and leukocyte counts correlated well with change in frequency of intake of high PAMP foodstuffs per individual (r = 0.540, P = 0.0095 and r = 0.6551, P = 0.0009, respectively). In an independent group of 13 healthy men, leukocyte counts and expression of the activation marker CD11b on granulocytes and monocytes were significantly reduced after a fresh onion meal (P < 0.05), but these effects were reversed by a high PAMP equivalent meal.


      A low PAMP diet is associated with reduced levels of several cardiometabolic risk factors, while a high PAMP diet reverses these effects. These findings suggest a novel potential mechanistic explanation for the observed association between processed food consumption and risk of cardiometabolic diseases. The study is registered at (reference NCT02430064).



      BLP (bacterial lipoprotein), HDL-C (high-density lipoprotein cholesterol), HOMA-IR (homeostatic model of insulin resistance), hsCRP (high sensitivity C-reactive protein), LDL-C (low-density lipoprotein cholesterol), LPS (lipopolysaccharide (endotoxin)), PAMP (pathogen-associated molecular pattern), PBMC (peripheral blood mononuclear cells), TLR (Toll-like receptor), WBC (white blood cell)
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        • Rocha V.Z.
        • Libby P.
        Obesity, inflammation, and atherosclerosis.
        Nat Rev Cardiol. 2009; 6: 399-409
        • Lopez-Garcia E.
        • Schulze M.B.
        • Fung T.T.
        • Meigs J.B.
        • Rifai N.
        • Manson J.E.
        • et al.
        Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction.
        Am J Clin Nutr. 2004; 80: 1029-1035
        • Chrysohoou C.
        • Panagiotakos D.B.
        • Pitsavos C.
        • Das U.N.
        • Stefanadis C.
        Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the ATTICA Study.
        J Am Coll Cardiol. 2004; 44: 152-158
        • van Woudenbergh G.J.
        • Kuijsten A.
        • Tigcheler B.
        • Sijbrands E.J.
        • van Rooij F.J.
        • Hofman A.
        • et al.
        Meat consumption and its association with C-reactive protein and incident type 2 diabetes: the Rotterdam Study.
        Diabetes Care. 2012; 35: 1499-1505
        • Fretts A.M.
        • Howard B.V.
        • McKnight B.
        • Duncan G.E.
        • Beresford S.A.
        • Mete M.
        • et al.
        Associations of processed meat and unprocessed red meat intake with incident diabetes: the Strong Heart Family Study.
        Am J Clin Nutr. 2012; 95: 752-758
        • Micha R.
        • Wallace S.K.
        • Mozaffarian D.
        Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus. A systematic review and meta-analysis.
        Circulation. 2010; 121: 2271-2283
        • Rohrmann S.
        • Overvad K.
        • Bueno-de-Mesquita H.B.
        • Jakobsen M.U.
        • Egeberg R.
        • Tjønneland A.
        • et al.
        Meat consumption and mortality – results from the European Prospective Investigation into Cancer and Nutrition.
        BMC Med. 2013; 11: 63
        • Curtiss L.K.
        • Tobias P.S.
        Emerging role of toll-like receptors in atherosclerosis.
        J Lipid Res. 2009; 50: S340-S345
        • Delzenne N.M.
        • Cani P.D.
        Gut microbiota and the pathogenesis of insulin resistance.
        Curr Diab Rep. 2011; 11: 154-159
        • McGillicuddy F.C.
        • de la Llera Moya M.
        • Hinkle C.C.
        • Joshi M.R.
        • Chiquoine E.H.
        • Billheimer J.T.
        • et al.
        Inflammation impairs reverse cholesterol transport in vivo.
        Circulation. 2009; 119: 1135-1145
        • Wiedermann C.I.
        • Kiechl S.
        • Dunzendorfer S.
        • Schratzberger P.
        • Egger G.
        • Oberhollenzer F.
        • et al.
        Association of endotoxaemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study.
        J Am Coll Cardiol. 1999; 34: 1975-1981
        • Erridge C.
        • Duncan S.H.
        • Bereswill S.
        • Heimesaat M.M.
        The induction of colitis and ileitis in mice is associated with marked increases in intestinal concentrations of stimulants of TLRs 2, 4, and 5.
        PLoS ONE. 2010; 5: e9125
        • Ghoshal S.
        • Witta J.
        • Zhong J.
        • de Villiers W.
        • Eckhardt E.
        Chylomicrons promote intestinal absorption of lipopolysaccharides.
        J Lipid Res. 2009; 50: 90-97
        • Erridge C.
        The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like receptors 2 and 4.
        Br J Nutr. 2010; 20: 1-9
        • Erridge C.
        Accumulation of stimulants of Toll-like receptor (TLR)-2 and TLR4 in meat products stored at 5 degrees C.
        J Food Sci. 2011; 2: H72-H79
        • Erridge C.
        Stimulants of Toll-like receptor (TLR)-2 and TLR-4 are abundant in certain minimally-processed vegetables.
        Food Chem Toxicol. 2011; 49: 1464-1467
        • Basu A.
        • Devaraj S.
        • Jialal I.
        Dietary factors that promote or retard inflammation.
        Arterioscler Thromb Vasc Biol. 2006; 26: 995-1001
        • Twig G.
        • Afek A.
        • Shamiss A.
        • Derazne E.
        • Tzur D.
        • Gordon B.
        • et al.
        White blood cell count and the risk for coronary artery disease in young adults.
        PLoS ONE. 2012; 7: e47183
        • Twig G.
        • Afek A.
        • Shamiss A.
        • Derazne E.
        • Tzur D.
        • Gordon B.
        • et al.
        White blood cells count and incidence of type 2 diabetes in young men.
        Diabetes Care. 2013; 36: 276-282
        • Taudorf S.
        • Krabbe K.S.
        • Berg R.M.
        • Pedersen B.K.
        • Møller K.
        Human models of low-grade inflammation: bolus versus continuous infusion of endotoxin.
        Clin Vaccine Immunol. 2007; 14: 250-255
        • Ambring A.
        • Johansson M.
        • Axelsen M.
        • Gan L.
        • Strandvik B.
        • Friberg P.
        Mediterranean-inspired diet lowers the ratio of serum phospholipid n−6 to n−3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects.
        Am J Clin Nutr. 2006; 83: 575-581
        • Chen G.
        • Wang H.
        • Zhang X.
        • Yang S.T.
        Nutraceuticals and functional foods in the management of hyperlipidemia.
        Crit Rev Food Sci Nutr. 2014; 54: 1180-1201
        • Feingold K.R.
        • Staprans I.
        • Memon R.A.
        • Moser A.H.
        • Shigenaga J.K.
        • Doerrler W.
        • et al.
        Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.
        J Lipid Res. 1992; 33: 1765-1776
        • Jenkins D.J.
        • Jones P.J.
        • Lamarche B.
        • Kendall C.W.
        • Faulkner D.
        • Cermakova L.
        • et al.
        Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial.
        JAMA. 2011; 306: 831-839
        • Erridge C.
        • Samani N.J.
        Saturated fatty acids do not directly stimulate Toll-like receptor signaling.
        Arterioscler Thromb Vasc Biol. 2009; 29: 1944-1949
        • Dell'agli M.
        • Di Lorenzo C.
        • Badea M.
        • Sangiovanni E.
        • Dima L.
        • Bosisio E.
        • et al.
        Plant food supplements with anti-inflammatory properties: a systematic review.
        Crit Rev Food Sci Nutr. 2013; 53: 403-413
        • Shibata T.
        • Nakashima F.
        • Honda K.
        • Lu Y.J.
        • Kondo T.
        • Ushida Y.
        • et al.
        Toll-like receptors as a target of food-derived anti-inflammatory compounds.
        J Biol Chem. 2014; 289: 32757-32772
        • Liu J.J.
        • Song C.W.
        • Yue Y.
        • Duan C.G.
        • Yang J.
        • He T.
        • et al.
        Quercetin inhibits LPS-induced delay in spontaneous apoptosis and activation of neutrophils.
        Inflamm Res. 2005; 54: 500-507
        • Garg N.
        • Churey J.J.
        • Splittstoesser D.F.
        Effect of processing conditions on the microflora of fresh-cut vegetables.
        J Food Protect. 1990; 53: 701-703
        • van Deventer S.J.
        • Buller H.R.
        • ten Cate J.W.
        • Aarden L.A.
        • Hack C.E.
        • Sturk A.
        Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways.
        Blood. 1990; 76: 2520-2526