Effect of hazelnut on serum lipid profile and fatty acid composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia: A randomized controlled trial

      Summary

      Background & aim

      Regular intake of nuts improves lipid profile and thus reduces the cardiovascular (CV) risk associated with hyperlipidemia. The aim of the study was to investigate the effect of a dietary intervention with hazelnuts (HZNs, 15–30 g/day, depending on patient weight) on serum lipid profile, anthropometric parameters and fatty acids (FAs) composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia.

      Methods

      Eight-week randomized, single blind, controlled, three-arm, parallel-group study. Sixty-six subjects were enrolled and randomized in 3 groups receiving: 1) hazelnuts with skin (HZN+S); 2) hazelnuts without skin (HZN-S); 3) dietary advices for hyperlipidemia only (controls). Before and after intervention, clinical parameters were measured and blood samples were collected for the evaluation of serum lipid levels and phospholipid FA composition of erythrocytes.

      Results

      Two-way ANOVA showed a significant effect of time on serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)/LDL-C ratio and non-HDL-C (p ≤ 0.001), but not of treatment and time × treatment interaction. In particular, HZN+S and HZN-S significantly reduced the concentrations of LDL-C and increased HDL-C/LDL-C ratio. HZNs also had a favorable impact on FAs composition of erythrocyte phospholipids, as demonstrated by time × treatment interaction, with a significant increase of monounsaturated fatty acids (MUFAs) (p = 0.008) and MUFAs/saturated fatty acids (SFAs) ratio (p = 0.002) with respect to the control group.

      Conclusions

      For the first time, we documented a positive effect of HZN consumption on lipid profile and FA composition of erythrocyte phospholipids in children with primary hyperlipidemia. Further studies are encouraged to better define HZN impact on the markers of CV risk in this population.
      The trial was registered under ISRCTN.com, ID no. ISRCTN12261900.

      Keywords

      Abbreviations:

      BMI (body mass index), CVD (cardiovascular disease), CHILD (cardiovascular health integrated lifestyle diet), FA (fatty acid), FCHL (familial combined hyperlipidemia), FH (familial hypercholesterolemia), GAE (gallic acid equivalents), HDL-C (high density lipoprotein cholesterol), HZN (hazelnuts), HZN+S (hazelnuts with skin), HZN-S (hazelnuts without skin), LDL-C (low-density lipoprotein cholesterol), MUFAs (monounsaturated fatty acids), non-HDL-C (non-high density lipoprotein cholesterol), PHC (polygenic hypercholesterolemia), PUFAs (polyunsaturated fatty acids), RBCs (red blood cells), SFAs (saturated fatty acids), TC (total cholesterol), TE (trolox equivalent), TG (triglycerides)
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      References

        • Juonala M.
        • Viikari J.S.A.
        • Kähönen M.
        • Solakivi T.
        • Helenius H.
        • Jula A.
        • et al.
        Childhood levels of serum apolipoproteins B and AI predict carotid intima-media thickness and brachial endothelial function in adulthood: the cardiovascular risk in young Finns study.
        J Am Coll Cardiol. 2008; 52: 293-299
        • Gidding S.S.
        • Dennison B.A.
        • Birch L.L.
        • Daniels S.R.
        • Gilman M.W.
        • Lichtenstein A.H.
        • et al.
        Dietary recommendations for children and adolescents.
        Circulation. 2005; 112: 2061-2075
      1. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report.
        Pediatrics. 2011; 128: 213-256
        • Nettleton J.A.
        • Lovegrove J.A.
        • Mensink R.P.
        • Schwab U.
        Dietary fatty acids: is it time to change the recommendations?.
        Ann Nutr Metab. 2016; 68: 249-257
        • Ros E.
        Health benefits of nut consumption.
        Nutrients. 2010; 2: 652-682
        • Sánchez-González C.
        • Ciudad C.
        • Noé V.
        • Izquierdo-Pulido M.
        Health benefits of walnut polyphenols: an exploration beyond their lipid profile.
        Crit Rev Food Sci Nutr. 2015; 29
        • O'Neil C.E.
        • Keast D.R.
        • Nicklas T.A.
        • Fulgoni 3rd, V.L.
        Out-of-hand nut consumption is associated with improved nutrient intake and health risk markers in US children and adults: National Health and Nutrition Examination Survey 1999–2004.
        Nutr Res. 2012; 32: 185-194
        • Sarkkinen E.S.
        • Agren J.J.
        • Ahola I.
        • Ovaskainen M.L.
        • Uusitupa M.I.
        Fatty acid composition of serum cholesterol esters, and erythrocyte and platelet membranes as indicators of long-term adherence to fat-modified diets.
        Am J Clin Nutr. 1994; 59: 364-370
        • Kuratko C.N.
        • Salem Jr., N.
        Biomarkers of DHA status.
        Prostagl Leukot Essent Fat Acids. 2009; 81: 111-118
        • Brigandi S.A.
        • Shao H.
        • Qian S.Y.
        • Shen Y.
        • Wu B.L.
        • Kang J.X.
        Autistic children exhibit decreased levels of essential fatty acids in red blood cells.
        Int J Mol Sci. 2015; 16: 10061-10076
        • Novgorodtseva T.P.
        • Kantur T.A.
        • Karaman Y.K.
        • Antonyuk M.V.
        • Zhukova N.V.
        Modification of fatty acids composition in erythrocytes lipids in arterial hypertension associated with dyslipidemia.
        Lipids Health Dis. 2011; 10: 18
        • Guardamagna O.
        • Abello F.
        • Saracco P.
        • Baracco V.
        • Rolfo E.
        • Pirro M.
        Endothelial activation, inflammation and premature atherosclerosis in children with familial dyslipidemia.
        Atherosclerosis. 2009; 207: 471-475
        • Ficarra A.
        • Lo Fiego D.P.
        • Minelli G.
        • Antonelli A.
        Ultra fast analysis of subcutaneous pork fat.
        Food Chem. 2010; 121: 809-814
        • Del Bo' C.
        • Simonetti P.
        • Gardana C.
        • Riso P.
        • Lucchini G.
        • Ciappellano S.
        Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers.
        Int J Food Sci Nutr. 2013; 64: 147-154
        • Ghirardello D.
        • Bertolino M.
        • Belviso S.
        • Dal Bello B.
        • Giordano M.
        • Rolle L.
        • et al.
        Phenolic composition, antioxidant capacity and hexanal content of hazelnuts (Corylus avellana L.) as affected by different storage conditions.
        Postharvest Biol Technol. 2015; 112: 95-104
        • Cacciari E.
        • Milani S.
        • Balsamo A.
        • Spada E.
        • Bona G.
        • Cavallo L.
        • et al.
        Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr).
        J Endocrinol Invest. 2006; 29: 581-593
        • Knopfholz J.
        • Disserol C.C.
        • Pierin A.J.
        • Schirr F.L.
        • Streisky L.
        • Takito L.L.
        • et al.
        Validation of the friedewald formula in patients with metabolic syndrome.
        Cholesterol. 2014; 2014261878
        • Simonetti P.
        • Ciappellano S.
        • Gardana C.
        • Bramati L.
        • Pietta P.
        Procyanidins from Vitis vinifera seeds: in vivo effects on oxidative stress.
        J Agric Food Chem. 2002; 50: 6217-6221
        • Orem A.
        • Yucesan F.B.
        • Orem C.
        • Akcan B.
        • Kural B.V.
        • Alasalvar C.
        • et al.
        Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects.
        J Clin Lipidol. 2013; 7: 123-131
        • Mikkilä V.
        • Räsänen L.
        • Raitakari O.T.
        • Pietinen P.
        • Viikari J.
        Consistent dietary patterns identified from childhood to adulthood: the cardiovascular risk in Young Finns Study.
        Br J Nutr. 2005; 93: 923-931
        • Niinikoski H.
        • Pahkala K.
        • Ala-Korpela M.
        • Viikari J.
        • Rönnemaa T.
        • Lagström H.
        • et al.
        Effect of repeated dietary counseling on serum lipoproteins from infancy to adulthood.
        Pediatrics. 2012; 129: 704-713
        • Reiner Ž.
        • Catapano A.L.
        • De Backer G.
        • Graham I.
        • Taskinen M.R.
        • Wiklund O.
        • et al.
        • Clinical Practice Guidelines Committee of the Spanish Society of Cardiology
        ESC/EAS Guidelines for the management of dyslipidaemias.
        Rev Esp Cardiol. 2011; 64: 1160-1168
        • Tey S.L.
        • Brown R.C.
        • Chisholm A.W.
        • Delahunty C.M.
        • Gray A.R.
        • Williams S.M.
        Effects of different forms of hazelnuts on blood lipids and α-tocopherol concentrations in mildly hypercholesterolemic individuals.
        Eur J Clin Nutr. 2011; 65: 117-124
        • Mercanligil S.M.
        • Arslan P.
        • Alasalvar C.
        • Okut E.
        • Akgül E.
        • Pinar A.
        • et al.
        Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hypercholesterolemic adult men.
        Eur J Clin Nutr. 2007; 61: 212-220
        • Yücesan F.B.
        • Orem A.
        • Kural B.V.
        • Orem C.
        • Turan I.
        Hazelnut consumption decreases the susceptibility of LDL to oxidation, plasma oxidized LDL level and increases the ratio of large/small LDL in normolipidemic healthy subjects.
        Anadulu Kardiyol Derg. 2010; 10: 28-35
        • Durak İ.
        • Köksal İ.
        • Kaçmaz M.
        • Büyükkoçak S.
        • Çimen B.M.
        • Öztürk H.S.
        Hazelnut supplementation enhances plasma antioxidant potential and lowers plasma cholesterol levels.
        Clin Chim Acta. 1999; 284: 113-115
        • Banel D.K.
        • Hu F.B.
        Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review.
        Am J Clin Nutr. 2009; 90: 56-63
        • Tey S.L.
        • Gray A.R.
        • Chisholm A.W.
        • Delahunty C.M.
        • Brown R.C.
        The dose of hazelnuts influences acceptance and diet quality but not inflammatory markers and body composition in overweight and obese individuals.
        J Nutr. 2013; 143: 1254-1262
        • Del Gobbo L.C.
        • Falk M.C.
        • Feldman R.
        Effects of tree nuts on blood lipids, apolipoproteins, and blood pressure: systematic review, meta-analysis, and dose-response of 61 controlled intervention trials.
        Am J Clin Nutr. 2015; 102: 1347-1356
        • Maguire L.S.
        • O'Sullivan S.M.
        • Galvin K.
        • O'connor T.P.
        • O'brien N.M.
        Fatty acid profile, tocopherol, squalene and phytosterol content of walnuts, almonds, peanuts, hazelnuts and the macadamia nut.
        Int J Food Sci Nutr. 2004; 55: 171-178
        • Alasalvar C.
        • Shahidi F.
        • Ohshima T.
        • Wanasundara U.
        • Yurttas H.C.
        • Liyanapathirana C.M.
        • et al.
        Turkish Tombul hazelnut (Corylus avellana L.). 2. Lipid characteristics and oxidative stability.
        J Agric Food Chem. 2003; 51: 3797-3805
        • Maranhão P.A.
        • Kraemer-Aguiar L.G.
        • de Oliveira C.L.
        • Kuschnir M.C.
        • Vieira Y.R.
        • Souza M.G.
        • et al.
        Brazil nuts intake improves lipid profile, oxidative stress and microvascular function in obese adolescents: a randomized controlled trial.
        Nutr Metab (Lond). 2011; 8: 32
        • Nergiz-Ünal R.
        • Kuijpers M.J.
        • de Witt S.M.
        • Heeneman S.
        • Feijge M.A.
        • Caraballo S.C.G.
        • et al.
        Atheroprotective effect of dietary walnut intake in ApoE-deficient mice: involvement of lipids and coagulation factors.
        Thromb Res. 2013; 131: 411-417
        • Caimari A.
        • Puiggròs F.
        • Suárez M.
        • Crescenti A.
        • Laos S.
        • Ruiz J.A.
        • et al.
        The intake of a hazelnut skin extract improves the plasma lipid profile and reduces the lithocholic/deoxycholic bile acid faecal ratio, a risk factor for colon cancer, in hamsters fed a high-fat diet.
        Food Chem. 2015; 167: 138-144
        • Vaya A.
        • Martinez Triguero M.
        • Reganon E.
        • Vila V.
        • Martinez Sales V.
        • Sola E.
        • et al.
        Erythrocyte membrane composition in patients with primary hypercholesterolemia.
        Clin Hemorheol Microcirc. 2008; 40: 289-294
        • Deon V.
        • Del Bo' C.
        • Guaraldi F.
        • Gargari G.
        • Bosusco A.
        • Simonetti P.
        • et al.
        Serum lipid profile and fatty acid composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia.
        Int J Food Sci Nutr. 2017; 68: 339-348
        • Fitschen P.J.
        • Rolfhus K.R.
        • Winfrey M.R.
        • Allen B.K.
        • Manzy M.
        • Maher M.A.
        Cardiovascular effects of consumption of black versus English walnuts.
        J Med Food. 2011; 14: 890-898
        • Harris W.S.
        • Pottala J.V.
        • Varvel S.A.
        • Borowski J.J.
        • Ward J.N.
        • McConnell J.P.
        Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients.
        Prostagl Leukot Essent Fat Acids. 2013; 88: 257-263
        • Rajaram S.
        • Haddad E.H.
        • Mejia A.
        • Sabaté J.
        Walnuts and fatty fish influence different serum lipid fractions in normal to mildly hyperlipidemic individuals: a randomized controlled study.
        Am J Clin Nutr. 2009; 89: 1657-1663
        • Ferreri C.
        • Masi A.
        • Sansone A.
        • Giacometti G.
        • Larocca A.V.
        • Menounou G.
        • et al.
        Fatty acids in membranes as homeostatic, metabolic and nutritional biomarkers: recent advancements in analytics and diagnostics.
        Diagnostics (Basel). 2016; 7
        • Aslibekyan S.
        • Campos H.
        • Baylin A.
        Biomarkers of dairy intake and the risk of heart disease.
        Nutr Metab Cardiovasc Dis. 2012; 22: 1039-1045
        • Von Schacky C.
        Omega-3 index and sudden cardiac death.
        Nutrients. 2010; 2: 375-388
        • Burrows T.
        • Collins C.E.
        • Garg M.L.
        Omega-3 index, obesity and insulin resistance in children.
        Int J Pediatr Obes. 2011; 6: 532-539