Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial

  • Hwang, Hyo-Jeong (ICAN Nutrition Education and Research) ;
  • Liu, Yanan (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Kim, Hyun-Sook (Department of Food and Nutrition, Sookmyung Women's University) ;
  • Lee, Heeseung (Department of Food and Nutrition, Kyung Hee University) ;
  • Lim, Yunsook (Department of Food and Nutrition, Kyung Hee University) ;
  • Park, Hyunjin (ICAN Nutrition Education and Research)
  • Received : 2018.07.16
  • Accepted : 2018.12.17
  • Published : 2019.04.01


BACKGROUND/OBJECTIVES: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. SUBJECTS/METHODS: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6 week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. RESULTS: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. CONCLUSION: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS. This trial is registered at as NCT03267901.


Supported by : California Walnut Commission


  1. Grundy SM, Hansen B, Smith SC Jr, Cleeman JI, Kahn RA; American Heart Association; National Heart, Lung, and Blood Institute; American Diabetes Association. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation 2004;109:551-6.
  2. Lim S, Shin H, Song JH, Kwak SH, Kang SM, Yoon JW, Choi SH, Cho SI, Park KS, Lee HK, Jang HC, Koh KK. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998-2007. Diabetes Care 2011;34:1323-8.
  3. Statistics Korea. Annual report on the causes of death statistics [Internet]. Daejeon: Statistics Korea; 2014 [cited 2017 August 8]. Available from:
  4. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. Korea Health Statistics 2014: Korea National Health and Nutrition Examination Survey (KNHANES VI-2). Cheongwon: Korea Centers for Disease Control and Prevention; 2014.
  5. Bamberger C, Rossmeier A, Lechner K, Wu L, Waldmann E, Stark RG, Altenhofer J, Henze K, Parhofer KG. A walnut-enriched diet reduces lipids in healthy Caucasian subjects, independent of recommended macronutrient replacement and time point of consumption: a prospective, randomized, controlled trial. Nutrients 2017;9:9.
  6. Rock CL, Flatt SW, Barkai HS, Pakiz B, Heath DD. Walnut consumption in a weight reduction intervention: effects on body weight, biological measures, blood pressure and satiety. Nutr J 2017;16:76.
  7. Chisholm A, Mann J, Skeaff M, Frampton C, Sutherland W, Duncan A, Tiszavari S. A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects. Eur J Clin Nutr 1998;52:12-6.
  8. Banel DK, Hu FB. 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.
  9. Aronis KN, Vamvini MT, Chamberland JP, Sweeney LL, Brennan AM, Magkos F, Mantzoros CS. Short-term walnut consumption increases circulating total adiponectin and apolipoprotein A concentrations, but does not affect markers of inflammation or vascular injury in obese humans with the metabolic syndrome: data from a double-blinded, randomized, placebo-controlled study. Metabolism 2012;61:577-82.
  10. Katz DL, Davidhi A, Ma Y, Kavak Y, Bifulco L, Njike VY. Effects of walnuts on endothelial function in overweight adults with visceral obesity: a randomized, controlled, crossover trial. J Am Coll Nutr 2012;31:415-23.
  11. Mukuddem-Petersen J, Stonehouse Oosthuizen W, Jerling JC, Hanekom SM, White Z. Effects of a high walnut and high cashew nut diet on selected markers of the metabolic syndrome: a controlled feeding trial. Br J Nutr 2007;97:1144-53.
  12. Casas-Agustench P, Lopez-Uriarte P, Bullo M, Ros E, Cabre-Vila JJ, Salas-Salvado J. Effects of one serving of mixed nuts on serum lipids, insulin resistance and inflammatory markers in patients with the metabolic syndrome. Nutr Metab Cardiovasc Dis 2011;21:126-35.
  13. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957;226:497-509.
  14. Morrison WR, Smith LM. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J Lipid Res 1964;5:600-8.
  15. Food and Drug Administration, Office of Nutritional Products, Labeling, and Dietary Supplements. Qualified Health Claims: Letter of Enforcement Discretion-Walnuts and Coronary Heart Disease [Docket No. 02P-0292]. College Park (MD): Center for Food Safety and Applied Nutrition; 2004.
  16. O'Neil CE, Fulgoni VL 3rd, Nicklas TA. Tree Nut consumption is associated with better adiposity measures and cardiovascular and metabolic syndrome health risk factors in U.S. Adults: NHANES 2005-2010. Nutr J 2015;14:64.
  17. O'Neil CE, Keast DR, Nicklas TA, Fulgoni VL 3rd. Nut consumption is associated with decreased health risk factors for cardiovascular disease and metabolic syndrome in U.S. adults: NHANES 1999-2004. J Am Coll Nutr 2011;30:502-10.
  18. Tapsell LC, Gillen LJ, Patch CS, Batterham M, Owen A, Bare M, Kennedy M. Including walnuts in a low-fat/modified-fat diet improves HDL cholesterol-to-total cholesterol ratios in patients with type 2 diabetes. Diabetes Care 2004;27:2777-83.
  19. Ryan E, Galvin K, O'Connor TP, Maguire AR, O'Brien NM. Fatty acid profile, tocopherol, squalene and phytosterol content of brazil, pecan, pine, pistachio and cashew nuts. Int J Food Sci Nutr 2006;57:219-28.
  20. Chen CY, Blumberg JB. Phytochemical composition of nuts. Asia Pac J Clin Nutr 2008;17 Suppl 1:329-32.
  21. Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, Fiol M, Gomez-Gracia E, Lopez-Sabater MC, Vinyoles E, Aros F, Conde M, Lahoz C, Lapetra J, Saez G, Ros E; PREDIMED Study Investigators. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11.
  22. Jenkins DJ, Kendall CW, Marchie A, Josse AR, Nguyen TH, Faulkner DA, Lapsley KG, Singer W. Effect of almonds on insulin secretion and insulin resistance in nondiabetic hyperlipidemic subjects: a randomized controlled crossover trial. Metabolism 2008;57:882-7.
  23. Jenkins DJ, Kendall CW, Banach MS, Srichaikul K, Vidgen E, Mitchell S, Parker T, Nishi S, Bashyam B, de Souza R, Ireland C, Josse RG. Nuts as a replacement for carbohydrates in the diabetic diet. Diabetes Care 2011;34:1706-11.
  24. Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 2003;52:1655-63.
  25. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, Nagai M, Matsuzawa Y, Funahashi T. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004;68:975-81.
  26. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adiposespecific protein, adiponectin, in obesity. 1999. Biochem Biophys Res Commun 2012;425:560-4.
  27. Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003;361:226-8.
  28. Laughlin GA, Barrett-Connor E, May S, Langenberg C. Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol 2007;165:164-74.
  29. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 2004;43:1318-23.
  30. Goodarzi MT, Babaahmadi-Rezaei H, Kadkhodaei-Eliaderani M, Haddadinezhad S. Relationship of serum adiponectin with blood lipids, $HbA_{1}c$, and hs-CRP in type II diabetic postmenopausal women. J Clin Lab Anal 2007;21:197-200.
  31. Esfahani M, Movahedian A, Baranchi M, Goodarzi MT. Adiponectin: an adipokine with protective features against metabolic syndrome. Iran J Basic Med Sci 2015;18:430-42.
  32. Gomes PM, Hollanda-Miranda WR, Beraldo RA, Castro AV, Geloneze B, Foss MC, Foss-Freitas MC. Supplementation of ${\alpha}$-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. Nutrition 2015;31:853-7.
  33. Fernandez-Real JM, Vendrell J, Ricart W. Circulating adiponectin and plasma fatty acid profile. Clin Chem 2005;51:603-9.
  34. Wu L, Piotrowski K, Rau T, Waldmann E, Broedl UC, Demmelmair H, Koletzko B, Stark RG, Nagel JM, Mantzoros CS, Parhofer KG. Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: a randomized controlled cross-over clinical trial. Metabolism 2014;63:382-91.