Therapeutic Effects of Walnuts (Juglans L.): Insights From Randomized Controlled Trials
-
Fatemeh Afra
,
Arman Zargaran
,
Shaghayegh Namvar
,
Nooshin Shirzad
,
Mahboobeh Hemmatabadi
,
Soha Namazi
Abstract
Background: This review elucidates the multifaceted therapeutic effects of Juglans L. (J.), a medicinal plant with a rich heritage in traditional medicine and promising potential in modern healthcare.
Methods: A narrative review was conducted focusing on randomized clinical trials (RCTs) published between 2000 and 2023. A comprehensive literature search was performed in databases including PubMed, Scopus, ClinicalKey, Google Scholar, and the Persian Scientific Information Database. The keywords “Juglans” and “J.” were used. Only human RCTs evaluating various parts of the plant (fruit, leaves, bark, internal septum) were included. Non-human and non-randomized studies were excluded.
Results: The findings reveal that while some trials report significant health benefits of J., others show minimal or no effects, suggesting the importance of personalized approaches in clinical application.
Conclusion: This review underscores the growing role of herbal medicine in preventive care and as a complement to standard treatments. Further studies are needed to clarify its mechanisms of action, determine optimal dosing, and evaluate long-term safety and efficacy. As global interest in natural remedies rises, J. stands out as a promising candidate in both preventive and therapeutic contexts
Silva N, Fernandes Júnior A. Biological properties of medicinal plants: a review of their antimicrobial activity. J Venom Anim Toxins Incl Trop Dis. 2010;16:402-13.
Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. The AAPS J. 2013;15:195-218.
Mohammadi J, Chatrroz B, Delaviz H. The effect of hydroalcoholic extract of Capparis spinosa on quality of sperm and rate of testosterone following induction of diabetes in rats. J Isfahan Med Sch. 2014;31(264):2042-57.
Rahman MA, Mossa JS, Al-Said MS, Al-Yahya MA. Medicinal plant diversity in the flora of Saudi Arabia 1: a report on seven plant families. Fitoterapia. 2004;75(2):149-61.
Witters LA. The blooming of the French lilac. J Clin Invest. 2001;108(8):1105-7.
Bailey CJ. Metformin: historical overview. Diabetologia. 2017;60(9):1566-76.
Hosseini S, Huseini HF, Larijani B, Mohammad K, Najmizadeh A, Nourijelyani K, et al. The hypoglycemic effect of Juglans leaves aqueous extract in diabetic patients: A first human trial. DARU J Pharm Sci. 2014;22:1-5.
Bayazit S, Kazan K, Gülbitti S, Cevik V, Ayanoğlu H, Ergül A. AFLP analysis of genetic diversity in low chill requiring walnut (Juglans L.) genotypes from Hatay, Turkey. Sci Hortic. 2007;111(4):394-8.
Zhao M-H, Jiang Z-T, Liu T, Li R. Flavonoids in Juglans L. leaves and evaluation of in vitro antioxidant activity via intracellular and chemical methods. Sci World J. 2014;2014.
Delaviz H, Mohammadi J, Ghalamfarsa G, Mohammadi B, Farhadi N. A review study on phytochemistry and pharmacology applications of Juglans plant. Pharmacogn Rev. 2017;11(22):145.
Ahvazi M, Khalighi-Sigaroodi F, Charkhchiyan MM, Mojab F, Mozaffarian V-A, Zakeri H. Introduction of medicinal plants species with the most traditional usage in Alamut region. Iran J Pharm Res. 2012;11(1):185.
Mohammadi J, Mirzaei A, Azizi A, Rouzbehi A, Delaviz H. The effects of hydroalcoholic extract of Juglans leaf on histological changes of Langerhans islet in diabetic rats model. Iran South Med J. 2012;15(4): 293-302.
Mohammadi J, Saadipour K, Delaviz H, Mohammadi B. Anti-diabetic effects of an alcoholic extract of Juglans in an animal model. Turk J Med Sci. 2011;41(4):685-91.
Mohammadi J, Delaviz H, Malekzadeh JM, Roozbehi A. The effect of hydro alcoholic extract of Juglans leaves in streptozotocin-nicotinamide induced diabetic rats. Pak J Pharm Sci. 2012;25(2):407-11.
Shah TI, Ganesh N, Akthar S. Preliminary phytochemical evaluation and antibacterial potential of different leaf extracts of Juglana : A ubiquitous dry fruit from Kashmir-India. Pharm Sci Rev Res. 2013;19:93-6.
Mouhajir F, Hudson J, Rejdali M, Towers G. Multiple antiviral activities of endemic medicinal plants used by Berber peoples of Morocco. Pharm Biol. 2001;39(5):364-74.
Ara I, Shinwari M, Rashed S, Bakir M. Evaluation of antimicrobial properties of two different extracts of Juglans tree bark and search for their compounds using gas chromatohraphy-mass spectrum. Int J Biol. 2013;5(2):92-102.
Ali‐Shtayeh M, Abu Ghdeib SI. Antifungal activity of plant extracts against dermatophytes. mycoses. 1999;42(11‐12):665-72.
Erdemoglu N, Küpeli E, Yeşilada E. Anti-inflammatory and antinociceptive activity assessment of plants used as remedy in Turkish folk medicine. J Ethnopharmacol. 2003;89(1):123-9.
Dehghani F, Mashhoody T, Panjeshahin R. Effect of aqueous extract of walnut septum on blood glucose and pancreatic structure in streptozotocin-induced diabetic mouse. Iran J Pharm Ther. 2012;11:10-4.
Asgary S, Parkhideh S, Solhpour A, Madani H, Mahzouni P, Rahimi P. Effect of ethanolic extract of Juglans L. on blood sugar in diabetes-induced rats. J Med Food. 2008;11(3):533-8.
Delaviz H, Mohammadi J, Ghalamfarsa G, Mohammadi B, Farhadi N. A Review Study on Phytochemistry and Pharmacology Applications of Juglans Plant. Pharmacogn Rev. 2017;11(22):145-52.
Rabiei K, Ebrahimzadeh MA, Saeedi M, Bahar A, Akha O, Kashi Z. Effects of a hydroalcoholic extract of Juglans (walnut) leaves on blood glucose and major cardiovascular risk factors in type 2 diabetic patients: a double-blind, placebo-controlled clinical trial. BMC Complement Med Ther. 2018;18(1):1-7.
Edussuriya ASJ, Subhashini SYS, Amarasinghe KDS, Kumari GSD, Perera K, Munidasa K. Experiences of Patients on Natural Herbal Treatments for Diabetes Mellitus at the Diabetes Clinic in Base Hospital - Matara, Sri Lanka. J Patient Exp. 2021;8:23743735211039313.
Khosroyar S, Ghofranpur Sh. The Effect of Walnut Oil, Septum and leaves aqueous extract in Alloxan-Induced Diabetic rats. Int J ChemTech Res. 2017;10(10):46-54.
Dehghani F, Mashhoody T, Panjehshahin M. Effect of aqueous extract of walnut septum on blood glucose and pancreatic structure in streptozotocin-induced diabetic mouse. Iran J Pharm Ther. 2012;11(1):10-4.
Ghiravani Z, Hosseini M, Taheri MMH, Fard MH, Abedini MR. Evaluation of hypoglycemic and hypolipidemic effects of internal septum of walnut fruit in alloxan-induced diabetic rats. Afr J Tradit Complement Altern Med. 2016;13(2):94-100.
Asgary S, Parkhideh S, Solhpour A, Madani H, Mahzouni P, Rahimi P. Effect of ethanolic extract of Juglans L. on blood sugar in diabetes-induced rats. J Med Food. 2008;11(3):533-8.
Pereira JA, Oliveira I, Sousa A, Valentão P, Andrade PB, Ferreira IC, et al. Walnut (Juglans L.) leaves: phenolic compounds, antibacterial activity and antioxidant potential of different cultivars. Food Chem Toxicol. 2007;45(11):2287-95.
Ortiz-Andrade RR, García-Jiménez S, Castillo-España P, Ramírez-Avila G, Villalobos-Molina R, Estrada-Soto S. alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent. J Ethnopharmacol. 2007;109(1):48-53.
Abdoli M, Dabaghian FH, Goushegir A, Shirazi MT, Nakhjavani M, Shojaii A, et al. Anti-hyperglycemic effect of aqueous extract of Juglans L. leaf (walnut leaf) on type 2 diabetic patients: a randomized controlled trial. Adv Integr Med. 2017;4(3):98-102.
Ma Y, Njike VY, Millet J, Dutta S, Doughty K, Treu JA, et al. Effects of walnut consumption on endothelial function in type 2 diabetic subjects: a randomized controlled crossover trial. Diabetes care. 2010;33(2):227-32.
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(6):415-23.
Afra F, Zargaran A, Shirzad N, Hemmatabadi M, Ebrahimpur M, Karimi M, et al. The hypoglycemic effects of Juglans L. internal septum in type 2 diabetic patients: A double-blind, randomized, placebo-controlled clinical trial. J Cardiovasc Thorac Res. 2023;15(3):145-53.
Anderson KJ, Teuber SS, Gobeille A, Cremin P, Waterhouse AL, Steinberg FM. Walnut polyphenolics inhibit in vitro human plasma and LDL oxidation. J Nutr. 2001;131(11):2837-42.
Fukuda T, Ito H, Yoshida T. Effect of the walnut polyphenol fraction on oxidative stress in type 2 diabetes mice. Biofactors. 2004;21(1‐4):251-3.
Damasceno NRT, Pérez-Heras A, Serra M, Cofán M, Sala-Vila A, Salas-Salvadó J, et al. Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers. Nutr Metab Cardiovasc Dis. 2011;21:S14-S20.
Holy EW, Forestier M, Richter EK, Akhmedov A, Leiber F, Camici GG, et al. Dietary α-linolenic acid inhibits arterial thrombus formation, tissue factor expression, and platelet activation. Arterioscler Thromb Vasc Biol. 2011;31(8):1772-80.
Berryman CE, Grieger JA, West SG, Chen C-YO, Blumberg JB, Rothblat GH, et al. Acute consumption of walnuts and walnut components differentially affect postprandial lipemia, endothelial function, oxidative stress, and cholesterol efflux in humans with mild hypercholesterolemia. J Nutr. 2013;143(6):788-94.
McKay D, Chen C, Yeum K, Matthan N, Lichtenstein A, Blumberg J. Chronic and acute effects of walnuts on antioxidant capacit y and nutritional status in humans: A randomized, cross-over pilot study. Nutr J. 2010;9(1):1-10.
West SG, Krick AL, Klein LC, Zhao G, Wojtowicz TF, McGuiness M, et al. Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function. J Am Coll Nutr. 2010;29(6):595-603.
Ros E, Núñez I, Pérez-Heras A, Serra M, Gilabert R, Casals E, et al. A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial. Circulation. 2004;109(13):1609-14.
Wainwright P. Nutrition and behaviour: the role of n-3 fatty acids in cognitive function. Br J Nutr. 2000;83(4):337-9.
Yehuda S, Rabinovitz S, Mostofsky DI. Essential fatty acids and the brain: from infancy to aging. Neurobiol Aging. 2005;26 Suppl 1:98-102.
Crews C, Hough P, Godward J, Brereton P, Lees M, Guiet S, et al. Study of the main constituents of some authentic walnut oils. J Agric Food Chem. 2005;53(12):4853-60.
Fukuda T, Ito H, Yoshida T. Antioxidative polyphenols from walnuts (Juglans L.). Phytochemistry. 2003;63(7):795-801.
Reiter RJ, Manchester LC, Tan DX. Melatonin in walnuts: influence on levels of melatonin and total antioxidant capacity of blood. Nutrition. 2005;21(9):920-4.
Innis SM. Dietary (n-3) fatty acids and brain development. J Nutr. 2007;137(4):855-9.
Joseph JA, SHUKITT‐HALE B, Lau FC. Fruit polyphenols and their effects on neuronal signaling and behavior in senescence. Ann N Y Acad Sci. 2007;1100(1):470-85.
Pribis P, Bailey RN, Russell AA, Kilsby MA, Hernandez M, Craig WJ, Grajales T, Shavlik DJ, Sabatè J. Effects of walnut consumption on cognitive performance in young adults. Br J Nutr. 2012;107(9):1393-401.
Sala-Vila A, Valls-Pedret C, Rajaram S, Coll-Padrós N, Cofán M, Serra-Mir M, et al. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. 2020;111(3):590-600.
Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e563-e95.
USDA ARSUNNDfSR, Release 24. Nutrient Data Laboratory Home Page. http://www.nal.usda.gov/fnic/foodcomp/search/, 2012 (accessed 10 may 2021).
Robbins KS, Shin E-C, Shewfelt RL, Eitenmiller RR, Pegg RB. Update on the healthful lipid constituents of commercially important tree nuts. J Agric Food Chem. 2011;59(22):12083-92.
Morgan JM, Horton K, Reese D, Carey C, Walker K, Capuzzi DM. Effects of walnut consumption as part of a low-fat, low-cholesterol diet on serum cardiovascular risk factors. Int J Vitam Nutr Res. 2002;72(5):341-7.
Olmedilla-Alonso B, Granado-Lorencio F, Herrero-Barbudo C, Blanco-Navarro I, Blázquez-García S, Pérez-Sacristán B. Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study. J Am Coll Nutr. 2008;27(2):342-8.
Tapsell LC, Gillen LJ, Patch CS, Batterham M, Owen A, Baré M, et al. 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(12):2777-83.
Chan JK, Bruce VM, McDonald BE. Dietary alpha-linolenic acid is as effective as oleic acid and linoleic acid in lowering blood cholesterol in normolipidemic men. Am J Clin Nutr. 1991;53(5):1230-4.
Murad S AAQ, Saif S. Juglans Contain Polyunsaturated Fats, and Essential Fatty Acid Omega-3. Austin J Pharmacol Ther. 2019;7(2): 1115.
Iwamoto M, Sato M, Kono M, Hirooka Y, Sakai K, Takeshita A, et al. Walnuts lower serum cholesterol in Japanese men and women. J Nutr. 2000;130(2):171-6.
Ashraf S, Arfeen A, Amjad S, Ahmed Z. Effect of walnut (Juglans ) consumption on hyperlipidemic adults. Food Sci Technol. 2021;41.
Zibaeenezhad MJ, Rezaiezadeh M, Mowla A, Ayatollahi SM, Panjehshahin MR. Antihypertriglyceridemic effect of walnut oil. Angiology. 2003;54(4):411-4.
Spaccarotella KJ, Kris-Etherton PM, Stone WL, Bagshaw DM, Fishell VK, West SG, et al. The effect of walnut intake on factors related to prostate and vascular health in older men. Nutr J. 2008;7:13.
Mirshekari M, Zargaran A, Shirzad N, Hemmatabadi M, Khanavi M, Ebrahimpur M, et al. Effect of Juglans L. Ridge on Blood Lipids in Type 2 Diabetic Patients with Dyslipidemia: A Double-blind Placebo-Controlled Randomized Clinical Trial. Pharm Sci. 2023;29(2):182-9.
Fraser GE, Sabaté J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med. 1992;152(7):1416-24.
Hu FB, Stampfer MJ, Manson JE, Rimm EB, Colditz GA, Rosner BA, et al. Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study. BMJ. 1998;317(7169):1341-5.
Ellsworth JL, Kushi LH, Folsom AR. Frequent nut intake and risk of death from coronary heart disease and all causes in postmenopausal women: the Iowa Women's Health Study. Nutr Metab Cardiovasc Dis. 2001;11(6):372-7.
Hu FB, Stampfer MJ, Manson JE, Rimm EB, Wolk A, Colditz GA, et al. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr. 1999;69(5):890-7.
Wei L D-YL, Hai-Dong W. Juglans Hexane Extract Exerts Antitumor Effect,Apoptosis Induction and Cell Circle Arrest in ProstateCancer Cells In vitro. Trop J Pharm Res. 14 (2015) 399-405.
Amaral J SR, Andrade PB, Valentão P, Pereira JA, Ferreres F. Phenolic profile in the quality control of walnut (Juglans L.) leaves. Food Chem.2004; 88(3):373-379.
Hardman WE. Walnuts have potential for cancer prevention and treatment in mice. J Nutr. 2014;144(4 Suppl):555s-60s.
Jahanbani R, Ghaffari SM, Salami M, Vahdati K, Sepehri H, Sarvestani NN, et al. Antioxidant and Anticancer Activities of Walnut (Juglans L.) Protein Hydrolysates Using Different Proteases. Plant Foods Hum Nutr. 2016;71(4):402-9.
Carvalho M, Ferreira PJ, Mendes VS, Silva R, Pereira JA, Jerónimo C, et al. Human cancer cell antiproliferative and antioxidant activities of Juglans L. Food Chem Toxicol. 2010;48(1):441-7.
Kendall CW, Esfahani A, Truan J, Srichaikul K, Jenkins DJ. Health benefits of nuts in prevention and management of diabetes. Asia Pac J Clin Nutr. 2010;19(1):110-6.
Bulló M, Lamuela-Raventós R, Salas-Salvadó J. Mediterranean diet and oxidation: nuts and olive oil as important sources of fat and antioxidants. Curr Top Med Chem. 2011;11(14):1797-810.
Hudthagosol C, Haddad EH, McCarthy K, Wang P, Oda K, Sabaté J. Pecans acutely increase plasma postprandial antioxidant capacity and catechins and decrease LDL oxidation in humans. J Nutr. 2011;141(1):56-62.
Maranhão PA, Kraemer-Aguiar LG, de Oliveira CL, Kuschnir MC, Vieira YR, Souza MG, 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(1):32.
Bitok E, Sabaté J. Nuts and Cardiovascular Disease. Prog Cardiovasc Dis. 2018;61(1):33-7.
Almario RU, Vonghavaravat V, Wong R, Kasim-Karakas SE. Effects of walnut consumption on plasma fatty acids and lipoproteins in combined hyperlipidemia. Am J Clin Nutr. 2001;74(1):72-9.
Rock CL, Flatt SW, Barkai H-S, 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(1):76.
Farr OM, Tuccinardi D, Upadhyay J, Oussaada SM, Mantzoros CS. Walnut consumption increases activation of the insula to highly desirable food cues: A randomized, double-blind, placebo-controlled, cross-over fMRI study. Diabetes Obes Metab. 2018;20(1):173-7.
Bitok E, Rajaram S, Jaceldo-Siegl K, Oda K, Sala-Vila A, Serra-Mir M, et al. Effects of Long-Term Walnut Supplementation on Body Weight in Free-Living Elderly: Results of a Randomized Controlled Trial. Nutrients. 2018;10(9):1317.
Ghiravani Z, Hassanzadeh-Taheri M, Hassanzadeh-Taheri M, Hosseini M. Internal septum of walnut kernel: a neglected functional food. Res J Pharmacogn. 2020; 7(2): 81-92.
Arpadjan S, Momchilova S, Elenkova D, Blagoeva E. Essential and toxic microelement profile of walnut (Juglans L.) cultivars grown in industrially contaminated area - Evaluation for human nutrition and health. J Food Nutr Res. 2013;52:121-7.
| Files | ||
| Issue | Vol 13, No 2 (Spring 2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/jpc.v13i2.19311 | |
| Keywords | ||
| Herbal Medicine Drug Effect Therapeutic Use Juglans Walnut Effect | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
