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Walnut

Scientific Name(s): Juglans nigra L., Juglans regia L.
Common Name(s): American walnut, Black walnut, Caucasian walnut, Circassian walnut, English walnut, European walnut, Persian walnut

Clinical Overview

Use

The inclusion of walnuts in the diet is recommended as a dietary source of polyunsaturated fatty acids and other nutrients, and to improve the lipid profile in hyperlipidemic individuals. Cardiac benefits of walnut consumption are described. Walnuts have also been studied in metabolic syndrome with limited benefit demonstrated. The effect of walnut extract in Alzheimer disease is being investigated.

Dosing

Daily dosages used in clinical trials range from 20 to 84 g/day (4 shelled walnuts equal approximately 20 g).

Contraindications

Contraindications have not been identified. Cross-hypersensitivity between tree nuts is known to exist.

Pregnancy/Lactation

White walnut is generally recognized as safe when used as food; the possibility of in utero sensitization has been debated without conclusion.

Avoid use of black walnut preparations. Documented adverse reactions (mutagenic properties). Possible cathartic effects have been observed at higher doses.

Interactions

None well documented. Walnut interferes with the absorption of iron.

Adverse Reactions

Allergy and fatal anaphylaxis to walnut have been reported.

Toxicology

Information is lacking. Juglone, a constituent of walnut, is toxic in animals.

Botany

There are approximately 15 species of Juglans walnuts. "Walnut" refers to several varieties, most commonly the English walnut (J. regia) and the black walnut (J. nigra). Walnut trees have short trunks with round-topped crowns and can grow up to 45 m in height. The black walnut is native to the deciduous forests of the eastern United States (central Mississippi and Appalachian regions) and Canada. Walnut tree leaves are compound and between 15 and 30 cm long. The male flowers are long, drooping catkins, while the female flowers are short spikes. Walnut trees self-pollinate and cross-pollinate. J. regia is native to Asia but is now cultivated in France and other parts of Europe, North Africa, North America, and East Asia.1 The wood is valued for its rich beauty and is used to make furniture, cabinets, and gun stocks. The black walnut fruit is an elongated drupe containing a 4-ribbed edible nut within a thick, hard, black shell that is smaller than the English walnut.1, 2

History

Walnuts have been found in prehistoric deposits in Europe dating from the Iron Age and are mentioned in Old Testament references to King Solomon's nut garden. The genus name Juglans comes from the Latin Jovis glans, meaning "nut of Jupiter" or "nut of the Gods." Many legends have been associated with the walnut; the ancient Greeks and Romans regarded them as symbols of fertility. In the Middle Ages, walnuts were thought to ward off witchcraft, the evil eye, and epileptic fits because of the belief that evil spirits lurked in the walnut branches.3

Historically, walnut oil was prescribed for colic, to soothe intestines, and to relieve diarrhea and hemorrhoids.3, 4, 5 Further folk uses include treating rickets, frostbite, and glandular disturbances, and as an astringent, tonic restorative, and disinfectant.6, 7 Some cultures use walnut bark for cleaning the teeth, possibly improving oral hygiene because it increases the pH of saliva.8 Walnut may possess anti-helminthic activity.7 It is considered helpful in inflammatory conditions, including rheumatoid arthritis, and certain skin disorders. Blisters, ulcers, itchy scalp/dandruff, sunburn, and perspiration are some of the conditions treated with various walnut preparations.6

The traditional black walnut herbal medicine is extracted from the black, tarry, sticky part in the outermost hull, and has been used in skin conditions, including eczema, pruritus, psoriasis, warts, and parasitic skin conditions. Treatment of eye irritations and styes are other uses for black walnut. Extract of black walnut was used to dye the hair, skin, and clothing.3, 6, 7 As a food, black walnut is commonly used in baked goods, candies, and frozen foods.3, 9

Walnuts are a common food source and are used in cooking and baking.3, 9 Walnut extract is an old-fashioned hair dye and also has been used to darken (stain) the skin.6, 9 Walnut shell flour has been used as a carrier for insecticides, filler for building materials, and stuffing in toys.9

Chemistry

Walnuts contain 3% to 4% water, 60% oil, and 15% to 20% protein, bearing approximately 700 calories per 100 g.9 The mineral content includes iron and zinc (approximately 3 mg per 100 g each), sodium (2 mg per 100 g), selenium (19 mcg per 100 g), calcium, magnesium, potassium, copper, and phosphorus.7, 9, 10 Vitamins E and C also are found in walnut.5, 11

Walnuts differ from other nuts in that they predominantly contain the polyunsaturated fatty acids alpha linolenic (n-3) acid and linoleic (n-6) acid, rather than mono-unsaturated fatty acids.12, 13 L-arginine (a precursor to nitric oxide) is also found in significant amounts in walnuts.12

The chief known chemical constituent in walnut is juglone (5-hydroxy-1,4-naphthagulone). Also present are alpha-hydrojuglone (1,4,5-trihydroxynaphthalene) and its glycoside beta-hydrojuglone, along with caffeic acid, ellagic acid, hyperin, and kaempferol, and the tannins galloylglucose and ellagitannins.6, 9 In one report, 45 volatile compounds were isolated from whole green walnuts.14 Gamma lactones are present in walnut oils.15

Some differences in chemical composition between J. regia and J. nigra have been noted.16, 17

Uses and Pharmacology

Lipid profile and cardiovascular effects

Animal data

Research reveals no animal data regarding the use of black walnuts for cardiovascular effect.

Clinical data

Clinical trials conducted in healthy adults12, 18, 19, 20, 21, 22 and in patients with type 2 diabetes23, 24 and metabolic syndrome25, 26, 27 have been critically reviewed.13, 28 Studies in patients with heart disease are lacking.28

The majority of studies show a reduction of total cholesterol and low-density lipoprotein–cholesterol to cardioprotective levels. Effects on high-density lipoprotein–cholesterol are inconsistent, as are those for triglycerides. The diminishing positive effects observed may be a consequence of increased fat intake with higher dosages used (and lesser effects due to lower dosages).13, 28

Limited effect has been shown in patients with metabolic syndrome.25, 26, 27

The role of walnut in atherosclerosis is unclear. Improved endothelial function has been demonstrated, possibly due to alpha linolenic acid or L-arginine content.12, 29 In another study, walnut activated the nuclear transcription factor identified in human atherosclerotic plaques in healthy men.30 Assessment of data from 6,705 participants without baseline atrial fibrillation in the PREDIMED trial revealed a significant relevant reduction in risk of atrial fibrillation (38%) with the Mediterranean diet supplemented with extravirgin olive oil (50 g/day or more) but not with the Mediterranean diet supplemented with nuts (almonds, hazelnuts, walnuts).31 There is general agreement that no gain in body weight results from the addition of walnuts to the diet.19, 23, 28

A small study (n=36) attempted to investigate the difference between the 2 species with respect to cardiovascular benefit of dietary supplementation. Effect on endothelial function was reported to be absent in participants fed black walnut in comparison to the English variant.32

Antioxidant effect

Animal data

Black walnut leaf was evaluated for its antioxidant activity. Radical scavenging and antiradical-generating effects were demonstrated.33, 34 For this reason, black walnut has been proposed as a candidate for chemotherapy because of the toxic nature of juglone and plumbagin; however, studies to support this are lacking.35, 36

Apoptosis and necrosis effects have been demonstrated in cancer cells with extracts of black walnut. Juglone and plumbagin, the yellow quinone pigments of black walnut, were shown to decrease cell viability and cell death.36, 37

Clinical data

Results of studies investigating the effects of walnuts on oxidative stress and apoprotein response are variable.25, 28, 30 Research reveals no clinical data regarding the use of black walnuts for antioxidant activity.

Other uses

Alzheimer disease

Walnut extract was demonstrated to inhibit and defibrillize amyloid beta protein—a feature of the amyloid plaque seen in the brains of patients with Alzheimer disease.38

Antimicrobial

A study from China found borneol-walnut oil to be superior to neomycin in treating otitis media without any toxic effects.39 The constituent juglone has been demonstrated to possess antimicrobial and antifungal effects.8

Diabetes

As a component of medical nutrition therapy for patients with types 1 or 2 diabetes, the American Diabetes Association Standards of Care (2014) recommend an increase in foods containing alpha-linolenic acid based on beneficial effects observed on lipoprotein profiles, heart disease prevention, and overall positive health in patients with diabetes (moderate-quality evidence). Likewise, as a component of medical nutrition therapy for patients with type 2 diabetes, the American Diabetes Association Standards of Care (2014) recommend higher quality dietary fat intake, as an alternative to decreased fat intake, by replacing saturated and/or trans fats with mono- and poly-unsaturated fatty acids in the diet. This Mediterranean-style approach to eating may improve glycemic control and cardiovascular disease risk factors (moderate-quality evidence).40

Dosing

Daily dosages used in clinical trials range from 20 (moderate intake) to 84 g/day (4 shelled walnuts equals approximately 20 g).28, 41, 42

Walnut leaves have been approved by the German Commission E for external application for excessive perspiration and skin inflammation.43

Pregnancy / Lactation

White walnut is generally recognized as safe when used as food. The possibility of in utero sensitization has been debated.44

Avoid use of black walnut preparations. Documented adverse reactions (mutagenic properties).36, 45 Possible cathartic effects have been observed at higher doses.46

Interactions

None well documented. Walnut interferes with the absorption of iron.28

Adverse Reactions

Allergies to nuts are common in the United States (an estimated 1%)47 with walnut and other tree nut allergy considered to be second only to peanuts (a legume) in anaphylactic reactions. However, cross-reactivity to the proteins from tree nuts among peanut-allergic people is considered low. A co-allergy is probably the cause of allergic reactions among atopic individuals.44, 47 Cross-reactivity between walnut and peach lipid transfer protein allergen has been noted.48, 49, 50

Fatalities from anaphylaxis to walnuts have been recorded.48

Walnut allergens identified include Jug r 1 (walnut 2S albumin), Jug 3 r (vicillin-like protein), and Jug 3 r (a 9-kd lipid transfer protein).48, 49

Toxicology

Little data exist; however, the naphthaquinone juglone, present in all of the family Juglandaceae, is a known animal toxin.51 The risk of contamination with aflatoxin must also be considered.52

References

1. Juglans regia L. and Juglans nigra L.USDA, NRCS. 2017. The PLANTS Database (http://plants.usda.gov, April 2017). National Plant Data Team, Greensboro, NC 27401-4901 USA.
2. Weber RW. Black walnut. Ann Allergy Asthma Immunol. 2003;91(3):A-6.
3. Rosengarten F. The Book of Edible Nuts. New York, NY: Walker and Company; 1984:239-262.
4. Bisset NG, trans-ed. Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL: CRC Press; 1994:281-282.
5. Bruneton J. Hatton CK, trans. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris; New York: Lavoisier Publishing; 1995:348.
6. D'Amelio FS. Botanicals: A Phytocosmetic Desk Reference. Boca Raton, FL: CRC Press; 1999:209-210.
7. Hocking GM. A Dictionary of Natural Products. Medford, NJ: Plexus Publishing; 1997:409-410.
8. Alkhawajah AM. Studies on the antimicrobial activity of Juglans regia. Am J Chin Med. 1997;25(2):175-180.9288364
9. Ensminger AH, et al. Foods and Nutrition Encyclopedia. Vol. 2. 2nd ed. Boca Raton, FL: CRC Press; 1993:2277-2278.
10. Murray MT. The Healing Power of Foods. Rocklin, CA: Prima Publishing; 1993:384.
11. Zwarts L, Savage GP, McNeil DL. Fatty acid content of New Zealand-grown walnuts (Juglans regia L.). Int J Food Sci Nutr. 1999;50(3):189-194.10627834
12. Ros E, Nunez I, Perez-Heras A, Serra M, et al. A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial. Circulation. 2004;109(13):1609-1614.15037535
13. Mukuddem-Petersen J, Oosthuizen W, Jerling JC. A systematic review of the effects of nuts on blood lipid profiles in humans. J Nutr. 2005;135(9):2082-2089.16140880
14. Buttery RG, Light DM, Nam Y, Merrill GB, Roitman JN. Volatile components of green walnut husks. J Agric Food Chem. 2000;48(7):2858-2861.10898636
15. Ruiz Del Castillo ML, Herraiz M, Blanch GP. Determination of the enantiomeric composition of gamma-lactones in edible oils by on-line coupled high performance liquid chromatography and gas chromatography. J Agric Food Chem. 2000;48(4):1186-1190.10775370
16. Juglans regia L. and Juglans nigra L. U.S. Department of Agriculture, Agricultural Research Service. 1992-2016. Dr. Duke's Phytochemical and Ethnobotanical Databases. Home Page, http://phytochem.nal.usda.gov/ http://dx.doi.org/10.15482/USDA.ADC/1239279.
17. Warmund MR, Elmore JR, Adhikari K, McGraw S. Descriptive sensory analysis of light, medium, and dark colored kernels of black walnut cultivars. J Sci Food Agric. 2009;89:1969-1972.
18. Zibaeenezhad MJ, Shamsnia SJ, Khorasani M. Walnut consumption in hyperlipidemic patients. Angiology. 2005;56(5):581-583.16193197
19. Sabate J, Fraser GE, Burke K, Knutsen SF, Bennett H, Lindsted KD. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med. 1993;328(9):603-607.8357360
20. Zambon D, Sabate J, Munoz S, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. A randomized crossover trial. Ann Intern Med. 2000;132(7):538-546.10744590
21. Lavedrine F, Zmirou D, Ravel A, Balducci F, Alary J. Blood cholesterol and walnut consumption: a cross-sectional survey in France. Prev Med. 1999;28(4):333-339.10090861
22. Chisholm A, Mann J, Skeaff M, et al. A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects. Eur J Clin Nutr. 1998;52(1):12-16.9481526
23. Tapsell LC, Gillen LJ, Patch CS, 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):2777-2783.15562184
24. Gillen LJ, Tapsell LC, Patch CS, Owen A, Batterham M. Structured dietary advice incorporating walnuts achieves optimal fat and energy balance in patients with type 2 diabetes mellitus. J Am Diet Assoc. 2005;105(7):1087-1096.15983525
25. Davis L, Stonehouse W, Loots du T, et al. The effects of high walnut and cashew nut diets on the antioxidant status of subjects with metabolic syndrome. Eur J Nutr. 2007;46(3):155-164.
26. Mukuddem-Petersen J, Stonehouse Oosthuizen W, Jerling J, Hanekorn 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(6):1144-1153.17381974
27. Schutte AE, Van Rooyen JM, Huisman HW, et al. Modulation of baroreflex sensitivity by walnuts versus cashew nuts in subjects with metabolic syndrome. Am J Hypertens. 2006;19(6):629-636.16733237
28. Feldman EB. The scientific evidence for a beneficial health relationship between walnuts and coronary heart disease. J Nutr. 2002;132(5):1062S-1101S.11983840
29. Cortes B, Nunez I, Cofan M, et al. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol. 2006;48(8):1666-1671.17045905
30. Bellido C, Lopez-Miranda J, Blanco-Colio LM, et al. Butter and walnuts, but not olive oil, elicit postprandial activation of nuclear transcription factor kappa B in peripheral blood mononuclear cells from healthy men. Am J Clin Nutr. 2004;80(6):1487-1491.15585759
31. Martinez-Gonzalez MA, Toledo E, Aros F, et al. Extravirgin olive oil consumption reduces risk of atrial fibrillation-the PREDIMED (prevencion con dieta mediterranea) trial. Circulation. 2014;130:18-26.24787471
32. Fitschen PJ, Rolfhus KR, Winfrey MR, et al. Cardiovascular effects of consumption of black versus English walnuts. J Med Food. 2011;14(9):890-898.21488754
33. Halvorsen BL, Holte K, Myhrstad MC, et al. A systematic screening of total antioxidants in dietary plants. J Nutr. 2002;132(3):461-471.
34. Choi HR, Choi JS, Han YN, Bae SJ, Chung HY. Peroxynitrite scavenging activity of herb extracts. Phytother Res. 2002;16(4):364-367.
35. Segura-Aguilar J, Jönsson K, Tidefelt U, Paul C. The cytotoxic effects of 5-OH-1,4-naphthoquinone and 5,8-diOH-1,4-naphthoquinone on doxorubicin-resistant human leukemia cells (HL-60). Leuk Res. 1992;16(6-7):631-637.
36. Montoya J, Varela-Ramirez A, Estrada A, Martinez LE, Garza K, Aguilera RJ. A fluorescence-based rapid screening assay for cytotoxic compounds. Biochem Biophys Res Commun. 2004;325(4):1517-1523.
37. Inbaraj JJ, Chignell CF. Cytotoxic action of juglone and plumbagin: a mechanistic study using HaCaT keratinocytes. Chem Res Toxicol. 2004;17(1):55-62.
38. Chauhan N, Wang KC, Wegiel J, Malik MN. Walnut extract inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils. Curr Alzheimer Res. 2004;1(3):183-188.15975066
39. Liu SL. Therapeutic effects of borneol-walnut oil in the treatment of purulent otitis media [in Chinese]. Zhong Xi Yi Jie He Za Zhi. 1990;10(2):93-95,69.2364470
40. American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37(suppl 1):S14-S80.24357209
41. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr. 2006;83(suppl 6):1526S-1535S.16841863
42. Marangoni F, Colomo C, Martiello A, Poli A, Paoletti R, Galli C. Levels of the n-3 fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are significantly raised in blood lipids by the intake of four walnuts a day in humans. Nutr Metab Cardiovasc Dis. 2007;17(6):457-461.17008073
43. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000.
44. Sicherer SH, Sampson HA. Peanut and tree nut allergy. Curr Opin Pediatr. 2000;12(6):567-573.11106277
45. Brinker FJ. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
46. McGuffin M, et al, ed. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press; 1997.
47. Enrique E, Pineda F, Malek T, et al. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005;116(5):1073-1079.16275379
48. Pastorello EA, Pompei C, Pravettoni V, et al. Lipid transfer proteins and 2S albumins as allergens. Allergy. 2001;56(suppl 67):45-47.11298008
49. Pastorello EA, Farioli L, Pravettoni V, et al. Lipid transfer protein and vicilin are important walnut allergens in patients not allergic to pollen. J Allergy Clin Immunol. 2004;114(4):908-914.15480333
50. Asero R, Mistrello G, Roncarolo D, et al. Immunological cross-reactivity between lipid transfer proteins from botanically unrelated plant-derived foods: a clinical study. Allergy. 2002;57(10):900-906.12269935
51. True RG, Lowe JE. Induced juglone toxicosis in ponies and horses. Am J Vet Res. 1980;41(6):944-945.7436086
52. Abdel-Hafez AI, Saber SM. Mycoflora and mycotoxin of hazelnut (Corylus avellana L.) and walnut (Juglans regia L.) seeds in Egypt. Zentralbl Mikrobiol. 1993;148(2):137-147.8480455

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