Black Walnut

Generic name: Juglans Nigra L., Juglans Regia L.
Brand names: American Walnut, Black Walnut, Caucasian Walnut, Circassian Walnut, English Walnut, European Walnut, Persian Walnut

Usage of Black Walnut

Alzheimer disease

A neuropharmacological review of bioactive constituents of nuts, including walnut, referenced clinical and animal studies showing improvement in cognitive and motor performance with a diet enriched with walnuts.(Gorji 2018) A review article concluded that beneficial effects of walnuts on cognition and brain health were evident in clinical and animal studies, and that walnuts in the diet may reduce the risk and/or progression of mild cognitive impairment and Alzheimer disease. It was stated that the benefits of a walnut-enriched diet in brain disorders and other chronic diseases was due to additive or synergistic effects of walnut components for protection against oxidative stress and inflammation in these diseases.(Chauhan 2020)

Animal and in vitro data

In vitro, walnut extract was shown to inhibit and defibrillize amyloid-beta protein, a principal feature of the amyloid plaque seen in the brains of patients with Alzheimer disease.(Chauhan 2004)

Walnut supplementation in the diet of a Tg2576transgenic mouse model of Alzheimer disease significantly improved memory, learning ability, and anxiety.(Gorji 2018)

Clinical data

The Walnuts and Healthy Aging (WAHA) study was a randomized controlled trial (N=708) in older individuals 63 to 79 years of age that investigated the effects of a 2-year diet intervention with walnuts on cognitive decline. Results showed that walnut supplementation for 2 years had no effect on cognition in healthy older people. However, brain function magnetic resonance imaging and post hoc analyses by site suggested that walnuts might delay cognitive decline in subgroups at higher risk.(Sala-Vila 2020)

Antimicrobial effects

In vitro data

The constituent juglone has demonstrated antimicrobial and antifungal effects.(Alkhawajah 1997)

Clinical data

A systematic review and meta-analysis of randomized controlled trials evaluating nuts and their effects on gut microbiota, gut function, and gut symptoms in healthy adults concluded that nuts had no effect on bacterial phyla, diversity, or stool output.(Creedon 2020)

Antioxidant effects

Black walnut leaf has been evaluated for its antioxidant activity. Screening studies suggest compounds with both radical scavenging and antiradical-generating effects.(Choi 2002, Halvorsen 2002) The antioxidant capacity of walnut husk could be due to high concentrations of antioxidants in this part of the fruit. Findings suggest the possibility of using walnut husk as a food antioxidant or for antioxidant supplementation. The radical scavenging and antimicrobial effects of antioxidants in the green husk suggest that it may be a source of compounds with health protection potential and antimicrobial activity.(Jahanban-Esfahlan 2019)

In vitro data

In vitro, induction action of the endogenous antioxidant enzyme heme oxygenase-1 due to walnuts was critical in affording gastric defense against various irritants, including Helicobacter pylori infection, stress, alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. It was concluded that dietary walnut can act as a food factor to rescue NSAID-induced GI mucosal damage.(An 2020)

Clinical data

Results of clinical studies investigating the effects of walnuts on oxidative stress and apoprotein response are variable.(Bellido 2004, Davis 2007, Feldman 2002) Greater suppression of lipid peroxidation has been demonstrated in healthy adults following consumption of a black walnut muffin compared to a butter-based control muffin (P<0.01) with no difference observed between black versus English walnut-based muffins.(Rodrigues 2019)

Atrial fibrillation

Clinical data

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).(Martinez-Gonzalez 2014)

Blood pressure

Clinical data

A 2-year follow-up study (N=236) recruited participants 63 to 79 years of age, who were then randomized into a control group (usual diet without nut consumption) or an intervention group (approximately 15% of daily energy intake consisting of walnuts [approximately 30 to 60 g/day of walnuts]). The walnut diet resulted in a reduction of 8.5 mm Hg in systolic blood pressure in those whose baseline levels were more than 125 mm Hg; however, no changes were observed in diastolic blood pressure. Participants in the walnut group also required less uptitration of antihypertensive medication.(Domènech 2019, Santos 2020) In contrast, a recent meta-analysis did not support walnut consumption as a blood pressure–lowering strategy.(Santos 2020)

Cancer

The black walnut has been proposed as a candidate for chemotherapy because of the toxic nature of juglone and plumbagin, the yellow quinone pigments of black walnut; however, supportive studies are lacking.(Montoya 2004, Segura-Aguilar 1992)

In vitro data

Apoptosis and necrosis effects have been demonstrated in cancer cells with extracts of black walnut. In HaCAT keratinocytes, exposure to juglone and plumbagin decreased cell viability and cell death.(Inbaraj 2004, Montoya 2004)

Clinical data

Results of a pilot study conducted in postmenopausal women recently diagnosed with breast cancer confirmed that walnut consumption for 2 to 3 weeks led to changes in gene expression in the tumors that would be expected to slow proliferation, reduce inflammation, reduce metastasis, and increase cancer cell death. In the 2 to 3 weeks between diagnosis and surgery, the women consumed 2 ounces of walnuts daily while the control group avoided walnuts. None of the women had received chemotherapy or radiation. These results support and are aligned with data from previous animal and in vitro studies.(Hardman 2019)

Diabetes and glucose metabolism

Clinical data

In a randomized crossover trial that enrolled 194 healthy adults over the age of 50 years, secondary outcome results showed no significant change in fasting glucose during a 2-month walnut phase compared to a control period. However, a statistically significant but clinically irrelevant increase in HbA1c was documented. In addition to a chance finding, possible explanations for the change in glucose metabolism included increased calorie consumption during the walnut phase, statin therapy, decreased LDL, and genetic variants, all of which could increase HbA1c.(Bamberger 2017) No significant changes in fasting glucose were observed between the walnut and control group in the 2-year WAHA study conducted in 636 free-living older adults aged 63 to 79 years.(Rajaram 2021) Walnut consumption is also associated with a lower risk of type 2 diabetes in women and improvement of endothelial function, according to clinical studies.(Gorji 2018)

In a study of patients with diabetes, a hydroalcoholic extract of walnut leaves resulted in reduced weight and blood pressure; however, no effects on blood glucose or insulin resistance were noted.(Rabiei 2018)

As a component of medical nutrition therapy for patients with type 1 or type 2 diabetes, the American Diabetes Association Standards of Care (2022) recommend an increase in foods containing alpha linolenic acid, including nuts, to improve lipid profiles and reduce the risk of developing atherosclerotic cardiovascular disease (Level B). Likewise, as a component of medical nutrition therapy for patients with type 2 diabetes, the guidelines recommend higher-quality dietary fat intake, as an alternative to decreased fat intake, by replacing saturated and/or trans fats with mono- and polyunsaturated fatty acids in the diet. This Mediterranean-style approach to eating may improve glycemic control and cardiovascular disease risk factors. However, in patients with type 2 diabetes, they note that carbohydrate sources high in protein, such as nuts, should not be used to treat or prevent hypoglycemia due to the potential concurrent rise in endogenous insulin. In patients with prediabetes (level B), an emphasis on whole grains, legumes, nuts, fruits, and vegetables and minimally processed foods is associated with a lower risk of type 2 diabetes.(ADA 2021a, ADA 2021b, ADA 2022)

Gut microbiome and disease risk

Clinical data

Data from a small crossover conducted in 18 healthy adults also demonstrated that walnut consumption led to significant increases ranging from 49% to 160% in the Firmicutes phylum (P=0.04) and Faecalibacterium, Clostridium, Roseburia, and Dialister genera (P<0.05) as well as increases in the Actinobacteria phylum (P=0.02) compared to the control period. Additionally, lower abundances of Ruminococcus, Dorea, Oscillospira, and Bifidobacterium genera were observed during the walnut phase (P<0.05). Some of the changes in these microbial communities were associated with changes in colonic inflammatory bile acids, specifically the microbial-produced secondary bile acids deoxycholic acid and lithocholic acid. Although primary bile acids were unaffected by walnut consumption, these 2 proinflammatory bile acids were reduced by 25% and 45%, respectively (P<0.01), during the walnut phase and a positive correlation was documented between decreases in the Dorea genus and decreased lithocholic acid (P=0.05). These data support previous reports of reduced gut inflammation associated with reduced secondary bile acid concentrations and changes in the gut microbiome (eg, increased Faecalibacterium). With regards to the significant reductions that were observed in total and LDL cholesterol during the walnut phase, no association was found between changes in the gut microbiome and changes in lipid parameters. No significant changes were found in fungal or archaea communities.(Holscher 2018)

Dietary supplementation with whole walnuts (fatty acids, fiber, and bioactive compounds) as well as a walnut fatty acid-matched diet (without fiber and bioactive components) were both shown to differentially and positively affect the gut microbiota and associated cardiovascular risk factors compared to a standard Western diet (SWD). In this randomized, fully controlled, weight-maintenance feeding intervention cross-over study, 45 overweight or obese patients with elevated blood pressure and LDL cholesterol were placed on 3 diets for 6 weeks following a 2-week run-in period on a SWD comprised of 12% saturated fatty acids. The 3 study diets consisted of 7% saturated fatty acids and included a walnut diet (57 to 99 g/day whole walnuts; 2.7% alpha-linolenic acid [ALA]), a walnut fatty acid-matched diet (no walnuts; 2.6% ALA), and an oleic acid-replaces-ALA diet (no walnuts, little to no ALA [0.4%]). Of the 9 bacterial taxa that increased significantly with the walnut diet compared to the SWD, Roseburia, Eubacterium eligensgroup, and Lachnospiraceae UCG001 and UCG004 were the 4 that showed the greatest magnitude of enrichment. Similarly, Roseburia and E. eligensgroup demonstrated the biggest increase with the walnut fatty acid-matched diet. Subsequent analyses showed significant inverse correlations between percentages of enriched E. eligensgroup as well as Lachnospiraceae in the walnut diet and blood pressure parameters (ie, braChial MAP, central diastolic BP, central MAP). Additionally, a significant inverse association was seen between enriched Lachnospiraceae during the walnut diet and non-HDL cholesterol, however no significant correlations were observed between enriched bacteria and cardiovascular risk factors following either of the other 2 study diets.(Tindall 2020)

Lipid profile and cardiovascular risk

The beneficial effect of walnuts on lipids in healthy adults has been observed regardless of which macronutrient (ie, carbohydrate, fat, carbohydrate and fat) was replaced by walnuts or when they were consumed (ie, with a meal or as a snack). In all scenarios, non-HDL cholesterol, total cholesterol, LDL, VLDL, triglycerides, and apoproteinB improved significantly during a 2-month walnut period compared to the control period with no changes observed in HDL or lipoprotein(a). These results are based on a randomized crossover conducted in 194 healthy adults over the age of 50 years.(Bamberger 2017) The mechanism of lipid reduction with walnut consumption is unclear. Results from a subset of participants (n=352) in the WAHA study failed to identify any correlation between significant reductions in LDL and the significant modulation of microRNAs observed after one year of walnut consumption(Gil-Zamorano 2022) and no association was found between changes in gut microbiome and reductions in total or LDL cholesterol with walnut consumption.(Holscher 2018)

Clinical data

Clinical trials of walnut consumption conducted in healthy adults,(Chisholm 1998, Lavedrine 1999, Ros 2004, Sabate 1993, Zambon 2000, Zibaeenezhad 2005) patients with type 2 diabetes,(Gillen 2005, Tapsell 2004) and patients with metabolic syndrome(Davis 2007, Mukuddem-Petersen 2007, Schutte 2006) have been critically reviewed.(Feldman 2002, Mukuddem-Petersen 2005)

The majority of studies show a reduction of total cholesterol and LDL–cholesterol to cardioprotective levels and inconsistent effects on HDL–cholesterol and triglycerides.(Feldman 2002, Holscher 2018, Mukuddem-Petersen 2005) In the 2-year WAHA study completed by 636 free-living older adults (63 to 79 years of age), daily walnut supplementation to diverse diets that comprised approximately 15% of total daily energy led to significant decreases in mean total cholesterol by 4.4% (−8.5 mg/dL), LDL by 3.6% (−4.3 mg/dL), and intermediate-density lipoprotein cholesterol by 16.8% (−1.3 mg/dL). Total and small LDL particles, which have been consistently shown to be better predictors of cardiovascular disease (CVD) risk than LDL, decreased by 4.3% and 6.1%, respectively. Interestingly, a sexual dimorphic response was observed in LDL changes with a 7.9% reduction seen in men and a 2.6% reduction in women (P=0.007).(Rajaram 2021)

A diminished positive effect has been reported with higher dosages and may be a consequence of increased fat intake (with lesser effects seen with lower dosages).(Feldman 2002, Mukuddem-Petersen 2005) However, compared to baseline, a "placebo" dose of 5 g/day of walnuts for 4 weeks demonstrated a lipoprotein lipidomic response in hypercholesterolemic postmenopausal women. Walnut-induced changes were observed in the composition of oxylipin and fatty acids in lipoproteins. Although a 40-g/day dose also significantly affected the fatty acids and oxylipin composition of lipoproteins. It did not alter triglycerides, cholesterol, phospholipids, or protein levels. For example, walnuts increased arachidonic acid and DHA-derived epoxides specifically in HDL, and postprandial but not fasting levels of cholesterol and phospholipids in LDL were significantly decreased by 14% and 16% (P=0.0007 and P=0.009), respectively. Subsequent in vitro analyses using LDL isolated from these participants suggested that walnut consumption may correct the inflammatory status associated with the LDL load without correcting the hyperlipidemia.(Borkowski 2019)

In 25 adults with at least 3 cardiovascular risks (ie, age 45 to 65 years for men and postmenopausal women 50 to 70 years, body mass index (BMI) between 25 and 34.9, cholesterol between 220 and 290 mg/dL, blood pressure around 140/90 mm Hg, smoker), administration of meat products prepared with and without 20% walnut powder in a crossover design resulted in a significant reduction only in total cholesterol (−6.8 mg/dL, P=0.027) compared to consumption of meat products made without walnut powder. No other biomarkers associated with coronary heart disease were significantly affected (ie, HDL, LDL, triglycerides, alpha-tocopherol, body weight, blood pressure, homocysteine, folate, vitamins B6 and B12, platelet function). No evidence of adverse reactions or side effects were observed.(Olmedilla-Alonso 2008) A small, 3-period, crossover, randomized controlled feeding trial was conducted in individuals at risk of cardiovascular disease (N=45). The authors concluded that replacing saturated fat with walnuts or vegetable oils improves central blood pressure and serum lipids in adults at risk of cardiovascular disease.(Tindall 2019)

Limited effect has been shown in patients with metabolic syndrome.(Davis 2007, Mukuddem-Petersen 2007, Schutte 2006) A randomized controlled trial in 99 overweight and obese women determined that, in combination with a low-calorie diet, consumption of walnuts plus fish resulted in significant mean improvements in several cardiovascular risk factors compared to fish or walnuts alone. These included reductions in systolic blood pressure, fasting blood glucose, LDL, hs C-reactive protein, D-dimer, fibrinogen, ALT, AST, TNF-alfa and IL-6 as well as an increase in HDL with p-values ranging from P=0.03 to P<0.001. Meanwhile, a significant increase in triglycerides and decrease in diastolic blood pressure was observed in the both the walnut and the fish groups compared to the fish plus walnut group (P<0.001 and P=0.01, respectively).(Fahati 2019) A beneficial effect of walnuts on some lipid classes as well as insulin and glucose AUC was also observed in 10 obese adults in a 5-day inpatient double-blind, placebo-controlled cross-over. Fasting medium HDL, small VLDL, and atherogenic small LDL particles improved significantly (P<0.01, P<0.001, and P<0.02, respectively) during the walnut phase however no significant changes were observed in basic cholesterol panel parameters (ie, total cholesterol, clusterin, HDL, triglycerides, LDL, oxidized LDL). During the walnut phase, patients also demonstrated a significant decrease in lipoprotein insulin resistance scores (P<0.01) and significant increases in large HDL particles (P<0.01) and plasma ALA (P<0.02). Compared to the placebo (safflower oil plus walnut flavoring) phase, an overall significant decrease was observed in the total abundance of 19 lipid classes with walnuts.(Tuccinardi 2019) Favorable effects on LDL and systolic blood pressure have also been demonstrated in a cross-over study conducted in non-diabetic overweight/obese adults who consumed a walnut-enriched energy-restricted diet.(Rock 2017)

Walnut oil at a dosage of 15 mL daily significantly reduced total cholesterol, triglyceride, and LDL levels in patients with type 2 diabetes.(Zibaeenezhad 2017)

In a study in patients with chronic kidney disease, 30 g of walnuts per day was noted to be safe with regard to phosphorus, potassium, and other marker levels, while reducing LDL and blood pressure.(Sanchis 2019)

The role of walnut in atherosclerosis is unclear. Improved endothelial function has been demonstrated, possibly due to alpha linolenic acid or L-arginine content.(Cortes 2006, Ros 2004) In another study, walnut activated the nuclear transcription factor identified in human atherosclerotic plaques in healthy men.(Bellido 2004)

A small study (n=36) investigated any differences between dietary supplementation of the 2 walnut species with respect to cardiovascular benefit. Effect on endothelial function was reported to be absent in participants fed black walnut in comparison to the English variant.(Fitschen 2011) In contrast, endothelial markers were not significantly affected during the 2-month walnut phase compared to the control period in a crossover that enrolled 194 healthy adults over the age of 50 years.(Bamberger 2017)

Semen quality

Clinical data

In young healthy males who routinely ate a Western-style diet, the addition of 75 g/day of English walnuts for 12 weeks significantly improved sperm vitality (P=0.003), motility (P=0.009), morphology (P=0.03), and progressive motility (P=0.02) compared to those who avoided tree nuts. Serum omega-3 and omega-6 fatty acids increased significantly overall in the walnut group compared to controls (P=0.004 and P=0.003, respectively) with an increase in ALA as the only significant change seen in any individual parameter (P=0.0001). Sperm fatty acid profiles also increased in the walnut group and decreased in the control group (P=0.02). Although sperm chromosomal abnormalities were not significantly different between groups at baseline or at week 12, significant improvements occurred within the walnut group. Specifically, sex chromosome disomy as well as sperm missing a sex chromosome decreased (P=0.002 and P=0.01, respectively); sperm ALA was found to be inversely correlated with each of these sperm aneuploidy measures (P=0.002 and P=0.01, respectively). No significant changes were observed between groups in BMI, weight, physical activity, or days of abstinence.(Robbins 2012)

Vegetarian diet

Clinical data

The Academy of Nutrition and Dietetics' updated position paper on vegetarian diets (2016) states that adequate nutrition can be provided by a well-planned vegetarian diet that includes nuts. Therapeutic vegetarian diets are useful in maintaining a healthy weight and BMI, and are associated with a reduction in CVD risk and type 2 diabetes. Walnuts and walnut oil are some of the most concentrated plant sources of omega-3 fatty acids, and nuts, in general, are a source of protein and zinc.(Melina 2016)

Weight management and satiety effects

There is general agreement that no gain in body weight results from the addition of walnuts to the diet.(Feldman 2002, Sabate 1993, Tapsell 2004) Results from a sub-study in 356 participants in the 2-year WAHA study conducted in free-living older adults (63 to 79 years of age) support this. No significant differences were observed in changes in body weight, waist circumference, mean body fat, lean body mass, or weight-to-hip ratio between those who consumed walnuts daily (15% of total daily energy or 300 kcal) compared to those who did not (controls).(Bitok 2021)

Clinical data

In 100 non-diabetic overweight and obese adults, consumption of a walnut-enriched diet over several months led to significantly lower (worse) self-reported fullness scores at 3 months compared to a standard reduced-energy-density diet without walnuts (P=0.04). However, by month 6, a similar degree of weight loss (−8.9 and −9.4%, respectively) was observed in each group, and no significant differences in BMI, waist circumference, or satiety were found between groups.(Rock 2017) Similarly, acute postprandial satiety effects (hunger, fullness, anticipated consumption) in a smaller cross-over conducted in 28 non-diabetic overweight/obese adults were not significantly different between the test meal with walnuts and the test meal without walnuts. However, the postprandial GI peptide response which is usually indicative of satiety was significantly different between groups. Pancreatic polypeptide levels were observed to be significantly lower after the walnut meal at both 60 and 120 minutes (P=0.0014 and P=0.0002, respectively) as well as glucose-dependent insulinotropic peptide (P<0.0001 and P=0.0079, respectively). No significant differences were observed between groups at any time point for postprandial peptide YY, ghrelin, or cholecystokinin. Although insulin and C-peptide increased in both groups at 60 minutes, they were significantly lower in the walnut group at 120 minutes (P=0.0349 and P=0.0237, respectively); glucagon was also lower 120 minutes after the walnut meal (P=0.0069) compared to the reference meal.(Rock 2017)

In 36 healthy young university students enrolled in a randomized, single cross-over trial, consumption of a pre-dinner walnut snack or an isocaloric gummy candy snack led to significantly better scores in premeal fullness, sense of hunger, and desire to eat compared to no snack (P values ranged from P<0.001 to =0.019). Compared to having no snack, the walnut snack led to improved intake of saturated fat, cholesterol, and protein in the subsequent meal (P values ranged from P=0.013 to 0.014). However, the walnut snack led to significantly better intake of total fat, sodium, and fiber in the subsequent meal compared to the gummy candy snack as well as having no snack (P values ranged from P=0.006 to 0.037). No difference among groups in mealtime intake of sugar or total carbohydrates was observed. BMI and sex were identified as significant sources for variation in subsequent meal intake parameters.(Wilson 2022) In another small study (n=34), appetite suppression and fullness responses were significantly better following consumption of a walnut-based high-fat breakfast muffin than the butter-based version. Both black and English walnut muffins led to greater appetite suppression than the butter-based control muffin in healthy normal weight adults (P<0.01 and P=0.03, respectively), whereas only the black walnut muffin led to greater fullness compared to both the English walnut muffin (P<0.01) and the control muffin (P<0.001).(Rodrigues 2019)

Black Walnut side effects

Allergies to nuts are common in the United States (estimated 1% incidence),(Enrique 2005) with walnut and other tree nut allergies considered second only to peanut (a legume) allergy in causing 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.(Enrique 2005, Sicherer 2000) Cross-reactivity between walnut and peach lipid transfer protein allergen has also been noted.(Asero 2002, Pastorello 2001, Pastorello 2004)

Fatalities from anaphylaxis to walnuts have been recorded.(Pastorello 2004)

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).(Pastorello 2001, Pastorello 2004)

The high oxalate content in nuts is believed to be one of the contributing factors to kidney stone formation; however, the intestinal absorption of oxalate varies in individuals.(Gorji 2018)

Before taking Black Walnut

White walnut has GRAS status when used as food. The possibility of in utero sensitization has been debated without conclusion.(Sicherer 2000)

Avoid use of black walnut preparations. Mutagenic properties have been documented.(Brinker 1998, Montoya 2004) Possible cathartic effects have been observed at higher doses.(McGuffin 1997)

How to use Black Walnut

In a 2-year follow-up study evaluating effects on blood pressure, walnut dosing ranged from 30 to 60 g/day (4 shelled walnuts equals approximately 20 g).(Domènech 2019, Feldman 2002, Santos 2020)

Warnings

Data are limited; however, the naphthaquinone juglone, present in species belonging to the Juglandaceae family, is a known animal toxin.(True 1980) The risk of contamination with aflatoxin must also be considered.(Abdel-Hafez 1993)

What other drugs will affect Black Walnut

None well documented. Walnut interferes with the absorption of iron.(Feldman 2002)

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