Walnuts for Breast Cancer Prevention

Walnuts (Juglans regia, Juglans nigra, Juglans cinerea) are an extraordinary source of breast-cancer beating phytochemicals (natural plant chemicals). Walnuts are filled with antioxidants and contain more melatonin and alpha linolenic acid (ALA) than any other nut, along with an impressive array of phenols and flavonoids and other things which help to protect from breast cancer. In this article, I’ll share with you exactly why walnuts are so protective and why I think they should be included in your breast-healthy diet.

What Is In Walnuts That Makes Them So Protective?

Besides being healthy for the breast cancer survivor, walnuts are excellent for heart health, for improving the quality of blood and reducing LDL (the bad sort) cholesterol levels, helping to control blood sugar levels, and promoting good bone health.

Most of the research done thus far on walnuts as a whole (and not on the individual phytochemicals which comprise them, some of which I have discussed below) has only been with animals, however, we cannot and should not discount it. In one study, not only did the female animals who ate diets high in walnuts have lower rates of breast cancer, their daughters – who received the benefits of their mother’s diets in utero and then during nursing and later consuming walnut-rich diets themselves – also had lower rates of breast cancer. [1]

One 2019 clinical study [2] found that walnut consumption turned dozens of genes on and off. The genes affected by a walnut-rich diet influence the growth and development of the cells that line breast ducts, which is where most breast cancers arise. Genes that suppress cancer are turned on, while genes that promote cancer are turned off. Researchers stated “expression of 456 identified genes was significantly changed in the tumor due to walnut consumption.”

A 2015 study [3] looked into nut consumption and cancer risk. Researchers found that individuals who consumed higher quantities of peanuts, walnuts, and almonds had their risk of breast cancer reduced by 2–3 times.

It’s Those Impressive Phytochemicals!

Many of the phytochemicals in walnuts have anti-cancer activity, but it appears that it is the synergistic presence of all of them together that makes walnuts such great cancer-fighters. Here are the main protective phytochemicals in walnuts:

Melatonin – An important antioxidant hormone created by the body, but also made by plants. Melatonin has many effects in the body, the primary being a regulator of sleep. More relevant to the discussion at hand, however, melatonin has been discussed in a 2008 article in Current Cancer Drug Targets [4] as having anti-aromatase activity, reducing circulating estrogen, acting as a selective estrogen enzyme modulator (meaning that it selectively neutralizes circulating levels of estrogen in the body), and also acting as a SERM (selective estrogen receptor modulator), thus protecting mammary tissue from excessive estrogenic effects.

Three studies [5], [6], [7] have found that melatonin potently inhibits all types of breast cancer. A 2017 study [8] found that melatonin enhances the effects of chemotherapy while reducing the side effects, and one 2018 study [9] found that melatonin blocks elevated estrogen levels and proliferation of breast cancer cells created by the xenoestrogen bisphenol A (BPA).

Vitamin C – Walnuts even contain vitamin C. Vitamin C has long been known to be a potent inhibitor of cancer cells by alternative medicine doctors. A 2014 review [10] of ten studies investigating vitamin C and breast cancer found that vitamin C supplementation taken post-diagnosis was associated with a reduced risk of death, both from all causes and from breast cancer. A 2018 study [11] showed that vitamin C is definitely one of those epigenetic nutrients that are beneficial for our health. Researchers found that many women with breast cancer have decreased SVCT2 expression – a protein responsible for transporting vitamin C. In this study they found that vitamin C worked in a number of ways at the genetic level to promote apoptosis (planned cell death) in breast cancer cell lines.

Alpha Linolenic Acid (ALA) – This is one of those healthy fats that are not created in the body, but must be obtained through the diet. A 2009 study [12] found that ALA promoted apoptosis and inhibited cell growth of ER+/PR+ metastatic breast cancer cells.

A 2015 cell study [13] investigated ALA for its cytotoxic activity against estrogen-receptor positive (hereinafter “ER+”), estrogen-receptor negative (“ER-“), progesterone-receptor positive (“PR+”) , progesterone-receptor negative (“PR-“), triple negative breast cancer (which is ER-, PR-, HER2-), HER2 positive (“HER2+”) and HER2 negative (“HER2-“) breast cancer cell lines. ALA was found to reduce the growth of all breast cancer cell lines and induced apoptosis regardless of receptor expression and estrogen levels.

Ellagic acid – A flavonoid polyphenol and potent cancer inhibitor. Ellagic acid is an important antioxidant with anti-inflammatory, anti-mutagenic (meaning it is protective to DNA) and neuroprotective (nerve protective) properties. Ellagic acid has been shown in studies [14], [15]. [16], [17], [18], [19], [20], [21], [22] to inhibit the proliferation (rapid growth) of cancer cells, promote apoptosis, reduce tumor size and incidence, inhibit the aromatase enzyme, inhibit the action of estrogen receptor alpha (which is associated with proliferation of breast cells), inhibit Cyclin D1 (which acts as an oncogene in breast cancer by giving selective advantages to cancer cells), and inhibit the ability of breast cancer cells to move through the body (a process known as metastasis). Ellagic acid also suppresses MMP enzymes which help cancer cells to spread through the body. It also inhibits breast cancer stem cells, modulates the activity of over 4,700 genes (!), works synergistically with radiotherapy to increase its cancer-killing power whilst reducing its bad effect on healthy cells, and promotes production of an important anti-cancer enzyme, glutathione S-transferase.

Lignans – Lignans are polyphenols with antioxidative activity. Studies show that a higher intake of dietary lignans is associated with a reduced risk of breast cancer and cardiovascular disease. More importantly for breast cancer survivors, lignans also appear to have a moderate ability to inhibit CYP19, the gene that encodes for the aromatase enzyme. [23]

A 2012 study [24] found that dietary lignans could reduce breast cancer risk. After tracking the lignan intake of 683 women with breast cancer, and 611 healthy women without breast cancer, it was found that the women with the highest intake of lignans had a 40-50% lower risk of developing breast cancer, regardless of menopausal status. A 2014 German study [25] also found that high lignan intake was associated with reduced mortality in breast cancer patients.

Beta-sitosterol – A plant sterol chemically similar to that of cholesterol, beta-sitosterol acts to interfere with the absorption of cholesterol, so it is abundantly heart healthy. It has also been shown to be anti-inflammatory, immune balancing and cancer-fighting. A 2000 study [26] found that beta-sitosterol inhibited the growth of triple negative breast cancer cells, and stimulated apoptosis. A 2003 study [27] found that campesterol and beta-sitosterol (both are found in walnuts) inhibited the growth of triple negative breast cancer cells. A 2004 animal study [28] found that beta-sitosterol was associated with decreasing levels of circulating estrogen and inhibition of estrogen-driven breast cancer tumors.

A 2008 study [29] found that beta-sitosterol worked synergistically with Tamoxifen to inhibit the growth of ER+/PR+ metastatic breast cancer cells.

A 2013 review [30] of medical studies discussed the properties of plant sterols, including beta-sitosterol. They found that they stimulate the immune system through improving gut surveillance and increase levels of cytokines and NK cell activity. They are antioxidative, and interestingly, through their cholesterol-lowering effect, it has been found that plant sterols have inhibitory effects on cellular growth. Indeed, anti-cholesterol drugs known as statins have been suggested to be of use in breast cancer therapy, and I have definitely noticed that many foods (and also essential oils) which are known to inhibit breast cancer also reduce cholesterol. Plant sterols also have blood sugar-lowering effects and this benefits anyone with cancer. More importantly, plant sterols may bind to estrogen receptors and act as SERMs. Researchers also made mention of the fact that in a mouse model of melanoma, beta-sitosterol inhibited metastasis.

A 2015 study [31] found that beta-sitosterol had anti-cancer properties, interfering with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation in several cancer cell lines, including breast cancer.

Consumption Tips:

Choose Organic. Walnuts have a lot of pest issues and as such are saturated with pesticides and chemicals, more than any other nut. Their fat content allows them to absorb these chemicals so please buy organically grown walnuts.

Store In Fridge or Freezer. The high fat content of walnuts makes them extremely perishable so they should be stored in an airtight container in the refrigerator or freezer.

Don’t Eat Walnuts Along With These Oils. The body’s ability to utilize ALA can be blocked by the presence of vegetable oils with high omega-6 fatty acid content such as corn oil, soybean oil, safflower oil, sunflower oil, or grapeseed oil. It’s best if walnuts are consumed away from these oils.

If You Have Active Cancer In Your Body – Walnuts should be consumed in moderation only (or as a cold-pressed oil) because they do contain some copper. Copper is known to promote angiogenesis, the formation of new blood vessels by a tumor (so it can feed itself). While we do need copper in our diet, if you have active cancer in your body, it’s best to avoid copper as much as possible. Instead, have cold-pressed organic walnut oil, which contains virtually no copper but does contain the other nutrients in walnuts.

Don’t Heat Walnuts or Walnut Oil – they lose their protective nutrients when heated.

References:

[1] Dietary Walnut Suppressed Mammary Gland Tumorigenesis in the C(3)1 TAg Mouse – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474134/
[2] Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial – https://www.sciencedirect.com/science/article/pii/S0271531718311904
[3] The Protective Effect of Peanut, Walnut, and Almond Consumption on the Development of Breast Cancer – https://www.researchgate.net/profile/Jose_Guzman-Esquivel2/publication/285383810_Association_of_Milk_and_Meat_Consumption_with_the_Development_of_Breast_Cancer_in_a_Western_Mexican_Population/links/5665c87b08ae418a786f2c1a.pdf
[4] Melatonin as a selective estrogen enzyme modulator – https://www.ncbi.nlm.nih.gov/pubmed/19075592
[5] Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046452/
[6] Melatonin Represses Metastasis in Her2-postive Human Breast Cancer Cells by Suppressing RSK2 Expression – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107120/
[7] Melatonin regulates the tumor suppressor miR-148a-3p involved in angiogenesis and metastasis of breast cancer – http://cancerres.aacrjournals.org/content/77/13_Supplement/1477
[8] Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF-7 human breast cancer cells – https://www.spandidos-publications.com/10.3892/ijo.2017.4213
[9] Melatonin inhibits the proliferation of breast cancer cells induced by bisphenol A via targeting estrogen receptor-related pathways – https://www.ncbi.nlm.nih.gov/pubmed/29330934
[10] Vitamin C and survival among women with breast cancer: a meta-analysis – https://www.ncbi.nlm.nih.gov/pubmed/24613622
[11] Vitamin C promotes apoptosis in breast cancer cells by increasing TRAIL expression – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871772/
[12] Growth-inhibitory and proapoptotic effects of alpha-linolenic acid on estrogen-positive breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/19723055
[13] a-Linolenic Acid Reduces Growth of Both Triple Negative and Luminal Breast Cancer Cells in High and Low Estrogen Environments – https://www.ncbi.nlm.nih.gov/pubmed/26134471
[14] The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells – https://www.researchgate.net/publication/38021891_The_effect_of_dietary_polyphenols_on_the_epigenetic_regulation_of_gene_expression_in_MCF7_breast_cancer_cells
[15] Berries and Ellagic Acid Prevent Estrogen-Induced Mammary Tumorigenesis by Modulating Enzymes of Estrogen Metabolism – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896023/
[16] Evaluation of the anti-inflammatory effects of ellagic acid – https://www.ncbi.nlm.nih.gov/pubmed/20656257
[17] Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409373/
[18] Ellagic acid exerts anti-proliferation effects via modulation of Tgf-ß/Smad3 signaling in MCF-7 breast cancer cells — https://www.ncbi.nlm.nih.gov/pubmed/24528038
[19] Ellagic acid induces cell cycle arrest and apoptosis through TGF-ß/Smad3 signaling pathway in human breast cancer MCF-7 cells – https://www.ncbi.nlm.nih.gov/pubmed/25647396
[20] Ellagic Acid Enhances Apoptotic Sensitivity of Breast Cancer Cells to Gamma-Radiation – https://www.ncbi.nlm.nih.gov/pubmed/28718725
[21] Role of dietary bioactive natural products in estrogen receptor-positive breast cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033666/
[22] Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of ß-catenin stabilization in cancer stem cells – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712102/
[23] Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens – http://www.ncbi.nlm.nih.gov/pubmed/8382517
[24] Dietary Intakes of Total and Specific Lignans Are Associated with Clinical Breast Tumor Characteristics – http://jn.nutrition.org/content/142/1/91.short
[25] Enterolactone concentrations and prognosis after postmenopausal breast cancer: assessment of effect modification and meta-analysis – https://www.ncbi.nlm.nih.gov/pubmed/24436155
[26] Inhibition of growth and stimulation of apoptosis by beta-sitosterol treatment of MDA-MB-231 human breast cancer cells in culture – https://www.ncbi.nlm.nih.gov/pubmed/10762 26] 659/
[27] Effect of phytosterols on cholesterol metabolism and MAP kinase in MDA-MB-231 human breast cancer cells – https://www.ncbi.nlm.nih.gov/pubmed/12667603
[28] Beta-Sitosterol, Beta-Sitosterol Glucoside, and a Mixture of Beta-Sitosterol and Beta-Sitosterol Glucoside Modulate the Growth of Estrogen- Responsive Breast Cancer Cells In Vitro and in Ovariectomized Athymic Mice – https://www.ncbi.nlm.nih.gov/pubmed/15113961
[29] Beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by affecting ceramide metabolism – https://www.ncbi.nlm.nih.gov/pubmed/18338406/
[30] Plant Sterols as Anticancer Nutrients: Evidence for Their Role in Breast Cancer – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635199/
[31] Beta-Sitosterol: A Promising but Orphan Nutraceutical to Fight Against Cancer – https://www.ncbi.nlm.nih.gov/pubmed/26473555

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