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Linseed, Turmeric and Prostate cancer literature survey (work in progress)

Flax seeds are an excellent source of omega-3 fatty acids, iron, zinc, calcium, protein, potassium, magnesium, folate, soluble fiber and even boron. Flax is the #1 whole-food source of lignans, a phytonutrient associated with prolonged survival in cancer patients (especially breast cancer), having 800x more than any other food [1].

Evidence from preclinical and animal studies demonstrated an anticancer effect of flaxseed lignans, particularly enterolactone, against prostate cancer [2].

Two studies cited below, both discovered that men with higher serum levels of lignan have reduced rates of prostate cancer [2,3].

A lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia [4].

Certain flavonolignans can synergize with well-established chemotherapeutic agents for prostate cancer and perhaps this could apply to curcuminoids or other compounds in turmeric [5].

An experiment in France concluded that lignan-rich flaxseed hull extract prevented induced Benign Prostate Hyperplasia [6]

Several experimental and epidemiological evidences suggest that lignans may prevent human cancer in different organs [7]

Enterolactone and enterodiol, mammalian lignans derived from dietary sources such as flaxseed, sesame seeds, kale, broccoli, and apricots, may impede prostate tumor proliferation [8]

There is evidence that a mammalian lignan, enterolactone, decreases the proliferation rate of prostate cancer cells, and in contrast to previous studies, concentrations of this that are reported from diet do restrict the proliferation of early-stage tumourigenic prostate cell lines [9]

Enterolactone (EL) is an enterolignan produced by gut microbiota from dietary plant lignans. Epidemiological and experimental studies suggest that EL and plant lignans may reduce the risk of breast and prostate cancer as well as cardiovascular disease.[10]

Flaxseed is the richest in the vegetable world source of lignans (up to 1,5% of dry weight of seed). Plant lignans are characterized as natural phytoestrogen that reduce the risk of hormone dependent cancers of breast, uterus and prostate.

Evidence-based biomedical researches: on various models in experimental carcinogenesis, on the tumor cells in vitro, in clinical trials in patients with hormone-dependent tumors, and, finally, in epidemiological studies, have proved the anticarcinogenic activity of the components of the flaxseed and validity of recommendations for preventive and curative use in hormone-dependent tumors. [11]

Leukotriene B4 has been implicated in prostate and colon carcinogenesis, [12] and curcumin has been identified as a potent inhibitor of leukotriene B4 formation [13]. So a combination of turmeric and flaxseed is potentially a good weapon against prostate cancer.

Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. But the picture in this instance is not clear and no unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer.

Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.[14]

Experimenters in Italy showed for the first time that the integration of Flax Seeds into rabbit diets may improve sperm quality by modifying the sperm lipid composition, and prostatic granules [15]

Lignans such as secoisolariciresinol diglucoside in flaxseed, are metabolized to bioactive mammalian lignans. Because mammalian lignans have chemical structural similarity to the natural estrogen, they are thought to behave like selective estrogen receptor modulators and therefore have anticancer effect against hormone-related cancers. [16]

Chinese researchers drew the conclusion that dietary flaxseed lignan extract appreciably improves lower urinary tract symptoms in Benign Prostatic Hyperplasia subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors [17]

The mammalian lignan enterolactone is a major metabolite of plant-based lignans that has been shown to inhibit the growth and development of prostate cancer. However, little is known about the mechanistic basis for its anticancer activity. In this study, we report that enterolactone selectively suppresses the growth of LNCaP prostate cancer cells by triggering apoptosis [18]

Lignan is an important phytoestrogen with weakly estrogenic and anti-estrogenic properties, and possesses diverse bioactivities, including antioxidation, antitumor and antivirus etc. In particular, it may prevent hormone-dependent diseases, such as breast cancer, prostate cancer and benign prostatic hyperplasia [19]

Secoisolariciresinol (SECO ) is the major lignan found in flaxseed and is known to have a number of health benefits, including reduction of serum cholesterol levels, delay in theonset of type II diabetes and decreased formation of breast, prostate and colon cancers [20]

Prostate cancer is poised to become the most prevalent male cancer in the Western world. In Japan and China, incidence rates are almost 10-fold less those reported in the United States and the European Union. Epidemiological data suggest that environmental factors such as diet can significantly influence the incidence and mortality of prostate cancer. The differences in lifestyle between East and West are one of the major risk factors for developing prostate cancer. Traditional Japanese and Chinese diets are rich in foods containing phytoestrogenic compounds, whereas the Western diet is a poor source of these phytochemicals [21]

However a survey done at University Hospital of Amiens in 2004 showed few studies showed protective effect between phytoestrogen intake and prostate cancer risk but this is refuted by a lot of more recent research [22]

Researchers in Sweden found that Enterolactone, a phytoestrogen produced by the intestinal microflora from precursors in plant foods such as linseed, has been postulated to protect against hormone-dependent cancers. We studied the association between plasma enterolactone and risk of prostate cancer. Men with very low enterolactone levels had significantly higher risk of prostate cancer [23]

A study in Finland with a purified lignin supplemented in the diet started at the early phase of the tumor development, inhibits the growth of the human prostate cancer xenografts in athymic male mice [24]

Bibliography

2. Phyto-oestrogens and risk of prostate cancer in Scottish men.
British Journal of Nutrition. 2007 Aug;98(2):388-96.
https://www.ncbi.nlm.nih.gov/pubmed/17403269

3. Phyto-oestrogen intake in Scottish men: use of serum to validate a self-administered food-frequency questionnaire in older men.
European Journal of Clinical Nutrition. 2006 Jan;60(1):129-35.
https://www.nature.com/articles/1602277

4. The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor
Applied Physiology, Nutrition and Metabolism. 2016 Dec;41(12):1303-1310. Epub 2016 Sep 27.
https://www.ncbi.nlm.nih.gov/pubmed/27849354

5. The Potential of Flavonolignans in Prostate Cancer Management.
Current Medicinal Chemistry. 2016;23(34):3925-3950.
https://www.ncbi.nlm.nih.gov/pubmed/27557939

6.  Preventive effects of lignan extract from flax hulls on experimentally induced benign prostate hyperplasia.
Journal of Medicinal Food. 2014 Jun;17(6):650-6. doi: 10.1089/jmf.2013.0046. Epub 2014 Jan 24.
https://www.ncbi.nlm.nih.gov/pubmed/24460407

7. Pinoresinol inhibits proliferation and induces differentiation on human HL60 leukemia cells.
Nutrition and Cancer. 2013;65(8):1208-18. doi: 10.1080/01635581.2013.828089. Epub 2013 Oct 
https://www.ncbi.nlm.nih.gov/pubmed/24099079

8. Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer.
Journal of Medicinal Food. 2013 Apr;16(4):357-60. doi: 10.1089/jmf.2012.0159
https://www.ncbi.nlm.nih.gov/pubmed/23566060

9. Anti-proliferative effects of physiological concentrations of enterolactone in models of prostate tumourigenesis.
Molecular Nutrition and Food Research. 2013 Feb;57(2):212-24. doi: 10.1002/mnfr.201200362. Epub 2012 Nov 12.
https://www.ncbi.nlm.nih.gov/pubmed/23148045

10. A single dose of enterolactone activates estrogen signaling and regulates expression of circadian clock genes in mice.
Journal of Nutrition. 2011 Sep;141(9):1583-9. doi: 10.3945/jn.111.140277. Epub 2011 Jul 13.
https://academic.oup.com/jn/article-pdf/141/9/1583/23949339/1583.pdf

11
. Curcumin: a potent inhibitor of leukotriene B4 formation in rat peritoneal polymorphonuclear neutrophils (PMNL)
Planta Medica. 1992 Apr;58(2):226.
https://www.ncbi.nlm.nih.gov/pubmed/1326775

12. Phytoestrogenis properties of flaxseed lignans. [Full article is in Russian]
Voprosy Pitaniia. 2012;81(6):61-6.
https://www.ncbi.nlm.nih.gov/pubmed/23530438

13. Role of leukotriene B4 in celecoxib-mediated anticancer effect
Biochemical and Biophysical Research Communications. 2010 Nov 12;402(2):308-11. doi: 10.1016/j.bbrc.2010.10.022. Epub 2010 Oct 19. .
https://www.sciencedirect.com/science/article/pii/S0006291X10018735

14
. Assessment of information to substantiate a health claim on the prevention of prostate cancer by lignans.
Nutrients. 2010 Feb;2(2):99-115. doi: 10.3390/nu2020099. Epub 2010 Jan 28.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257165/

15. Effects of flaxseed dietary supplementation on sperm quality and on lipid composition of sperm subfractions and prostatic granules in rabbit. 
Theriogenology. 2010 Mar 15;73(5):629-37. doi: 10.1016/j.theriogenology.2009.10.019. Epub 2010 Jan 19.
https://www.ncbi.nlm.nih.gov/pubmed/20034660

16. Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. 
Clinical Cancer Research. 2009 Aug 15;15(16):5161-9. doi: 10.1158/1078-0432.CCR-09-0661. Epub 2009 Aug 11.
https://www.ncbi.nlm.nih.gov/pubmed/19671865

17. Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia
Journal of Medicinal Food. 2008 Jun;11(2):207-14. doi: 10.1089/jmf.2007.602.
https://www.ncbi.nlm.nih.gov/pubmed/18358071

18. Enterolactone induces apoptosis in human prostate carcinoma LNCaP cells via a mitochondrial-mediated, caspase-dependent pathway
Molecular Cancer Therapeutics. 2007 Sep;6(9):2581-90.
https://www.ncbi.nlm.nih.gov/pubmed/17876055

19. Lignan: an important natural estrogen from plants (Full article is in Chinese)
Zhongguo Zhong Yao Za Zhi (China Journal of Chinese materia medica). 2006 Dec;31(24):2021-5, 2093.
https://www.ncbi.nlm.nih.gov/pubmed/17357545

20. AAPH-mediated antioxidant reactions of secoisolariciresinol and SDG. 
Organic and Biomolecular Chemistry. 2007 Feb 21;5(4):644-54. Epub 2007 Jan 23.
https://www.ncbi.nlm.nih.gov/pubmed/17285173

21. Role of mammalian lignans in the prevention and treatment of prostate cancer.
Nutritional Cancer. 2005;52(1):1-14.
https://www.ncbi.nlm.nih.gov/pubmed/16090998

22. Phytoestrogens and prostate cancer risk. 
Preventive Medicine. 2005 Jul;41(1):1-6. Epub 2004 Dec 9.
https://www.ncbi.nlm.nih.gov/pubmed/15916986

23. Prospective study of plasma enterolactone and prostate cancer risk (Sweden)
Cancer Causes Control. 2004 Dec;15(10):1095-102.
https://www.ncbi.nlm.nih.gov/pubmed/15801493

24. Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.
Experimental Biology and Medicine (Maywood). 2005 Mar;230(3):217-23. 
https://www.ncbi.nlm.nih.gov/pubmed/15734725