Breast cancer in folate's Point of view

Folate, also known as folic acid, vitamin B9, is a water soluble vitamin, found abundantly in leafy vegetables, citrus fruits, beans, whole grain, etc. The vitamin plays an important role in synthesize DNA, repair DNA, and methylate DNA as well as to act as a cofactor in certain biological reactions, production of red blood cells for anemia prevention.

Scientific studies, linking folate in reduced risk of breast cancer have produced inconsistent results. It may be due to race, menopausal status or ER status(1).
In comparison of the dietary intakes of folate, B-vitamins (B2, B6, B12) and methionine, showed that high intake of folate is marginally associated with a reduced lower risk for ER- breast cancer(1a), among Hispanic and non-Hispanic white women(2), but  among Brazilian women, dietary intake of folate,  had no overall association with breast cancer risk and high folate intake increased risk of breast cancer in premenopausal women with the MTR 2756GG genotype(women carry this gene have a subtly reduced risk of breast cancer(3))(4). In breast cancer risk defined by oestrogen receptor (ER) and progesterone receptor (PR) status, dietary folate intake showed an significant inverse association of breast cancer risk  in all subtypes of ER and PR status(5).
In Japanese women with genotypes of MTHFR or MTR, dietary intake of folate and related B vitamins have no overall association with breast cancer risk in Japanese women(6).
Unfortunately. in rat model study, folate supplementation was found to be associated with significantly higher weight and volume of all mammary tumors and might enhance the progression of established mammary tumors(7). Also in the study of at weaning, female pups, maternal folic acid supplementation  significantly accelerated the rate of mammary adenocarcinoma appearance and significantly decreased DNA methyltransferase (protect host DNA against degradation by restriction enzymes) activity in nonneoplastic(not tumors) mammary glands of the offspring(8). In the finding of an anti breast caner conjugat used conjuction with Doxorubicin (Dox) which used for breast cancer treatment but causes serious side effects including cardiotoxicity, conjugation of  Dox-conjugated hairpin (DCH) with folic acid (FA) is found to be effective in increased internalization into breast cancer cells for safer and more effective chemotherapy with Dox(9). In MCF-7 and MDA-MB-231 breast cancer cells, hydrogel, based on ellagic acid and glycine containing folate acid significantly inhibit cell viability(10). In nude mice carrying xenograft MCF-7 tumours,  folate inTMX(Tamoxifen)-loaded folate-targeted systems anticancer action of TMX(11). Lipotropes are methyl group-containing essential nutrients (methionine, choline, folate and vitamin B12) in the experiment in MCF-7 cells, showed to significantly reduced cell growth and increased apoptosis, through upregulation of caspase-3(mechanisms of apoptosis) and P53(tumor antigen) enzyme activities(12). Also in the evaluation of MTHFR C677T-A1298C polymorphisms in patients with breast cancer, showed that at dose of 120 nmol/L FA could enhance apoptosis in cases with women who carry MTHFR C677T-A1298C genotype(13).

Taking altogether, folate used conjunction with other chem-drugs have shown effectively in enhancing the function the medicine in prevention and treatment of breast cancer cell lines with reduced side effects. Overdoses of folate may cause stomach problems, sleep problems, skin reactions, seizures, etc., please
 make sure you follow the guideline of the Institute of Medicine of the National Academies.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca  

References
(1) Associations of dietary folate, Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women by Gong Z, Ambrosone CB, McCann SE, Zirpoli G, Chandran U, Hong CC, Bovbjerg DH, Jandorf L, Ciupak G, Pawlish K, Lu Q, Hwang H, Khoury T, Wiam B, Bandera EV.(PubMed)

(1a) Dietary intake of folate, B-vitamins and methionine and breast cancer risk among Hispanic and non-Hispanic white women by Yang D, Baumgartner RN, Slattery ML, Wang C, Giuliano AR, Murtaugh MA, Risendal BC, Byers T, Baumgartner KB.(PubMed)
(2) Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Zhang CX, Ho SC, Chen YM, Lin FY, Fu JH, Cheng SZ.(PubMed)
(3) Cancer: New Insights for the Healthcare Professional: 2012 Edition
(4) Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women by Ma E, Iwasaki M, Junko I, Hamada GS, Nishimoto IN, Carvalho SM, Motola J Jr, Laginha FM, Tsugane S.(PubMed)
(5) Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Zhang CX, Ho SC, Chen YM, Lin FY, Fu JH, Cheng SZ.(PubMed)
(6) Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan by Ma E, Iwasaki M, Kobayashi M, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Tsugane S.(PubMed)
(7) Folic Acid supplementation promotes mammary tumor progression in a rat model. by Deghan Manshadi S¹, Ishiguro L¹, Sohn KJ², Medline A³, Renlund R⁴, Croxford R⁵, Kim Y1(PubMed)
(8) Effect of maternal and postweaning folic acid supplementation on mammary tumor risk in the offspring by Ly A, Lee H, Chen J, Sie KK, Renlund R, Medline A, Sohn KJ, Croxford R, Thompson LU, Kim YI.(PubMed)
(9)Site-Specific DNA-Doxorubicin Conjugates Display Enhanced Cytotoxicity to Breast Cancer Cells by Stuart CH, Horita DA, Thomas MJ, Salsbury FR Jr, Lively MO, Gmeiner WH.(PubMed)
(10) Anticancer activity of a hydrogel containing folic acid towards MCF-7 and MDA-MB-231 cells by Trombino S, Ferrarelli T, Pellegrino M, Ricchio E, Mauro L, Andò S, Picci N, Cassano R.(PubMed)
(11) Targeting Tamoxifen to Breast Cancer Xenograft Tumours: Preclinical Efficacy of Folate-Attached Nanoparticles Based on Alginate-Cysteine/Disulphide-Bond-Reduced Albumin by Martínez A, Muñiz E, Teijón C, Iglesias I, Teijón JM, Blanco MD.(PubMed)
(12) Lipotropes enhance the anti-proliferative effect of chemotherapeutic drugs in MCF-7 human breast cancer cells by Cho K, Mabasa L, Walters MW, Park CS.(PubMed)
(13) Interactions between MTHFR C677T-A1298C variants and folic acid deficiency affect breast cancer risk in a Chinese population by Wu XY, Ni J, Xu WJ, Zhou T, Wang X.(PubMed)

Breast cancer in Vitamin B12's Points of View

 Kyle J. Norton

Vitamin B12, also known as cobalamin, a water-soluble vitamin, found abundantly in a variety of foods, such as fish, shellfish, meat, eggs, dairy products, etc. plays an important role in regulating the functions of nervous system and formation of blood.
Breast cancer (malignant breast neoplasm) is a cancer started in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases of breast cancer started in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.

Epidemiological studies linking levels of plasma of vitamin B12 in reduced risk of breast cancer have produced inconclusive results. In premenopausal women, Plasma vitamin B(12) levels were inversely associated with breast cancer risk(1)(1a)(1b)(1c). Unfortunately, in the study of the same, showed vitamin B-12, may confer little or no reduction in overall risk of developing breast cancer (2)(3)(3a).
In human breast cancer cell line, MCF-7 and normal mammary cells, MCF-10A, lipotropes containing methionine, choline, folate, and vitamin B₁₂, showed an decrease of expression of bcl-2 in regulating apoptosis in lipotrope-treated MCF-7 cells of these suggestion of blocking  Bcl-2 might prove useful in sensitizing tumor cells to chemotherapy-induced apoptosis(4). In rat fed with  Lipotropes showed a reduction of tumor multiplicity and tumor volume significantly through decreased expression of histone deacetylase 1 (Hdac1) and DNA methyltransferase 1 (Dnmt1) genes in tumor tissues of the rats(5). In the study of Maternal high-methyl diet, Lipotropes showed significantly decreased tumor incidence, tumor multiplicity and tumor volume, while also displaying a significant increase in survival rate and tumor latency in rat offspring(6) and enhanced the efficacy of chemo durgs, SAHA and DOX through induced apoptosis, inhibited cell growth, and displayed anti-proliferation(7).

Taking all together, one can say that the effective of vitamin B12 in reduced risk of breast cancer and enhanced the efficacy of chemo-drugs was found in conjunction with other members of the methyl group but not the vitamin itself. Over doses of the vitamin may induce symptoms of toxicity, including headache, giddiness and abnormal heart functioning, etc., please make sure to follow the guideline of the Institute of Medicine of the National Academies.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca   

References
(1) Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer by Zhang SM, Willett WC, Selhub J, Hunter DJ, Giovannucci EL, Holmes MD, Colditz GA, Hankinson SE.(PubMed)
(1a) Association of dietary intake of folate, vitamin B6 and B12 and MTHFR genotype with breast cancer risk by Liu Y, Zhou LS, Xu XM, Deng LQ, Xiao QK.(PubMed)
(1b) Dietary intake of folate, B-vitamins and methionine and breast cancer risk among Hispanic and non-Hispanic white women by Yang D, Baumgartner RN, Slattery ML, Wang C, Giuliano AR, Murtaugh MA, Risendal BC, Byers T, Baumgartner KB.(PubMed)
(1c) Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women by Lajous M, Romieu I, Sabia S, Boutron-Ruault MC, Clavel-Chapelon F.(PubMed)
(2) Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women by Lin J, Lee IM, Cook NR, Selhub J, Manson JE, Buring JE, Zhang SM.(PubMed)
(3) Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer risk in four large cohorts by Schernhammer E, Wolpin B, Rifai N, Cochrane B, Manson JA, Ma J, Giovannucci E, Thomson C, Stampfer MJ, Fuchs C.(PubMed)
(3a) Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial by Zhang SM, Cook NR, Albert CM, Gaziano JM, Buring JE, Manson JE.(PubMed)
(4) Lipotropes regulate BCL-2 gene expression in the human breast cancer cell line, MCF-7 by Hyung H. Kim, Chung S. Park(PubMed)
(5) Pubertal supplementation of lipotropes in female rats reduces mammary cancer risk by suppressing histone deacetylase 1 by Cho K, Choi WS, Crane CL, Park CS.(PubMed)
(6) Maternal high-methyl diet suppresses mammary carcinogenesis in female rat offspring by Cho K, Mabasa L, Bae S, Walters MW, Park CS.(PubMed)
(7) Lipotropes enhance the anti-proliferative effect of chemotherapeutic drugs in MCF-7 human breast cancer cells by Cho K, Mabasa L, Walters MW, Park CS.(PubMed)

Breast cancer in Vitamin B6's Points of view

 By Kyle J. Norton

Epidemiological studies focusing vitamin B6 in reduced risk of breast cancer have produced conflict results. But the widespread of breast cancer has caused many concerns in the world leaders and scientific community. Every year, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
Vitamin B6, also known as pyridoxine, is a water soluble vitamin found abundantly in green peas, yams, broccoli, asparagus and turnip greens,Peanuts, sunflower seeds, cashews and hazelnuts, meat, fish etc., with functions of amino acid, carbohydrate  metabolism, brain health, and liver detoxification, etc.

In postmenopausal women, vitamin B6(Serum pyridoxal 5'-phosphate (PLP, active form of vitamin B6) levels) might be inversely associated with breast cancer risk(1)(1a). But in a case-control study in Brazilian women, MTHFR polymorphisms and dietary intake of  vitamin B6 had no overall association with breast cancer risk(2). Study of the Chinese women, genetic mutation of MTHFR and vitamin B 6 were associated with risk of breast cancer(3). Dietary intake of one-carbon nutrients, particularly folate, vitamin B(2) (riboflavin), vitamin B(6) , vitamin B(12) , and choline also linked to the risk of cancers of the colon and breast in both human and animal studies and maternal intake of these nutrients during gestation may also have an impact on the risk of cancer in offspring later in life(3a). In Japanese women study, neither dietary intake of folate, vitamin B2, vitamin B6, or vitamin B12 nor polymorphisms of MTHFR or MTR genes were significantly associated with breast cancer risk(4). In  estrogen receptor (ER) and progesterone receptor (PR) breast cancers, dietary vitamin B6 intakes were inversely associated with breast cancer risk, regardless to ER and/or PR status(5). In postmenopausal breast cancer study, women with highest quartile range of plasma PLP concentrations are associated to 30% reduced risk of invasive breast cancer compared with the women in the lowest PLP quartile(6)(7)(8). In rodent models, high dose of B(6) also suppressed cell proliferation and induced apoptosis of human breast adenocarcinoma MCF-7 cells through induction of IGFBP-3 by PN then by a p53-specific inhibitor(8)

Taking all together, The effective of vitamin B6, in reduced risk of breast cancer is deemed controversial. But no doubt, certain vitamins and minerals deficiencies may play a critic role in the influence of development of breast cancer. Over doses may induced the symptoms of difficulty coordinating movement, numbness, sensory changes, etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca   
References
(1) Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women by Ma E, Iwasaki M, Junko I, Hamada GS, Nishimoto IN, Carvalho SM, Motola J Jr, Laginha FM, Tsugane S.(PubMed)
(1a) Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Zhang CX, Ho SC, Chen YM, Lin FY, Fu JH, Cheng SZ.(PubMed)
(2) Association of dietary intake of folate, vitamin B6 and B12 and MTHFR genotype with breast cancer risk by Liu Y, Zhou LS, Xu XM, Deng LQ, Xiao QK.(PubMed)
(3) Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Japan by Ma E, Iwasaki M, Kobayashi M, Kasuga Y, Yokoyama S, Onuma H, Nishimura H, Kusama R, Tsugane S.(PubMed)
(3a) Maternal one-carbon nutrient intake and cancer risk in offspring by Ciappio ED, Mason JB, Crott JW.(PubMed)
(4) Dietary folate, vitamin B6, vitamin B12 and methionine intake and the risk of breast cancer by oestrogen and progesterone receptor status by Zhang CX, Ho SC, Chen YM, Lin FY, Fu JH, Cheng SZ(PubMed)
(5) Prediagnostic plasma pyridoxal 5'-phosphate (vitamin b6) levels and invasive breast carcinoma risk: the multiethnic cohort by Lurie G, Wilkens LR, Shvetsov YB, Ollberding NJ, Franke AA, Henderson BE, Kolonel LN, Goodman MT.(PubMed)
(6) Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women by Lin J, Lee IM, Cook NR, Selhub J, Manson JE, Buring JE, Zhang SM(PubMed)
(7) Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose-response meta-analysis by Wu W, Kang S, Zhang D.(PubMed)
(8) High dose of pyridoxine induces IGFBP-3 mRNA expression in MCF-7 cells and its induction is inhibited by the p53-specific inhibitor pifithrin-α by Nakari M, Kanouchi H, Oka T.(PubMed)

Prostate Cancer in Herbs' Points of View

By Kyle J. Norton 

The widespread of prostate cancer, once considered as a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to spread to younger age population. Suggestions emerged of over consuming bad fats in any time in history accompanied with unhealthy diet and life style may be the possible causes of the disease, linking to the economic prosperity over 2 decades. Herbal medicine for diseases' management have been prescribed in folk medicine over thousands of year as one of best medicine of nature in preventing and treating diseases, including prostate cancer.
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.
1. Aloe vera
Aloe Vera is species of succulent plant in the genus Aloe, belonging to the Family Xanthorrhoeaceae, native to Sudan. It has become very popular for commercial cultivation due to its health benefits. Aloe vera has been used in herbal medicine in treating many kinds of disease, including wound, burn healing, minor skin infections, sebaceous cysts, diabetes, and elevated of cholesterol, etc. It is also one of many popular herb studied in scientific ways with some conflicted results.
Aloe-emodin, a chemical constituent in Aloe vera, inhibited both proliferation and anchorage-independent growth of PC3 cells through activation of the downstream substrates of mTORC2, Akt and PKCα causes of apoptosis, cell proliferation(1). prostate cancer, LNCaP expression of N-acetylated by cytosolic N-acetyltransferase (NAT) activity and mRNA inhibited by aloe-emodin in doses depending manner through its kinase activity in cellular transformation(2)(3).

2. Cascara sagrada
Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.
Emodin, a cemical compoubd found in Cascara sagrada, inhibited cellular migration and invasion in prostate cancer through downregulate CXCR4 expression which is involved in promoting invasion and metastasis in tumors(4). In human prostate cancer cell LNCaP, amodin increased apoptosis and  decreased in cell proliferation through down regualting the expression of expression of androgen receptor (AR) and prostate specific antigen (PSA) and upregulating the expression of p53(Anti tumor antigen) and p21(( regulator of cell cycle progression at G₁ and S phase)(5), In other study, Emodin enhanced the  cytotoxic effectiveness of chemotherapeutic drugs in prostate cancer cells through ROS(reactive oxygen spiecies)-mediated suppression of multidrug resistance and hypoxia inducible factor-1(influence cell metabolism, cell survival and angiogenesis to maintain biological homeostasis)(6).

3. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Epigallocatechin-3-gallate (Chit-nanoEGCG), a phytochemical in green tea, exerted a significant inhibition of tumor growth and secreted prostate-specific antigen levels compared with EGCG and control groups, trough induction of poly (ADP-ribose) polymerases cleavage, increase in the protein expression of Bax(involved in p53-mediated apoptosis)  with accompanied decrease in Bcl-2(family of regulator proteins that regulate cell death), and activation of caspases(mechanisms of apoptosis) and reduction in Ki-67 and proliferating cell nuclear antigen(7). In androgen-independent prostate cancer, synthetic derivative, EGCG (EGCG-P) and EGCG treatment suppressed the growth of the tumor correlated with the decrease of serum PSA level together with the reduction in tumor angiogenesis and an increase in apoptosis on prostate cancer cells(8). In anticancer drug cisplatin, EGCG ehnaced the effectiveness of the chemo agent in reduction of cell survival of prostate cancer cell line PC3 and induced apoptosis(9).

4. Pomegranate
Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time.
POMx, a pomegranate extract (PE) formula, exhibited potent in vitro cytotoxicity in metastatic castration-resistant PCa cells through inhibition of survivin, induced apoptosis, retarded C4-2 tumor growth in skeleton and significantly enhanced the efficacy of docetaxel(Chemodrug) in athymic nude mice(10). Ellagic acid (EA) converted from Ellagitannins (ETs) found in from pomegranate juice (PJ) showed to induce apoptosis in both cell lines, DU-145 and PC-3 through induced  cell cycle arrest in S phase associated with decreased cyclin B1 and cyclin D1 levels in regulation of cell cycle progression(11). Pomegranate juice (PJ) PJ components luteolin, ellagic acid, and punicic acid together found to inhibit growth of hormone-dependent and hormone-refractory prostate cancer cells and their migration, increase the expression of cell adhesion genes and decrease expression of genes involved in cell cycle control through suppression microRNAs (miRNAs), decrease several oncogenic miRNAs, and inhibit the chemokines receptor type 4 (CXCR4)/SDF1α chemotaxis axis(decreased PSA cell migration)(12).

6. Garlic
Garlic (Allium sativum) is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia. It has been used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc.
In androgen-independent prostate cancer, garlic-derived organosulfur compound S-allylmercaptocysteinesuppresses invasion and cell motility of androgen-independent prostate cancer cells via the up-regulation of cell-adhesion molecule E-cadherin(Loss of E-cadherin expression has been implicated in cancer progression and metastasis)(16). Garlic compound diallyl disulfid,a oil soluble organosulfur compound of garlic, exerted its antiproliferative and inhibited effect on prostate cancer cells, through induction of DNA damage in a dose dependent manner(17). Garlic constituent diallyl trisulfide (DATS), induced apoptosis in prostate cancer cells is mediated in part by suppression of XIAP(a protein that stops apoptotic cell death) protein expression(18).

7. Chamomile
Chamomile is also known as camomile, common name of many species daisy-like plants in the family Asteraceae. The herb has been used in traditional medicine as antispasmodic and anti-inflammatory constituents and to treat menstrual cramps and sleep disorders, reduce cramping and spastic pain in the bowels, relieve excessive gas and bloating in the intestine, etc.
Phenolic profile of chamomile showed to inhibited the cell proliferation and to reduce IL-8 (an important mediator of the immune reaction in the innate immune system response) levels in PC3 prostate cancer cells(19). Traditional Botanical Supplement-101 (TBS-101), including the extracts of Panax ginseng, cranberry, green tea, grape skin, grape seed, Ganoderma lucidum and chamomile, showed to inhibit in hormone-refractory PC-3 cells and large aggressive PC-3 tumors cell growth in a dose-dependent manner(20). In human cancer cell lines PC-3, A-549 and MCF-7, Chamomile's essential oils, induced cytotoxicity of prostate carcinoma cell (PC-3), significantly stronger than on human lung carcinoma (A549) and human breast cancer (MCF-7) cell lines(21).

8. Onion
The onion is a close relation of garlic plant in the genus Allium, belonging to the family Alliaceae.  It is often called the "king of vegetables" because of its pungent taste and found in a large number of recipes and preparations, spanning almost the totality of the world's cultures. Depending on the variety, an onion can be sharp, spicy, tangy, pungent, mild or sweet.
Data from southern European populations showed intake of allium vegetables, including onion are  inversely associated reduced  risk of several common cancers, including prostate cancer(22).
 Fisetin, a chemical constituent found in Onion, in prostate cancer, it exerted anti cell profilerative effect as a dual inhibitor of the PI3K/Akt (anti-apoptosis and increased cell proliferation) and the mTOR(regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription) pathways(23). Quercetin, also found in onion, inhibited the prostate cancer line PC-3 through DNA fragmentation and protein expressions of Bcl-2, Bcl-xL, Bax and caspase-3 (cell apoptosis) pathways(24).

9. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
In PC-3M prostate cancer cell line, extract from turmeric, showed significant inhibitory effects on anti profilerative ability in PC-3M in clonogenic assays(25). Demethoxycurcumin (DMC), one of mjor chemical constituents found in turmeric, exerted it antitumor effects on prostate cancer cells via AMPK((cellular energy homeostasis))-induced down-regulation of HSP70 (upregulated by and toxic chemicals, particularly heavy metals) and EGFR(over expression of epidermal growth factor receptor  have been associated with a number of cancers)(26)(27). Curcumin, a non-nutritive yellow pigment derived from the turmeric showed a inhibitory effects on the expression of  NF-κB (a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis)correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells(28).

10. Ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root).
In a highly metastatic PC-3M prostate cancer cell line,  Ginsenoside Rg3 (Rg3), a bioactive extract from ginseng, suppressed migration of PC-3M cells by down-regulating AQP1(a molecular water channel protein) expression through p38 (highly expressed in aggressive and invasive cancers)MAPK(Increased MAPK expression and activity in primary human carcinoma) pathway and some transcription factors acting on the AQP1 promoter(29). Ginsenoside 20(S)-Rh2  of Ginsenosides, a main component of ginseng, found to be effective in proliferative inhibition on androgen-dependent and -independent prostate cancer cells(30). Formula of Botanical Supplement-101 (TBS-101), containing Panax ginseng, cranberry, green tea, grape skin, grape seed, Ganoderma lucidum and chamomile showed a significant inhibition of tumor growth and invasion in a dose-dependent manner(31).

11. Grape Seed Extract
Grape Seed Extract is the commercial extracts from whole grape seeds containing many concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc.. The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc.
Grape seed extract (GSE), inhibited HAT(HAT mutations are associated to certain cancers), leading to decreased AR(plays roles in prostate development and cancer (PCa))-mediated transcription and cancer cell growth, and implicate GSE as a novel candidate for therapeutic activity against prostate cancer(32). B2G2 from total GSE, derived from Procyanidin B2 3,3″-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract inhibited cell growth, decreased clonogenicity(colony expansion), and induced cell cycle arrest and apoptotic death, in various human PCa cell lines(33).
In a highly metastatic androgen-independent PC3 prostate cancer, Grape seed extract (GSE),  inhibited DNA-binding activity of the transcription factor nuclear factor kappa B (NFkappaB)(a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis), which in turn decreased NFkappaB-dependent uPA(in tumor invasion and metastasis) transcription(33).

12. Danshen (Salvia miltiorrhiza Bunge)
Dan Shen is also known as Red Sage Root. The bitter and slightly cold herb has been used in TCM as antithrombotic, antihypertonic (lowering blood pressure), antimicrobial, antipyretic, anti-inflammatory, sedative agent and to treat dysmenorrhea, amenorrhea, palpable tumors, angina,restlessness, insomnia, irritability, etc., by enhancing the functions of heart and liver channels.
Tanshinones, a chemical constituent found in Chinese herb Dan Shen, was found to be effective in inhibition of the growth of prostate cancer sell lines, in a dose-dependent manner through cell cycle arrest and apoptosis induction(34) specially in LNCaP cells and several androgen-independent PCa cell, through suppression of  prostate cancer growth and androgen receptor(AR) signaling.(35) or through induction of  G1 arrest via activation of p53(tumor antigen) signaling and inhibition of AR in LNCaP cells(36).

13. Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America. It has been used in traditional herbal medicine in treating impotence, memory loss,respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting.
Ginkgetin, isolated from leaves of Ginkgo biloba L, inhibited PC-3 cells in a concentration-dependent manner, through significantly increased the sub-G1(detection of cumulative apoptosis)  DNA contents of cell cycle by activated caspase-3 (mechanisms of apoptosis) and weakened  the expression of survival genes such as Bcl-2, Bcl-xL,(family of regulator proteins that regulate cell death) Survivin (baculoviral inhibitor), and Cyclin D1(regulating cell cycle progression) at protein and mRNA levels(37). Unfortunately, Some reseachers suggested that there were no associations for use of  ginkgo biloba in reduced risk of prostate cabcer(38)(39)

14. Licorice (Glycyrrhiza Glabra)
Licorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation.
Licochalcone-A, isolated from licorice, induced modest level of apoptosis of androgen-independent PC-3 prostate cancer cells through the cell cycle progression arresting cells in G2/M, accompanied by suppression of cyclin B1 and cdc2(cell division cycle 2)(40). Isoangustone A (IAA) in licorice,  attenuated the growth of prostate cancer cell cultures and xenograft tumors attributed to inhibition of the G1/S phase cell cycle transition and the accumulation of p27(cell cycle inhibitor)(41). Other chemical compound such as Glycyrrhetinic acid found in licorice, in the experiment of prostate cancer cell line DU-145, inhibited proliferation and growth of these cells by inducing apoptosis, through down regulated expression of NF-κB (p65). (42).

15. Peppermint
Peppermint is a hybrid mint with small purple or white flowers and downy leaves, in the genus Mentha, belonging to the family Lamiaceae, native to  Europe. The herb has been used in folk medicine as analgesic, antiseptic, antispasmodic, decongestant, agent and to relieve gas, nausea, and stomach pain due to an irritable bowel, intestinal cramps, or indigestion, infecttion, etc.
Essential oils of peppermint exerted its cytotoxic effect against of  prostate cancer (LNCaP) cell lines(43). Menthol, a naturally isolated from peppermint oil, induced cell death in PC-3 cells independent to Ca(2+) influx pathways(44). When combined with 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the most active form of vitamin D(3), menthol increased an anti-proliferation activity of 1alpha,25(OH)(2)D(3) in LNCaP prostate cancer cells, through evoking the increase in [Ca(2+)](45).

16. Wolfberry
Wolfberry is the common name for the fruit of two very closely related species, the genus of Lycium, belong to family Solanaceae, native to native to southeastern Europe and Asia.
Lycium barbarum polysaccharides (LBPs) in dose and time-dependently inhibited the growth of both PC-3 and DU-145 cells through exhibiting  the breakage of DNA strands of PC-3 and DU-145 cells and induced apoptosis(46). Extract from Lycium barbarum. showed an inhibited effect against  PC3 cell proliferation(47).

18. Rosemary 
Rosemary is a perennial herb with fragrant, evergreen, needle-like leaves, the genus Rosmarinus, belonging to the family Lamiaceae. Its fresh and dried leaves has been used frequently in traditional Mediterranean cuisine and as flavor foods while barbecuing.
Polyphenols isolated from rosemary, inhibited prostate cancer cell through targeting multiple signaling pathways involved in cell cycle modulation and apoptosis(48). Carnosic acid (CA), a polyphenolic diterpene, isolated from rosemary, induced apoptosis of PC-3 cells, by activation of PP2A(play critical roles in cell cycle and apoptosis) through modulation of Akt/IKK/NF-κB pathway(49).

Taking altogether, The above herbs have shown effectively in reduced risk and treatments of prostate cancer, through induced apoptosis, exhibited anti proliferation of prostate cancer cell line in cell cycle arrest, down regulation of pro cell growth pathways, etc.. Please consult with your doctor or related field specialist before applying.



Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca   

References
(1) Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2 by Liu K, Park C, Li S, Lee KW, Liu H, He L, Soung NK, Ahn JS, Bode AM, Dong Z, Kim BY, Dong Z.(PubMed)
(2) Effect of inhibition of aloe-emodin on N-acetyltransferase activity and gene expression in human malignant melanoma cells (A375.S2) by Lin SY, Yang JH, Hsia TC, Lee JH, Chiu TH, Wei YH, Chung JG.(PubMed)
(3) Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2 by Liu K, Park C, Li S, Lee KW, Liu H, He L, Soung NK, Ahn JS, Bode AM, Dong Z, Kim BY, Dong Z.(PubMed)
(4) Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4 by Ok S, Kim SM, Kim C, Nam D, Shim BS, Kim SH, Ahn KS, Choi SH, Ahn KS.(PubMed)
(5) Emodin induces apoptosis in human prostate cancer cell LNCaP by Yu CX, Zhang XQ, Kang LD, Zhang PJ, Chen WW, Liu WW, Liu QW, Zhang JY.(PubMed)
(6) Chemosensitization by emodin, a plant-derived anti-cancer agent: mechanism of action by Sun Y.(PubMed)
(7) Oral administration of naturally occurring chitosan-based nanoformulated green tea polyphenol EGCG effectively inhibits prostate cancer cell growth in a xenograft model by Khan N, Bharali DJ, Adhami VM, Siddiqui IA, Cui H, Shabana SM, Mousa SA, Mukhtar H.(PubMed)
(8) Effect of a prodrug of the green tea polyphenol (-)-epigallocatechin-3-gallate on the growth of androgen-independent prostate cancer in vivo by Lee SC, Chan WK, Lee TW, Lam WH, Wang X, Chan TH, Wong YC.(PubMed)
(9) Epigallocatechin-3-gallate promotes apoptosis and expression of the caspase 9a splice variant in PC3 prostate cancer cells by Hagen RM, Chedea VS, Mintoff CP, Bowler E, Morse HR, Ladomery MR.(PubMed)
(10) Pomegranate extract inhibits the bone metastatic growth of human prostate cancer cells and enhances the in vivo efficacy of docetaxel chemotherapy by Wang Y, Zhang S, Iqbal S, Chen Z, Wang X, Wang YA, Liu D, Bai K, Ritenour C, Kucuk O, Wu D.(PubMed)
(11) Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis by Vicinanza R, Zhang Y, Henning SM, Heber D.(PubMed)
(12) Specific pomegranate juice components as potential inhibitors of prostate cancer metastasis by Wang L, Ho J, Glackin C, Martins-Green M.(PubMed)
(13) Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline isolated from Uncaria tomentosa bark on human Ewing's sarcoma and breast cancer cell lines by García Giménez D, García Prado E, Sáenz Rodríguez T, Fernández Arche A, De la Puerta R.(PubMed)
(14) The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line by Riva L, Coradini D, Di Fronzo G, De Feo V, De Tommasi N, De Simone F, Pizza C.(PubMed)
(15) Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition by Pilarski R, Filip B, Wietrzyk J, Kuraś M, Gulewicz K.(PubMed)
(16) Garlic-derived S-allylmercaptocysteine is a novel in vivo antimetastatic agent for androgen-independent prostate cancer by Howard EW, Ling MT, Chua CW, Cheung HW, Wang X, Wong YC.(PubMed)
(17) Growth suppressing effect of garlic compound diallyl disulfide on prostate cancer cell line (PC-3) in vitro by Arunkumar A, Vijayababu MR, Kanagaraj P, Balasubramanian K, Aruldhas MM, Arunakaran J.(PubMed)
(18) Garlic constituent diallyl trisulfide suppresses x-linked inhibitor of apoptosis protein in prostate cancer cells in culture and in vivo by Kim SH, Bommareddy A, Singh SV.(PubMed)
(19) Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells by Kogiannou DA, Kalogeropoulos N, Kefalas P, Polissiou MG, Kaliora AC.(PubMed)
(20)The effect of a novel botanical agent TBS-101 on invasive prostate cancer in animal models by Evans S, Dizeyi N, Abrahamsson PA, Persson J.(PubMed)
(21) Activities of ten essential oils towards Propionibacterium acnes and PC-3, A-549 and MCF-7 cancer cells by Zu Y, Yu H, Liang L, Fu Y, Efferth T, Liu X, Wu N.(PubMed)
(22) Onion and garlic use and human cancer by Galeone C, Pelucchi C, Levi F, Negri E, Franceschi S, Talamini R, Giacosa A, La Vecchia C.(PubMed)
(23) Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management by Adhami VM, Syed DN, Khan N, Mukhtar H.(PubMed)
(24) Effects of quercetin on insulin-like growth factors (IGFs) and their binding protein-3 (IGFBP-3) secretion and induction of apoptosis in human  prostate cancer cells by J. Vijayababu MR, Arunkumar A, Kanagaraj P, Arunakaran (PubMed)
(25) Combinatorial cytotoxic effects of Curcuma longa and Zingiber officinale on the PC-3M prostate cancer cell line by Kurapati KR, Samikkannu T, Kadiyala DB, Zainulabedin SM, Gandhi N, Sathaye SS, Indap MA, Boukli N, Rodriguez JW, Nair MP.(PubMed)
(26) Demethoxycurcumin Modulates Prostate Cancer Cell Proliferation via AMPK-Induced Down-regulation of HSP70 and EGFR by Hung CM, Su YH, Lin HY, Lin JN, Liu LC, Ho CT, Way TD.(PubMed)
(27) Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus(Human Patholog)
(28) Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells by Wei X, DU ZY, Cui XX, Verano M, Mo RQ, Tang ZK, Conney AH, Zheng X, Zhang K.(PubMed)
(29) Ginsenoside Rg3 attenuates cell migration via inhibition of aquaporin 1 expression in PC-3M prostate cancer cells by Pan XY, Guo H, Han J, Hao F, An Y, Xu Y, Xiaokaiti Y, Pan Y, Li XJ.(PubMed)
(30) Stereospecificity of hydroxyl group at C-20 in antiproliferative action of ginsenoside Rh2 on prostate cancer cells by Liu J, Shimizu K, Yu H, Zhang C, Jin F, Kondo R.(PubMed)
(31) The effect of a novel botanical agent TBS-101 on invasive prostate cancer in animal models by Evans S, Dizeyi N, Abrahamsson PA, Persson J.(PubMed)
(32) Grape seed extract regulates androgen receptor-mediated transcription in prostate cancer cells through potent anti-histone acetyltransferase activity by Park SY, Lee YH, Choi KC, Seong AR, Choi HK, Lee OH, Hwang HJ, Yoon HG.(PubMed)
(32) Procyanidin B2 3,3″-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract, Induces Apoptosis in Human Prostate Cancer Cells Via Targeting NF-κB, Stat3, and AP1 Transcription Factors by Tyagi A, Raina K, Shrestha SP, Miller B, Thompson JA, Wempe MF, Agarwal R, Agarwal C.(PubMed)
(33) NFkappaB-dependent regulation of urokinase plasminogen activator by proanthocyanidin-rich grape seed extract: effect on invasion by prostate cancer cells by Uchino R, Madhyastha R, Madhyastha H, Dhungana S, Nakajima Y, Omura S, Maruyama M.(PubMed)
(34) Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice by Gong Y, Li Y, Lu Y, Li L, Abdolmaleky H, Blackburn GL, Zhou JR.(PubMed)
(35) Tanshinones from Chinese medicinal herb Danshen (Salvia miltiorrhiza Bunge) suppress prostate cancer growth and androgen receptor signaling by Zhang Y, Won SH, Jiang C, Lee HJ, Jeong SJ, Lee EO, Zhang J, Ye M, Kim SH, Lü J.(PubMed)
(36) Activation of p53 signaling and inhibition of androgen receptor mediate tanshinone IIA induced G1 arrest in LNCaP prostate cancer cells by Won SH, Lee HJ, Jeong SJ, Lü J, Kim SH.(PubMed)
(37) Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells by You OH, Kim SH, Kim B, Sohn EJ, Lee HJ, Shim BS, Yun M, Kwon BM, Kim SH.(PubMed)
(38) Specialty supplements and prostate cancer risk in the VITamins and Lifestyle (VITAL) cohort by Brasky TM, Kristal AR, Navarro SL, Lampe JW, Peters U, Patterson RE, White E.(PubMed)
(39) Ginkgo biloba and risk of cancer: secondary analysis of the Ginkgo Evaluation of Memory (GEM) Study by Biggs ML, Sorkin BC, Nahin RL, Kuller LH, Fitzpatrick AL.(PubMed)
(40) Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells by Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, Wu JM.(PubMed)
(41) CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth by Lee E, Son JE, Byun S, Lee SJ, Kim YA, Liu K, Kim J, Lim SS, Park JH, Dong Z, Lee KW, Lee HJ.(PubMed)
(42) 18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes by Shetty AV, Thirugnanam S, Dakshinamoorthy G, Samykutty A, Zheng G, Chen A, Bosland MC, Kajdacsy-Balla A, Gnanasekar M.(PubMed)
(43) Seasonal variation in content, chemical composition and antimicrobial and cytotoxic activities of essential oils from four Mentha species by Hussain AI, Anwar F, Nigam PS, Ashraf M, Gilani AH.(PubMed)
(44) Menthol regulates TRPM8-independent processes in PC-3 prostate cancer cells by Kim SH, Nam JH, Park EJ, Kim BJ, Kim SJ, So I, Jeon JH.(PubMed)
(45) Menthol Enhances an Antiproliferative Activity of 1alpha,25-Dihydroxyvitamin D(3) in LNCaP Cells by Park EJ, Kim SH, Kim BJ, Kim SY, So I, Jeon JH.(PubMed)
(46) Lycium barbarum polysaccharides induce apoptosis in human prostate cancer cells and inhibits prostate cancer growth in a xenograft mouse model of human prostate cancer by Luo Q, Li Z, Yan J, Zhu F, Xu RJ, Cai YZ.(PubMed)
(47) [Extraction and isolation of active component for inhibiting PC3 cell proliferation in vitro from the fruit of Lycium barbarum L].[Article in Chinese] by Liu XL, Sun JY, Li HY, Zhang L, Qian BC.(PubMed)
(48) Polyphenols from the Mediterranean herb rosemary (Rosmarinus officinalis) for prostate cancer. by Petiwala SM, Puthenveetil AG, Johnson JJ.(PubMed)
(49) Carnosic acid modulates Akt/IKK/NF-κB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells by Kar S, Palit S, Ball WB, Das PK.(PubMed)

Breast cancer in Vitamin E's Points of View

By Kyle J. Norton

Epidemiological studies, linking vitamin E in reduced risk of breast cancer focused on variant α-tocopherol with inconsistent results. In recent study, research in γ-tocopherol,  δ-tocopherol, have shown a promising potential as the vaiants exerted  a greater ability in reducing inflammation, cell proliferation, and inhibiting the development of mammary hyperplasia and tumorigenesis(1)(1a)(1b)

 Vitamin E,  a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(2), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..

A  cohort study from the Breast Cancer Serum Bank in Columbia, free of cancer sample blood donated  to the bank did not found any evidence for protective effects of  alpha-tocopherol in breast cancer(3). Observation of her-2/neu indicated the correlation with Her2/neu receptor and reduced TAP expression found in  breast cancer stage and nodal stage in paired normal and cancerous breast tissue samples, α-tocopheryl succinate (α-TOS), a synthetic derivative of α-tocopherol, enhanced the efficacy of doxorubicin resulting in a reduction in cell viability in breast cancers(3a). In MCF-7 breast cancer cell line, dl-alpha-tocopherol showed evidence of a general inhibition of cell proliferation(3b). In HER-2/neu breast cancer cells and in comparison of the  anticancer effect of alpha-, gamma-, and delta-tocotrienols with alpha-tocopheryl succinate (alpha-TOS), the non-alpha form of T3 is more potent in inhibition of cancer activity than the synthetic VE-derivative alpha-TOS, possibly through the mitochondrial pathway, and the expression of senescent-like growth arrest markers(which provides a possible marker for the process) as p53tumor antigen), p21(regulator of cell cycle progression at G₁ and S phase), , and p16(multiple tumor suppressor 1)(3c). Delta-tocotrienol, isolated from the tocotrienol-rich fraction of palm oil, showed a positive effective against metastatic breast cancers(3d). Other in the study of estrogen-responsive MCF7 cells and the estrogen-nonresponsive MDA-MB-435 cells, RRR-alpha-, beta-, gamma-and delta-tocotrienols and and RRR-delta-tocopherol induced MDA-MB-435 cells to undergo apoptosis, with the exception of RRR-delta-tocopherol, the tocopherols (alpha, beta, and gamma) and the acetate derivative of RRR-alpha-tocopherol (RRR-alpha-tocopheryl acetate)(3e).

In aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil showed a positive effect in induction of anti-proliferation and apoptosis through DNA repair protein and NF-κB, an apoptotic cell death signalling pathway(4). In HER-2/neu-overexpressing human SKBR3 and murine TUBO breast cancer cells, vitamin E form δ-tocotrienol (δ-T3) possessed significantly high cytotoxic and apoptotic activity in SKBR3 cells than other facttions of vitamin E, through  mitochondrial destabilization, energy failure, and unbalanced activity of stress/survival MAPKs, namely p38 ((highly expressed in aggressive and invasive breast cancers) and ERK1/2(cell regulation) pathways(5). In human MDA-mB-231 breast cancer cells, delta-tocotrienol exerted its anti cancer effect trough suppression of site-specific Rb phosphorylation and mediation of  by the loss of cyclin D1(6). In estrogen-nonresponsive MDA-MB-435 and estrogen-responsive MCF-7 human breast cancer cells, vitamin E succinate (VES) or dl-alpha-tocopherol (refers to eight naturally occurring and synthetic tocopherols and tocotrienols and their acetate and succinate derivatives), induced apoptosis involving up-regulation of TGF-beta receptor II (tumor suppressor gene) expression and TGF-beta-(cell prcess), Fas- (associated with the induction of apoptosis) and JNK- (cellular apoptosis) signaling pathways(7). These results indicated that tocotrienols exerted directly inhibitory effects on the growth of breast cancer cells irrespective of estrogen receptor status, not via an estrogen receptor-mediated pathway(8).
Also in  human (MCF-7 and MDA-MD-231) mammary tumor cells lines, γ-tocotrienol induced apoptosis through induction of autophagy with evidences of the presence of relatively large increase in the accumulation of monodansylcadaverine (MDC)-labeled vacuoles, a marker of autophagosome formation(9). In neoplastic(gene modification)  +SA(high malignance) mammary epithelial cells, treatment with 4 microM gamma-tocotrienol, a dose that inhibited +SA cell growth by more than 50% compared with that of untreated control cells, decreased intracellular levels of activated PI3K/Akt (anti-apoptosis and increased cell proliferation) pathway(10). On mouse (+SA) and human (MCF-7, and MDA-MB-231) mammary cancer cell lines, Combined γ-tocotrienol and SU11274 (Met inhibitor) treatment resulted in synergistic inhibition through reduction in Akt (multiple cellular processes) STAT1/5 (activator of transcription 1,5 )and NFκB(a transcription factor that has crucial roles in inflammation, immunity, cell proliferation and apoptosis) activation and corresponding blockade in epithelial-to-mesenchymal transition( a process by which epithelial cells lose their cell polarity and cell-cell adhesion and start a the initiation of metastasis for cancer progression.), as indicated by increased expression of E-cadherin, β-catenin, and cytokeratins 8/18 (epithelial markers) and corresponding reduction in vimentin (mesenchymal marker) and reduction in cancer cell motility(11). In other study, treatment of gamma-tocopherol (γT) and gamma-tocotrienol (γT3) in human breast cancer cell lines, induced apoptosis via de novo ceramide synthesis(key molecules in cellular life and death decisions and the precursors to complex sphingolipids found in membranes) dependent activation of JNK/CHOP((C/EBP homologous protein)/DR5 pro-apoptotic signaling(12) and in γ-tocopherol (γT) alone,  the variant showed to suppress inflammatory markers, inhibited E2 -induced cell proliferation, and up regulated PPARγ(regulation of cellular differentiation, development, and metabolism) and Nrf2 (antioxidant response pathway)expression in mammary hyperplasia(13) or  modulated ER stress signaling targeting ATF3(activating transcription factor 3, involved in the complex process of cellular stress response)  in breast cancer cells(14). In HER2/neu, vitamin E analog namely alpha-tocopheryloxyacetic acid, inhibited the proliferation of kills both HER2/neu positive and HER2/neu negative breast cancer cells with less toxic than existing chemotherapeutic drugs when used in combination with HER2/neu antibody(15).

Taken the evidences of the effects of tocotrienols, dietary vitamin E or vitamin E supplement may provide significant health benefits in the reduced risk and prevention and/or treatment of breast cancer when used either alone or in combination with other anticancer agents(16).


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca    

References
(1) Chemopreventive activity of vitamin E in breast cancer: a focus on γ- and δ-tocopherol by Smolarek AK, Suh N.(PubMed)
(1a) Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells by Sylvester PW, Shah SJ.(PubMed)
(1b) Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer by Smolarek AK, So JY, Burgess B, Kong AN, Reuhl K, Lin Y, Shih WJ, Li G, Lee MJ, Chen YK, Yang CS, Suh N.(PubMed)
(2) Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411.
(3) Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States) by Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N, Stephenson HE Jr(PubMed)
(3a) Alteration of α-tocopherol-associated protein (TAP) expression in human breast epithelial cells during breast cancer development by Tam KW, Ho CT, Lee WJ, Tu SH, Huang CS, Chen CS, Lee CH, Wu CH, Ho YS.(PubMed)
(3b) dl-alpha-tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells by Sigounas G, Anagnostou A, Steiner M.(PubMed)
(3c) Gamma- and delta-tocotrienols exert a more potent anticancer effect than alpha-tocopheryl succinate on breast cancer cell lines irrespective of HER-2/neu expression by Pierpaoli E, Viola V, Pilolli F, Piroddi M, Galli F, Provinciali M.(PubMed)
(3d) Synthesis of fluorescent analogues of the anticancer natural products 4-hydroxyphenylmethylene hydantoin and delta-tocotrienol by Mudit M, Behery FA, Wali VB, Sylvester PW, El Sayed KA.(PubMed)
(3e) Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols by Yu W, Simmons-Menchaca M, Gapor A, Sanders BG, Kline K.(PubMed).
(4) Tocotrienols promote apoptosis in human breast cancer cells by inducing poly(ADP-ribose) polymerase cleavage and inhibiting nuclear factor kappa-B activity by Loganathan R, Selvaduray KR, Nesaretnam K, Radhakrishnan AK.(PubMed)
(5) Mitochondrial-dependent anticancer activity of δ-tocotrienol and its synthetic derivatives in HER-2/neu overexpressing breast adenocarcinoma cells by Viola V, Ciffolilli S, Legnaioli S, Piroddi M, Betti M, Mazzini F, Pierpaoli E, Provinciali M, Galli F.(PubMed)
(6) Growth inhibition of human MDA-mB-231 breast cancer cells by delta-tocotrienol is associated with loss of cyclin D1/CDK4 expression and accompanying changes in the state of phosphorylation of the retinoblastoma tumor suppressor gene product by Elangovan S, Hsieh TC, Wu JM.(PubMed)
(7) Pro-apoptotic mechanisms of action of a novel vitamin E analog (alpha-TEA) and a naturally occurring form of vitamin E (delta-tocotrienol) in MDA-MB-435 human breast cancer cells by Shun MC, Yu W, Gapor A, Parsons R, Atkinson J, Sanders BG, Kline K.(PubMed)
(8) Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status by Nesaretnam K, Stephen R, Dils R, Darbre P.(PubMed)
(9)γ-Tocotrienol-induced autophagy in malignant mammary cancer cells by Tiwari RV, Parajuli P, Sylvester PW.(PubMed)
(10) Gamma-tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor kappaB activity by Shah SJ, Sylvester PW.(PubMed)
(11) Combined γ-tocotrienol and Met inhibitor treatment suppresses mammary cancer cell proliferation, epithelial-to-mesenchymal transition and migration by Ayoub NM, Akl MR, Sylvester PW.(PubMed)
(12) Involvement of de novo ceramide synthesis in gamma-tocopherol and gamma-tocotrienol-induced apoptosis in human breast cancer cells by Gopalan A, Yu W, Jiang Q, Jang Y, Sanders BG, Kline K.(12)
(13) Dietary tocopherols inhibit cell proliferation, regulate expression of ERα, PPARγ, and Nrf2, and decrease serum inflammatory markers during the development of mammary hyperplasia by Smolarek AK, So JY, Thomas PE, Lee HJ, Paul S, Dombrowski A, Wang CX, Saw CL, Khor TO, Kong AN, Reuhl K, Lee MJ, Yang CS, Suh N.(PubMed)
(14) Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells by Patacsil D, Tran AT, Cho YS, Suy S, Saenz F, Malyukova I, Ressom H, Collins SP, Clarke R, Kumar D.(PubMed)
(15) The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer by Hahn T, Bradley-Dunlop DJ, Hurley LH, Von-Hoff D, Gately S, Mary DL, Lu H, Penichet ML, Besselsen DG, Cole BB, Meeuwsen T, Walker E, Akporiaye ET.(PubMed)
(16) Potential role of tocotrienols in the treatment and prevention of breast cancer by Sylvester PW, Akl MR, Malaviya A, Parajuli P, Ananthula S, Tiwari RV, Ayoub NM.(PubMed)

Polycystic Ovarian Syndrome (PCOs) Diets

By Kyle J. Norton

Approximately half of women with polycystic ovary syndrome (PCOs) are either obese or overweight. Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5% to 10% of women worldwide.
1. High Protein Diet with Low-Glycemic-Load Hypocaloric Diet
Diet with 30% of protein is now considered reasonable, high protein diet is the term reserved for consumption of 50% or more.
Suggestions in linking High Protein Diet with Low-Glycemic-Load Hypocaloric Diet to control and combat polycystic ovary syndrome (PCOS) have drawn attention in scientific community over last decade. It may be due to its effect in reduced appetites and calorie intake. But epidemiological studies focusing the benefit of diets in treating obese and overweight patients have produced an inclusive results. The National Nutrition and Food Technology Research Institute showed that both composition of hypocaloric and hypocaloric diet lead to significantly  reduced body weight and androgen levels.  Compared with a conventional diet, the combination of high-protein and low-glycemic-load foods and Hypocaloric diett also found to be effective in enhanced insulin sensitivity and decreased hsCRP level (1). But the alternation of metabolic rate of hypocaloric diet  in glucose utilization and decreased antioxidant defenses, in some cases may result in life-threatening(8a).

2. Hypocaloric diet
 Comparison with Metformin in the same subjects, hypocaloric(low calories) diet showed a reduction of 5-10% of weight on markers of insulin resistance with  equal efficacy with Metformin in decreasing serum hs-CRP levels(2) and improving inflammatory biomarkers and adipokines independently of dietary composition(3). In a 20 weeks of a high-protein energy-restricted diet to evaluate the Markers of endothelial dysfunction, including elevated markers of endothelial dysfunction, presented in overweight and obese women with polycystic ovary syndrome, showed an significant weight loss, improved testosterone, sex hormone-binding globulin and the free androgen index (FAI) and insulin resistance(4). Sibutramine(the hydrochloride monohydrate salt) removed from the market because of the concerns of risk of heart attack and stroke, in a comparison test with hypocaloric diet, showed a significant weight loss in overweight and obese women with PCOS and improvement in hyperandrogenemia and insulin sensitivity after 6 months of treatment(5). Clomiphene citrate (CC) used conjunction with hypocaloric diet with structured exercise training (SET) after 6 weeks in overweight and obese CC-resistant PCOS patients, enhanced the probability of ovulation under CC treatment, through a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes(6).
Comparison of  a hypocaloric low-fat diet with those of a very low carbohydrate diet, showed the positive effects in both diets in significant improvements in BMI, WC, and menstrual function and induced weight loss through targeting both the menstrual dysfunction and risk factors for long-term morbidity associated with PCOS in adolescents(7). Short-term hypocaloric diet including high protein (HP: 30% protein, 40% carbohydrate, and 30% fat) or high carbohydrate (HC: 15% protein, 55% carbohydrate, and 30% fat) showed a significant weight loss reduction and  improvement in their reproductive and metabolic abnormalities with no increased benefit to a high-protein diet(8).
Some researchers suggested that Hypocaloric (low-calorie) diets can alter your metabolic rate in glucose utilization and decreased antioxidant defenses, in some case may result in life-threatening(8a).

3. Low-carbohydrate diet
  A high-fat, adequate-protein, low-carbohydrate diet has been used in medicine primarily to treat difficult-to-control (refractory) epilepsy in children with purpose to induce the body to burn fat other than carbohydrate. In a women 24 weeks study with  limit carbohydrate intake to 20 grams or less per day for women diagnosed with PCOs, showed non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair but improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity(9). According to the University of Padova study, "Epidemiological studies over last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors"(10). Some researchers insisted that the presence of high levels of insulin in the blood causes unnecessary water retention in the body(10a), the diet may produce a short term effect through eliminating excess body fat but may cause dehydration as an early-onset complication(10b)

4. Low glycemic index diet
Glycemic index diet originally is developed to help improve blood sugar control in diabetes by choosing foods Low-GI foods (55 and under) for steadier rise in blood sugar. In a Twenty-six participants recruited at baseline, 22 commenced and 21 participants completed the low-GI dietary intervention phase, low glycemic diet improved insulin sensitivity, changes of lipids(11). Comparison of low glycemic index with a conventional healthy diet in overweight and obese premenopausal women, low glycemic index attendants showed to improve more in glucose tolerance through oral-glucose-tolerance test (ISI(OGTT)), menstrual cyclicity, with serum fibrinogen concentrations significant differences between diets(12). Researchers also suggested that longer term compliance needs more evaluation in subsequent studies to reduced long term health risks to women with PCOS on a low GI diet(13). In comparison of low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus, some researchers suggested that the diet containing fewer carbohydrates, the low-carbohydrate, ketogenic diet, was more effective for improving glycemic control than the low glycemic diet(12a).

5. High-protein diet
High-protein diet is a diet mostly recommended for people who want to build muscle and lose fat. A comparison of a high protein (HP) and a normal protein (NP) diet on patients with polycystic ovary syndrome (PCOS) in 8-week randomized trial, showed a significantly reduced body weight, body mass index (BMI), waist circumference, percent of body fat,  decreased total testosterone in PCOs(14).  In fact, increased dietary protein-to-carbohydrate ratios showed no differences in testosterone, sex hormone-binding globulin, and blood lipids between the groups after 6 months, but adjustment for weight changes led to significantly lower testosterone concentrations in the standard-protein (SP) diet group, according to the University of Copenhagen(15). Unfortunately, some studies showed that consumption of HP diets may cause alterations in renal health status and some metabolic parameters(15a) and reduce the level of osteocalcin(15b)

7. High monounsaturated fat diet
High monounsaturated fat diet is a diet high in monounsaturated fatty acids (HMUFA)  for  a replacment of daily intake of bad fat. In a comparison of Carbohydrate-restricted diets high in either monounsaturated fat or protein, showed that magnitude of weight loss was smaller in the LF-HP group than in the HF-SP(16). The Mediterranean diet, a High monounsaturated fat diet is characterized by a high intake of olive oil, plant products, fish and seafood; a low intake of dairies, meat and meat products; and a moderate ethanol intake, but unfortunately, exploring the relationship between the Mediterranean diet and overweight/obesity is complex with inclusive results. Some studies indicated a significantly related to less overweight/obesity or more weight loss but many found no evidence of this association(16a).

8. Low fat diet 
Low fat diet restricts consumption of fat and stresses foods high in carbohydrates, mostly recommended to patients with some gallbladder conditions. Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome, showed a reduction of free testosterone within 2 hours after both meals, however, the levels of testosterone remained below premeal values for 4 hours after the isocaloric low-fat, high-fiber meal (HIFIB) meal and 6 hours after the a high-fat, Western meal (HIFAT) meal. Levels of glucose was higher for 1 hour after the HIFIB meal compared with the HIFAT meal. DHEAS decreased 8%-10% within 2-3 hours after both meals, then increased during the remainder of the study period. Cortisol decreased during the 6-hour period after both meals(17). Suggestion of individuals on a low-fat vegan must ensure adequate intakes of  of vitamin D, vitamin K, folic acid, calcium, magnesium, zinc, vitamin B12, phosphorous, and selenium(17a).

Taking all together, there are subtle differences but correlation between diets, a monounsaturated fat-enriched diet induced greater weight loss, a low-glycemic index diet enhanced menstrual regularity, a high-carbohydrate diet increased free androgen index, a low-carbohydrate or low-glycemic index dietgreater reductions in insulin resistance, fibrinogen, total testosterone, and high-density lipoprotein cholesterol, a low-glycemic index diet improved quality of life, a high-protein diet.improved depression and self-esteem for a high-protein diet. Maximize weight loss control is important for women with PCOS regardless of dietary composition which should target all overweight women with PCOS through reducing calories with adequate nutritional intake and healthy food choices irrespective of diet composition(18).


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months 

Back to Researched articles - Points of view of Vitamins, Foods and Herbs
http://kylejnorton.blogspot.ca/p/blog-page_24.html

Back to Kyle J. Norton Home page http://kylejnorton.blogspot.ca   
 
References
(1) Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in overweight and obese women with polycystic ovary syndrome: a randomized controlled intervention study by Mehrabani HH, Salehpour S, Amiri Z, Farahani SJ, Meyer BJ, Tahbaz F.(PubMed)
(2) Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome by Esfahanian F, Zamani MM, Heshmat R, Moini nia F.(PubMed)
(3) Effect of a low-fat versus a low-gycemic-load diet on inflammatory biomarker and adipokine concentrations by Heggen E, Klemsdal TO, Haugen F, Holme I, Tonstad S.(PubMed)
(4) The effect of diet and exercise on markers of endothelial function in overweight and obese women with polycystic ovary eby Thomson RL, Brinkworth GD, Noakes M, Clifton PM, Norman RJ, Buckley JD.(PubMed)
(5) Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic features in overweight and obese women with polycystic ovary syndrome: a randomized, 24-week study by Florakis D, Diamanti-Kandarakis E, Katsikis I, Nassis GP, Karkanaki A, Georgopoulos N, Panidis D.(PubMed)
(6) Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial by Palomba S, Falbo A, Giallauria F, Russo T, Rocca M, Tolino A, Zullo F, Orio F.(PubMed)
(7) Effect of weight loss on menstrual function in adolescents with polycystic ovary syndrome by Ornstein RM, Copperman NM, Jacobson MS.(PubMed)
(8) A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome by Stamets K, Taylor DS, Kunselman A, Demers LM, Pelkman CL, Legro RS.(PubMed)
(8a) Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue by Diniz YS, Fernandes AA, Campos KE, Mani F, Ribas BO, Novelli EL.(PubMed)
(9) The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study by Mavropoulos JC, Yancy WS, Hepburn J, Westman EC.(PubMed)
(10) Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets by Paoli A, Rubini A, Volek JS, Grimaldi KA.(PubMed)
(1a) Eades, M. (1995) The Protein Power Lifeplan, Warner Books.
(1b) Early- and Late-onset Complications of the Ketogenic Diet for Intractable Epilepsy by Hoon Chul Kang¹, Da Eun Chung¹, Dong Wook Kim², Heung Dong Kim (Wily online library)(11) An isocaloric low glycemic index diet improves insulin sensitivity in women with polycystic ovary syndrome by Barr S, Reeves S, Sharp K, Jeanes YM.(PubMed)
(12) Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome by Marsh KA, Steinbeck KS, Atkinson FS, Petocz P, Brand-Miller JC.(PubMed)
(12a) The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus by Eric C Westman^1*, William S Yancy¹², John C Mavropoulos¹, Megan Marquart¹ and Jennifer R McDuffie(Nutrition&Metabolism)
(13) Evaluating compliance to a low glycaemic index (GI) diet in women with polycystic ovary syndrome (PCOS) by Egan N, Read A, Riley P, Atiomo W.(PubMed)
(14) Effect of high-protein or normal-protein diet on weight loss, body composition, hormone, and metabolic profile in southern Brazilian women with polycystic ovary syndrome: a randomized study by Toscani MK, Mario FM, Radavelli-Bagatini S, Wiltgen D, Matos MC, Spritzer PM.(PubMed)
(15) Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids by Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, Foster P, Clifton PM.(PubMed)
(15a) Effects of high-whey-protein intake and resistance training on renal, bone and metabolic parameters in rats by Aparicio VA, Nebot E, Porres JM, Ortega FB, Heredia JM, López-Jurado M, Ramírez PA.(PubMed)
(15b) Effects of dietary protein and glycaemic index on biomarkers of bone turnover in children by Dalskov SM¹, Müller M², Ritz C¹, Damsgaard CT¹, Papadaki A³, Saris WH⁴, Astrup A¹, Michaelsen KF¹, Mølgaard C¹; on behalf of DiOGenes(PubMed)
(16) Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids by Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, Foster P, Clifton PM.(PubMed)
(16a) Obesity and the Mediterranean diet: a systematic review of observational and intervention studies by Buckland G, Bach A, Serra-Majem L.(PubMed)

(17) Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome by Katcher HI, Kunselman AR, Dmitrovic R, Demers LM, Gnatuk CL, Kris-Etherton PM, Legro RS.(PubMed)
(17a) Effects of a low-fat vegan diet and a Step II diet on macro- and micronutrient intakes in overweight postmenopausal women by Turner-McGrievy GM, Barnard ND, Scialli AR, Lanou AJ.(PubMed)

(18) Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines by Moran LJ, Ko H, Misso M, Marsh K, Noakes M, Talbot M, Frearson M, Thondan M, Stepto N, Teede HJ.(PubMed)