Thursday 27 March 2014

Benign prostatic hyperplasia(BPH) in Vitamin C Points of View

Kyle J. Norton

Benign prostatic hyperplasia(BPH) is defined as a condition of increased in the number of cells of prostate gland, causing partial, or sometimes virtually complete obstruction of the urinary tract. According to statistic, BPH commonly starts at age of 30 and symptoms usually can not be realized until age of 50. More than half of men between age of 60-70 are experience symptoms of BPH and only 10% are required treatment.

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Epidemiological studies linking dietary vitamin C in reduced risk of Benign prostatic hyperplasia(BPH) may be inconclusive(a)(b)(c).

The study of Vitamin C supplementation for its effect of HIF-1alpha, highly expressed in hyperplasic prostates and prevents prostate cell death by Soul National University College of Medicine indicated that vitamin C effectively prevent prostate hyperplasia through its suppression on HIF-1alpha via prolyl hydroxylation(1). The study of phenol composition and antioxidant capacity of Epilobium species at the 1Semmelweis University, also support the role vitamin C in reduced risk of BHP through its radical-scavenger activity(2). Some researchers suggested that  free radicals and reactive oxygen species (ROS) are produced more with advancement of age, causing oxidative stress associated with BPH, due to significant decrease in plasma alpha-Toc and Asc level in BPH patients(3). The comparison of the effectiveness of  cimetidine 1 g/day for 4 weeks and 30 received vitamin C 1 g/day for the same period of a total of 60 patients with benign prostatic hypertrophy (BPH) study, showed no significant difference between the 2 groups (mean urinary flow, subjective obstructive or irritative symptoms, or prostate size) but Cimetidine was found to be no more active than vitamin C in treating benign prostatic hypertrophy(4). Regardless how effective the supplements are, some researchers ruled out the use of supplements because over consumption can be harmful(5).



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References
(a) Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men by Rohrmann S1, Giovannucci E, Willett WC, Platz EA.(PubMed)
(b) Intake of selected micronutrients and the risk of surgically treated benign prostatic hyperplasia: a case-control study from Italy by Tavani A1, Longoni E, Bosetti C, Maso LD, Polesel J, Montella M, Ramazzotti V, Negri E, Franceschi S, La Vecchia C.(PubMed)
(c) A case-control study of prostatic cancer with reference to dietary habits by Oishi K1, Okada K, Yoshida O, Yamabe H, Ohno Y, Hayes RB, Schroeder FH.(PubMed)
(1) Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1alpha by Li SH1, Ryu JH, Park SE, Cho YS, Park JW, Lee WJ, Chun YS.(PubMed)
(2) Polyphenol composition and antioxidant capacity of Epilobium species byHevesi Tóth B1, Blazics B, Kéry A.(PubMed)
(3) Oxidative stress in benign prostate hyperplasia by Aryal M1, Pandeya A, Gautam N, Baral N, Lamsal M, Majhi S, Chandra L, Pandit R, Das BK.(PubMed)
(4) Controlled study of cimetidine in the treatment of benign prostatic hypertrophy by Lindner A1, Ramon J, Brooks ME.(PubMed)
(5) Dietary patterns and prostatic diseases by Sebastiano C1, Vincenzo F, Tommaso C, Giuseppe S, Marco R, Ivana C, Giorgio R, Massimo M, Giuseppe M.(PubMed)

Wednesday 26 March 2014

Benign prostatic hyperplasia(BPH) in Herbs Points of View

 Kyle J. Norton

Benign prostatic hyperplasia(BPH) is defined as a condition of increased in the number of cells of prostate gland, causing partial, or sometimes virtually complete obstruction of the urinary tract. According to statistic, BPH commonly starts at age of 30 and symptoms usually can not be realized until age of 50. More than half of men between age of 60-70 are experience symptoms of BPH and only 10% are required treatment. Epidemiological studies, linking herbal medicine in reduced risk of benign prostate hyperplasia have produced certain positive results, but multi centers and large sample size studies are necessary to identify the principle ingredients to improve their validations.

1. Serenoa repens (Saw palmetto)
Saw Palmetto, is a small palm like tree of the genus in the genus Serenoa, belonging to the family, native to o southeastern North America. The herb has been used in The North American Seminole Indians for infertility, PMS, reproductive or urinary tract problems, urinary tract infections, stomach aches, indigestion and dysentery, etc. In rat study, a liposterolic extract of saw palmetto  showed to inhibited the contractions of prostate gland consistently with smooth muscle relaxant activity(1). In a total of 297 patients recruited, with 87 into the group TAM, 97 into the group SR and 81 into the group tamsulosin (TAM) + Serenoa repens (SR), SR and TAM treatment of BPH had showed to be efficacy as in alone, a combined therapy (TAM + SR) does not provide extra benefits(2). On the mRNA gene expression profiles of two representative models of BPH,  BPH1 cell line and primary stromal cells derived from BPH, lipidosterolic extract of Serenoa repens (LSESr) significantly altered gene expression patterns, categorized as part of proliferative, apoptotic, and inflammatory pathways(3). Unfortunately, a meta-analysis of two high quality long-term trials (n = 582), conducted by the,  showed no effect of Sere noa repens, at double and triple doses, in improving urinary flow measures or prostate size in men with lower urinary tract symptoms consistent with BPH(4).

2. Cuban royal palm
Cuban royal palm is a genus Roystonea, belonging to the family  Arecoideae, native to southern Florida, Mexico and parts of Central America and the northern
Caribbean. The roots of the tree has been used as a diuretic, and for treatment of diabetes. In rat study, 
D-004, a lipid extract from Cuban royal palm fruits incomparison of Saw palmetto and tamsulosin,
selective alpha(1A)-adrenoceptor antagonist, indicated that D-004 was moderately more effective
 than Saw palmetto, a phytotherapeutic standard used to treat BPH, but less effective than tamsulosin, a 
selective alpha(1A)-adrenoceptor antagonist(5).
Other study of the same by the Center of Natural Products from the National Center for Scientific
Research, showed that oral administration of D-004 for 14 days prevented the
increase of prostate size and the testosterone-induced prostate enlargement with in rodents(6)(7).

3. Prunus africana
Prunus africana. also known as Red Stinkwood, is a an evergreen tree,  genus Prunus, belonging to the family Rosaceae, native to the montane regions of Sub-Saharan Africa. The herb has been used in traditional medicine to treat fevers, malaria, wound dressing, arrow poison, stomach pain, purgative, kidney disease, appetite stimulant, gonorrhoea, and insanity(8).
Pygeum africanum extract, in a multicentre trial in central Europe, treatment found to be effective in changes in subjective scores, International Prostate Symptom Score (IPSS) and QoL, after the two-month period the extract also was highly statistically significant with mean improvements of 40% and 31% and with the overall result of a substantial improvement in QoL(9)(10). Although many evidences suggested that P. africanum modestly and significantly, improved urologic symptoms and flow measures, further research is needed using standardized preparations of P. africanum to determine its long-term effectiveness and ability to prevent complications associated with benign prostatic hyperplasia(11).

4. 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. The levels or activity of androgen hormones are associated to the risk of BPH, green tea catechin, (-)epigallocatechin-3-gallate, exhibited its modulation of androgenic activity that may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia(12). 5 alpha-reductase activity may be involved in the development of benign prostatic hyperplasia. The Ben May Institute for Cancer Research, and The Tang Center for Herbal Medicine Research study showed that green tea catechin (-)-epigallocatechin gallate (EGCG) is potent inhibition in cell-free and in replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors(13). The study by the Oregon State University, also showed that in the study of male noble rats implanted with estradiol and testosterone divided into 4 dietary groups: control, soy, tea, or soy+tea, the combinartion of  soy and tea attenuated prostate malignancy by decreasing prostate hyperplasia(14). Also, green tea catechin, (-)epigallocatechin-3-gallate, according to Dr. Liao S., may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia, due to its modulation of androgenic activity, possibly through increasing in testosterone metabolism, down-regulation of androgen receptors or activation of oestrogen receptors (15).

5. Licorice
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, arthritis, etc. Glycyrrhiza glabra extract with doses of 150 and 300 mg/kg showed a significant reduction in prostate weight, total estosterone and VP epithelium/stroma ratio (V/V)(16).

6. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. A multicenter case-control study of 1369 patients with BPH and 1451 controls, indicated an inverse association of intake of garlic related to the risk of BPH, consistent across age strata(17). Other researchers suggested that garlic potential in treating BPH due to its anti-inflammatory, anti-cancer and antioxidant effects as well as its effectiveness for the treatment of prostate cancer and relief of BPH symptoms(18).

7. Epilobium parviflorum
Epilobium parviflorum also known as Smallflower Hairy Willowherb, is a genus Epilobium, belonging to the family Onagraceae. The herb has been used in traditional medicine as an antioxidant and 
antiinflammatory agent and  in treating BPH, bladder and kidney, etc.
According to the study by Farmakognózia Intézet, willow-herb possess remarkable antioxidant and COX-inhibitory action and may be effective in treating benign prostatic hyperplasia (BPH)(19). Other study suggested a protective effect against benign prostatic hyperplasia (BPH), through inhibited oxidative damage, generated in fibroblast cells, decreased the PGE(2) release and inhibited COX-enzyme(20).

8. Urtica dioica
Sting Nettle is a flower plant in the genus Urtica, belonging tothe family Urticaceae, native to Europe, Africa, Asia, and North America.The herb has been used in traditional medicine as diuretic and laxative agent and to treat diarrhea and urinary disorders, to relieve pain, treat arthritis, asthma, bronchitis, sinusitis, etc.
In a 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial with placebo in 620 patients conducted by Shaheed Beheshti University of Medical Sciences, Urtica dioica showed to improve International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR) and prostate size(21). Composition of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) found to improve  the amelioration of LUTS as measured by the I-PSS, obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms of BPH(22)(23). Bazoton uno (459 mg dry extract of stinging nettle roots), in a study of a total of 246 patients, reduced irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects(24).

9. 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). Ginseng, one of the most popular herb has been used in human history in treating vary types of diseases. Panax ginseng or Red ginseng water extract and its chemical constituent 20(S)-Rg3 showed to inhibit testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis, through inhibition of testosterone-induced expression of human kallikrein-3 mRNA and activation of androgen receptor (AR)(25).

10. Rye (Secale cereal)
Rye (Secale cereal) is a grass in the genus Secale, belonging to the family Poaceae, native to the  central and eastern Turkey, and in adjacent areas. The herb has been used
in folk medicine as laxative due to its fibrous seed coat. Cernilton, isolated
from the rye-grass pollen Secale cereal, in randomized controlled trials or controlled clinical trials
comparing with placebo or other BPH medications in men with BPH showed a modestly
improves overall urologic symptoms including nocturia(26). In a 444 men enrolled in 2
placebo-controlled and 2 comparative trials lasting from 12 to 24 weeks, conducted by Department
of Veterans Affairs Coordinating Center,  Cernilton improved "self rated urinary symptoms", reduced
nocturia, but not improve urinary flow rates, residual volume or prostate size compared to placebo or
the comparative study agents(27). 

Taken altogether, without going into reviews, herbal medicine mentioned above may be effective in
reduced risk and treatment of Benign prostatic hyperplasia(BPH), but further studies are necessary to 
identify the
principle ingredients through comparison with Western medicine in use with large sample size and
multi centers involvement. As always, all articles written by Kyle J. Norton are for information &
education only, please consult your Doctor & Related field specialist before applying



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References
(1) Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): Effects on rat prostate contractility by Chua T1, Eise NT2, Simpson JS3, Ventura S(PubMed)
(2) Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia? byArgirović A1, Argirović D2.(PubMed)
(3) Lipidosterolic extract of serenoa repens modulates the expression of inflammation related-genes in benign prostatic hyperplasia epithelial and stromal cells by Sirab N1, Robert G, Fasolo V, Descazeaud A, Vacherot F, Taille Ade L, Terry S.(PubMed)
(4) Serenoa repens for benign prostatic hyperplasia by Tacklind J1, Macdonald R, Rutks I, Stanke JU, Wilt TJ.(*PubMed)
(5) Effect of D-004, a lipid extract from the Cuban royal palm fruit, on atypical prostate hyperplasia induced by phenylephrine in rats by Arruzazabala ML1, Más R, Molina V, Noa M, Carbajal D, Mendoza N.(PubMed)
(6) Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats by Noa M1, Arruzazabala ML, Carbajal D, Más R, Molina V.(PubMed)
(7) Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents by Arruzazabala ML1, Carbajal D, Más R, Molina V, Rodríguez E, González V.(PubMed)
(8) Stewart KM."The African cherry (Prunus africana): can lessons be learned from an over-exploited medicinal tree?." [Review] Journal of Ethnopharmacology. 89(1):3-13, 2003 Nov.
(9)Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe by Breza J1, Dzurny O, Borowka A, Hanus T, Petrik R, Blane G, Chadha-Boreham H.(PubMed)
(10) Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension by Chatelain C1, Autet W, Brackman F.(PubMed)
(11) Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis by Ishani A1, MacDonald R, Nelson D, Rutks I, Wilt TJ.(PubMed)
(12) The medicinal action of androgens and green tea epigallocatechin gallate by Liao S.(PubMed)
(13) Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols by Hiipakka RA1, Zhang HZ, Dai W, Dai Q, Liao S.(PubMed)
(14) Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model by Hsu A1, Bruno RS, Löhr CV, Taylor AW, Dashwood RH, Bray TM, Ho E.(PubMed)
(15) The medicinal action of androgens and green tea epigallocatechin gallate by Liao S.(PubMed)
(16) Antiandrogenic activities of Glycyrrhiza glabra in male rats by Zamansoltani F1, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA.(PubMed)
(17) Onion and garlic intake and the odds of benign prostatic hyperplasia by Galeone C1, Pelucchi C, Talamini R, Negri E, Dal Maso L, Montella M, Ramazzotti V, Franceschi S, La Vecchia C.(PubMed)
(18) Is garlic a promising food for benign prostatic hyperplasia and prostate cancer? by Devrim E1, Durak I.(PubMed)
(19) [Epilobium parviflorum--in vitro study of biological action].[Article in Hungarian] by Hevesi Tóth B1, Kéry A.(PubMed)
(20) Antioxidant and antiinflammatory effect of Epilobium parviflorum Schreb by Hevesi BT1, Houghton PJ, Habtemariam S, Kéry A.(PubMed)
(21) Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study by Safarinejad MR.(PubMed)
(22) Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial by Lopatkin N1, Sivkov A, Walther C, Schläfke S, Medvedev A, Avdeichuk J, Golubev G, Melnik K, Elenberger N, Engelmann U.(PubMed)
(23) Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms--long-term follow-up of a placebo-controlled, double-blind, multicenter trial by Lopatkin N1, Sivkov A, Schläfke S, Funk P, Medvedev A, Engelmann U.(PubMed)
(24) [Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebo controlled multicenter study after 12 months].

[Article in German] by Schneider T1, Rübben H.(PubMed)
(25) Red ginseng and 20(S)-Rg3 control testosterone-induced prostate hyperplasia by deregulating androgen receptor signaling by Bae JS1, Park HS, Park JW, Li SH, Chun YS.(PubMed)
(26) Cernilton for benign prostatic hyperplasia by Wilt T1, Mac Donald R, Ishani A, Rutks I, Stark G.(PubMed)
(27) systematic review of Cernilton for the treatment of benign prostatic hyperplasia by MacDonald R1, Ishani A, Rutks I, Wilt TJ.(PubMed)

Tuesday 25 March 2014

Ovarian Cancer in B12 Points of View

  Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States were diagnosed with ovarian cancer and 13,850 deaths.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some vitamins have showed to inhibit the progression of cancer with little or no side effects.

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.

Epidemiological studies, linking vitamin B12 in reduced risk of ovarian cancer have drawn into inconclusive results. Suggestion of Folate, methionine, vitamin B(6) and vitamin B(12) may influence carcinogenesis due to their roles in the one-carbon metabolism pathway. In a study among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008, have indicated that One-carbon metabolism(metabolic network of interdependent biosynthetic pathways) related nutrients,  may lower ovarian cancer risk(1). Nitrosylcobalamin (NO-Cbl), a chemotherapeutic pro-drug derived from vitamin B12 has been found effectively in antiproliferative activity against several human cancer cell lines, including ovarian carcinoma (NIH-OVCAR-3) cells, through induction of apoptosis via a death receptor/caspase-8 pathway(2). In patients with epithelial ovarian cancer under treatment of Paclitaxel (T) and Carboplatin (J) combination chemotherapy, vitamin B12 was effective in relieving symptoms of arthralgia and muscular pain(3).

Taking altogether, vitamin B12 may be effective in reduced riak and treatment of ovarian cancer, but large sample and multu centers studies to validate its effects are necessary. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying. 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.

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References
(1) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR1, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)
(2) Nitrosylcobalamin promotes cell death via S nitrosylation of Apo2L/TRAIL receptor DR4 by Tang Z1, Bauer JA, Morrison B, Lindner DJ.(PubMed)
(3) [The efficacy of Shakuyaku-Kanzo-to for peripheral nerve dysfunction in paclitaxel combination chemotherapy for epithelial ovarian carcinoma].

[Article in Japanese by Fujii K1, Okamoto S, Saitoh K, Sasaki N, Takano M, Tanaka S, Kudoh K, Kita T, Tode T, Kikuchi Y.(PubMed)

Monday 24 March 2014

Ovarian Cancer in Folate Points of View

 Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States were diagnosed with ovarian cancer and 13,850 deaths.
Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.
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.

Epidemiological studies, focusing folate in reduced risk of ovarian cancer have been inconclusive.
Folate, a member of B vitamin plays an important role in DNA synthesis and methylation, may process an anti proliferative effect in ovarain cancer cell lines. The Australian Ovarian Cancer Study (1363 cases, 1414 controls) self-completed risk factor and food-frequency questionnaires, showed a little evidence to support the effect of folate in reduced risk of ovarian cancer(1) and  ovarian cancer survival(2). Other researchers suggested that no specific dietary factors are consistently associated with ovarian cancer risk, including folate(3), neither folate intake, MTHFR C677T polymorphism(4) nor one-carbon metabolism(5)
A prospective case-control study of the effect of Folic acid and methylenetetrahydrofolate reductase (MTHFR) against ovarian cancers in 215 ovarian cancer patients and 218 controls (all Chinese) between Jan. 2004 and Jan. 2007, indicated a result of a 2.43-fold increased risk of ovarian cancer among MTHFR 677TT carriers, and a decreased risk of ovarian cancer in individuals with high folate intake(6). Intravenous administration of composition of  FA-NP showed more potent in anti proliferation than NP against both SKOV3 cells and SKOV3/TAX cells, but at the same dose failed to induce apoptosis and inhibit tumor nodule number. Of these results, researchers suggested that the combined use of both FN-NP locally and targetly might prolong the survival time in patients with drug-resistant ovarian cancer(6). The Brigham and Women's Hospital study also supported the evidence of one-carbon metabolism related nutrients, especially vitamin B(7) and methionine inlowering ovarian cancer risk, with a 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008(8).

Taking all together, there are either enough evidences supported or unsupported  the effectiveness of folate in reduced risk of ovarian cancer. Further studies with large sample size and mutli centers studies are necessary to clarify the effect of folate in ovarian cancer risk. At the mean time as always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying



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Back to Researched articles - Points of view of Vitamins, Foods and Herbs
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References
(1) Folate and related micronutrients, folate-metabolising genes and risk of ovarian cancer by Webb PM1, Ibiebele TI, Hughes MC, Beesley J, van der Pols JC, Chen X, Nagle CM, Bain CJ, Chenevix-Trench G; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group.(PubMed)
(2) Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival by Dixon SC1, Ibiebele TI2, Protani MM1, Beesley J2, Defazio A3, Crandon AJ4, Gard GB5, Rome RM6, Webb PM1, Nagle CM7; on behalf of the Australian Ovarian Cancer Study Group.(PubMed)
(3) Dietary intake and ovarian cancer risk: a systematic review, by Crane TE1, Khulpateea BR, Alberts DS, Basen-Engquist K, Thomson CA.(PubMed)
(4) Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis by Li C1, Chen P, Hu P, Li M, Li X, Guo H, Li J, Chu R, Zhang W, Wang H.(PubMed)
(5) Relationship between dietary and supplemental intake of folate, methionine, vitamin B6 and folate receptor alpha expression in ovarian tumors by Kotsopoulos J1, Hecht JL, Marotti JD, Kelemen LE, Tworoger SS(PubMed)
(6) Folate intake and methylenetetrahydrofolate reductase gene polymorphisms as predictive and prognostic biomarkers for ovarian cancer risk by Zhang L1, Liu W, Hao Q, Bao L, Wang K.(PubMed)
(7) Folic acid-coupled nano-paclitaxel liposome reverses drug resistance in SKOV3/TAX ovarian cancer cells by Tong L1, Chen W, Wu J, Li H.(PubMed)
(8) Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR1, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)

Ovarian Cancer in Vitamin B6 Points of View

 Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal cells growth of ovaries. It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.

Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some vitamins have showed to inhibit the progression of cancer with little or no side effects.
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.

Epidemiological studies, linking vitamin B6 in reduced risk of ovarian cancer have been inconsistent. 
The study of the Brigham and Women's Hospital, Boston, indicated that intake of one-carbon metabolism related nutrients, especially vitamin B(6) and methionine, may lower ovarian cancer risk (1). In 80,254 Nurses' Health Study participants, during 22 years of follow-up (1980-2002), researchers found little evidence to support dietary folate, methionine, and vitamin B(6) in related ovarian cancer risk(2), But
in the study to compare the effectiveness of acupuncture plus vitamin B6 PC6 points injection of 142 patients, between March 1, 2006, and June 30, 2008 indicated that acupuncture plus vitamin B6 PC6 points injection relieved nausea and vomiting in patients with ovarian cancer, undergoing a highly emetogenic chemotherapy regimen(3). In a  total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) conducted by the Albert Einstein Cancer Center, showed that although  administration of pyridoxine significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with  cisplatin (DDP) and hexamethylmelamine (HMM) regimens(4). In the assessed dietary intakes and factors associated with diet in women with family history of breast and/or ovarian cancer (FHBOC) study, suggest that women with FHBOC should be encouraged to meet dietary guidelines for cancer prevention, including intake of vitamin B6(5).

Taking altogether, vitamin B6 may be associated to reduced risk and treatment of ovarian cancer when it is used in conjunction with acupuncture, but further study with large sample and multi center studies are necessary to improve the validation. 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

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References
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1)Folate, vitamin B(6) , vitamin B(12) , methionine and alcohol intake in relation to ovarian cancer risk by Harris HR1, Cramer DW, Vitonis AF, DePari M, Terry KL.(PubMed)
(2) Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer by Tworoger SS1, Hecht JL, Giovannucci E, Hankinson SE.(PubMed)

(3) Vitamin B6 points PC6 injection during acupuncture can relieve nausea and vomiting in patients with ovarian cancer by You Q1, Yu H, Wu D, Zhang Y, Zheng J, Peng C.(PubMed)
(4) Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group by Wiernik PH1, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J.(PubMed)
(5) Diet and predictors of dietary intakes in women with family history of breast and/or ovarian cancer by McEligot AJ1, Mouttapa M, Ziogas A, Anton-Culver H.(PubMed)

Sunday 23 March 2014

Ovarian Cancer in Vitamin K Points of View

 Kyle J. Norton
Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovaries,  It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.

Researchers at the Showa University indicated that vitamin K may process the anti wide array of human cancer cell lines properties through differentiation and apoptosis(1). DR. Shibayama-Imazu, the leader of the research team said that these inductions may be through interruption of the morphological changes and DNA fragmentation via the loss of mitochondrial membrane potential (DeltaPsim caused by superoxide(1).  Vitamin K2 also induced apoptosis of human ovary cancer cells (TYK-nu cells), through the process of production of superoxide, induced oxidative stress in mitochondria might damage mitochondrial membranes(2). In PA-1 ovarian cancer cells, vitamin exhibited apoptosis through increased in the synthesis of TR3 and the accumulation of TR3 in mitochondria and in nuclei via a JNK signaling pathway(3). Against human ovarian carcinoma cell line (MDAH 2774), the composition of VC (ascorbic acid) and VK3 (menadione), inhibited cell proliferation through DNA degradation(4) and exposure to the composition also expressed the anti proliferation of cell death through autoschizis (43%), apoptosis (3%), and oncosis (1.9%)(5). In the comparison of the effect of vitamin K(2) (menaquinone 4) and  geranylgeraniol (GGO)inhuman cancer cell line, showed that GGO inhibited the growth of all eight cell lines derived from solid tumors, while vitamin K(2) selectively inhibited the proliferation and induced apoptosis in both ovarian cell lines(6). Study of the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma, indicated a positive effects of the composition in induced cell death  (displayed characteristics of both apoptosis and necrosis), through cycle arrest and degradation of chromosomal DNA(7).

Taking all together, vitamin VK2 and VK3 are found effectively in reduced risk and treatment of ovarian cancer through activation of cell death mechanism, via activation of RSO, cell cycle arrest,  and inhibition of cell proliferation via degradation of DNA. Large sample and multi centers studies to validate this effectiveness are necessary. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, 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) Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential. by Shibayama-Imazu T1, Aiuchi T, Nakaya K. (PubMed)
(2) Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells by Shibayama-Imazu T1, Sonoda I, Sakairi S, Aiuchi T, Ann WW, Nakajo S, Itabe H, Nakaya K.(PubMed)
(3) Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei by Sibayama-Imazu T1, Fujisawa Y, Masuda Y, Aiuchi T, Nakajo S, Itabe H, Nakaya K.(PubMed)
(4) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate:menadione treatment. Nuclear and DNA degradation by Gilloteaux J1, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL.(PubMed)
(5) Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitamin C:K3 treatment by Gilloteaux J1, Jamison JM, Arnold D, Taper HS, Von Gruenigen VE, Summers JL.(PubMed)
(6) Vitamin K(2) selectively induced apoptosis in ovarian TYK-nu and pancreatic MIA PaCa-2 cells out of eight solid tumor cell lines through a mechanism different from geranylgeraniol by Shibayama-Imazu T1, Sakairi S, Watanabe A, Aiuchi T, Nakajo S, Nakaya K.(PubMed)
(7) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma by von Gruenigen VE1, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, Summers JL.(PubMed)

Saturday 22 March 2014

Ovarian Cancer in Vitamin E Points of View


By Kyle J. Norton

Ovarian cancer is defined as a condition of  abnormal ovarian cells growth of ovarian cells,  It is one of most common cancer in US. According to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States were diagnosed with ovarian cancer and 13,850 deaths.

Depending to the stage and grade of the cancer, chemotherapy such as cisplatin, carboplatin, paclitaxel, liposomal doxorubicin may be necessary to prevent the spread and recurrence of the cancer. Epidemiological studies focusing in vegetables and fruits in reduced risk and treatment of ovarian cancer have not been conclusive(a)(b)(c)(d), some herbs have showed to inhibit the progression of cancer with little or no side effects.

 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.

Epidemiological studies, linking serum of vitamin E in the risk of ovarian cancer have produced inconsistent results.  Serum levels of vitamin are not associated to ovarian cancer risk, according to Tampere University Central Hospital and (1) but the study by Johns Hopkins University School of Hygiene and Public Health, indicated that the higher serum alpha-tocopherol levels are associated with an increased risk of ovarian cancer but diminished after adjustment for cholesterol(2). Other study suggested that lower alpha-tocopherol concentrations may be associated with the toxicity of  chemotherapy(3).

Alpha-TEA , a novel vitamin E analogue found to induce apoptosis a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture and inhibit tumor burden and metastasis in a syngeneic mouse mammary tumor model,(4). Other study suggested that vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, excluding normal human mammary epithelial cells(5). In SK-OV-3 human ovarian adenocarcinoma along with its multi-drug resistant version SK-OV-3-paclitaxel-resistant (TR) cells, combination treatment of vitamin E co-loaded with curcumin and paclitaxel(a mitotic inhibitor) exhibited  a three-fold tumor inhibition with each of these cell lines(6). According to the University of Strathclyde, intravenous administration tocotrienol-rich fraction (TRF), showed to exhibit tumor regression and improved animal survival in a murine xenograft model(7). In MDAH2774 human ovarian cancer cells combined treatment of Adenovirus-mediated mda-7 (Ad-mda7) plus VES inhibited tumor progression through activation of two apoptotic extrinsic and intrinsic pathways (specifically Fas expression and cleavage of Bid and caspase-8 and disruption of mitochondrial in activation of downstream capase-9 and caspase-3 via cytochrome C releasE) but not the normal fibroblasts(8). and treatment with Ad-mda7-mediated alone induced apoptosis of  human ovarian cancer cells via activation of the Fas-FasL signaling pathway(9).

Taking altogether,  vitamin E succinate and analogue may be effective in reduced risk and treatment of ovarian cancer. Large sample size and multi center studies to validate the claims are necessary. Over doses of vitamin E supplement can cause symptoms of blurred vision, weakness, dizziness, nausea, diarrhea, 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
(a) Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition by Schulz M1, Lahmann PH, Boeing H, Hoffmann K, Allen N, Key TJ, Bingham S, Wirfält E, Berglund G, Lundin E, Hallmans G, Lukanova A, Martínez Garcia C, González CA, Tormo MJ, Quirós JR, Ardanaz E, Larrañaga N, Lund E, Gram IT, Skeie G, Peeters PH, van Gils CH, Bueno-de-Mesquita HB, Büchner FL, Pasanisi P, Galasso R, Palli D, Tumino R, Vineis P, Trichopoulou A, Kalapothaki V, Trichopoulos D, Chang-Claude J, Linseisen J, Boutron-Ruault MC, Touillaud M, Clavel-Chapelon F, Olsen A, Tjønneland A, Overvad K, Tetsche M, Jenab M, Norat T, Kaaks R, Riboli E.(PubMed)
(b) Fruits and vegetables and ovarian cancer risk in a pooled analysis of 12 cohort studies by Koushik A1, Hunter DJ, Spiegelman D, Anderson KE, Arslan AA, Beeson WL, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Fraser GE, Freudenheim JL, Genkinger JM, Goldbohm RA, Hankinson SE, Koenig KL, Larsson SC, Leitzmann M, McCullough ML, Miller AB, Patel A, Rohan TE, Schatzkin A, Smit E, Willett WC, Wolk A, Zhang SM, Smith-Warner SA(PubMed).
(c) Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk by Riboli E1, Norat T.(PubMed)
(d) Risk of ovarian carcinoma and consumption of vitamins A, C, and E and specific carotenoids: a prospective analysis by Fairfield KM1, Hankinson SE, Rosner BA, Hunter DJ, Colditz GA, Willett WC.(PubMed)
(1) Serum vitamins A and E and carotene in patients with gynecologic cancer by Heinonen PK1, Kuoppala T, Koskinen T, Punnonen R.(PubMed)
(2) Prospective study of serum micronutrients and ovarian cancer by Helzlsouer KJ1, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW.(PubMed)
(3) Serum alpha-tocopherol, retinol and neopterin during paclitaxel/carboplatin chemotherapy by Melichar B1, Kalábová H, Krcmová L, Urbánek L, Hyspler R, Malírova E, Solichová D.(PubMed)
(4) Vitamin E and breast cancer by Kline K1, Yu W, Sanders BG.(PubMed)
(5) Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA by Anderson K1, Simmons-Menchaca M, Lawson KA, Atkinson J, Sanders BG, Kline K.(PubMed)
(6) Polyethylene glycol-phosphatidylethanolamine (PEG-PE)/vitamin E micelles for co-delivery of paclitaxel and curcumin to overcome multi-drug resistance in ovarian cancer by Abouzeid AH1, Patel NR1, Torchilin VP2(PubMed)
(7) Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles by Fu JY1, Blatchford DR, Tetley L, Dufès C.(PubMed)
(8) Vitamin E succinate in combination with mda-7 results in enhanced human ovarian tumor cell killing through modulation of extrinsic and intrinsic apoptotic pathways by Shanker M1, Gopalan B, Patel S, Bocangel D, Chada S, Ramesh R.(PubMed)
(9) Activation of the Fas-FasL signaling pathway by MDA-7/IL-24 kills human ovarian cancer cells by Gopalan B1, Litvak A, Sharma S, Mhashilkar AM, Chada S, Ramesh R.(PubMed)