Friday, March 7, 2014

Alzheimer's disease in Foods Points of View

 Kyle J. Norton(Draft Article)

Alzheimer's disease is a brain disorder correlated with major reductions of neurons to the respective target areas, named after German physician Alois Alzheimer. Alzheimer's destroys brain cells, causing cognitive modalities severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal. 
According to statistic, over 25 million people in the world today are affected by dementia and most are suffering from Alzheimer's disease. It may be a result of  cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions and psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity)(1) Strong evidences emerged in epidemiological studies suggested that certain foods(2) may have potential in reduced risk and treatments of Alzheimer's disease.

1. Cruciferous vegetables
Cruciferous vegetables are the group of vegetables belonging to the family Brassicaceae, including cauliflower, cabbage, cress, bok choy, broccoli etc..
Epidemiological studies has demonstrated reduced risk of prostate cancer in cruciferous consumption. The study of 2148 community-based elderly subjects (aged > or = 65 years) without dementia in New York, after 3.9 years,  253 subjects developed AD during a follow-up. Dietary pattern (DP) analysis of food combination indicated that higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter are associated to reduced risk of  AD.(1)

2. Tomatos
Tomato is a red, edible fruit, genus Solanum, belonging to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose and often in green house.
Lycopene and alpha carotene found in tometos induced symptoms of AD through inhibition of amyloid beta (Aβ) formation, deposition and fibril formation either by reducing the levels of p35 or inhibiting corresponding enzymes(2). In the study of Antioxidants, such as tocopherols and carotenoids, have been implicated in the prevention of degenerative diseases showed that aging population exhibit a age related decline of levels retinol, total tocopherols, total xanthophylls and total carotenoids(3).

3. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties.
 S-allyl-L-cysteine (SAC), an active chemical constituents of garlic, showed to inhibit several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD. through up and down regulations(4) with intervention to prevent free radicals causes of deterioration of cognitive functions and neurobehavioral activities(5). The Central Food Technological Research Institutesupported the binding ability of SAC to Abeta and inducing a partially folded conformation in Abeta.(6) and suggested that consumption of garlic may reduced risk of AD, due to inhibition of Abeta aggregation in human brain(7).

4. Ginger
Ginger (
Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil. It has been used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, colic, etc.

In the Alzheimer disease (AD) rat model, ginger root extract (GRE) was administered intra-gastrically to rats after 35 days, exhibited the protective effect against AD through reversed behavioral dysfunction and prevented AD-like symptoms(8).  [6]-gingerol, a pungent ingredient of ginger, pretreatment protected against Aβ(25-35)-induced cytotoxicity and apoptotic cell death such as DNA fragmentation, disruption of mitochondrial membrane potential, elevated Bax/Bcl-2 ratio, and activation of caspase-3 via augmentation of antioxidant capacity(9) and inhibition of acetylcholinesterase activities and prevention of lipid peroxidation in the brain(10).

5. 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.
 

Evidences of epidemiological studies suggestion of curcumin in reduced risk of Ad progression. Suggestion of curcumin in treating Alzheimer's disease (AD) depend on the ability to penetrate the blood-brain barrier(11) and showed to inhibit progression of deposit of  beta-amyloid aggregation.(12).
A novel polymeric nanoparticle (PEG-PLGA) encapsulated curcumin, induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway(secreted signalling proteins  released by one cell population will trigger concentration-dependent responses in other cells located some distance away)(13) triggering brain self-repair mechanis(14).  Unfortunately, a 24-week randomized, double blind, placebo-controlled study conducted by the David Geffen School of Medicine at UCLA, oral administration showed no biochemical evidence of efficacy of Curcumin C3 Complex® in AD(15).

6. Cinnamon
Cinnamon is a spice derived from the inner bark of tree, native to South East Asia, of over 300 species of the genus Cinnamomum, belonging to the family Lauraceae.. The herb has been use in herbal and traditional medicine as anti-fungal and bacteria level to improve reproductive organ, prevent flatulence and intestinal cramping, treat indigestion, diarrhea, bad breath, headache, migraine, etc.
Aqueous extract of cinnamon showed to inhibit tau aggregation in vitro and can even induce dissociation of tangles isolated from AD brain and cinnamaldehyde (CA), the organic compound of cinnamon
protected tau from oxidation caused by the reactive oxygen species, H2O2, and prevented subsequent formation of high molecular weight species that are considered to stimulate tangle formation(16) and inhibited tau aggregation associated with Alzheimer's disease in vitro(17). Other study insisted that cinnamon extract (CEppt), markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells and oral administration in AD patients, showed to reduce longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in the brain(18).

7. Black pepper
Black pepper is a  is a flowering vine in the genus Pipper, belonging to the family Piperaceae. It has been used in folk medicine in treating constipation, diarrhea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, etc.
Piperine, a main active alkaloid in black pepper exhibited significantly improved memory impairment and neurodegeneration in hippocampus associated with the decrease lipid peroxidation and acetylcholinesterase enzyme(19). In the evaluation the Piperine therapeutic effects in Alzheimer's Disease. at 2 mg/kg dose, reduced the SOD values, increased the acetylcholenesterase values, and reduced immobility and has shown superior results than Donepezil (5 mg/kg), AD drug(20).

8. 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.
Green tea polyphenols (GTPs) may be a next potential agent in protection of neurodegenerative diseases such as Alzheimer's disease (AD). GTPs have found to inhibit amyloid fibril formation and protect neurons from toxicity induced by β-amyloid and OA-induced neurotoxicity by enhancing the amelioration of learning and memory impairments and also reduction of tau hyperphosphorylation(21). Epigallocatechin gallate polyphenols, isolated from green tea, in a a selective inhibitor of PKC., combination of EGCG and resveratrol protected against GF 109203X-induced cell death and cytoskeleton degeneration, with a maximal effect at 1 and 3 μM, respectively and cells treated increased PKC gamma (γ) activation and promoted neuronal interconnections(22). (-)-epigallocatechin-3 gallate (EGCG) alone also showed to reduce amyloid-β (Aβ) production in both neuronal and mouse Alzheimer's disease (AD) models(23).

9. Coffee
Coffee made from the roasted seeds of the genus Coffee, belonging to the family Rubiaceae native to southern Arabia. Coffee may consist certain substances, effecting the risk of Alzheimers' disease. AD mice given caffeine in their drinking water from young adulthood into older age showed to inhibit memory and cgnitive impairment and lower brain levels of amyloid-beta; Abeta)(24)(25). In mice with Alzheimers' disease caused by dysregulated endoplasmic reticulum (ER) calcium (Ca 2+), induced deletion of RyanR3, showed the enhancement of coffee in activation of RyanRs which protects AD neurons from synaptic and network dysfunction(26). Intake of 5 cups of coffee per day(moderate caffeine intake) found to protect against the development of certain cognitive impairment and decreased hippocampal amyloid-beta (Abeta) levels through suppression of both beta-secretase (BACE1), a beta-site amyloid precursor protein cleaving enzyme 1 and presenilin 1 (PS1)/gamma-secretase expression(mutations in the presenilin proteins)(27) and  protect against or treat AD in a mouse model(28)

10. Red wine
Red wine made from made  dark-coloured (black) grape varieties as a result of anthocyan pigments  present in the skin of the grape.
Red wine may be a therapeutic potential  for treating AD patinets through reduction of forming of beta-amyloid peptid. In human umbilical vein endothelial cells (HUVECs), black grape skin extract rinhibited the ROS production, protects the cellular membrane from oxidative damage, and consequently prevents DNA fragmentation(29).  Red wine extract resveratrol, inother study inhibited the expression of soluble oligomers of of the amyloid-β (Aβ) peptide cause neurotoxicity, synaptic dysfunction, and memory impairments(30). Polyphenols derived from red wine, according to Mount Sinai School of Medicine, New York, may protect against cognitive deterioration of Alzheimer's disease, thriugh generation and assembly of β-amyloid peptides into neurotoxic oligomeric aggregated species(31).

10. Olive oil
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Oleuropein aglycone, the main polyphenol derived from extra virgin olive oil, in the study of the double transgenic TgCRND8 mice, showed to improve the cognitive performance and reduce ß-amyloid levels and plaque deposits, through  increase of autophagic markers expression and of lysosomal (break down waste materials and cellular debris)activity(32), induction of the Aβ transgene expression(33) and enhancement of Aβ clearance from the brain(34). the study by VA Medical Center, aslo dound that EVOO inhibited learning and memory deficits found in aging and diseases, due to overproduction of amyloid-β protein, and reversed oxidative damage in the brain(35).

11. Fish oil
Fish oil derived from the tissues of oily fish, contains high amount of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), etc.
Epidemiological studies suggested that higher dietary intake of ω-3 PUFA reduced risk of incident AD and slower cognitive decline(36) through reduction of plasma levels of Aβ42(37) and may induce the PTEN expression(ova tumor suppressor gene) by activation of peroxisome proliferator-activated receptor(regulating the expression of genes)(38). genetically, defection of the ε4 allele of the APOE gene (APOE4), the Central Michigan University, in the mu-p75 saporin (SAP)-induced mouse model of AD, daily treatments of Cerise(®) Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil), reduced the severity of cognitive deficits in disorders involving cholinergic deficits(39). 

Taking altogether, without going into reviews, The list of foods above may be effective in reduced risk and treatment of Alzheimers' disease through improvment of cognitive function in reduced plasma levels of Aβ42 and ß-amyloid levels and plaque deposits. Some researchers suggested that larger sample and multi centers studies are necessary to indentify the principle ingredients and validate their effectiveness. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

References
(1) Food combination and Alzheimer disease risk: a protective diet by Gu Y1, Nieves JW, Stern Y, Luchsinger JA, Scarmeas N.(PubMed)
(2) Carotenoids and Alzheimer's disease: an insight into therapeutic role of retinoids in animal models by Obulesu M1, Dowlathabad MR, Bramhachari PV.(PubMed)
(3) Carotenoid, tocopherol, and retinol concentrations in elderly human brain by Craft NE1, Haitema TB, Garnett KM, Fitch KA, Dorey CK.(PubMed)
(4) The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD) by Ray B1, Chauhan NB, Lahiri DK.(PubMed)
(5) S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type by Javed H1, Khan MM, Khan A, Vaibhav K, Ahmad A, Khuwaja G, Ahmed ME, Raza SS, Ashafaq M, Tabassum R, Siddiqui MS, El-Agnaf OM, Safhi MM, Islam F.(PubMed)
(6) Anti-amyloidogenic activity of S-allyl-L-cysteine and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro by Gupta VB1, Rao KS.(PubMed)
(7) Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: relevance to Alzheimer's disease by Gupta VB1, Indi SS, Rao KS(PubMed)
(8) Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats by Zeng GF1, Zhang ZY, Lu L, Xiao DQ, Zong SH, He JM.(PubMed)
(9) [6]-Gingerol attenuates β-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system by Lee C1, Park GH, Kim CY, Jang JH.(PubMed)
(10) Inhibition of acetylcholinesterase activities and some pro-oxidant induced lipid peroxidation in rat brain by two varieties of ginger (Zingiber officinale) by Oboh G1, Ademiluyi AO, Akinyemi AJ.(PubMed)

(11) Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice by Cheng KK1, Yeung CF, Ho SW, Chow SF, Chow AH, Baum L.(PubMed)
(12) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study by Ringman JM1, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM.(PubMed)
(13) Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt/β-Catenin Pathway by Tiwari SK1, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, Karmakar M, Kumari M, Chauhan LK, Patel DK, Srivastava V, Singh D, Gupta SK, Tripathi A, Chaturvedi RK, Gupta KC.(PubMed)
(14) Curcumin-Loaded Nanoparticles Potently Induce Adult Neurogenesis and Reverse Cognitive Deficits in Alzheimer's Disease Model via Canonical Wnt/β-Catenin Pathway by Tiwari SK1, Agarwal S, Seth B, Yadav A, Nair S, Bhatnagar P, Karmakar M, Kumari M, Chauhan LK, Patel DK, Srivastava V, Singh D, Gupta SK, Tripathi A, Chaturvedi RK, Gupta KC.(PubMed)
(15) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study by Ringman JM1, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM.(PubMed)
(16) Interaction of cinnamaldehyde and epicatechin with tau: implications of beneficial effects in modulating Alzheimer's disease pathogenesis by George RC1, Lew J, Graves DJ.(PubMed)
(17) Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro by Peterson DW1, George RC, Scaramozzino F, LaPointe NE, Anderson RA, Graves DJ, Lew J.(PubMed)
(18) Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models by Frydman-Marom A1, Levin A, Farfara D, Benromano T, Scherzer-Attali R, Peled S, Vassar R, Segal D, Gazit E, Frenkel D, Ovadia M(PubMed)
(19) Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer's disease. by Chonpathompikunlert P1, Wattanathorn J, Muchimapura S.(PubMed)
(20) Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer's disease model by Yusuf M1, Khan M, Khan RA, Ahmed B.(PubMed)
(21) Green tea polyphenols protect against okadaic acid-induced acute learning and memory impairments in rats by Li H1, Wu X1, Wu Q1, Gong D1, Shi M1, Guan L1, Zhang J1, Liu J1, Yuan B1, Han G2, Zou Y3(PubMed)
(22) Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma. Menard C1, Bastianetto S2, Quirion R3(PubMed)
(23) Octyl gallate markedly promotes anti-amyloidogenic processing of APP through estrogen receptor-mediated ADAM10 activation by Zhang SQ1, Sawmiller D, Li S, Rezai-Zadeh K, Hou H, Zhou S, Shytle D, Giunta B, Fernandez F, Mori T, Tan J.(PubMed)
(24) Caffeine and coffee as therapeutics against Alzheimer's disease by Arendash GW1, Cao C.(PubMed)
(25) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice by Arendash GW1, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.(PubMed)
(26) The role of ryanodine receptor type 3 in a mouse model of Alzheimer disease by Liu J1, Supnet C2, Sun S1, Zhang H1, Good L3, Popugaeva E4, Bezprozvanny I5.(PubMed)
(27) Caffeine reverses cognitive impairment and decreases brain amyloid-beta levels in aged Alzheimer's disease mice by Arendash GW1, Mori T, Cao C, Mamcarz M, Runfeldt M, Dickson A, Rezai-Zadeh K, Tane J, Citron BA, Lin X, Echeverria V, Potter H.(PubMed)
(28) Caffeine and coffee as therapeutics against Alzheimer's disease by Arendash GW1, Cao C.
(PubMed)
(29) Red wine micronutrients as protective agents in Alzheimer-like induced insult by Russo A1, Palumbo M, Aliano C, Lempereur L, Scoto G, Renis M.(PubMed)
(30) rion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1 by Rushworth JV1, Griffiths HH, Watt NT, Hooper NM(PubMed)
(31) Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications by Pasinetti GM.(PubMed)
(32) The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology by Grossi C1, Rigacci S, Ambrosini S, Dami TE, Luccarini I, Traini C, Failli P, Berti A, Casamenti F, Stefani M(PubMed)
(33) Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit by Diomede L1, Rigacci S, Romeo M, Stefani M, Salmona M(PubMed)
(34) Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: in vitro and in vivo studies by Abuznait AH1, Qosa H, Busnena BA, El Sayed KA, Kaddoumi A(PubMed).
(35) Extra virgin olive oil improves learning and memory in SAMP8 mice by Farr SA1, Price TO, Dominguez LJ, Motisi A, Saiano F, Niehoff ML, Morley JE, Banks WA, Ercal N, Barbagallo M.(PubMed)
(36) Current evidence for the clinical use of long-chain polyunsaturated n-3 fatty acids to prevent age-related cognitive decline and Alzheimer's disease by Dacks PA1, Shineman DW, Fillit HM.(PubMed)
(37) Nutrient intake and plasma β-amyloid by Gu Y1, Schupf N, Cosentino SA, Luchsinger JA, Scarmeas N.(PubMed)
(38) Diets involved in PPAR and PI3K/AKT/PTEN pathway may contribute to neuroprotection in a traumatic brain injury by Kitagishi Y1, Matsuda S.(PubMed)
(39) Combinatorial treatment of tart cherry extract and essential fatty acids reduces cognitive impairments and inflammation in the mu-p75 saporin-induced mouse model of Alzheimer's disease.
Matchynski JJ1, Lowrance SA, Pappas C, Rossignol J, Puckett N, Sandstrom M, Dunbar GL.(PubMed)

Thursday, March 6, 2014

Vitamin B12 and Endometrial Cancer

Kyle J. Norton

The incidence of endometrial cancer among white women are higher in comparison of black. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.
Vitamin B12, also known as cobalamin, is a water-soluble vitamin, found abundantly in a variety of foods, such as fish, shellfish, meat, eggs, dairy products, etc. and plays an important role in regulating the functions of nervous system and formation of blood.

Epidemiological studies, focusing vitamin B12 in reduced risk of endometrial cancer have produced inconsistent results, but in certain studies, vitamin B12 composted with other micro nutrients was found to be effective. Neurotoxicity caused by Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) may induce peripheral neuropathy, the study of Goshajinkigan (a traditional Japanese herbal medicine) composed with vitamin B12, showed to inhibit the progression of peripheral neuropathy, thus alleviating the symptoms of endometrial cancer(1). One-carbon metabolism, vitamin B12 showed no influence endometrial cancer risk but for women with with the MTHFR 677 TT or MTHFR 1298 CC genotype, the dietary factors including vitamin B12 are associated to the protective effect against endometrial cancer(2). Due to the influence of Folate, methionine, vitamin B(6) and vitamin B(12)  in the one-carbon metabolism pathway which is critical for DNA synthesis, methylation and repair some researchers suggested that intake of these nutrients may be associated with an reduced risk of breast, colon and endometrial cancers(3).

Taking altogether. without going into reviews, vitamin B12 composed with other micronutrients may be efective in reduced risk and treatment of endometrial cancer but large example size are necessary to validate their claims. 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) Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study by Kaku H1, Kumagai S, Onoue H, Takada A, Shoji T, Miura F, Yoshizaki A, Sato S, Kigawa J, Arai T, Tsunoda S, Tominaga E, Aoki D, Sugiyama T.(PubMed)
(2) One-carbon metabolism factors and endometrial cancer risk by Liu JJ1, Hazra A, Giovannucci E, Hankinson SE, Rosner B, De Vivo I.(PubMed)
(3) 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)

Wednesday, March 5, 2014

Folate and Endometrial Cancer

The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

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 receptor alpha (FRA) in diagnosis of  risk and  dietary in reduced risk of endometrial cancer have been inconclusive. Folate receptor alpha (FRA)  can be overexpressed by a number of epithelial-derived tumors including ovarian, breast, renal, lung, colorectal, and brain, the study emphasized the correlation of the receptor expression in endometrial cancer showed no significant difference in women with endometrial cancer after chemotherapy(1) but an associated growth advantage, rather than the process of tumorigenesis resulting in aberrant expression of FRA per se.(2). But in  "high risk" endometrial carcinomas, Moderate/strong FRalpha staining was significantly associated with other poor prognostic factors including: advanced stage, nonendometrioid histology and high grade of the diseases(3)
One-carbon metabolism dietary factors, including levels of folate, choline, methionine, vitamin B2, vitamin B6 or vitamin B12, do not effect the endometrial incidence(4). But in Type I and II endometrial cancer study, intake of use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.(5). The Folate (FOL) mediated poly-lactide-co-glycolide-polyethylene glycol nanoparticles (FOL-PEG-PLGA NPs) bearing paclitaxel (PTX),  was found to be effective in  indcution of cytotoxicity against HEC-1A cancer cells in vitro and in vivo, through possibly induced apoptosis(6). The joint study of the effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk among women between the ages of 30 and 69 years in urban Shanghai, China, showed an inverse association of folate intake and risk of endometrial cancer and modufied effects in women with encode gene MTHFR polymorphisms(7).

Taking altogether, without going into reviews, dietary folate may associated to reduced risk and treatment of endometrial cancer, but further studies are necessary to validate its effectiveness with large example size. 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.

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Back to Researched articles - Points of view of Vitamins, Foods and Herbs
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References
(1) Folate receptor alpha (FRA) expression remains unchanged in epithelial ovarian and endometrial cancer after chemotherapy by Despierre E1, Lambrechts S, Leunen K, Berteloot P, Neven P, Amant F, O'Shannessy DJ, Somers EB, Vergote I.(PubMed)
(2) Expression of folate receptor-α (FRA) in gynecologic malignancies and its relationship to the tumor type by O'Shannessy DJ1, Somers EB, Smale R, Fu YS.(PubMed)
(3) Rationale for folate receptor alpha targeted therapy in "high risk" endometrial carcinomas.
Brown Jones M1, Neuper C, Clayton A, Mariani A, Konecny G, Thomas MB, Keeney G, Hartmann L, Podratz KC.(PubMed)
(4) One-carbon metabolism factors and endometrial cancer risk by Liu JJ1, Hazra A, Giovannucci E, Hankinson SE, Rosner B, De Vivo I.(PubMed)
(5) Dietary and supplemental intake of one-carbon nutrients and the risk of type I and type II endometrial cancer: a prospective cohort study by Uccella S1, Mariani A, Wang AH, Vierkant RA, Robien K, Anderson KE, Cerhan JR.(PubMed)
(6) Improved therapeutic effect of folate-decorated PLGA-PEG nanoparticles for endometrial carcinoma by Liang C1, Yang Y, Ling Y, Huang Y, Li T, Li X.(PubMed)
(7) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women by Xu WH1, Shrubsole MJ, Xiang YB, Cai Q, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO(PubMed)

Tuesday, March 4, 2014

Vitamin B6 and Endometrial Cancer

Kyle J. Norton(Draft Article)

The incidence of endometrial cancer among white women are higher in comparison of black. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

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 endometrial cancer have been inconclusive, but the composition of vitamin B6 and other micro nutrient have found to be effective in some studies. One-carbon metabolism in 26 years of follow-up data from the Nurses' Health Study, do not appear to influence endometrial cancer incidence but showed protective effect for women with MTHFR 677 TT or MTHFR 1298 CC genotype(1) and a case of case-control study in Greece, indicated that intkae of Retinol, nicotinic acid, vitamin B- 6, and riboflavin  were  inversely associated with the disease(2).
But in a study between 1997 and 2003, 1,204 newly diagnosed endometrial cancer cases and 1,212 controls recruited among women between the ages of 30 and 69 years in urban Shanghai, China, showed dietary intake of vitamin B6 was not related to risk of endometrial cancer for women with enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), encoded by the MTHFR gene(3). Due to small size of some studies, some researchers suggested that large example size and multi centers studies are necessary to validate the effectiveness of any micro nutrient in endometrial cancer risk.

Taking altogether, without going into reviews, the composition of vitamin B6 and other micro nutrients may be effective in reduced risk and treatment of endometrial 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.

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Use The Revolutionary Findings To Achieve 
Optimal Health And Loose Weight


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
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References
(1) One-carbon metabolism factors and endometrial cancer risk by Liu JJ1, Hazra A, Giovannucci E, Hankinson SE, Rosner B, De Vivo I.(PubMed)
(2)Diet in relation to endometrial cancer risk: a case-control study in Greece by Petridou E1, Kedikoglou S, Koukoulomatis P, Dessypris N, Trichopoulos D.(PubMed)

(2) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women by Xu WH1, Shrubsole MJ, Xiang YB, Cai Q, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)

Monday, March 3, 2014

Vitamin B2 and Endometrial Cancer

Kyle J. Norton (Draft Article)

Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain Vitamins, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.

Vitamin B2 also known as  Riboflavin, is a water-soluble, yellow-orange organic compound found abundantly in milk, meat, eggs, nuts, enriched flour, green vegetables, etc. The vitamin is essential for normal cellular growth and function and best known for converting energy from protein, fat, and carbohydrates during metabolism and its antioxidant effects in oxidation-reduction reactions.

Epidemiological studies. linking dietary vitamin B2 in reduced risk of endometrial cancer have produced inconclusive results. The study of Harvard School of Public Health showed a inverse association of vitamin B2  related to the risk of endometrial cancer in a relatively small size of study(5). the co administration of  riboflavin (45 mg/kg bw/day), niacin (100 mg/kg bw/day) and ascorbic acid (200 mg/kg bw/day) along with tamoxifen (45 mg/kg bw/day), in experimental animals with endometrial cancer bearing rats, exhibited a significant decrease in the activity of glycolytic enzymes and a significant increase in the deficient activities of gluconeogenic enzymes to near normal levels, but not individually(6). Unfortunately, the study of Fu Dan University School of Public Health indicted no significant association was observed for dietary vitamin B1 or vitamin B2 and risk of endometrial cancer, in a population-based case-control study of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls(7)(8). IN the study of one-carbon metabolism correlated to the incidence of endometrial cancer using 26 years of follow-up data from the Nurses' Health Study, indicated a no association of endometrial cancer risk with dietary levels of folate, choline, methionine, vitamin B2, vitamin B6 or vitamin B1(9).

Taking altogether, without going into reviews, composition administration of vitamin B2  and other micro nutrients such as niacin  and ascorbic acid, but not vitamin B2 itself may be associated in reduced risk and treatment of endometrial cancer. But large example and multi-centers studies are necessary to identify their effectiveness. Over doses for a prolong period may cause symptoms of skin rashes, hypersensitivity, high blood pressure etc., please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)(5) Diet in relation to endometrial cancer risk: a case-control study in Greece by Petridou E1, Kedikoglou S, Koukoulomatis P, Dessypris N, Trichopoulos D(PubMed)
(6) Therapeutic potential of riboflavin, niacin and ascorbic acid on carbohydrate metabolizing enzymes in secondary endometrial carcinoma bearing rats by Sundravel S1, Shanthi P, Sachdanandam P.(PubMed)
(7) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH1, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(8) Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women by Xu WH1, Shrubsole MJ, Xiang YB, Cai Q, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)


Sunday, March 2, 2014

Vitamin E and Endometrial Cancer

The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain Vitamins, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.

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..

Antioxidants in epidemiological evidences, are associated to reduced risk of endometrial cancer caused by DNA damage have been controversal. In dose-response meta-analyse, the study bu suggested that dietary intakes of beta-carotene, vitamin C, and vitamin E from food sources, consisted an inverse relationship of endometrial cancer risk(5)(6). The study association between intakes of selected food groups and nutrients with EC risk among 541 women with histologically confirmed EC and 541 women with an intact uterus and noncancer diagnoses seen at Roswell Park Cancer Institute between 1982 and 1998, indicated that intake of vegetable dietary vitamin E are associated with decreased risk of EC(7)(8)(9). But in the study of Instituto de Biotecnología y de Biomedicina with endometrial cells incubated at several hydrogen peroxide concentrations, alpha-tocopherol included in liposomes (1.6 microg) found to no antioxidant effect was detected in cells in culture(7)


Taking altogether, vitamin E may be effective in reduced risk and treatment of endometrial cancer, but large example size and muticenter studies are necessary to validate its effectiveness. 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.

Chinese Secrets To Fatty Liver And Obesity Reversal
Use The Revolutionary Findings To Achieve 
Optimal Health And Loose Weight

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
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)
(5)  Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis by Bandera EV1, Gifkins DM, Moore DF, McCullough ML, Kushi LH(PubMed)
(6) Higher intakes of vegetables and vegetable-related nutrients are associated with lower endometrial cancer risks. by Yeh M1, Moysich KB, Jayaprakash V, Rodabaugh KJ, Graham S, Brasure JR, McCann SE(PubMed)
(7) Higher intakes of vegetables and vegetable-related nutrients are associated with lower endometrial cancer risks by Yeh M1, Moysich KB, Jayaprakash V, Rodabaugh KJ, Graham S, Brasure JR, McCann SE(PubMed)
(8) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH1, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(9) Intake of selected micronutrients and the risk of endometrial carcinoma by Negri E1, La Vecchia C, Franceschi S, Levi F, Parazzini F.(PubMed)



(10) Antioxidant activity of N-acetylcysteine, flavonoids and alpha-tocopherol on endometrial cells in culture by Estany S1, Palacio JR, Barnadas R, Sabes M, Iborra A, Martínez P(PubMed)

Thursday, February 27, 2014

Vitamin A and Endometrial Cancer

 Kyle J. Norton

The incidence of endometrial cancer among white women are higher in comparison of black women. According to the statistic, the risk of endometrial cancer among women is 1 in 7000. Every year, about 40,000 women in US are diagnosed with the disease. Women who carry certain mutation genes, such as  BRCA1 or the BRCA2 are associated to increased risk of endometrial cancer.

Depending to the stage and grade of the cancer, chemotherapy such as Doxorubicin, Cisplatin. Paclitaxel, Carboplatin, Topotecan may be necessary after surgery with certain side effects. Although epidemiological studies focusing the effective of vegetables and fruits in reduced risk and treatment of endometrial cancer with inconclusive results(1)(2)(3)(4), certain Vitamins, through clinical studies have found to be effective in reduced risk and treatment of endometrial cancer with little or no side effect.

Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Epidemiological studies, linking vitamin A in reduced risk of endometrial cancer have been inclusive.
1. Retinols
 The Istituto di Ricerche Farmacologiche Mario Negr study in dietary intake of carotenoids and retinol showed no association of retinols in reduced risk of endometrial cancer(5). In the Ishikawa endometrial cancer cell line, Retinoic acid is a metabolite of Retinol inhibited cell proliferation and the expression of RAR(retinoic acid receptor) alpha, RAR beta, and RAR gamma in the Ishikawa endometrial cancer cell line(6). the University Feinberg School of Medicine study in assessing the roles of RA and the RA agonist (AM580) in the growth of endometrial cancer cells, found that both RA and AM580 markedly inhibited endometrial cancer cell proliferation(7). Fenofibrate, an agonist of PPAR-alpha, potentiated by retinoic acid inhibited G1/S phase progression of endometrial cells through the cell cycle arrest(8). In endometrial carcinoma cells line (RL 95-2), RAs exerted its inhibitory effect on the growth of RL 95-2 cells through the estrogen pathway in estrogen-responsive endometrial cancer cells(9) or by interfering with the epidermal growth factor receptor (EGF-R) signaling pathway(10).

2. Carotenoids(beta-carotene, alpha-carotene, gamma-carotene and beta-cryptoxanthin)
Carotenoids, plant pigments, converted to vitamin A after intake, play an important role in prevention and treatment of some diseases through it antioxidant effects. The Brigham and Women's Hospital and Harvard Medical School, in the study of antioxidants intake and risk of endometrial cancer, found no association between intakes of vitamins A, C, E or carotenoids from foods or supplements and cancer risk(11). In a dose-response meta-analysis, intakes of beta-carotene is associated to an inverse risk of endometrial cancer(12). the Medical University of Białystok study in the study suggested that endometrioid adenocarcinoma may be associated to certain enzymatic defects in carotenoid metabolism in the course of the neoplastic process or some metabolic modifications(13). The population-based case-control study in Shanghai, China of 1,204 newly diagnosed endometrial cancer cases and 1,212 age frequency-matched controls, indicated that dietary macronutrients with endometrial cancer associated to cancer risk may depend on the sources, dietary retinol, beta-carotene may decrease the risk of endometrial cancer(14)(15)

Taking altogether, without going into reviews, vitamin A may be associated to reduced risk and treatment of endometrial cancer through inhibition of cell cycle progression, modification of cells differentiated mechanisms. Overdoses can lead to toxic symptoms. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Conference on "Multidisciplinary approaches to nutritional problems". Symposium on "Nutrition and health". Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence BY Kim MK, Park JH(PubMed)
(2) Epidemiological studies on brassica vegetables and cancer risk by Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA(PubMed)
(3) Brassica vegetables and cancer prevention. Epidemiology and mechanisms by van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA.(PubMed)
(4) Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis by Bandera EV, Kushi LH, Moore DF, Gifkins DM, McCullough ML(PubMed)
(5) Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study by Pelucchi C1, Dal Maso L, Montella M, Parpinel M, Negri E, Talamini R, Giudice A, Franceschi S, La Vecchia C.(PubMed)
(6) Expression of retinoic acid receptors in human endometrial carcinoma by Tanabe K1, Utsunomiya H, Tamura M, Niikura H, Takano T, Yoshinaga K, Nagase S, Suzuki T, Ito K, Matsumoto M, Hayashi S, Yaegashi N(PubMed)
(7) Retinoic acid inhibits endometrial cancer cell growth via multiple genomic mechanisms by Cheng YH1, Utsunomiya H, Pavone ME, Yin P, Bulun SE(PubMed)
(8) In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer by Saidi SA1, Holland CM, Charnock-Jones DS, Smith SK(PubMed)
(9) Divergent effects of retinoic acids on the expression of ERalpha and 17beta-hydroxysteroid dehydrogenase type 2 in endometrial carcinoma cells (RL 95-2) by Li XH1, Li H, Xiao ZJ, Piao YS.(PubMed)
(10) Retinoic acid affects the EGF-R signaling pathway during differentiation induction of human endometrial adenocarcinoma cells by Carter CA1, Shaw BL(PubMed)
(11) Antioxidant intake and risk of endometrial cancer: results from the Nurses' Health Study by Cui X1, Rosner B, Willett WC, Hankinson SE(PubMed)
(12) Antioxidant vitamins and the risk of endometrial cancer: a dose-response meta-analysis by Bandera EV1, Gifkins DM, Moore DF, McCullough ML, Kushi LH.(PubMed)
(13) Dietary carotenoids in normal and pathological tissues of corpus uteri by Czeczuga-Semeniuk E1, Wołczyński S(PubMed)
(14) Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China by Xu WH1, Dai Q, Xiang YB, Zhao GM, Ruan ZX, Cheng JR, Zheng W, Shu XO.(PubMed)
(15) Intake of selected micronutrients and the risk of endometrial carcinoma by Negri E1, La Vecchia C, Franceschi S, Levi F, Parazzini F.(PubMed)