Herbal Ginseng and Erectile Dysfunction

 Kyle J. Norton(Draft Article)

In finding a whole food and herb, comparing to the presently pharmaceutical medicine in use with little and no adverse effect(4), scientific communities have looking into herbal ginseng which has been used extensively in traditional Chinese medicine for treatment of sexual dysfunction of both sex.

According to statistic, in US alone, more than18 Million Men over 20 of ages are affected by Erectile Dysfunction and approximately 5% of 40-year-old men and between 15% and 25% of 65-year-old men experience ED on a long-term basis)National Institutes of Health). Astonishingly, lifetime use of ED medications was reported by 24% of men. Almost 69% of ED medication users reported obtaining ED medications from a physician. Fifty-nine percent of ED medication users reported taking the medications to enhance their sexual experience rather than to treat ED, which was marginally associated with stimulant use. according to Department of Veterans Affairs Puget Sound Health Care System, Seattle(1).

In comparison of the effect of erectile dysfunction with diabetes and men with erectile dysfunction due to other causes study indicated that the diseases not only affect Sexual Experience-Psychological Impact domains but also Emotional Life-Psychological Impact domain(2).

Ginseng, the King of Chinese herb, according to the literature in Chinese medicine found by Emperor Shen-Nung, the second of China's mythical emperors (3500-2600 BCE), through his treatise 'Shen Nung Benchau Jing', expressed the efficacy of herbal ginseng well being as a resemblance of human form and its rejuvenative and aphrodisiac properties. The use of ginseng for erectile dysfunction by Emperor Shen-Nung was unique for its time. It continues to hold parallels as a modern-day herbal aphrodisiac 5000 years on(3).

Panax notoginseng saponins (PNS), a major ingredient found in ginseng,  in the study of erectile dysfunction and the underlying mechanism by using a rat diabetic erectile dysfunction model in diabetic rat, showed a positive effect in deduction of oxidative stress cause of erectile dysfunction and and restored functions of endothelial cells and smooth muscle cells in the penis, through reduced level of malondialdehyde and increased levels of superoxide dismutase, glutathione and Akt(5) and possibly via the NO/cGMP pathway and restores the function of endothelium in corpus cavernosum(6).

In root-derived Korean red ginseng (KRG; Panax ginseng) study, researchers at the Yonsei University College of Medicine, found that GB0710  relax the penile corpus cavernosum smooth muscle (CCSM), through ntracellular NO production in human microvascular endothelial cells by  N(G)-monomethyl-L-arginine induction and inhibition(7).

In a 119 men with mild-to-moderate ED participated in a multicenter, randomized, double-blind, parallel, placebo-controlled clinical study, oral administration of the SKGB extract improved all domains of sexual function(8)(9).

According to Chinese medicine has been prescribed ginseng over 5000 years of history to promote yang and to improve cardiac function, short of breath, blood pressure. Panax ginseng can generates fluids and reduce thirst, to treat anxiety, insomnia, dizziness/headache, forgetfulness, impotence, diabetes, bleeding in the vagina not during period, etc.

Dr. Shergis JL and the researcher team at the School of Health Sciences and Health Innovations Research Institute-HIRi, RMIT University, told PubMed " Overall, the quality of Panax ginseng (andomized controlled trials ) RCT methodology has improved since the CONSORT checklist was introduced. However, more can be done to improve the methodological quality of, and reporting in, RCTs"(10)

But the use of herbal medicine in treating erectile dysfunction should be taken with care. Dr Ho CC and Dr. Tan HM. said" Many herbal therapies appear to have potential benefits, and similarly, the health risks of various phytotherapeutic compounds need to be elucidated. Properly designed human trials should be worked out and encouraged to determine the efficacy and safety of potential phytotherapies"(11). As the herb has shown mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation in dose depending manner(12).

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Reference
(1) Erectile dysfunction medication use among men seeking substance abuse treatment.

Horvath KJ, Calsyn DA, Terry C, Cotton A.(PubMed)

(2) Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database by Penson DF, Latini DM, Lubeck DP, Wallace KL, Henning JM, Lue TF; Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database(PubMed) 

(3) The history of ginseng in the management of erectile dysfunction in ancient China (3500-2600 BCE) by Nair R, Sellaturay S, Sriprasad S.(PubMed) 

(4) Erectile dysfunction: Viagra and other oral medications(Mayo clinic)

(5) Panax notoginseng Saponins Improve Erectile Function through Attenuation of Oxidative Stress, Restoration of Akt Activity and Protection of Endothelial and Smooth Muscle Cells in Diabetic Rats with Erectile Dysfunction by Li H, He WY, Lin F, Gou X.(PubMed)

(6) Panax notoginseng saponins improve the erectile dysfunction in diabetic rats by protecting the endothelial function of the penile corpus cavernosum by Lin F, Gou X.(PubMed) 

(7) Effects of Korean ginseng berry extract (GB0710) on penile erection: evidence from in vitro and in vivo studies by Cho KS, Park CW, Kim CK, Jeon HY, Kim WG, Lee SJ, Kim YM, Lee JY, Choi YD.(PubMed) 

(8) Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study by Choi YD, Park CW, Jang J, Kim SH, Jeon HY, Kim WG, Lee SJ, Chung WS(PubMed) 

(9) Effects of tissue-cultured mountain ginseng (Panax ginseng CA Meyer) extract on male patients with erectile dysfunction by Kim TH, Jeon SH, Hahn EJ, Paek KY, Park JK, Youn NY, Lee HL.(PubMed) 

(10) Quality and risk of bias in Panax ginseng randomized controlled trials: a review by Shergis JL, Zhang AL, Zhou W, Xue CC.(PubMed)

(11) Rise of herbal and traditional medicine in erectile dysfunction management by Ho CC, Tan HM.(PubMed)
(12) Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers by Lee NH, Yoo SR, Kim HG, Cho JH, Son CG.(PubMed)

Food Therapy - Papaya

Papaya is a species of Carica Papaya, belongs to the family Caricaceae and native to the tropics of the Americas, and was first cultivated in Mexico and several centuries

Nutritients
1. Carbohydrates
2. Sugars
3. Fiber
4. Protein
5. Vitamin A
6. Thiamine (Vitamin B1)
7. Riboflavin (Vitamin B2)
8. Niacin (Vitamin B3)
9. Vitamin B6
10. Vitamin C
11. Vitamin E
12. Vitamin K
13. Calcium
14. Iron
15. Magnesium
16. Phosphorus
17. Potassium
18. Sodium
19. Etc.

Chemical constituents
Alkaloids, Cardenolides, Anthraquinones, Saponins, Tannin, phenol, flavonoid, anthocyanin, Benzyl glucosinolate, benzylisothiocyanate, 5-(Hydroxymethyl)-2-furancarboxaldehyde, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one and 1,3-dihydroxy-2-propanone, etc.(a)

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1. Papaya and cancers
Although with no clinical or animal cancer studies but in vitro, papaya extract may be the next potential pharmacological target to identify the ingredients for treatment of cancers(2). According to the World center fund International, in 2012, there was 14.1 million cancer cases, affecting  7.4 million in men and 6.7 million in women. This number is expected to increase to 24 million by 2035(3).

Its nutrients including Vitamin A, Thiamine (Vitamin B1), Riboflavin (Vitamin B2), Niacin (Vitamin B3), Vitamin B6, Vitamin C, Iron, Magnesium, Phosphorus, Potassium, etc. and major chemical constituent and ethanol extract including benzylisothiocyanate are said to exhibit immunomodulatory, anti-inflammatory, anti hyperlipidemic, anti cellular oxidative stress, anti neural tube defect, etc. effects(1).

Papaya, a species of Carica Papaya, belonging to the family Caricaceae, native to the tropics of the Americas, has been used in traditional medicine as remedies for many various ailments, including  gastric problems, inflammation, and cancer(12). 

Aqueous extract, according to University of Tokyo, on various tumor cell lines, showed to inhibit significant growth activity, through immunomodulatory effects including, interleukin 12 (also known as natural killer cell stimulatory factor 2), IL-12p70(a heterodimer), IFN-gamma(regulation of immunologically relevant genes) and TNF-alpha(innate immune response against viral infection)(4).

Fermented papaya, a traditional dish of many Southeast Asian cultures, is said to process antioxidant and immune-modulating potentials, through influence of signaling cascades associated with cell growth and survival, from epidemiological and in-vitro studies of patient with diabetes(5). In Azoxymethane (AOM) induced colon cancer in rats, papaya peel extract (PapPE), showed a significantly ameliorated the cytotoxic effects of AOM, through its potent anti-oxidant activities in reduction of oxidative stress (glutathione depletion, lipid peroxidation)(6).

In cultured human lung cancer H69 cell, Benzyl glucosinolate (BG) found in the pulp and the seed of papaya, inhibit the cancer cell proliferation in an administration of doses of 6.5 μmol(7), probably through its effect in superoxide generation and apoptosis induction(8).
Benzylisothiocyanate (BITC) found in papaya, also mediated apoptosis of prostate and pancreases cancer cells through activation both procaspase-8 pathways(initiation of apoptosis) and cell cycle arrest(9), inhibited advanced ovarian cancer cell lines through activation of caspase-3(activation in the apoptotic cell) and -9(activation of apoptotic process), and cleavage of PARP-1(repair of DNA damage)(10) and breast cancer through generation of reactive oxygen species and cleavage of caspase-9, caspase-8, and caspase-3(11)

Taken altogether, fermented papaya and it major chemical constituents such as Benzyl glucosinolate (BG) and Benzylisothiocyanate (BITC) may be effective in reduced risk and treatment for certain types of cancer, but further studies with large sample size and muti centers are necessary to identify the main ingredients in comparison of currently pharmacological medicine use to improve its validation. 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) #Healthy #Foods - Fruits - Papaya (Carica Papaya)(Better living and living health)
(2) Anticancer activity of Carica papaya: a review by Nguyen TT¹, Shaw PN, Parat MO, Hewavitharana AK.(PubMed)
(3) Cancer statistics Worldwide(World center fund International)
(4) Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects by Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C.(PubMed)
(5) Diabetes as a risk factor to cancer: Functional role of fermented papaya preparation as phytonutraceutical adjunct in the treatment of diabetes and cancer by Aruoma OI, Somanah J, Bourdon E, Rondeau P, Bahorun T(PubMed)
(6) Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts by Waly MI, Al-Rawahi AS, Al Riyami M, Al-Kindi MA, Al-Issaei HK, Farooq SA, Al-Alawi A, Rahman MS.(PubMed)
(7) Content determination of benzyl glucosinolate and anti-cancer activity of its hydrolysis product in Carica papaya L, by Li ZY¹, Wang Y, Shen WT, Zhou P.(PubMed)
(8) Papaya seed represents a rich source of biologically active isothiocyanate by Nakamura Y, Yoshimoto M, Murata Y, Shimoishi Y, Asai Y, Park EY, Sato K, Nakamura Y.(PubMed)
(9) Dietary isothiocyanate mediated apoptosis of human cancer cells is associated with Bcl-xL phosphorylation by Basu A, Haldar S.(PubMed)
(10) Benzyl isothiocyanate (BITC) induces apoptosis in ovarian cancer cells in vitro by Kalkunte S, Swamy N, Dizon DS, Brard L(PubMed)
(11) Benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak by Xiao D¹, Vogel V, Singh SV.(PubMed)
(12) Ficus carica L. (Moraceae): Phytochemistry, Traditional Uses and Biological Activities by Mawa S, Husain K, Jantan I.(PubMed)


2. Carica papaya and diabetes
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

Water extract from papaya, through inhibition of enzymes, α-amylase and α-glucosidase linked to type 2 diabetes, in  sodium nitroprusside (SNP)-induced lipid peroxidation in rat pancreas in vitro, and in a dose-dependent manner(1) and reduced oxidative stress in Fe²⁺-induced oxidative stress in rat pancreas(2). Carica papaya leaves in streptozotocin-induced diabetic rats, according to Universidad Juárez Autónoma de Tabasco (UJAT), not only exert hypoglycemic effects in both animals and humans studies, but also help islet regeneration manifested as preservation of cell size as well as prevented hepatocyte disruption(3), as well as controlled blood glucose levels and improved lipid profile in diabetic rats(4). In short term supplementation of a fermented papaya, showed to exhibit its effect in management of diabetes and for those at risk for cardiovascular disease, neurological disease and other conditions worsened by overt inflammation and oxidative stress(5).

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References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR¹, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water-extractable phytochemicals from unripe pawpaw fruit (Carica papaya). by Oboh G, Olabiyi AA, Akinyemi AJ, Ademiluyi AO.(PubMed)
(2) Inhibitory effect of aqueous extract of different parts of unripe pawpaw (Carica papaya) fruit on Fe²⁺-induced oxidative stress in rat pancreas in vitro by Oboh G¹, Olabiyi AA, Akinyemi AJ.(PubMed)
(3) Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats by Juárez-Rojop IE¹, Díaz-Zagoya JC, Ble-Castillo JL, Miranda-Osorio PH, Castell-Rodríguez AE, Tovilla-Zárate CA, Rodríguez-Hernández A, Aguilar-Mariscal H, Ramón-Frías T, Bermúdez-Ocaña DY.(PubMed)
(4) Antihyperglycemic and hypolipidemic activities of aqueous extract of Carica papaya Linn. leaves in alloxan-induced diabetic rats by Maniyar Y¹, Bhixavatimath P(PubMed)
(5) Effects of a short term supplementation of a fermented papaya preparation on biomarkers of diabetes mellitus in a randomized Mauritian population by Somanah J¹, Aruoma OI, Gunness TK, Kowelssur S, Dambala V, Murad F, Googoolye K, Daus D, Indelicato J, Bourdon E, Bahorun T.(PubMed)

3. Carica papaya and cholesterol
Cholesterol is needed for our body to build cell walls, make hormones and vitamin D, and create bile salts that help you digest fat. However too much of it can be dangerous because cholesterol cannot dissolve in your blood
Ficus carica leaf extract modulates, on hyperlipidemia in high fat diet (HFD)-induced obese male rats, showed to improve the lipid profile and decreased adipogenic risk factors, most likely mediated through an increase in HDL-C levels(1) and streptozotocin-induced diabetic rats, it also exerted hypoglycemic and antioxidant effect;, through improved the lipid profile and affected integrity and function of both liver and pancreas(2). Ether- and water-soluble fractions of Carica papaya ethanol extract, on the other hand, in dose-dependent manner inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL) level, and significantly increased high-density lipoprotein (HDL) level(3). Unfortunately, according to the Institute for Medical Research, C. papaya leaf extract at a dose over fourteen times the levels employed in practical use in traditional medicine may induce toxicity(4).


References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR¹, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Ficus carica leaf extract modulates the lipid profile of rats fed with a high-fat diet through an increase of HDL-C by Joerin L¹, Kauschka M, Bonnländer B, Pischel I, Benedek B, Butterweck V.(PubMed)
(2) Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats by Juárez-Rojop IE¹, Díaz-Zagoya JC, Ble-Castillo JL, Miranda-Osorio PH, Castell-Rodríguez AE, Tovilla-Zárate CA, Rodríguez-Hernández A, Aguilar-Mariscal H, Ramón-Frías T, Bermúdez-Ocaña DY.(PubMed)
(3) Effect of ether- and water-soluble fractions of Carica papaya ethanol extract in experimentally induced hyperlipidemia in rats by Iyer D¹, Sharma BK, Patil UK.(PubMed)
(4) Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats by Afzan A¹, Abdullah NR, Halim SZ, Rashid BA, Semail RH, Abdullah N, Jantan I, Muhammad H, Ismail Z.(PubMed)

4. Papaya and hypertension
Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. High blood pressure means raising pressure in your heart.If it stays high over time it can damage the body in many ways.
Carica papaya, according to the Faculty of Medicine and Health Sciences Universiti Putra Malaysia, in alpha-amylase inhibition assay, may consist a nutraceutical potential ofor hyperglycemia and hypertension prevention associated with type 2 diabetes(1). Fruit juice of Carica papaya (L.) study, in the testing of Male albino Wistar rats, exhibited anti hypertensive effective through activation of alpha-adrenoceptor(2). According to University of Naples "Federico II", papaya might interact with Warfarin, the most common cardiovascular drug(3).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR¹, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) In vitro inhibitory potential of selected Malaysian plants against key enzymes involved in hyperglycemia and hypertension by Loh SP¹, Hadira O.(PubMed)
(2) Blood pressure depression by the fruit juice of Carica papaya (L.) in renal and DOCA-induced hypertension in the rat by Eno AE¹, Owo OI, Itam EH, Konya RS.(PubMed)
(3) Cardiovascular pharmacotherapy and herbal medicines: the risk of drug interaction by Izzo AA¹, Di Carlo G, Borrelli F, Ernst E.(PubMed)


5. Papaya and Cellular oxidative stress
In Azoxymethane (AOM) induced oxidative stress and carcinogenesis in rat colon and oxidative stress-induced insult in human SH-SY5Y neuronal cells, papaya peel extract (PapPE) and papaya epicarp extract (PEE) showed to significantly ameliorated the cytotoxic effects through its potent anti-oxidant activities(1)(2)as well as in reducing the neurological health diseases associated with various oxidative stress insults(3). Fermented papaya preparation (FPP), according to Hadassah-Hebrew University Medical Center, exhibited ROS scavenging effect on blood cells in vitro or in vivo (in thalassemic patients and experimental animals), through its related antioxidant mechanism, at least in part, to iron chelation(4).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR¹, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts by Waly MI, Al-Rawahi AS, Al Riyami M, Al-Kindi MA, Al-Issaei HK, Farooq SA, Al-Alawi A, Rahman MS¹.(PubMed)
(2) Papaya epicarp extract protects against aluminum-induced neurotoxicity by Waly MI¹, Guizani N, Ali A, Rahman MS.(PubMed)
(3) Papaya epicarp extract protects against hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuronal cells by Guizani N¹, Waly MI, Ali A, Al-Saidi G, Singh V, Bhatt N, Rahman MS.(PubMed)
(3) The antioxidant effect of fermented papaya preparation involves iron chelation by Prus E¹, Fibach E.(PubMed)

6. Papaya and Anemia
Anemia is characterized by deficiency in the hemoglobin of the red blood cells diminishing the ability of the blood to transport oxygen to our cells and to removing carbon dioxide.
Sickle cell disease (SCD) is a genetic disease  associated with unusually large numbers of immature blood cells. According to Covenant University, Methanolic extracts from S. monostachyus, C. papaya seed oil, exhibited particular antisickling properties coupled with the potential to reduce stress in sickle cell patients(1). In In beta-hemoglobinopathies, fermented papaya preparation (FPP), increased the content of reduced glutathione (GSH) in red blood cells (RBC), and decreased their reactive oxygen species (ROS) generation, membrane lipid peroxidation, and externalization of phosphatidylserine (PS), indicating amelioration of their oxidative status, without a significant change in the hematological parameters, probably through addition of an iron chelator(2) and alleviated symptoms associated with oxidative stress in severe forms of thalassemia(3) as well as significant reduction in the number of sickle cells(4).

References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR¹, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)
(1) Solenostemon monostachyus, Ipomoea involucrata and Carica papaya seed oil versus Glutathione, or Vernonia amygdalina: methanolic extracts of novel plants for the management of sickle cell anemia disease by Afolabi IS¹, Osikoya IO, Fajimi OD, Usoro PI, Ogunleye DO, Bisi-Adeniyi T, Adeyemi AO, Adekeye BT.(PubMed)
(2) Amelioration of oxidative stress in red blood cells from patients with beta-thalassemia major and intermedia and E-beta-thalassemia following administration of a fermented papaya preparation by Fibach E¹, Tan ES, Jamuar S, Ng I, Amer J, Rachmilewitz EA.(PubMed)(3) Fermented papaya preparation as redox regulator in blood cells of beta-thalassemic mice and patients by Amer J¹, Goldfarb A, Rachmilewitz EA, Fibach E(PubMed)
(4) Preliminary in vitro antisickilng properties of crude juice extracts of Persia Americana, Citrus sinensis, Carica papaya and Ciklavit® by Iweala EE¹, Uhegbu FO, Ogu GN.(PubMed)

7. Papaya and anti inflammatory effects
The immune system is the set of cells and their activity against antigens or infectious agents that comprises of the body's defense system against diseases.
According to Universiti Putra Malaysia, papaya exhibited anti inflammatory effects through T cells
regulated regulation through suppression of inflammatory cytokines(1). Mangiferin (MF), a natural glucosyl xanthone found in papaya showed a significant protection against sepsis-induced ALI through inhibiting inflammatory signaling and proinflammatory mediators(2). Fermented papaya preparation, a functional food supplement, in the study of Touro College of Pharmacy exhibited anti-inflammatory, antioxidant, immunostimulatory (at the level of the mucus membrane) and induction of antioxidant enzymes(3).
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References
(a) Chemical composition and bioactivity of dried fruits and honey of Ficus carica cultivars Dottato, San Francesco and Citrullara by Loizzo MR¹, Bonesi M, Pugliese A, Menichini F, Tundis R.(PubMed)(1) Carica papaya increases regulatory T cells and reduces IFN-γ+ CD4+ T cells in healthy human subjects by Abdullah M¹, Chai PS, Loh CY, Chong MY, Quay HW, Vidyadaran S, Seman Z, Kandiah M, Seow HF.(PubMed)
(2) Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1 by Gong X¹, Zhang L, Jiang R, Ye M, Yin X, Wan J.(PubMed)
(3) Applications and bioefficacy of the functional food supplement fermented papaya preparation by Aruoma OI¹, Hayashi Y, Marotta F, Mantello P, Rachmilewitz E, Montagnier L.(PubMed)

Cervical cancer in Vitamin B12 Points of View

 According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(1).
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 focusing vitamin B12 in reduced risk of cervical  cancer have produced conflict results(a)(b)(c)(d). Mahidol University, showed that lower levels of serum of vitamin B12 may be associated to the risk of cervical cancer, in the vitamin B12 statuses of Thai women with high- and low-grade cervical dysplasia study(1). Other researchers suggested that there may be a link between serum concentrations of folate, vitamin B12, and homocysteine and the risk of cervical cancer due to vitamins role in role in the synthesis and repair of DNA. In a a community-based cohort of women who donated blood in 1974 for a serum bank in Washington County, Maryland, 39 cases of cervical cancer diagnosed between 1975 and mid-1990 were included in the study (13 cases of invasive cervical cancer and 26 cases of carcinoma in situ). vitamin B12 was found to mimic those for folate and lower homocysteine, a marker of low B vitamin concentrations was associated to increased risk of the disease(1). In cervical cancer progression, folate showed to have an influence on B12 levelsbut not those of MTHFR polymorphisms, serum homocysteine(3). improving folate and vitamin B12 status may have a beneficial impact on the prevention of CC, because of their role in interventions of HR-HPV infections(4)(5). The National Cancer Center, Goyang, Korea, showed a positive effect of vitamins intake in protection of  on cervical neoplasms in case-control studies due to antioxidant activities(6). Other researchers suggested the lower levels of vitamin B12 and folate may be due to abnormal Intestinal malabsorptionof that can lead to deficiency and reduced length of survival(7). On the other hand, the University of Hawai study indicated that thiamin, riboflavin, folate, and vitamin B12 may play a protective role in cervical carcinogenesis(8). Unfortunately, the Arizona Cancer Center study do not support the role of folate, vitamin B12, or homocysteine in HPV persistence or cervical dysplasia(9), the leading cause of cervical cancer.

Taking altogether, in take of vitamin B12 may be effective in reduced risk and treatment of cervical cancer when used conjunction with folate. 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) Cerical cancer (Amerrican cancer society)
(a) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12 by Hernandez BY¹, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT.(PubMed)
(b) A case control study of nutritional factors and cervical dysplasia by Liu T¹, Soong SJ, Wilson NP, Craig CB, Cole P, Macaluso M, Butterworth CE Jr.(PubMed)
(c) [Chemoprevention of cervical cancer--intervention study of cervical precancerous lesions by retinamide II and riboflavin].[Article in Chinese] byChen RD.(PubMed)
(d) Epidemiologic studies of vitamins and cancer of the lung, esophagus, and cervix by Ziegler RG.(PubMed)
(1) Vitamin B12 status of Thai women with neoplasia of the cervix uteri by Kwanbunjan K¹, Saengkar P, Cheeramakara C, Tangjitgamol S, Chitcharoenrung K.(PubMed)

(2) The risk of cervical cancer in relation to serum concentrations of folate, vitamin B12, and homocysteine by Alberg AJ¹, Selhub J, Shah KV, Viscidi RP, Comstock GW, Helzlsouer KJ.(PubMed)
(3) A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression by Ragasudha PN¹, Thulaseedharan JV, Wesley R, Jayaprakash PG, Lalitha P, Pillai MR.(PubMed)
(4) Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs) by Piyathilake CJ¹, Badiga S, Paul P, Vijayaraghavan K, Vedantham H, Sudula M, Sowjanya P, Ramakrishna G, Shah KV, Partridge EE, Gravitt PE.(PubMed)
(5) Lower risk of cervical intraepithelial neoplasia in women with high plasma folate and sufficient vitamin B12 in the post-folic acid fortification era by Piyathilake CJ¹, Macaluso M, Alvarez RD, Bell WC, Heimburger DC, Partridge EE.(PubMed)


(6) Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis by Myung SK¹, Ju W, Kim SC, Kim H; Korean Meta-analysis (KORMA) Study Group.(PubMed)
(7) Intestinal malabsorption in long-term survivors of cervical cancer treated with radiotherapy by Vistad I¹, Kristensen GB, Fosså SD, Dahl AA, Mørkrid L.(PubMed)
(8) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12 by Hernandez BY¹, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT.(PubMed)

Herbal Ginseng and Infertility

Kyle J. Norton

Ginseng, the King of Chinese herb, according to the literature in Chinese medicine may be the next  single herb in enhancing male fertility. According to the statistic from Centers for Disease Control and Prevention (CDC), approximately 7.3 million women of childbearing age (between 15 and 44) in the US are likely to have impaired fecundity. 11% of population in the US alone were infertile.

Beside improving general well-being, the herb has been used in used in traditional Chinese medicine to treat sexual dysfunction as well as to enhance sexual behavior.

Recent animal studies and confirmed in human case control studies, ginseng has shown a positive effects of ginseng in enhancing libido, and copulatory performances. Ginsenosides, an active chemical compound extracted from ginseng was found not only to improve the sperm quality and count of healthy individuals as well as patients with treatment-related infertility, but also facilitate penile erection through directly inducing the vasodilatation and relaxation of penile corpus cavernosum.

In treatment of sexual dysfunction and ginsenoside induced Nitric oxide (NO) function in the process involving psychogenic and hormonal input, and a neurovascular nonadrenergic, noncholinergic mechanism.

Dr. Murphy LL and Lee TJ. at the Southern Illinois University, School of Medicine, told PubMed, "Treatment with American ginseng also affects the central nervous system and has been shown to significantly alter the activity of hypothalamic catecholamines involved in the facilitation of copulatory behavior and hormone secretion"

In 30 male rats randomly allocated into three groups of 10 rats each: 1. controls, 2. diabetes (D) and 3. diabetes + ginseng (DG) study, oral administration of ginseng extract showed a significant improvement of fertility parameters and testicular antioxidants together with a decrease in malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis and testicular pathological signs including degenerative changes of the seminiferous tubules. In infertile women with Polycystic ovarian syndrome (PCOS), Korean red ginseng extract (KRGE), lowered the high numbers of antral follicles and increased the number of corpora lutea in the polycystic ovaries.

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).
The herb has been used in traditional and Chinese medicine to promote yang and to improve cardiac function, short of breath, blood pressure. Panax ginseng can generates fluids and reduce thirst, to treat anxiety, insomnia, dizziness/headache, forgetfulness, impotence, diabetes, bleeding in the vagina not during period, etc.

The composition of  carnitine, acetyl carnitine, L-arginine and ginseng in treatment of men with asthenopermia promoted the improvement of sperm motility and enhanced libido and sexual performance.

Its nutrients and chemical constituents include koryoginsenoside, ginsenoside, ginseng saponins, ginseng oils and phytosterol, carbohydrates and sugars, organic acids, nitrogenous substances, amino acids and peptides, vitamins and minerals, may hold the power of enhancing immunity through stimulating antiviral cytokine IFN-γ production, improved survival of human lung epithelial cells upon influenza virus infection, vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury, etc. These findings with the diverse pharmacological activities of ginseng may be the reason for ginseng to be named the king of all herbs in improved general well-being.

Taken altogether, ginseng, especially Panax ginseng and its major chemical compound ginsenosides
may be effective in enhancing the chance of fertility in both sexes, through vary mechanisms. Overdoses may cause nausea, diarrhea, high blood pressure, low blood pressure, breast pain, tremors, nervousness, headache, vomiting, insomnia, nose bleeding, etc.. 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) Ginseng and male reproductive function by Wah Leung K, Wong AS.(PubMed)
(2) The role of nitric oxide in erectile dysfunction: implications for medical therapy by Burnett AL.(PubMed)
(3) Ginseng, sex behavior, and nitric oxide by Murphy LL, Lee TJ.(PubMed)
(4) Effect of ginseng extract supplementation on testicular functions in diabetic rats by Sawiress FA, Ziada MS, Bebawy WS, Amer HA.(PubMed)
(5) The chemical constituents of ginseng plants by Hou JP.(PubMed)
(6) Therapeutic effect of korean red ginseng extract on infertility caused by polycystic ovaries by Jung JH, Park HT, Kim T, Jeong MJ, Lim SC, Nah SY, Cho IH, Park SH, Kang SS, Moon CJ, Kim JC, Kim SH, Bae CS.(PubMed)
(7) [Treatment with carnitine, acetyl carnitine, L-arginine and ginseng improves sperm motility and sexual health in men with asthenopermia].[Article in Italian] by Morgante G, Scolaro V, Tosti C, Di Sabatino A, Piomboni P, De Leo V.(PubMed)
(8) Immunomodulatory activity of red ginseng against influenza A virus infection by Lee JS, Hwang HS², Ko EJ³, Lee YN⁴, Kwon YM⁵, Kim MC⁶, Kang SM(PubMed)
(9)Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides by Yue PY, Mak NK, Cheng YK, Leung KW, Ng TB, Fan DT, Yeung HW, Wong RN(PubMed)
(10) Popular Herbs - Ginseng, Asian (Panax ginseng) and Ginseng, North America by Kyle J. Norton

Cervical cancer in Folate Points of View

 Kyle J. Norton

 According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(1).

 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 or vitamin B9 in reduced risk of cervical  cancer have produced conflict results(a)(b)(c)(d).
Levels of serum of folate
Suggestion of lower levels of serum of folate or deficiency of folate and vitamin B12  may induce risk of cervical caner. According to a case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75 years) study by Kyunghee University College of Medicine, serum of folate is associated to reduced risk of cervical cancer but MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status(2). The Shanxi Medical University, in the study of the effects of folate against human cervical cancer cell line and HPV indicated that different concentration of folate inhibited cervical cancer cell proliferation and enhanced cell apoptosis, but not interaction between folate and HPV16 in cervical cancer cell(3). Also, in regard of serum folate, vitamin B12, MTHFR polymorphisms and serum homocysteine (chemiluminescence assay) among 322 women from Kerala, South India, found that no significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis but these parameters acted as effect modifiers of serum vitamin B12, implicating a synergistic role of these 2 vitamins in invasive cervical cancer(4). Other suggestion of high-expression of DNMT1 protein or mRNA and folate deficiency was significantly associated with cervical carcinogenesis(5) and adequate foleta could effectively inhibit the proliferation of cervical cancer cells and facilitate their apoptosis in vitro, thus would reverse the aberration protein expression of DNMT1 and MeCP2(6).

The effects
The All India Institute of Medical Sciences,study, alood and tissue samples collected from normal (n = 35), SILs (n = 27), and cervical cancer patients (n = 38) in the age group of 26-70 years, indicated a role of folate and vitamin B(12) in modulating the risk of cervical cancer(7). Women with higher concentrations of serum folate and vitamin B12 may have a beneficial impact on the prevention of CC. and a lower risk of being positive for HR-HPVs, according to the University of Alabama at Birmingham (UAB)(8). Other researchers suggested that  low levels of folate might increase the risk of cervical cancer, and there may be a potential interaction between low level of serum folate and HPV16 in the development of cervical cancer(9) and  Improved folate status in people who are at risk of getting infected or already infected with high-risk HPV may have a beneficial impact in the prevention of cervical cancer(9). IGFBP3, insulin-like growth factor binding protein 3, decreased associated to the progression of cervical cancer, folic acid increased levels of IGF-BP3, of that lead to inhibition of cervical cancer cell growth(10).


Taking altogether, serum concentration of folate is associated to reduced risk and treatment of cervical cancer and supplement folate may improve people who are at risk of cervical due to HPV infection.
Over doses of folate may induce the symptoms of difficulty of 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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For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) Cerical cancer (Amerrican cancer society)
(a) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12 by Hernandez BY¹, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT.(PubMed)
(b) A case control study of nutritional factors and cervical dysplasia by Liu T¹, Soong SJ, Wilson NP, Craig CB, Cole P, Macaluso M, Butterworth CE Jr.(PubMed)
(c) [Chemoprevention of cervical cancer--intervention study of cervical precancerous lesions by retinamide II and riboflavin].[Article in Chinese] byChen RD.(PubMed)
(d) Epidemiologic studies of vitamins and cancer of the lung, esophagus, and cervix by Ziegler RG.(PubMed)
(2) Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12 by Tong SY¹, Kim MK, Lee JK, Lee JM, Choi SW, Friso S, Song ES, Lee KB, Lee JP.(PubMed)
(3) [Effect of folate on the proliferation of human cervical cancer cell and relationship with HPV16].

[Article in Chinese] by Ding L¹, Ma J, Zhou Q, Wang J.(PubMed)

(4) A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression by Ragasudha PN¹, Thulaseedharan JV, Wesley R, Jayaprakash PG, Lalitha P, Pillai MR.(PubMed)
(5) Folate deficiency and aberrant expression of DNA methyltransferase 1 were associated with cervical cancerization by Jin-Tao W¹, Ling D, Shi-Wen J, Junxia H, Wei-Min Z, Qin Z, Zuo-Kai Y, Li Z.(PubMed)
(6) [Effect of folate in modulating the expression of DNA methyltransferase 1 and methyl-CpG-bingding protein 2 in cervical cancer cell lines].

[Article in Chinese]by Wang JT¹, Wu TT, Bai L, Ding L, Hao M, Wang Y.(PubMed)

(7) Cervical cancer pathogenesis is associated with one-carbon metabolism by Pathak S¹, Bhatla N, Singh N(PubMed)

(8) Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs) by Piyathilake CJ¹, Badiga S, Paul P, Vijayaraghavan K, Vedantham H, Sudula M, Sowjanya P, Ramakrishna G, Shah KV, Partridge EE, Gravitt PE.(PubMed) 

(9) Folate is associated with the natural history of high-risk human papillomaviruses by Piyathilake CJ¹, Henao OL, Macaluso M, Cornwell PE, Meleth S, Heimburger DC, Partridge EE.(PubMed) 

(10) In vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer. by Mathur RS¹, Mathur SP.(PubMed)

Cervical cancer in Vitamin B6 Points of View

 Kyle J. Norton (Draft Article)

Epidemiological studies focusing vitamin B6 in reduced risk of cervical  cancer have produced conflict results(a)(b)(c)(d). According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(e).
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.

Suggestion of polymorphisms in genes related to folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia, according to the study of Dr.Cardoso MA and the research team(1). In the study of Vitamin B6 status in patients with cancer of the uterine cervix, researchers found that  23-35%the patients with cervical cancer, a 23-35% are associated with deficiency of vitamin B6(2). Other in the research of serum homocysteine  and cervical cancer risk indicated a strongly and significantly predictive of invasive cervical cancer risk associated with folate, B12 and/or B6 inadequacy, or genetic polymorphisms affecting one-carbon metabolism(3). In a multiethnic case-control study for examination of the association of dietary folate and MTHFR genotype with the odds ratios (ORs) for cervical dysplasia among women identified from several clinics on Oahu, Hawaii, between 1992 and 1996 indicated that dietary intakes of folate, vitamin B(6), and vitamin B(12) were inversely related to the ORs for cervical squamous intraepithelial lesions (SILs)(4). The study at the University of Arizona, showed that folate, vitamin B12, vitamin B6, and methionine may function to prevent cervical cancer through their role in DNA methylation(5)

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References
(a) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12 by Hernandez BY¹, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT.(PubMed)
(b) A case control study of nutritional factors and cervical dysplasia by Liu T¹, Soong SJ, Wilson NP, Craig CB, Cole P, Macaluso M, Butterworth CE Jr.(PubMed)
(c) [Chemoprevention of cervical cancer--intervention study of cervical precancerous lesions by retinamide II and riboflavin].[Article in Chinese] byChen RD.(PubMed)
(d) Epidemiologic studies of vitamins and cancer of the lung, esophagus, and cervix by Ziegler RG.(PubMed)
(a) Cerical cancer (Amerrican cancer society)
(1) Nutritional and genetic inefficiencies in one-carbon metabolism and cervical cancer risk. by Ziegler RG¹, Weinstein SJ, Fears TR.(PubMed)
(2) Vitamin B6 status in patients with cancer of the uterine cervix by Ramaswamy PG, Natarajan R.(PubMed)
(3) Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women by Weinstein SJ¹, Ziegler RG, Selhub J, Fears TR, Strickler HD, Brinton LA, Hamman RF, Levine RS, Mallin K, Stolley PD.(PubMed)
(4) Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia by Goodman MT¹, McDuffie K, Hernandez B, Wilkens LR, Bertram CC, Killeen J, Le Marchand L, Selhub J, Murphy S, Donlon TA.(PubMed)
(5) Human papillomavirus persistence and nutrients involved in the methylation pathway among a cohort of young women by Sedjo RL¹, Inserra P, Abrahamsen M, Harris RB, Roe DJ, Baldwin S, Giuliano AR.(PubMed)

Cervical cancer in Vitamin B2 Points of View

 Kyle J. Norton(Draft Article)

 According to the American Cancer Society's, in 2014, 12,360 new cases of invasive cervical cancer will be diagnosed with the death of  4,020 patients. The risk of cervical cancer is higher in Hispanic women followed by African-Americans, Asians and Pacific Islanders, and whites(a).

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 vitamin B2 in reduced risk and treatment of cervical cancer have been inclusive(a)(b)(c)(d). Suggestion of serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. In the study of cervical cancer risk factors through at-home interview and blood drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls, suggested that elevated serum homocysteine increases risk of cervical cancer are associated to the inadequacy of folate, B12 and/or B6, or genetic polymorphisms affecting one-carbon metabolism(1)(2). Other researchers indicated that deficiencies in dietary B-vitamin input and genetic polymorphisms for the enzymes in one-carbon metabolism are associated with a host of human health concerns,including cancer(3). Other suggestion of vitamin B2 deficiency may lead to with cervical cancer and precancerous lesions. researchers at the the First Affiliated Hospital of Xinjiang Medical University, found the inverse association  between tissue riboflavin levels and C20orf54 mRNA and protein expression in cervical squamous cell carcinoma (CSCC)(4), serum and tissues of vitamin B2 may be linked to the risk of the cervical cancer development. In the methylenetetrahydrofolate reductase (MTHFR) gene, researchers at the ¹University of Alabama at Birmingham, Birmingham showed that women who have the MTHFR polymorphism and low riboflavin status, were less likely to develop cervical intraepithelial neoplasia (CIN) 2 or 3, than women who was without the polymorphism and high riboflavin status(5). In the analysis of the cancer site, MTHFR C677T polymorphism interacted with folate and riboflavin in modulating cancer risk in a manner, depending to the types of cancer but  the effect on cervical cancer risk is not clear(6).

Taking altogether, Vitamin B2 deficiency and defection of methylenetetrahydrofolate reductase (MTHFR) gene may be associated to increased risk of cervical cancer, but further studies are necessary to validate its claims. At the mean time, please make sure you follow the guideline of the Institute of Medicine of the National Academies as  over doses for a prolong period may cause symptoms of skin rashes, hypersensitivity, high blood pressure etc.,

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Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(a) Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12 by Hernandez BY¹, McDuffie K, Wilkens LR, Kamemoto L, Goodman MT.(PubMed)
(b) A case control study of nutritional factors and cervical dysplasia by Liu T¹, Soong SJ, Wilson NP, Craig CB, Cole P, Macaluso M, Butterworth CE Jr.(PubMed)
(c) [Chemoprevention of cervical cancer--intervention study of cervical precancerous lesions by retinamide II and riboflavin].[Article in Chinese] byChen RD.(PubMed)
(d) Epidemiologic studies of vitamins and cancer of the lung, esophagus, and cervix by Ziegler RG.(PubMed)
(1) Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women.

Weinstein SJ¹, Ziegler RG, Selhub J, Fears TR, Strickler HD, Brinton LA, Hamman RF, Levine RS, Mallin K, Stolley PD.(PubMed)

(2) Nutritional and genetic inefficiencies in one-carbon metabolism and cervical cancer risk by Ziegler RG¹, Weinstein SJ, Fears TR.(PubMed) 

(3) Mathematical Models of Cell Metabolism(Fred Hutchinson cancer research center)
(4) Association of the plasma and tissue riboflavin levels with C20orf54 expression in cervical lesions and its relationship to HPV16 infection by Aili A¹, Hasim A, Kelimu A, Guo X, Mamtimin B, Abudula A, Upur H.(PubMed)
(5) Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status by Piyathilake CJ¹, Azrad M, Macaluso M, Johanning GL, Cornwell PE, Partridge EE, Heimburger DC.(PubMed)
(6) Interaction among folate, riboflavin, genotype, and cancer, with reference to colorectal and cervical cancer. by Powers HJ.(PubMed)