Weight loss in Herbs and Foods points of view

The prevalence of extreme overweight and obesity has caused concerns of scientific community in the South East Asian population, due unhealthy diet and life style change over 2 decades of economic prosperity. Overweight and obesity have reached epidemic proportions in many Asian countries, affecting even younger age than in Western populations with economic burden in the development of  obesity-related disorders such as diabetes, hypertension, and cardiovascular diseases(1).  One of six Malaysian are either extreme overweight or obese, according to Datin Paduka Santha Kumari, chairman of the Selangor branch of the Malaysian Diabetes Association and  according to global health observatory, at least 2.8 million people die each year as a result of being overweight or obese, and an estimated 35.8 million (2.3%) of global DALYs are caused by overweight or obesity, worldwide(2).
Epidemiological studies, linking herbal medicine, foods and vitamins in preventing and treating these diseases have been inconclusive(a)
Some researchers suggested that intake of certain herbal medicine may enhance appetite suppression. According to the Georgetown University Medical Center, average daily food intake was decreased only with the herbal formulation, not the phenylpropanolamine (PPA) at the low and high doses, in comparison of the effectiveness among herbal formulation and a commonly available(3). Other researchers insisted that using herbs and supplements to induce weight loss should be taken with care, as a  considerable number of reports have been published on hepatotoxicity associated with herbal products attributed with weight-reducing properties(4)(5)(6)(7). the College of Medicine, The Ohio State University insisted that various dietary, lifestyle, and psychologic factors are involved in the etiology of Prameha, particularly in relation to disturbances in fat and carbohydrate metabolism(8), without effective management, obtaining a workable weight loss plan may be extremely difficult.
A. Weight loss in herbs points of view
1. Ephera (Ma Huang)
Ma Huang is also known as ephedra. The acrid, slightly bitter and warm herb has been used in TCM to promote urination and sweating, and rid of cold,  sooth wheezing asthma, etc. as it calms dyspnea,  asthma, cough, etc., by enhancing the functions of lung and bladder channels(9)
Ephedra sinica, the Chinese herb may be effective in induced weigh loss. According to the Dongguk University, certain chemicals found in Ephera showed an association with changes of BW and BMI through alteration of gut microbiota varied by indigenous microbiota of each subject(10). The combined study of a low-calorie diet and Ephera, in 125 otherwise healthy obese women, showed  effective in reducing BMI. RMR change was not compensated for by the herbal medicines tried. resting metabolic rate (RMR) change seemed to be affected by constitution and body composition rather than by medicine(11). The Dongeui University study of composition GGEx18( Laminaria japonica, Rheum palmatum, and Ephedra sinica) in high fat diet-induced obese mice suggested that GGEx18 improves obesity through skeletal muscle AMPK and AMPK-stimulated expression of PPARα and its target enzymes for fatty acid oxidation, through inhibited lipid accumulation, and similar activation of genes(12).
Please note that  due to its  adverse reactions of palpitations, stress, headache and insomnia and stroke, heart attacks, cardiac arrhythmias, seizures and psychotic,  the Dutch Inspectorate for Health Care and the Ministry of Health in Canada have recently requested a market recall of some ephedrine-containing herbal products in response to above adverse reactions reported in association with these products. In the Netherlands, the status of Ephedra-containing products is currently reconsidered(13).

2. Ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root)(14).
In 10 obese middle-aged Korean women took Panax ginseng extracts for 8 wk, ginseng showed to be effective in influence on gut microbiota in promoting weigh loss but depending to the composition of gut microbiota prior to ginseng intake(15). In mice fed on a high-fat diet, ginseng saponin and ginsenosides not only exerted anti-obesity effects via the modulation of physiological lipid metabolism in vivo or intracellular signalling in cell culture systems, but also promoted anti-obesity effects, through abnormal physiology via HFD. Leptin, insulin, and adiponectin, which carry out critical functions in energy and lipid metabolism(16).

3. Zingiber Officinale(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.(17).
According to the Tehran University of Medical Sciences, Slimax (extract of several plants including Zingiber officinale and Bofutsushosan) showed a significant decrease in body weight or inhibition of weight gain(18). The composition of multi-ingredient supplement containing primarily raspberry ketone, caffeine, capsaicin, garlic, ginger and Citrus aurantium, also found the improvements in body composition, waist and hip girth, in an eight-week diet and exercise weight loss program(19). In a comparison of the weight loss effect of Orlistat, a pharmacological agent promoting weight loss and ginger (Zingiber officinale Roscoe, Zingiberacae) in male albino rats, researchers at the Ain Shams University Cairo, found that ginger has a great ability to reduce body weight without inhibiting pancreatic lipase level, or affecting bilirubin concentration, with positive effect on increasing peroxisomal catalase level and HDL-cholesterol(20).

4. Cissus quadrangularis (CQ)
Cissus quadrangularis is an ancient herb used to treat a variety of indications, belonging to the grape family, probably native to India or Sri Lanka. A randomized, double-blind, placebo-controlled design involving 123 overweight and obese persons (47.2% male; 52.8% female; ages 19-50). conducted by University of Yaoundé I, the herb showed a statistically significant net reductions in weight and central obesity, as well as causes of metabolic syndrome(21). In comparison of the effectiveness of Cissus quadrangularis-only and a Cissus quadrangularis/Irvingia gabonensis combination, on weight loss in overweight and obese human subjects, Cissus quadrangularis-only group showed significant reductions on all variables compared to the placebo group, the Cissus quadrangularis/Irvingia gabonensis combination resulted in even larger reductions(22). CQR-300, a proprietary extract of Cissus quadrangularis, also showed a significant reductions in weight and blood glucose levels, while decreasing serum lipids thus improving cardiovascular risk factors, according to the University of Yaoundé I,(23).

5. Sambucus nigra
Elder also known as Common Elder, is a shrub or small tree of the genus Sambucus of 30 specie, belonging to the family Adoxaceae, native to the temperate-to-subtropical regions of both the Northern Hemisphere and the Southern Hemisphere.The herb has been used in traditional and herbal medicine to treat constipation, colic, diarrhea, colds, flu, bronchial and upper-respiratory, irritation of the skin, rheumatism, etc.
In a composition of supplement with Sambucus nigra and Asparagus officinalis study, showed an effectiveness in reduced weight, blood pressure, enhanced physical and emotional well-being and the quality of life had significantly improved (ITT analysis)(24). In Tehran University of Medical Sciences, Sambucus nigra, showed a significant decrease in body weight in numbers of animal studies(25).

6. Asparagus officinalis
Asparagus is a flowering plant belong to species the genus Asparagus, native to the western coasts of northern Spain, north to Ireland, Great Britain, and northwest Germany, northern Africa and western Asia. Asparagus has been used from early times as a vegetable and medicine, because of its delicate flavour and diuretic properties(26). Asparagus officinalis L. powder tablets provided 19 mg saponins per day study showed an effectiveness of the tablets in reduced mean weight, blood pressure, and ebhanced physical and emotional well-being and the quality of life with the rate of very good or good by most of the completers(27). In 12 weeks supplementation of a botanical extract-based weight loss formula, including Asparagus, researchers at the Poznan University of Medical Science, indicated a significantly change of the Body Composition Improvement Index (BCI), induce greater weight loss than placebo, probably through a concurrently performed exercise program--a recommended strategy for life style modification(28).

7. Slimax
Slimax (extract of several plants including Zingiber officinale and Bofutsushosan), in the reviews of the data base of studies published, showed a significant decrease in body weight. In 41 animal studies, the formaula was found to be effective in significant induced weight loss or inhibited of weight gain(29).

B. Weight loss in foods points of view
Epidemiological studies, linking certain foods in reduced weight loss for obese individual have produced certain positive results, but researchers emphasized that weight loss can not be in the expenses of intake of nutrients(30a).
1. Oats
Oat is a species of cereal grain grown for its seed and was first cultivated in Europe but is now grown all over the world, especially in Scotland and England. It is one of good crop to plant in the poor soil after crops are harvested in the Fall(30).
Oat, rich in beta-glucan, may hold a magic power in regulation of  metabolism and liver-protecting effect. According to Chung-Shan Medical University, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions with no adverse effects(31). Whole-grain ready-to-eat oat cereal, in a randomized study of 144 Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL, had favorable effects on fasting lipid levels and waist circumference(32). Other study suggested that at-derived beta-glucan, combined with moderate exercise also improved lipid profile and caused a decrease in weight(33).

2. Salmon
Salmon is the common name for Salmonidae. They are anadromous, born in fresh water, migrate to the ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die(34).
Dietary salmon oil, in rat study showed to reduced weight loss of CXB-E and -H tested mice, but induced with weight gain in recombinant inbred strains. This findings may suggested that body weight response to salmon oil feeding is controlled by multiple genes(35). A novel oral form of salmon calcitonin (sCT), according to the study at ¹Nordic Bioscience, also showed to improve fasting and postprandial glycemic control and insulin sensitivity and may be considered as a promising agent for the treatment of obesity-related insulin resistance and type 2 diabetes patients(36)(37).

3. Brown rice
Brown rice or unpolished rice is a kind of whole, natural grain with very brown color of which only the outermost layer of the rice kernel are removed, thus preventing the lost of nutrients(38).
The study of the weigh effect of brown rice on metabolic parameters in type 2 diabetes, showed a positive effect of consumption of the brown rice (LB)  in association with a decreased waist circumference in type 2 diabetic patients(39). Other randomized study of forty women between 20 and 35 years of age in the comparison of white rice and mixed rice of weight control, including brown rice, indicated that meal replacement with mixed rice was superior to replacement with white rice in weight control, improving antioxidant enzyme activity(40).

4. Chicken
Chicken are domesticated fowl belonging to the subspecies of Gallus domesticus and is raised all over the world for its delicious meats and eggs. It can be roasted, broiled, grilled or poached into a very delicious, tasteful and nutritious meal(41).
In the comparison of weight loss and total lipid profile changes in overweight women consuming beef or chicken, researchers at ¹Rippe Lifestyle Institute, Shrewsbury showed a interest result of weight loss and improved lipid profile can be accomplished through diet and exercise, regardless to dietary protein source including lean beef or chicken(42). But the study at University of Navarra, showed a opposite result in the study of frequent consumption of selenium-enriched chicken meat(43), it may be the result of the presence of antioxidant selenium in the meat.

5. Water
According to Virginia Tech, consuming 500 ml water prior to each main meal may lead to greater weight loss than a hypocaloric diet alone in middle-aged and older adults, because of it acutely reduces meal energy intake(EI)(44) but not younger subjects(45). The Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial, suggested that replacing caloric beverages with water or diet beverages induced 2% to 2.5% weight loss(46).

6. Nuts
Dietary consumption of nuts with  rich sources of multiple nutrients is associated with health benefits and weight loss,epidemiologically.  but in well-controlled nut-feeding trials, no changes in body weight were observed(47). Pistachio nuts, a member of the cashew family, can be consumed as a portion-controlled snack for individuals restricting calories to lose weight without concern that pistachios will cause weight gain(48).

7. 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.
According to Maastricht University, caffeine intake and green tea supplementation are associated to improved weight maintenance, partly through thermogenesis and fat oxidation, in a randomized placebo-controlled double blind parallel trial in 76 overweight and moderately obese subjects(49). Catechins the antioxiands found abundantly in green tea, significantly decreased body weight and significantly maintained body weight after a period of weight loss, depending to the moderators of habitual caffeine intake and ethnicity(50). In a high-protein diet, green tea-caffeine mixture, failed to exert the same effect on body weight maintenance(51).

8. 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.
In a randomized, double-blind, placebo-controlled, linear dose, crossover study, green coffee extract, consistent with human and animal studies and a meta-analysis may be an effective nutraceutical in reducing weight in preobese adults(52). Mannooligosaccharides (MOS), extracted from coffee, exhibited a potential functional use for weight management and improvement in adipose tissue distribution, but varying in gender(53)
Unfortunately, green coffee extract (GCE), according to University of Exeter, in reviews of the effect against weight loss of existed data, showed a significant poor methodological quality and suggested that more rigorous trials are needed to assess the usefulness of GCE as a weight loss tool(54). Other study, reported a case of Brazil Potent Slimming Coffee and possibly also other weight-loss products may be contaminated with sibutramine and as a result cause severe adverse reactions after stabbing herself in the stomach with a knife(55).

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References
(1) Rising Burden of Obesity in Asia by Ambady Ramachandran and Chamukuttan Snehalatha(Journey of Obesity)
(2) Obesity - Situation and trends(WHO)
(3) Influence of a combination of herbs on appetite suppression and weight loss in rats by Talpur NA¹, Echard BW, Manohar V, Preuss HG.(PubMed)
(4) [Hepatotoxicity induced by herbs and medicines used to induce weight loss].[Article in Spanish]by Herrera S¹, Bruguera M.(PubMed)
(5) A case report of adult lead toxicity following use of Ayurvedic herbal medication by Breeher L¹, Gerr F, Fuortes L.(PubMed)
(6) [Chronic lead intoxication associated with Ayurvedic medication].[Article in Dutch] by Kanen BL¹, Perenboom RM.(PubMed)
(7) Potential toxicity of caffeine when used as a dietary supplement for weight loss by Pendleton M¹, Brown S, Thomas C, Odle B.(PubMed)
(8) Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial by Hackman RM¹, Havel PJ, Schwartz HJ, Rutledge JC, Watnik MR, Noceti EM, Stohs SJ, Stern JS, Keen CL.(PubMed)
(9) Ma Huang(Popular Chinese herbs)
(10) Prameha in Ayurveda: correlation with obesity, metabolic syndrome, and diabetes mellitus. Part 2--management of Prameha by Sharma H¹, Chandola HM.(PubMed)
(11) Effect of herbal Ephedra sinica and Evodia rutaecarpa on body composition and resting metabolic rate: a randomized, double-blind clinical trial in Korean premenopausal women by Kim HJ¹, Park JM, Kim JA, Ko BP(PubMed)
(12) The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica reduces obesity via skeletal muscle AMPK and PPARα by Shin SS¹, Park D, Lee HY, Hong Y, Choi J, Oh J, Lee H, Lee HR, Kim MR, Shen ZB, Cui HH, Yoon M.(PubMed)
(13) [Ephedrine and ephedra in weight loss products and other preparations].[Article in Dutch] by van der Hooft CS¹, Stricker BH.(PubMed)
(14) Ginseng, Asian (Panax ginseng) and Ginseng, North America(Popular Chinese Herbs)
(15) Influence of Panax ginseng on obesity and gut microbiota in obese middle-aged Korean women by Song MY¹, Kim BS², Kim H(PubMed)
(16) Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet by Song YB¹, An YR, Kim SJ, Park HW, Jung JW, Kyung JS, Hwang SY, Kim YS.(PubMed)
(17) Popular #Herbs - #Ginger (Zingiber officinale)(Popular Chinese herbs)
(18) A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity by Hasani-Ranjbar S¹, Nayebi N, Larijani B, Abdollahi M.(PubMed)
(19) Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women by Lopez HL¹, Ziegenfuss TN, Hofheins JE, Habowski SM, Arent SM, Weir JP, Ferrando AA.(PubMed)
(20) Comparative evaluation of the efficacy of ginger and orlistat on obesity management, pancreatic lipase and liver peroxisomal catalase enzyme in male albino rats by Mahmoud RH¹, Elnour WA.(PubMed)
(21) The use of a Cissus quadrangularis formulation in the management of weight loss and metabolic syndrome by Oben J¹, Kuate D, Agbor G, Momo C, Talla X.(PubMed)
(22) The use of a Cissus quadrangularis/Irvingia gabonensis combination in the management of weight loss: a double-blind placebo-controlled study. by Oben JE¹, Ngondi JL, Momo CN, Agbor GA, Sobgui CS.(PubMed)
(23) The effect of Cissus quadrangularis (CQR-300) and a Cissus formulation (CORE) on obesity and obesity-induced oxidative stress by Oben JE¹, Enyegue DM, Fomekong GI, Soukontoua YB, Agbor GA.(PubMed)
(24) An observational study and quantification of the actives in a supplement with Sambucus nigra and Asparagus officinalis used for weight reduction by Chrubasik C¹, Maier T, Dawid C, Torda T, Schieber A, Hofmann T, Chrubasik S.(PubMed)
(25) A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity by Hasani-Ranjbar S¹, Nayebi N, Larijani B, Abdollahi M(PubMed)
(26) #Healthy #Foods - Vegetables - Asparagus (Asparagus officinalis)(health tips for better living and living health)
(27) An observational study and quantification of the actives in a supplement with Sambucus nigra and Asparagus officinalis used for weight reduction by Chrubasik C¹, Maier T, Dawid C, Torda T, Schieber A, Hofmann T, Chrubasik S.(PubMed)
(28) Efficacy of 12 weeks supplementation of a botanical extract-based weight loss formula on body weight, body composition and blood chemistry in healthy, overweight subjects--a randomised double-blind placebo-controlled clinical trial by Opala T¹, Rzymski P, Pischel I, Wilczak M, Wozniak J.(PubMed)
(29) A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity by Hasani-Ranjbar S¹, Nayebi N, Larijani B, Abdollahi M.(PubMed)
(30) #Healthy #Foods - Oats ((Avena sativa) (Health tips for better living and living health)
(31a) Association between mood and diet quality in subjects with metabolic syndrome participating in a behavioural weight-loss programme: A cross-sectional assessment by Perez-Cornago A, Zulet MA, Martinez JA.(PubMed)
(31b) Dietary quality-adherence to the dietary guidelines in Tehranian adolescents: Tehran Lipid and Glucose Study by Mirmiran P¹, Azadbakht L, Azizi F.(PubMed)
(31) Oat prevents obesity and abdominal fat distribution, and improves liver function in humans by Chang HC¹, Huang CN, Yeh DM, Wang SJ, Peng CH, Wang CJ.(PubMed)
(32) Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods by Maki KC¹, Beiseigel JM, Jonnalagadda SS, Gugger CK, Reeves MS, Farmer MV, Kaden VN, Rains TM.(PubMed)
(33) Oat-derived beta-glucan significantly improves HDLC and diminishes LDLC and non-HDL cholesterol in overweight individuals with mild hypercholesterolemia, Reyna-Villasmil N¹, Bermúdez-Pirela V, Mengual-Moreno E, Arias N, Cano-Ponce C, Leal-Gonzalez E, Souki A, Inglett GE, Israili ZH, Hernández-Hernández R, Valasco M, Arraiz N.(PubMed)
(34) #Healthy #Foods - Seafoods - Salmon (Healthy tips for better living and living health)
(35) Genetically determined body weight loss in mice fed diets containing salmon oil by LeBoeuf RC¹, Veldee MS.(PubMed)
(36) Oral salmon calcitonin improves fasting and postprandial glycemic control in lean healthy rats by Feigh M¹, Nielsen RH, Hansen C, Henriksen K, Christiansen C, Karsdal MA.(PubMed)
(37) A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats by Feigh M¹, Henriksen K, Andreassen KV, Hansen C, Henriksen JE, Beck-Nielsen H, Christiansen C, Karsdal MA.(PubMed)
(38) #Healthy #Foods - Whole Grain - Brown rice or Hulled rice's(Health tips for beter living and living health)
(39) Intake of brown rice lees reduces waist circumference and improves metabolic parameters in type 2 diabetes by Kim TH¹, Kim EK, Lee MS, Lee HK, Hwang WS, Choe SJ, Kim TY, Han SJ, Kim HJ, Kim DJ, Lee KW.(PubMed)
(40) Meal replacement with mixed rice is more effective than white rice in weight control, while improving antioxidant enzyme activity in obese women by Kim JY¹, Kim JH, Lee da H, Kim SH, Lee SS.(PubMed)
(41) #Healthy #Foods - Chicken (Gallus gallus domesticus)(Health tips for btter living and living health)
(42) Weight loss and total lipid profile changes in overweight women consuming beef or chicken as the primary protein source by Melanson K¹, Gootman J, Myrdal A, Kline G, Rippe JM.(PubMed)
(43) Frequent consumption of selenium-enriched chicken meat by adults causes weight loss and maintains their antioxidant status by Navas-Carretero S¹, Cuervo M, Abete I, Zulet MA, Martínez JA.(PubMed)
(44) Water consumption increases weight loss during a hypocaloric diet intervention in middle-aged and older adults by Dennis EA¹, Dengo AL, Comber DL, Flack KD, Savla J, Davy KP, Davy BM(PubMed)
(45) Pre-meal water consumption reduces meal energy intake in older but not younger subjects by

Van Walleghen EL¹, Orr JS, Gentile CL, Davy BM.(PubMed)

(46) Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial by  Tate DF¹, Turner-McGrievy G, Lyons E, Stevens J, Erickson K, Polzien K, Diamond M, Wang X, Popkin B.(PubMed)
(47) Nut consumption and body weight by Sabaté J.(PubMed)
(48) Pistachio nuts reduce triglycerides and body weight by comparison to refined carbohydrate snack in obese subjects on a 12-week weight loss program by Li Z¹, Song R, Nguyen C, Zerlin A, Karp H, Naowamondhol K, Thames G, Gao K, Li L, Tseng CH, Henning SM, Heber(PubMed)
(48) Impact of peanuts and tree nuts on body weight and healthy weight loss in adults by Mattes RD¹, Kris-Etherton PM, Foster GD.(PubMed)
(49) Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation by Westerterp-Plantenga MS¹, Lejeune MP, Kovacs EM.(PubMed)
(50) The effects of green tea on weight loss and weight maintenance: a meta-analysis by Hursel R¹, Viechtbauer W, Westerterp-Plantenga MS.(PubMed)
(51) Green tea catechin plus caffeine supplementation to a high-protein diet has no additional effect on body weight maintenance after weight loss by Hursel R¹, Westerterp-Plantenga MS.(PubMed)
(52) Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects by Vinson JA¹, Burnham BR, Nagendran MV.(PubMed)
(53) A weight-loss diet including coffee-derived mannooligosaccharides enhances adipose tissue loss in overweight men but not women, by St-Onge MP¹, Salinardi T, Herron-Rubin K, Black RM.(PubMed)
(54) The use of green coffee extract as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials by Onakpoya I¹, Terry R, Ernst E.(PubMed)
(55) [Life-threatening psychosis caused by using sibutramine-contaminated weight-loss coffee].

[Article in Dutch] by Bertholee D¹, ter Horst PG, Wieringa A, Smit JP.(PubMed)

Cervical cancer in Vitamin K 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(1).
Vitamin K(K1, phylloquinone; K2, menaquinones), is a fat soluble vitamin, found abundantly in leafy green vegetables, broccoli, and Brussels sprouts, etc. It is best known for promotion of coagulation and bone health.

Vitamin K3 (2-methyl-1,4-naphthoquinone), also known as menadione, found effectively in inhibition of the profileration of human cervical epithelial cancer cells (HeLa), through binding of tubulin, a small family of globular proteins, including α-tubulin and β-tubulin posible with function of cell division and the movement of materials within cells(1)(2). Other synthetic vitamin K analogue, 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or compound 5 (Cpd 5) found effectively inhibited tumors through arrested cell cycle progression at both G1 and G2-M(3). In cervical carcinoma SiHa cells, Vitamin K3 (VK3)exerted its anti proliferative effects through inhibited cyclin expression via cell cycle arrest and transition of the aphidicolin-synchronised SiHa cells(4)and induced cytotoxicity in human cervical-carcinoma tsgh8302 cells, through exhibited chromatin condensation and DNA fragmentation(5).

Taking altogether, synthetic Vitamin K and its analogue have shown to reduced risk of and treatment of cervical cancer through cell cycle arrest and regulation of cancer cell proliferation. Further studies with large sample size and multi center studies to validate the effectiveness are necessary. Overdoses can induce symptoms of Skin rash,  Diarrhea, Nausea, Vomiting, Anemia, etc. Please make sure you follow the guideline of the Institute of Medicine of the National Academies.

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References
(1)Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity by Acharya BR¹, Choudhury D, Das A, Chakrabarti G.(PubMed)
(2) Mystery of Vital Cell Protein Solved After 30 Years. Receive News Releases Immediately Via E-mail By Lynn Yarris, lcyarris@lbl.gov (Berkeley Lab)
(3) Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K analogue by Tamura K¹, Southwick EC, Kerns J, Rosi K, Carr BI, Wilcox C, Lazo JS.(PubMed)

(3) Vitamin K3 induces cell cycle arrest and cell death by inhibiting Cdc25 phosphatase by Wu FY¹, Sun TP.(PubMed)
(4) Vitamin-k-3 induces cell-death via apoptosis in human cervical-carcinoma tsgh8302 cells by Wu F, Chang W, Sun T.(PubMed)

 

Cervical cancer in Vitamin E 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(1).
Epidemiological studies, linking vitamin E in reduced risk of cervical cancer have not been consistent(1a)(1b)(1c)(1d), but no doubt of its effectiveness in improvement of quality of life, through reduction of oxidative stress(2)(2a)

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(3), 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..

The Universidad Autónoma de Ciudad Juarez study indicated the effectiveness of  dietary supplements, including vitamin E are associated to reduced risk of cervical cancer but depending to the specific factors of the diseases(4)(5). The study from ¹National Cancer Center, of Korea, showed a strong inverse effect of antioxidants vitamin E against risk of cervical cancer in a 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models(6). Tocotrienols, variants of vitamin E, including alpha-, beta-, gamma-, and delta-  of palm oil in the testing against human cervical cancer cell line showed a strong effects of alphaT3 and gammaT3  induced cell death.through cell cycle arrest at G2/M phase and triggered apoptosis in  a dose-dependent and time-dependent manner(7).
The Vilnius University study in the assessing the parameters of immune and antioxidant systems in patients with cervical cancer indicated a lower levels of antioxidant vitamin E and the activity of the antioxidant enzyme superoxide dismutase in comparison with the control group(8)(8a). Oral administration of alpha-tocopherol and quercetin, exerted their antioxidants effects in protection of  DNA damage against free radicals through detoxification by increased glutathione and glutathione-s-transferase (9). The study at the University of Colorado Health Sciences Center of three human cancer cell lines, including cervical cancer (HeLa), indicated that d-alpha-tocopheryl succinate (alpha-TS)  induced chromosomal damage in both human cervical cancer cells and ovarian cancer cells, but not in human normal fibroblasts in culture and enhanced the level of radiation-induced chromosomal damage in cancer cells, but it protected normal cells against such damage(10).

Taking altogether, without going into reviews, Vitamin E and its variants may have a protective effect in reduced risk of cervical cancer through its antioxidant properties. But further studies with large sample sizes and multi centers studies are necessary to validate its claims. 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.

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References
(1) Cerical cancer (Amerrican cancer society)
(1a) Dietary intakes of selected nutrients and food groups and risk of cervical cancer by Ghosh C¹, Baker JA, Moysich KB, Rivera R, Brasure JR, McCann SE.(PubMed)
(1b) Intakes of selected nutrients and food groups and risk of ovarian cancer by McCann SE¹, Moysich KB, Mettlin C.(PubMed)
(1c) Food consumption pattern in cervical carcinoma patients and controls by Labani L¹, Andallu B, Meera M, Asthana S, Satyanarayana L.(PubMed)
(1d) A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators by Herrero R¹, Potischman N, Brinton LA, Reeves WC, Brenes MM, Tenorio F, de Britton RC, Gaitan E.(PubMed)
(2)[Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer].

[Article in Spanish] by Fuchs-Tarlovsky V¹, Bejarano-Rosales M, Gutiérrez-Salmeán G, Casillas MA, López-Alvarenga JC, Ceballos-Reyes GM (PubMed)

(2a) Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer by Palan PR¹, Woodall AL, Anderson PS, Mikhail MS.(PubMed)

(3) Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411.
(4) [Dietary supplements as a treatment for cervical cancer: a systematic review].

[Article in Spanish] by Arellano Ortiz AL¹, Jiménez Vega F¹, Salcedo Vargas M².(PubMed)

(5) 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)

(6) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J¹, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)

(7) Tocotrienols inhibited growth and induced apoptosis in human HeLa cells through the cell cycle signaling pathway by Wu SJ¹, Ng LT.(PubMed)

(8) [Changes in the parameters of immune and antioxidant systems in patients with cervical cancer].

[Article in Lithuanian] by Kazbariene B¹, Prasmickiene G, Krikstaponiene A, Sukeliene D, Burneckis A, Didziapetriene J.(PubMed)

(8a) Plasma concentrations of coenzyme Q10 and tocopherols in cervical intraepithelial neoplasia and cervical cancer by Palan PR¹, Mikhail MS, Shaban DW, Romney SL.(PubMed)

(9) Comparative evaluation of cancer chemopreventive efficacy of alpha-tocopherol and quercetin in a murine model by De S¹, Chakraborty RN, Ghosh S, Sengupta A, Das S.(PubMed)
(10) D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells by Kumar B¹, Jha MN, Cole WC, Bedford JS, Prasad KN.(PubMed)

Cervical cancer in Vitamin D 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(a).

Vitamin D is a fat-soluble secosteroids found in small amount in few foods, including salmon, mackerel, sardines and tuna. The vitamin plays an important role in modulation of cellular proliferation, apoptosis induction, tumor growth suppression and promotion in absorption of minerals, including calcium, iron, magnesium, phosphate and zinc.


The Medical Center Bonn Friedensplatz, study showed a preferential risk factor of cancer in patient with low levels of concentration of serum vitamin D, including cervix carcinoma(1). 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), a biologically active metabolite of vitamin D, showed to regulate the growth of various cell types. The expression of VDR, 25-OHase, 1alpha-OHase, and 24-OHase in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) might have the ability to synthesize 1alpha,25(OH)2D3 within the cells. Locally in regulating the proliferation and differentiation of the tissues(2). In the study of the same, 25(OH)D3-1alpha-hydroxylase have shown to express in normal cervical tissue, in cervical cancer and in HeLa cells. This local synthesization of 1alpha, 25(OH)2D3 may be of significant importance in the regulation of growth control in normal and malignant cervical tissue(3).
In human epithelioid carcinoma cells of cervix HeLa S3K, vitamins D3-induced alkaline phosphatase activity in malignant cells(4).
In a selected 405 incident cervical neoplasias (333 invasive carcinomas and 72 cervical intraepithelial neoplasias grade III (CIN3)) and 2025 age-matched non-cancer controls in Japanese women showed an inverse correction  between dietary calcium and vitamin D intake and cervical neoplasia risk(5).

Taking together, decreased serum of vitamin D might be associated to increased risk of  cervical cancer. Receptor of vitamin D and its active metabolite of vitamin D may be used to regulation of the cervical cancer tissues. Over doses of vitamin D supplement may cause excessive calcium absorption, calcification, Urinary stones etc. please make sure to follow the guideline of the Institute of Medicine of the National Academies.

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References
(1) Circulating 25-hydroxyvitamin D concentration in German cancer patients by Reinhold U¹, Schmitz B, Kurbacher C, Nagel W, Schmidt M, Malaisse WJ.(PubMed)
(2) Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer by Friedrich M¹, Rafi L, Mitschele T, Tilgen W, Schmidt W, Reichrath J.(PubMed)
(3) Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in cervical tissue by Friedrich M¹, Villena-Heinsen C, Axt-Fliedner R, Meyberg R, Tilgen W, Schmidt W, Reichrath J.(PubMed)
(4) Effect of vitamin D3 and 1,25(OH)2D3 on growth of neoplastically derived cell lines and their alkaline phosphatase activity by Kholodova YuD¹, Bondar OP, Melnykovych G.(PubMed)

(5) Association between dietary calcium and vitamin D intake and cervical carcinogenesis among Japanese women by Hosono S¹, Matsuo K, Kajiyama H, Hirose K, Suzuki T, Kawase T, Kidokoro K, Nakanishi T, Hamajima N, Kikkawa F, Tajima K, Tanaka H.(PubMed)

Food Therapy - Mushrooms(Agaricus bisporus)

Mushroom is a standard name of white button mushroom, the fleshy, spore-bearing fruiting body of a fungus produced above ground on soil or on its food source, It is a genus A. Muscaria and belong to the family Amanitaceae and has been cultivation in many cultures all over the world for foods and health benefits.
Nutrients1. Carbohydrates
2. Protein
3. Thiamine (Vitamin B1)
4. Riboflavin (Vitamin B2)
5. Niacin (Vitamin B3)
6. Pantothenic acid (Vitamin B5)
7. Calcium
8. Phosphorus
9. Potassium
10. Sodium
11. Selenium
12. Iron
13. Copper
14. Zinc
15. Etc.
Chemical constituents
Astraodorol, Psilocybin, Lectin, adustin, ribonuclease, nicotine, 2-hydroxy-4-methoxy-6-methylbenzoic acid, orsellinic acid, melleolide, ergosterol, genistein, daidzein, daucosterol, genistin, uracil and D-mannitol(a).


1. Button Mushroom and Ovarian cancer
Ovarian cancer is defined as a condition of abnormal cells growth of ovarian cells as that have become cancerous. It is one of most common cancer in US, according to the statistics adapted from the American Cancer Society's publication, Cancer Facts & Figures 2010, an estimated 21,880 women in the United States will be diagnosed with ovarian cancer and 13,850 deaths.
button mushrooms (Agaricus bisporus), in scientific literature suggests that dietary components may exert cancer preventive effects(1). According to the Curtin University and National Institute of Hygiene and Epidemiology, Hanoi, Vietnam, high levels of intake mushroom is associated to  reductions in cancer risk, especially in the incidence of epithelial ovarian cancer in southern Chinese women, in the study of 500 incident patients with epithelial ovarian cancer and 500 controls(2), But some researchers concerned that minerals of nutritional value are common constituents of mushrooms collected from natural habitats, the problem is however their co-occurrence with some hazardous elements including Cd, Pb, Hg, Ag, As, and radionuclides(3).


References
(a) [Chemical constituents from fungus Armillaria mellea]. by [Article in Chinese] by Yuan XL¹, Yan LH, Zhang QW, Wang ZM.(PubMed)
(1) The cancer preventive effects of edible mushrooms by Xu T¹, Beelman RB, Lambert JD.(PubMed)
(2) Mushroom intake and risk of epithelial ovarian cancer in southern Chinese women by Lee AH¹, Pasalich M, Su D, Tang L, Tran VD, Binns CW.(PubMed)
(3) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks. by Falandysz J¹, Borovička J.(PubMed)

2.  Button Mushroom and Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
Dietary intake of with button Mushroom  showed  to protect against breast cancer, but  little effect on the growth of human colon, prostate, gastric cancer, and murine Sarcoma 180 cells(1), may be through ROS-mediated mitochondrial apoptotic pathway(2)
In MCF-7 human breast cancer cells. extract from white button (WB, Agaricus bisporus) mushrooms or water alone (5% v/v), exerted its protective effect with significant suppression of  cellular proliferation(3).

References
(a) [Chemical constituents from fungus Armillaria mellea]. by [Article in Chinese] by Yuan XL¹, Yan LH, Zhang QW, Wang ZM.(PubMed)
(1) Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms by Jeong SC¹, Koyyalamudi SR, Jeong YT, Song CH, Pang G.(PubMed)
(2) ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells by Shi X¹, Zhao Y, Jiao Y, Shi T, Yang X.(PubMed)
(2) Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells by Martin KR¹, Brophy SK.(PubMed)

3. Button Mushroom and colon cancer
Bowel cancer also known as colorectal cancer, is defined as a condition of the abnormal proliferation of cells in the colon, rectum, or vermiform appendix. It is the third most commonly diagnosed cancer in developed countries, including US and Canada.
A. bisporus showed to inhibit colon cancer cell line through positively increased GPx-1 and GPx-2 gene expression and GPx-1 enzyme activity in rat colon, due to the presented selenium(1). the Methodist Research Institute, Indianapolis study showed a positive effect of A. bisporus in inhibition of colon cancer (HT-29, HCT-116) cells, through cell cycle arrest at G0/G1 phase(2) and reversibly inhibits cell proliferation occurred within 30 min of the lectin being bound to the cell surface(3).
References
(a) [Chemical constituents from fungus Armillaria mellea]. by [Article in Chinese] by Yuan XL¹, Yan LH, Zhang QW, Wang ZM.(PubMed)
(1) Selenium-enriched Agaricus bisporus increases expression and activity of glutathione peroxidase-1 and expression of glutathione peroxidase-2 in rat colon by Maseko T¹, Howell K, Dunshea FR, Ng K.(PubMed)
(2) Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway by Jedinak A¹, Sliva D.(PubMed)
(3) Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells Lu-Gang Yu¹, David G. Fernig² an Jonathan M. Rhodes (The Febs Journal)

4. Button mushroom and Cardiovascular disease (CVD)
Scientists may have found one of the natural food used in many different culture with a potential in reduced risk and protect against CVD.
Dietary fungi, such as, mushrooms, can protect against chronic disease by altering inflammatory environments through inhibition of inhibit cellular processes under pro-inflammatory conditions which are associated with CVD.
Strong evidences through epidemiological studies suggested that regular consumption of fruits and vegetables is strongly associated with a reduced risk of cardiovascular disease (CVD).
According to Dr. Martin KR., ergothioneine (ERT), a novel antioxidant, presented in edible mushrooms, accumulated through diet was found effective in interrupted pro-inflammatory induction of adhesion molecule expression associated with atherogenesis.
Mushroom, a standard name of white button mushroom, the fleshy, spore-bearing fruiting body of a fungus produced above ground on soil or on its food source, contains several important nutrients including Thiamine (Vitamin B1), Riboflavin (Vitamin B2), Niacin (Vitamin B3), Pantothenic acid (Vitamin B5),  Calcium, Phosphorus, Potassium, Sodium, Selenium, Iron, Copper and Zinc which are necessary to maintain the growth, body functions as well as protect against chronic diseases.
Its antioxidants such as Astraodorol, Psilocybin, Lectin, adustin, ribonuclease, nicotine, etc. may also consist the magic power in reduced risk and treatment of vary types of cancer, including colon, breast and gastric cancers through inhibition of cell cycle arrest, significant suppression of  cellular proliferation, n tested cancer cell lines.
These findings showed to support the notion of dietary mushrooms in protection of CVD, but multi canters and large sample size studies to identify the main ingredient which comparable to current medicine used are necessary to improve its validation.
But, the study of University of Gdańsk, in the reviews and updates data on macro and trace elements and radionuclides in edible wild-grown and cultivated mushrooms suggested that the coexistence of
minerals of nutritional value collected from natural habitats, and co-occurrence with some hazardous elements including Cd, Pb, Hg, Ag, As, and radionuclides should be taken certain precautions.



References
(1) The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease by Martin KR.(PubMed)
(2) Both common and specialty mushrooms inhibit adhesion molecule expression and in vitro binding of monocytes to human aortic endothelial cells in a pro-inflammatory environment by Martin KR.(PubMed)
(3) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks. by Falandysz J¹, Borovička J.(PubMed)
(4) Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells Lu-Gang Yu¹, David G. Fernig² an Jonathan M. Rhodes (The Febs Journal)
(5) Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells by Martin KR¹, Brophy SK.(PubMed)
(6) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks. by Falandysz J¹, Borovička J.(PubMed)
(7) Macro and trace mineral constituents and radionuclides in mushrooms: health benefits and risks.
(8) Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data by Oyebode O¹, Gordon-Dseagu V, Walker A, Mindell JS.(PubMed)
(9) Seasonal consumption of salad vegetables and fresh fruit in relation to the development of cardiovascular disease and cancer by Cox BD¹, Whichelow MJ, Prevost AT.(PubMed)
(10) Intakes of fruits, vegetables and carbohydrate and the risk of CVD by Joshipura KJ¹, Hung HC, Li TY, Hu FB, Rimm EB, Stampfer MJ, Colditz G, Willett WC.(PubMed)

5. Button mushroom and Prostate cancer
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams(1).
In athymic mice, conjugated linoleic acid (CLA), found in white button mushroom extract and its major component showed to inhibit proliferation in the prostate cancer cell lines in vitro within 72 hours and to decrease the prostate tumor size of DU145 and PC3(2). But according to the study by University of Western Sydney, Agaricus bisporus white button mushroom (WBM), in a tetrazolium dye [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]-based assay, it showed a little effect on the growth of human colon, prostate, gastric cancer, and murine Sarcoma 180 cells but breast cancer cell line MCF-7(3). Button mushrooms with a rich source of vitamin D2 that when consumed can increase and maintain blood levels of 25-hydroxyvitamin D in a healthy range(4) of that may lead to reduced risk of prostate cancer(5).

References
(1) Prostate Cancer (Health tips for better living and living health)
(2) White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice by Adams LS¹, Phung S, Wu X, Ki L, Chen S.(PubMed)
(3) Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms by Jeong SC¹, Koyyalamudi SR, Jeong YT, Song CH, Pang G.(PubMed)
(4)  Photobiology of vitamin D in mushrooms and its bioavailability in humans by Keegan RJ, Lu Z, Bogusz JM, Williams JE, Holick MF.(PubMed)
(5) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland) by Merja H. Ahonen, Leena Tenkanen, Lyly Teppo, Matti Hakama, Pentti Tuohimaa (Springer link)

6. Button Mushroom and Immunologic 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. The immune system does a great job of keeping people healthy and preventing infections. Beside foods and nutritional supplements, herbs also play a important role in helping the immune system defend against viruses and bacteria attacks.
In number of studies, Mushrooms have been shown to enhance immune response. according to Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, white button mushroom showed to enhance both innate and T cell-mediated immunity leading to a more efficient surveillance and defense mechanism against microbial invasion and tumor development, through promotion of DC maturation and enhance their antigen-presenting function.(1). A. bisporus polysaccharides isolated from white button mushrooms, exhibited macrophage immunomodulating and antitumor activities, through stimulation the production of nitric oxide, interleukin-6, and tumor necrosis factor-α via activation of nuclear factor-κB with the production p50/105 heterodimers(2).

References
(1) White button mushroom enhances maturation of bone marrow-derived dendritic cells and their antigen presenting function in mice by Ren Z¹, Guo Z, Meydani SN, Wu D.(PubMed)
(2) Macrophage immunomodulating and antitumor activities of polysaccharides isolated from Agaricus bisporus white button mushrooms by Jeong SC¹, Koyyalamudi SR, Jeong YT, Song CH, Pang G(PubMed)

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7. Button mushroom and Anti-inflammatory activities
Chronic inflammatory processes contribute to the pathogenesis of many age-related diseases. Button mushroom showed to retain anti-inflammatory activities even after 'cooking', allowing its active compounds to reach therapeutic levels in target tissues, through inhibited NO production, according to selection of 115 samples prepared by a generic food-compatible processing method involving heating by University of Western Sydney(1). Ethanolic extract of white button mushroom, also showed a significantly enhanced the activities of antioxidant enzymes in serums, livers and hearts of administration of mice, in vitro and vivo(2).

References
(1) Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods by Gunawardena D¹, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Münch G.(PubMed)
(2) In vitro and in vivo antioxidant activity of ethanolic extract of white button mushroom (Agaricus bisporus) by Liu J¹, Jia L, Kan J, Jin CH.(PubMed)


8.  Button mushroom and Hepatic Steatosis
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. The special particle called lipoprotein moves this waxy, soft substance from place to place.
Hepatic Steatosis is the early stage of Non-alcoholic Fatty Liver Disease which is defined as a condition of the fatty liver diseases as a result of accumulated of fat in the liver, not caused by abusive alcohol consumption.
In HepG2 cell line, button mushroom (WBM), Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX) mice, though down regulating genes related to the fatty acid biosynthesis pathway, particularly for fatty acid synthetase (Fas) and fatty acid elongase 6 (Elovl6)(1).

References
(1) Protective effects of white button mushroom (Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women by Kanaya N¹, Kubo M, Liu Z, Chu P, Wang C, Yuan YC, Chen S.(PubMed)


9. Button mushroom and Arthritis
Arthritis is a condition of inflammation of one or more joints
According to Oklahoma State University, white button mushroom in the  reduce the incidence and severity of collagen-induced arthritis(CIA) in dilute brown non-agouti mice, through deduction of reduce the CIA index and plasma TNFα(1).
References
(1) White button and shiitake mushrooms reduce the incidence and severity of collagen-induced arthritis in dilute brown non-agouti mice by Chandra L¹, Alexander H, Traoré D, Lucas EA, Clarke SL, Smith BJ, Lightfoot SA, Kuvibidila S.(PubMed)

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Cervical cancer in Vitamin C Points of View

 Kyle J. Norton(Draft Article)

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin, found in fresh fruits, berries and green vegetables. It is best known for its free radical scavengers activity and regenerating oxidized vitamin E for immune support.
Epidemiological studies linking vitamin C in reduced risk of cervical cancer may be inconclusive(1)(1c)(1a)(1b), but no doubt in acceptance of improved quality of life(QoL)(2).

D-Glucopyranosyl-L-ascorbic acid (AA-2βG), a novel stable vitamin C analog isolated from Lycium barbarum fruit induced Hela cell apoptosis through cell cycle arrest(3). A  case-control study including 239 cases diagnosed with squamous cell carcinoma of the cervix and 979 hospital patients with nonneoplastic found a significant reductions in risk of approximately 40-60% observed for women in the highest vs. lowest tertiles of dietary intake, including vitanin C(4)(4a). In human cervical cancer CaCx patients of the age group of 25-65 years, oral administration of vitamin C reduced oxidative stress risk of CaCx with no side effect(5). A nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract inhibited 100% of invasion of human cervical cancer cells CCL-2 and DoTc2 4510 at 500 microg/mL NM, according to the study of Matthias Rath Research Institute(6).
The study at All India Institute of Medical Sciences, in the study of the effects of vitamin C in cervical cancer patients, indicated that vitamin C downregulates the redox sensitive transcription factor AP-1 and decreases one of its transcription targets HPV E6, and stabilizes P53 through increase in Bax and decrease in Bcl-2 and telomerase activity(7). In deed, the study at Kidwai Memorial Institute of Oncology also found s significant low levels of of carotene, vitamin A, and vitamin C measured in the serum of patients with cancer of the uterine cervix(8).
Other researchers suggested malnutrition may  be a significant cause for the increased prevalence of cervical cancer in women with evidences of low levels of GSH, GPx, GST, SOD, vitamin E and vitamin C in the circulation of cervical cancer patient(9).

Taking altogether, oral administration of vitamin C  may be associated to reduced risk and treatment of cervical cancer and precancer but malnutrition and nutrients deficiency may play an important role in enhancing the start of the cancer itself. Daily ingestion of high-dose vitamin C may be considered safe, but in rare incidence, overdoses in a prolonged period of time, may cause intra-renal oxalate crystal deposition, a fatal nephrotoxicity(10)(11).

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References
(1) Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study by González CA¹, Travier N, Luján-Barroso L, Castellsagué X, Bosch FX, Roura E, Bueno-de-Mesquita HB, Palli D, Boeing H, Pala V, Sacerdote C, Tumino R, Panico S, Manjer J, Dillner J, Hallmans G, Kjellberg L, Sanchez MJ, Altzibar JM, Barricarte A, Navarro C, Rodriguez L, Allen N, Key TJ, Kaaks R, Rohrmann S, Overvad K, Olsen A, Tjønneland A, Munk C, Kjaer SK, Peeters PH, van Duijnhoven FJ, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Naska A, Lund E, Engeset D, Skeie G, Franceschi S, Slimani N, Rinaldi S, Riboli E.(PubMed)
(1a) 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)
(1b) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J¹, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(1c) Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial by Lin J¹, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, Buring JE, Manson JE.(PubMed)
(2) [Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer].

[Article in Spanish] by Fuchs-Tarlovsky V¹, Bejarano-Rosales M, Gutiérrez-Salmeán G, Casillas MA, López-Alvarenga JC, Ceballos-Reyes GM.(PubMed)

(3) Selective suppression of cervical cancer Hela cells by 2-O-β-D-glucopyranosyl-L-ascorbic acid isolated from the fruit of Lycium barbarum L by Zhang Z¹, Liu X, Wu T, Liu J, Zhang X, Yang X, Goodheart MJ, Engelhardt JF, Wang Y.(PubMed) 

(4) Dietary intakes of selected nutrients and food groups and risk of cervical cancer by Ghosh C¹, Baker JA, Moysich KB, Rivera R, Brasure JR, McCann SE.(PubMed) 

(4a) Involvement of oxidative stress in the pre-malignant and malignant states of cervical cancer in women by Gonçalves TL¹, Erthal F, Corte CL, Müller LG, Piovezan CM, Nogueira CW, Rocha JB.(PubMed)

(5) Oxidative stress and antioxidant status in cervical cancer patients by Naidu MS¹, Suryakar AN, Swami SC, Katkam RV, Kumbar KM.(PubMed) 

(6) Suppression of human cervical cancer cell lines Hela and DoTc2 4510 by a mixture of lysine, proline, ascorbic acid, and green tea extract by Roomi MW¹, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M.(PubMed) 

(7) Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing P53 by Reddy VG¹, Khanna N, Singh N.(PubMed) 

(8) Serum carotene, vitamin A, and vitamin C levels in breast cancer and cancer of the uterine cervix by Ramaswamy G¹, Krishnamoorthy L.(PubMed)

(9) Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study by Manju V¹, Kalaivani Sailaja J, Nalini N.(PubMed) 

(10) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)

(11) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)

Cervical cancer in Vitamin A Points of View

 Kyle J. Norton(Draft Article)

Vitamins form an important part in human diet. Epidemiological studies, linking vitamin A in reduced risk of cervical cancer have produced uncleared result(1)(5)(8)(9). But in certain studies, vitamin A in form of retinoids and carotenoids is effective in inhibition of cervical  cancer cell lines through many anti porfilerative and apoptotic pathways.

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.


1. The serum of vitamin A
In a total of 144 cervical cancer cases and 288 age-matched, hospital-based controls using unconditional logistic regression models showed a statistically lower mean dietary intakes of vitamin A compared to control(2). Other study found that serum and urine collected  are lower from12 women diagnosed with cervical intraepithelial neoplasia(3)(4)(4a). But the study of Nizam Institute of Medical Sciences, showed no correction of levels of vitamin A intake between cervical cancer patients and normal controls, in a total of total of 60 consecutive patients and 60 controls were enrolled from a referral hospital during the year 2004(6)(7).

2. Retinols
A combination of retinoids with histone deacetylase (HDAC) inhibitors effectively inhibited the growth of cervical cancer cells  due to the restore RARβ2 expression, associated with a significant upregulation of p21(CIP1) and p53 as well as a pronounced decrease in p-Stat3(10). In cervical cancer cells line HeLa and CaSki, All-trans retinoic acid (ATRA) derived from retinols, inhibited the proliferation of cervical cancer cells line HeLa but showed no effect on proliferation CaSki cells(11).
Other derivatives of retinols, all-trans and 9-cis retinoic acid induced profilerative activity of CaSki cells through cell cycle arrest via exhibited the increase in the level of immunophenotypic expression of wild type p53 and inhibited E6/E7 transcription(12). the study of composition of tea polyphenol, (-)-epigallocatechin gallate (EGCG) and retinoic acid (RA), showed to prevent cervical adenocarcinoma, though induced apoptosis and inhibited telomerase activity(13).

3. Carotenoids
According to the University of Arizona, in the analysis of cervical tissue (cancerous, precancerous, and noncancerous) samples obtained from 87 patients (age, 21-86 years), showed that maintaining an adequate serum concentration of beta-carotene may be necessary for the prevention of cervical cancer and precancer(14). Crocetin is a natural carotenoid dicarboxylic acid, inhibited the cell profileration of Hela cells through cell cycle arrest via p53-dependent and -independent mechanisms(15). According to Albert Einstein College of Medicine and Montefiore Medical Center, showed a lower correction of mean plasma levels of carotenoids (beta-carotene, lycopene, and canthaxanthin), as well as alpha-tocopherol, in women with cervical intraepithelial neoplasia (CIN)and cervical cancer and suggested that antioxidant deficiency may be associated to the pathogenesis of CIN and carcinoma of the cervix(16). Dr. Harris RW, and the researcher team in the study of Cancer of the cervix uteri and vitamin A indicated the strong correction of significantly reduced serum beta carotene concentrations in in women with pre-invasive disease compared to the controls(17).

Taking altogether, Vitamin A may be associated to reduced risk and treatment of cervical cancer, but further studies are necessary to validate its effectiveness. maintaining the adequate levels of vitamin A may be a choice to prevent the disease from start. 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.

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References
(1) Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study by González CA¹, Travier N, Luján-Barroso L, Castellsagué X, Bosch FX, Roura E, Bueno-de-Mesquita HB, Palli D, Boeing H, Pala V, Sacerdote C, Tumino R, Panico S, Manjer J, Dillner J, Hallmans G, Kjellberg L, Sanchez MJ, Altzibar JM, Barricarte A, Navarro C, Rodriguez L, Allen N, Key TJ, Kaaks R, Rohrmann S, Overvad K, Olsen A, Tjønneland A, Munk C, Kjaer SK, Peeters PH, van Duijnhoven FJ, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Naska A, Lund E, Engeset D, Skeie G, Franceschi S, Slimani N, Rinaldi S, Riboli E.(PubMed)
(2) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea by Kim J¹, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)
(3) Rapid HPLC method for the determination of vitamin A and E and cotinine concentration in human serum in women with CIN and cervical cancer by Bystrowska B¹, Gomółka E, Szczudrawa A, Brandys J, Pawlik M, Milewicz T, Dulińska-Litewka J, Jach R.(PubMed)
(4) A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators.

Herrero R¹, Potischman N, Brinton LA, Reeves WC, Brenes MM, Tenorio F, de Britton RC, Gaitan E.(PubMed)

(4a) Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand by Shannon J¹, Thomas DB, Ray RM, Kestin M, Koetsawang A, Koetsawang S, Chitnarong K, Kiviat N, Kuypers J.(PubMed)

(5) Intakes of vitamin A, C, and E, and beta-carotene are associated with risk of cervical cancer: a case-control study in Korea(5)Kim J¹, Kim MK, Lee JK, Kim JH, Son SK, Song ES, Lee KB, Lee JP, Lee JM, Yun YM.(PubMed)

(6) Food consumption pattern in cervical carcinoma patients and controls by Labani L¹, Andallu B, Meera M, Asthana S, Satyanarayana L.(PubMed)
(7) Dietary micronutrients and cervical dysplasia in southwestern American Indian women by Buckley DI¹, McPherson RS, North CQ, Becker TM.(PubMed)
(8) Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary by Dolara P¹, Bigagli E, Collins A.(PubMed)
(9) Vitamin A and risk of cervical cancer: a meta-analysis by Zhang X¹, Dai B, Zhang B, Wang Z.(PubMed)
(10) Combination of valproic acid and ATRA restores RARβ2 expression and induces differentiation in cervical cancer through the PI3K/Akt pathway by Feng D¹, Cao Z, Li C, Zhang L, Zhou Y, Ma J, Liu R, Zhou H, Zhao W, Wei H, Ling B.(PubMed)
(11) Proliferation of cells and expression of RARs, RXRs and HPV viral E6 and E7 proteins in cervical cancer cell lines after treatment with ATRA by Myga-Nowak M¹, Pacholska-Bogalska J, Kwaśniewski W, Kwaśniewska A, Goździcka-Józefiak A.(PubMed)
(12) The effect of all-trans and 9-cis retinoic acid on the steady state level of HPV16 E6/E7 mRNA and cell cycle in cervical carcinoma cells by Narayanan BA¹, Holladay EB, Nixon DW, Mauro CT.(PubMed)
(13) Antiproliferative effects of the major tea polyphenol, (-)-epigallocatechin gallate and retinoic acid in cervical adenocarcinoma by Yokoyama M¹, Noguchi M, Nakao Y, Ysunaga M, Yamasaki F, Iwasaka T.(PubMed)
(14) Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases by Peng YM¹, Peng YS, Childers JM, Hatch KD, Roe DJ, Lin Y, Lin P.(PubMed)
(15) Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms by Zhong YJ¹, Shi F, Zheng XL, Wang Q, Yang L, Sun H, He F, Zhang L, Lin Y, Qin Y, Liao LC, Wang X.(PubMed)
(16) Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer by Palan PR¹, Mikhail MS, Goldberg GL, Basu J, Runowicz CD, Romney SL.(PubMed)
(17) Cancer of the cervix uteri and vitamin A byb Harris RW, Forman D, Doll R, Vessey MP, Wald NJ.(PubMed)