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Online Library: Liver Disease

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting liver disease. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis*.

Source: New England journal of medicine 2010;362(18):1675-85

Author: Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; NASH CRN.

Affiliation: Virginia Commonwealth University, Richmond, USA.

Abstract: Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. The authors randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone* at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant. Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone, as compared with placebo, and both agents were associated with reductions in hepatic steatosis and lobular inflammation but not with improvement in fibrosis scores. Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups.Conclusion: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes.

*Fatty liver disease
*Pioglitazone is a prescription drug of the class thiazolidinedione (TZD) with hypoglycemic (antihyperglycemic, antidiabetic) action. Pioglitazone is marketed as trademarks Actos in the USA, the UK and Germany

Differential regulation of hepatic transcription factors in the wistar rat offspring born to dams fed folic Acid, vitamin B12 deficient diets and supplemented with omega-3 Fatty acids.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24587285

Author: Meher A, Joshi A, Joshi S.

Affiliation: Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, Maharashtra, India.

Abstract: Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of this study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARá and PPARă expression was lower in the BD group although there were no differences in the expression of SREBP-1c, LXRá and RXRá expression. Omega-3 fatty acids supplementation to this group normalized levels of both PPARá and PPARă but reduced SREBP-1c, LXRá and RXRá expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced PPARá, SREBP-1c and RXRá expression. Pup liver global methylation levels were higher in both the micronutrients deficient groups and could be normalized by omega-3 fatty acid supplementation. The researchers’ novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the offspring.

Betaine

Alleviation of Dimethylnitrosamine-Induced Liver Injury and Fibrosis by Betaine Supplementation in Rats

Source: Chemico-Biological Interactions 2009; 177(3): 204-11.

Author: Kim S.K., Seo J.M., Chae Y.R., Jung Y.S., Park J.H., Kim Y.C.

Affiliation: College of Pharmacy, Chungnam National University, 220 Gung-Dong, Yuseong-Ku, Daejeon, Republic of Korea.

Abstract: This study examined the protective effects of betaine on chronic liver injury and fibrosis induced by dimethylnitrosamine (DMN). Male rats were supplemented with betaine (1%, w/v) in drinking water from 2 weeks prior to the initiation of DMN treatment (10mg/(kg day), i.p., 3 days/week, for 1, 2, or 4 weeks) until sacrifice. Induction of liver injury was determined by quantifying serum alanine aminotransferase, aspartate aminotransferase activities, bilirubin levels, hepatic xenobiotic-metabolizing capacity, histopathological changes and 4-hydroxyproline levels. Development of oxidative injury was estimated by malondialdehyde (MDA) levels and total oxyradical scavenging capacity (TOSC) of liver and serum toward hydroxyl, peroxyl radicals, and peroxynitrite. Betaine supplementation markedly attenuated the induction of hepatotoxicity and fibrosis by DMN. Elevation of MDA and the reduction of TOSC were also depressed significantly. Development of liver injury corresponded well with the induction of oxidative stress in rats treated with DMN, both of which are inhibited effectively by betaine supplementation. It is suggested that betaine may protect liver from fibrogenesis by maintaining the cellular antioxidant capacity.

Alleviation of Acute Ethanol-Induced Liver Injury and Impaired Metabolomics of S-Containing Substances by Betaine Supplementation

Source: Biochemical and Biophysical Research Communications 2008; 368(4): 893-8

Author: Kim S.J., Jung Y.S., Kwon do Y., Kim Y.C.

Affiliation: College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.

Abstract: This study investigated the induction of oxidative damage in association with changes in hepatic concentrations of sulfur-containing substances in mice challenged with binge-like ethanol administration. Also the protective effect of dietary betaine against ethanol-induced liver injury was determined. Serum alanine aminotransferase activity, TNFalpha level, and hepatic malondialdehyde level were increased significantly by ethanol administration. Ethanol administration decreased hepatic S-adenosylmethionine, cysteine, and glutathione, but elevated hypotaurine and taurine levels. Betaine supplied in drinking water for 2 weeks attenuated the induction of alcoholic liver injury and Cyp2e1 significantly. Reduction of hepatic S-adenosylmethionine and glutathione was alleviated, and elevation of hypotaurine and taurine was depressed. The results suggest that betaine may protect the liver against ethanol-induced oxidative injury most probably via its effects on the sulfur-amino acid metabolism.

Effect of Betaine Supplementation on Changes in Hepatic Metabolism of Sulfur-Containing Amino Acids and Experimental Cholestasis Induced by Alpha-Naphthylisothiocyanate

Source: Food and Chemical Toxicology 2005; 43(5): 663-70

Author: Kim Y.C., Jung Y.S., Kim S.K.

Affiliation: College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.

Abstract: This study examined the effects of betaine supplementation (1% in drinking water) for 2 weeks on the hepatotoxicity and changes in the sulfur amino acid metabolism induced by alpha-naphthylisothiocyanate (ANIT) treatment. Acute ANIT challenge elevated the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, and total bilirubin contents from 5 h after the treatment, reaching a peak at t = 48-72 h. Hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) levels were decreased significantly in a manner almost inversely proportional to the changes in serum parameters measured to determine the ANIT-induced toxicity. Betaine supplementation blocked or significantly attenuated induction of the hepatotoxicity by ANIT. The decrease in SAM and SAH levels was also inhibited by betaine intake. The results indicate that betaine supplementation may antagonize the induction of experimental cholestasis and changes in the metabolism of sulfur amino acids associated with ANIT treatment. The underlying mechanism and pharmacological significance of its action are discussed.

Carnitine

The effect of carnitine on liver regeneration after partial hepatectomy.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24579679

Author: Parlak O, et al.

Affiliation: Department of General Surgery, Ankara Ataturk Research and Education Hospital, Bilkent-Yolu, Ankara, Turkey.

Abstract: The aim of this study was the research the role of carnitine in liver regeneration. Can carnitine given externally increase and/or fasten the beginning of liver regeneration? Wistar Albino rats were used. Group 1: The group, which was applied parenteral carnitine after partial hepatectomy and sacrificed on the 1st day. Group 2: The group, which was applied parenteral carnitine after partial hepatectomy and sacrificed on the 7th day. Group 3: The group, which wasn't applied parenteral carnitine after partial hepatectomy and sacrificed in the 1st day. Group 4: The group which wasn't applied parenteral carnitne after partial hepatectomy and sacrificed on the 7th day. To all the rats, partial liver resection with the rate of 70 % was applied. Being started shortly after the resection, 100 mg/kg/day parenteral L-carnitine was applied to the first and second group. On the 1st and 7th days after the resection, eight subjects from each group were sacrificed. To evaluate the liver regeneration Ki-67 monoclonal antibody was used. After the examinations carried out by pathological clinic, detected mitosis number were examined. The 1st and 7th day mitosis number of the rats taken into the study was seen as statistically significantly higher than the mitosis number of the rats in the control group. Conclusions: As a result, among the rats, which were applied hepatectomy, if met by the major conditions triggering liver regeneration following the external carnitine supplementation, the scientists say with the help of the information provided by the study measuring the regeneration capacity by analysing Ki-67 proliferation index, that external carnitine support can increase the capacity of regeneration if it is given in appropriate dose (Tab. 6, Fig. 7, Ref. 17).

Dr. Rath Cellular Nutrient Synergy Approach

A Nutrient Mixture Suppresses Carbon Tetrachloride Induced Hepatic Toxicity in ICR Mice

Source: Human & Experimental Toxicology 2008; 27(7): 559-66.

Author: Roomi M., Kalinovsky T., Roomi N.W., Ivanov V., Rath M., Niedzwiecki A.

Affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050

Abstract: We examined the effect of a nutrient mixture (NM) that contains lysine, proline, ascorbic acid, and green tea extract in mice treated with carbon tetrachloride (CCl4), a model of liver injury in which free radical, oxidative stress, and cytokine production are closely linked. Seven-week-old male Imprinting Control Region (ICR) mice were divided into four groups (A-D) of five animals each. Groups A and C mice were fed a regular diet for 2 weeks, whereas groups B and D mice were supplemented with 0.5% NM (w/w) during that period. Groups A and B received corn oil i.p., whereas groups C and D received CCl4 (25 microL/kg, in corn oil, i.p.). All animals were killed 24 h after CCl4 administration, serum was collected to assess liver and kidney functions, and livers and kidneys were excised for histology. Mean serum aspartate aminotransferase and alanine aminotransferase were comparable in groups A and B, increased markedly in group C, and significantly lowered in group D compared with group C. CCl4 had no significant effect on renal markers (blood urea nitrogen [BUN], creatinine, and BUN/creatinine ratio). CCl4 administration caused an intense degree of liver necrosis that was less severe in the NM fed group D. These results indicate that NM could be a useful supplement in preventing acute chemical-induced liver toxicity.

Suppression of Growth and Hepatic Metastasis of Murine B16FO Melanoma Cells by a Novel Nutrient Mixture.

Source: Oncology Reports 2008; 20(4): 809-17.

Author: Roomi M.W., Kalinovsky T., Roomi N.W., Ivanov V., Rath M., Niedzwiecki A.

Affiliation: Oncology Division, Dr Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.

Abstract: Highly metastatic melanoma is resistant to existing therapies. Our main objective was to investigate the effect of a nutrient mixture (NM) on B16FO tumor growth and hepatic metastasis. Tumor growth was studied in athymic nude male mice, 5-6 weeks old, inoculated with 10(6) B16FO melanoma cells subcutaneously and fed either a regular diet or one supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors excised, weighed and processed for histology. Metastasis was studied in C57BL/6 mice, which received 10(6) B16FO melanoma cells by intrasplenic injection, as well as a regular or 0.5% NM-supplemented diet for 2 weeks. NM inhibited the growth of B16FO melanoma cells by 50%. The survival time of mice receiving NM supplementation and B16FO cells i.p. was greater than in mice which were fed the regular diet. To confirm effects in vivo, we investigated the effect of NM on murine B16FO melanoma cells in vitro, including cell proliferation by MTT assay, morphology by hematoxylin and eosin (H&E) staining and apoptosis using live green caspase detection kit. In vitro, NM was not toxic at 100 microg/ml concentration, but exhibited 44% toxicity over the control at 500 and 1000 microg/ml. H&E did not indicate any changes up to 100 microg/ml. NM induced slight apoptosis at 100 microg/ml, moderate at 500 and extensive at 1000 microg/ml concentration.

EGCG (Epigalocatechin Gallate)

Epigallocatechin Gallate Prevents Carbon Tetrachloride-Induced Rat Hepatic Fibrosis by Inhibiting the Expression of the PDGFRbeta and IGF-1R.

Source: Chemico-Biological Interactions 2009; 182(2-3): 159-64

Author: Yasuda Y., Shimizu M., Sakai H., Iwasa J., Kubota M., Adachi S., Osawa Y, Tsurumi H., Hara Y., Moriwaki H.

Affiliation: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.

Abstract: Hepatic fibrosis is a major complication of various chronic liver diseases. Activated hepatic stellate cells (HSCs) play a critical role in the development of liver fibrosis and the axis of platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR), a member of receptor tyrosine kinases (RTKs), is closely associated with the activation of HSC. Insulin-like growth factor (IGF)-1 receptor (IGF-1R), which also belongs to RTKs, interacts with the PDGF/PDGFR axis, thereby cooperatively promoting hepatic fibrosis. The study examined the effects of epigallocatechin gallate (EGCG), which inhibits the activation of several types of RTKs, on the development of rat liver fibrosis induced by carbon tetrachloride (CCl(4)). Drinking water with 0.1% EGCG significantly decreased the serum levels of both aspartate aminotransferase and alanine aminotransferase raised by CCl(4), thus indicating an improvement of liver injury. In CCl(4)-injected rats, EGCG markedly attenuated hepatic fibrosis and decreased the amount of hydroxyproline in the experimental liver. The expression of PDGFRbeta and IGF-1R mRNAs in the liver was significantly lowered by the treatment with EGCG. EGCG also decreased the expression of PDGFRbeta and alpha-smooth muscle actin proteins, thus indicating the inhibition of HSC activation. These findings suggest that EGCG can exert, at least in part, an anti-fibrotic effect on the liver by targeting PDGFRbeta and IGF-1R. EGCG might therefore be useful in both the prevention and treatment of hepatic fibrosis.

The Major Green Tea Polyphenol, Epigallocatechin-3-Gallate, Inhibits Obesity, Metabolic Syndrome, and Fatty Liver Disease in High-Fat-Fed Mice

Source: The Journal of Nutrition 2008; 138(9): 1677-83.

Author: Bose M., Lambert J.D., Ju J., Reuhl K.R., Shapses S.A., Yang C.S.

Affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.

Abstract: This study investigated the effects of the major green tea polyphenol, epigallocatechin-3-gallate (EGCG), on high-fat-induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat-induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat-fed control mice (P < 0.05). The results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat-induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms.

Effect of Dietary Epigallocatechin-3-Gallate on Cytochrome P450 2E1-Dependent Alcoholic Liver Damage: Enhancement of Fatty Acid Oxidation

Source: Bioscience, Biotechnology and Biochemistry 2007; 71(12): 2999-3006.

Author: Yun J.W., Kim Y.K., Lee B.S., Kim C.W., Hyun J.S., Baik J.H., Kim J.J., Kim B.H.

Affiliation: Amorepacific Corporation R&D Center, Yongin-si, Gyeonggi-do, Republic of Korea.

Abstract: This study was designed to determine whether dietary epigallocatechin-3-gallate (EGCG), the most abundant catechin polyphenol in green tea, can protect the liver from cytochrome P450 2E1 (CYP2E1)-dependent alcoholic liver damage. Compared with an ethanol group, when EGCG was present in the ethanol diet, the formation of a fatty liver was significantly reduced and the serum aspartate transaminase (AST) and alanine transaminase (ALT) levels were much lower. Ethanol treatment significantly elevated hepatic CYP2E1 expression while simultaneously reducing hepatic phospho-acetyl CoA carboxylase (p-ACC) and carnitine palmitoyl-transferase 1 (CPT-1) levels. While EGCG markedly reversed the effect of ethanol on hepatic p-ACC and CPT-1 levels, it had no effect on the ethanol-induced elevation in CYP2E1 expression. EGCG prevents ethanol-induced hepatotoxicity and inhibits the development of a fatty liver. These effects were associated with improvements in p-ACC and CPT-1 levels. The use of EGCG might be useful in treating patients with an alcoholic fatty liver.

Green Tea Polyphenol Epigallocatechin-3-Gallate Inhibits Oxidative Damage and Preventive Effects on Carbon Tetrachloride-Induced Hepatic Fibrosis

Source: The Journal of Nutritional Biochemistry 2007; 18(12): 795-805.

Author: Zhen M.C., Wang Q., Huang X.H., Cao L.Q., Chen X.L., Sun K., Liu Y.J., Li W., Zhang LJ.

Affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.

Abstract: The aim of the study was to examine the effects of epigallocatechin-3-gallate (EGCG) on hepatic fibrogenesis and on cultured hepatic stellate cells (HSCs). The rat model of carbon tetrachloride (CCl(4))-induced hepatic fibrosis was used to assess the effect of daily intraperitoneal injections of EGCG on the indexes of fibrosis. Histological and hepatic hydroxyproline examination revealed that EGCG significantly arrested progression of hepatic fibrosis. EGCG caused significant amelioration of liver injury (reduced activities of serum alanine aminotransferase and aspartate aminotransferase). The development of CCl(4)-induced hepatic fibrosis altered the redox state with a decreased hepatic glutathione and increased the formation of lipid peroxidative products, which were partially normalized by treatment with EGCG, respectively. Moreover, EGCG markedly attenuated HSC activation as well as matrix metalloproteinase (MMP)-2 activity. In cultured stellate cell, the expression of MMP-2 mRNA and protein were substantially reduced by EGCG treatment. Concanavalin A-induced activation of secreted MMP-2 was inhibited by EGCG through the influence of membrane type 1-MMP activity. These results demonstrate that administration of EGCG may be useful in the treatment and prevention of hepatic fibrosis.

Epigallocatechin-3-Gallate Protects Mice from Concanavalin A-Induced Hepatitis Through Suppressing Immune-Mediated Liver Injury

Source: Clinical and Experimental Immunology 2006; 145(3): 485-92

Author: Wang Y., Mei Y., Feng D., Xu L.

Affiliation: Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanhai, China.

Abstract: Epigallocatechin-3-gallate (EGCG) is the major active component of green tea. This study investigated the effect of EGCG on concanavalin A (ConA)-induced hepatitis (CIH) in mice, a model of immune-mediated liver injury in humans. Mice were pretreated with EGCG before ConA injection, and then measured alanine aminotransferase (ALT) levels in plasma, inflammatory infiltration and hepatocyte apoptosis in liver. Potential therapeutic mechanisms were elucidated further by measuring several inflammatory mediators. Mice pretreated with EGCG exhibited much less increased ALT levels in plasma, reduced inflammatory infiltration and hepatocyte apoptosis in liver compared with control mice pretreated with vehicle solutions. The study further investigated the mechanisms of the protective effects of EGCG. In EGCG-pretreated mice, the study found abrogated tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma at both protein levels in plasma and mRNA levels in liver. At the same time, the concentration of nitrite in plasma and inducible nitric oxide synthase production in liver were both down-regulated in these mice. Moreover, IFN-inducible protein-10 and macrophage inflammatory protein-1alpha expressions in liver were decreased significantly. Therefore, EGCG is capable of regulating immune-mediated liver injury in vivo. The protective effect depended on its suppressive effect on the production of important inflammatory mediators.

Epigallocatechin-3-Gallate, a Polyphenol Component of Green Tea, Suppresses Both Collagen Production and Collagenase Activity in Hepatic Stellate Cells

Source: International Journal of Molecular Medicine 2005; 16(4): 677-81.

Author: Nakamuta M., Higashi N., Kohjima M., Fukushima M., Ohta S., Kotoh K., Kobayashi N, Enjoji M.

Affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Abstract: Catechins such as epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), and epigallocatechin (EGC) are polyphenol components of green tea. EGCG is the major component and has been reported to possess a wide range of biological properties including anti-fibrogenic activity. In hepatic fibrosis, activated hepatic stellate cells (HSCs) play a central role. This study investigated the effect of catechins, including EGCG, on collagen production and collagenase activity in rat primary HSCs and activated human HSC-derived TWNT-4 cells. EGCG (50 microM) suppressed type I collagen production in rat HSCs more than ECG (50 microM) did; however, EGC (50 microM) did not show suppressive effects. EGCG also inhibited both collagen production and collagenase activity (active matrix metalloproteinase-1 [MMP-1]) in a dose-dependent manner, but did not affect the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) production in TWNT-4 cells. Real-time PCR unexpectedly revealed that EGCG enhanced the transcription of type I collagen and TIMP-1, but did not affect the transcription of alpha-smooth muscle actin (alpha-SMA), and reduced the transcription MMP-1 in TWNT-4 cells. These findings demonstrated that EGCG inhibited collagen production regardless of enhanced collagen transcription and suppressed collagenase activity, and suggested that EGCG might have therapeutic potential for liver fibrosis.

Studies on the Effects of Tea Catechins Against Hepatitis B Virus Infection

Source: Zhonghua Yu Fang Yi Xue Za Zhi [Chinese journal of preventive medicine] 2001; 35(6): 404-7

Author: Li J, Zhou L, Zhang Y.

Affiliation: Department of Health Toxicology, Nuclear Medicine College, Soochow University, Suzhou 215007, China.

Abstract: The objective of this study was to examine the effects of tea catechins against hepatitis B virus and their roles in protecting liver damage. A duck hepatitis B virus infection model was established by using one-day-old Beijing ducklings. The infected ducklings were divided into six groups: three treatment groups of different dosages (60, 120 and 240 mg/kg of tea catechins p.o., 93.7% total catechins and 48.7% EGCG), positive control group (Are-AMP, i.v.), model group (water, p.o.) and negative control group (no DHBV, no catechins). The results show that levels of DHBsAg and DHBV-DNA in duck serum were significantly decreased in all the three catechin treated groups (P < 0.05, P < 0.01). Activities of ALT and AST were also significantly decreased after treatment for 25 days and 14 days after the end of the treatment (P < 0.05, P < 0.01). Results of liver pathological examinations also provided positive evidence. The study concludes that protective effects of tea catechins against hepatitis B virus infection are significant. Tea catechins protected the liver functions and reduced the pathological changes of the liver tissue.

Glutamine

Protective Effects of Glutamine Dipeptide and Alpha-Tocopherol Against Ischemia-Reperfusion Injury in the Isolated Rat Liver

Source: Clinical Nutrition 2009; 28(3): 331-7.

Author: Schuster H., Blanc M.C, Bonnefont-Rousselot D., Nakib S., Le Tourneau A., Furst P., Cynober L., De Bandt J.P.

Affiliation: Laboratory of Nutrition Biology EA 2498, Paris Descartes University, France.

Abstract: Glutamine and vitamin E may prevent hepatic ischemia-reperfusion (I/R) injuries. The aim of this study was to investigate the effects of glutamine, either alone or combined with vitamin E, against I/R in the isolated perfused rat liver. The results show that the association of glutamine with vitamin E led to lower degrees NO (-83%, p<0.05) production, better preserved hepatic glutathione content and, as with vitamin E alone, preserved hepatic vitamin A and significantly decreased malondialdehyde (-85%, p<0.05). The study concludes that both glutamine, by attenuating inflammatory response, and vitamin E, via its antioxidative properties, showed complementary protective effects against I/R-induced hepatic injury. These data emphasize the potential benefit of combining glutamine and vitamin E supplementation in hepatic I/R injury.

Intestinal Intraluminal Injection of Glutamine Increases Trolox Total Equivalent Antioxidant Capacity (TEAC) in Hepatic Ischemia-Reperfusion

Source: Acta cirúrgica brasileira 2006; 21 Suppl 4: 69-73

Author: Salomao A.B., Aguilar-Nascimento J.E., Percario S., Sano V., Marques N.R., Dias C.C.

Affiliation: Department of Surgery, Federal University of Mato Grosso, Brazil.

Abstract: The aim of this study was to evaluate the effects of intraluminal injection of glutamine on the serum trolox equivalent antioxidant capacity in an experimental model of ischemia-reperfusion of the liver in 30 Wistar rats observing the applicability of modifications on the original assay method. The results show that total antioxidant capacity was significantly greater in glutamine group than in both control group (1.60[1.55-1.77] vs 1.44[1.27-1.53]) and sham group (1.60[1.55-1.77] vs 1.48[1.45-1.59]). The study concludes that glutamine enhanced serum antioxidant capacity. The assay technique consistently reflected the changes in the antioxidant defenses in this experimental model.

Interorgan Ammonia, Glutamate, and Glutamine Trafficking in Pigs with Acute Liver Failure

Source: Am J Physiol Gastrointest Liver Physiol., 2006 September; 291(3): pp. G373-81.

Author: Ytrebo L.M., Sen S., Rose C., Ten Have G.A., Davies N.A., Hodges S., Nedredal G.I., Romero-Gomez M., Williams R., Revhaug A., Jalan R., Deutz N.E.

Affiliation: Liver Failure Group, Institute of Hepatology, Univ. College London, 69-75 Chenies Mews, London WC1E 6HX, UK.

Abstract: Ammonia reduction is the target for therapy of hepatic encephalopathy, but lack of quantitative data about how the individual organs handle ammonia limits our ability to develop novel therapeutic strategies. The study aims were to evaluate ammonia metabolism in the liver quantitatively in a devascularized pig model of acute liver failure (ALF). Ammonia and amino acid fluxes were measured across the portal drained viscera (PDV), kidneys, hind leg, and lungs in ALF pigs. Data suggest that the lungs are able to remove ammonia from the circulation during the initial stage of ALF. Our study provides new data supporting the concept of glutamate deficiency in a pig model of ALF. Furthermore, the kidneys are quantitatively as important as PDV in ammonia production, and the muscles play an important role in ammonia removal.

Selenium

Protective Effects of Selenium (Se) and Zinc (Zn) on Cadmium (Cd) Toxicity in the Liver of the Rat: Effects on the Oxidative Stress

Source: Ecotoxicology and Environmental Safety 2009; 72(5): 1559-64.

Author: Jihen el H., Imed M., Fatima H., Abdelhamid K.

Affiliation: Departement de Biophysique, Faculte de Medecine de Monastir, Unite de Recherche, Elements Traces, Radicaux Libres, Antioxydants, Pathologies Humaines et Environnement, Tunisie.

Abstract: Cadmium (Cd) is a very harmful environmental pollutant that transfers between various levels of the food chain. To study the protective effect of Se and Zn on Cd-induced oxidative stress in livers, male rats received either, tap water, Cd, Cd+Zn, Cd+Se or Cd+Zn+Se in their drinking water, for 35 days. The activities of total superoxide dismutase (SOD), copper, zinc-superoxide dismutase (CuZn SOD), glutathione peroxidase (GPx) and catalase (CAT), malondialdehyde (MDA) level and the ratio of CuZn SOD to GPx activity, were determined in the liver. Exposure to Cd lowered total SOD, CuZn SOD, GPx and CAT activities, while it increased MDA level and the ratio of CuZn SOD to GPx activity, in the organ studied. With Se or Zn administration during exposure to Cd, only partial corrective effects on Cd-induced oxidative stress in the liver have been observed, while Se and Zn together assured a more efficient protection of the organ against the observed oxidative stress.

Combination of Selenium and Three Naturally Occurring Antioxidants Administration Protects D-Galactosamine-Induced Liver Injury in Rats

Source: Biological Trace Element Research 2008; 122(2): 127-36.

Author: Catal T., Bolkent S.

Affiliation: Department of Molecular Biology and Genetics, Faculty of Sciences and Letters, Istanbul Technical University, 34469, Maslak, Istanbul, Turkey.

Abstract: The aim of this study was to investigate the role of selenium, ascorbic acid, beta-carotene, and alpha-tocopherol on liver injury induced by D- galactosamine (D-GaIN) in rats by morphological and immunohistochemical means. In this study, Sprague-Dawley female rats were divided into four groups. Group I consists of rats injected physiologic saline solution intraperitoneally. Group II consists of rats given selenium (0.2 mg/kg per day), ascorbic acid (100 mg/kg per day), beta-carotene (15 mg/kg per day), and alpha-tocopherol (100 mg/kg per day) for 3 days via gavage method. Group III consists of the single dose of D-GaIN (500 mg/kg)-injected animals. Group IV are the D-GaIN-injected animals given the same antioxidant combination. Selenium and other three antioxidants combination clearly suppressed an increase in apoptotic cells with TUNEL assay and caspase-3 activity. In addition, it suppressed D-GaIN-induced cell proliferation in the liver. These results indicate that selenium and three naturally occurring antioxidants shows a protective effect against liver injury induced by D-GaIN. These results suggest that supplementation with the combination of selenium, ascorbic acid, beta-carotene, and alpha-tocopherol may help prevent the development of liver injury.

Vitamin B

Vitamins B Depletion, Lower Iron Status and Decreased Antioxidative Defense in Patients with Chronic Hepatitis C Treated by Pegylated Interferon Alfa and Ribavirin

Source: Clinical Nutrition 2009; 28(1): 34-8.

Author: Lin C.C., Yin M.C.

Affiliation: Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City, Taiwan, ROC.

Abstract: The aim of this study was to examine the impact of pegylated interferon combined with ribavirin upon the status of B vitamins, iron and oxidative stress in patients with hepatitis C virus (HCV) infection. METHODS: Blood levels of B vitamins, iron status, and oxidative stress associated biomarkers were determined for 152 healthy controls and 109 HCV patients treated by pegylated interferon and ribavirin at three stages: before therapy, week 24 of treatment, and 48 weeks after therapy. The results show that HCV infection significantly lowered vitamin B(6) and folate (p<0.05). Therapy caused further decrease in vitamin B(6) (p<0.05), and also significantly decreased vitamins B(1) and B(2) (p<0.05). This anti-HCV therapy caused more patients to exhibit insufficient iron status. Thus, the supplement of antioxidant agents, B vitamins and/or iron should be considered for patients with this therapy in order to avoid other healthy risk.

B Vitamins Deficiency and Decreased Anti-Oxidative State in Patients with Liver Cancer

Source: European Journal of Nutrition 2007; 46(5): 293-9.

Author: Lin C.C., Yin M.C.

Affiliation: Dept. of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Chien Kuo N. Rd, Taichung, 402, Taiwan, ROC.

Abstract: This study examined the status of oxidative stress and B vitamins in hepatocellular carcinoma (HCC) patients in different tumor-node-metastasis stages. Patients were divided into two groups as I + II (n = 21) and III + IV (n = 19). Plasma levels of lipid oxidation, alpha-tocopherol, beta-carotene, vitamin C, glutathione and the activity of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase, and xanthine oxidase) were determined for evaluating oxidative status. Blood B vitamins (B(1), B(2), B(6), B(12), and folate) and serum ghrelin were analyzed, and the relationship between serum ghrelin and vitamins B(2) (or B(6)) was evaluated. This study provided novel clinical findings regarding the status of oxidative stress and B vitamins in HCC patients. Plasma glutathione level may be a proper biomarker for evaluating oxidative status for HCC patients. Data indicate that HCC patients might need B vitamins supplementation. The increased serum level of triglyceride and cholesterol might be a consequence of an impaired hepatic fat metabolism, and might be improved by a lower fat administration to these patients.

Vitamin C

Ascorbic Acid Supplementation Has a Cytoprotective Effect on Secondary Biliary Cirrhosis: Experimental Study in Young Rats

Source: Jornal de pediatria 2008; 84(6): 522-8.

Author: Passoni C.R., Coelho C.A.

Affiliation: Department of Clinical Medicine, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil.

Abstract: The objective of this study was to test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. The study examined 40 Wistar rats weaned at the 21st postnatal day. Each group of 10 was subjected to one of the following four treatments, until 49th postnatal day, when they suffered euthanasia: 1) LC-double ligature and resection of the common bile duct and daily administration of ascorbic acid [100 mg/g of body weight (bw)]; 2) LA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw); 3) SC-sham operation and daily administration of ascorbic acid (100 mg/g bw); 4) SA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw). The results show that ascorbic acid supplementation attenuated the effects of cholestasis: decreased the pentobarbital sleeping time, serum globulin, and the liver fat content. The results corroborate the hypothesis that ascorbic acid supplementation has a cytoprotective effect in secondary biliary cirrhosis.

Scurvy Diagnosed in a Pediatric Liver Transplant Patient Awaiting Combined Kidney and Liver Retransplantation

Source: Pediatric Transplantation 2008; 12(3): 363-7.

Author: Samonte V.A., Sherman P.M., Taylor G.P., Carricato M.N., Fecteau A., Ling S.C., Ng V.L.

Affiliation: Pediatric Academic Multi Organ Transplant (PAMOT) Program, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Abstract: First described in the 1500 s, scurvy is infrequently seen in industrialized countries today, although vulnerable patient groups remain. A 15-yr-old girl underwent liver transplantation at age 26 months for a primary diagnosis of biliary hypoplasia, and subsequently developed late allograft failure and progressive renal insufficiency culminating in listing for combined liver retransplantation and kidney transplantation at age 13 yr. She required regular hemodialysis treatment for 12 months prior to deceased donor organ availability, with a complicated clinical course including recurrent septic episodes and severe cachexia. Ten months after initiation of hemodialysis, she presented with severe bone pain, purpura, ecchymoses, gingival hyperplasia, mucosal bleeding, and subconjunctival hemorrhages. Serial serum ascorbic acid levels were found to be extremely low (<10 micromol/L) despite routine supplementation both in her dialysate and via regular oral supplementation. Histopathology from skin biopsy revealed purpura, hyper- and parakeratosis, and follicular plugging. She had ECG and 2D echocardiogram disturbances, as well as osteopenia and sclerosis of the extremities on radiological evaluations. Therapy with high-dose ascorbic acid (1 g/day orally) led to complete resolution of skin lesions. This case highlights the importance of awareness and recognition of this historic diagnosis, and particularly in children with end-stage organ disease with severely compromised nutrition.

Effect of Ascorbic Acid and Thiamine Supplementation at Different Concentrations on Lead Toxicity in Liver

Source: The Annals of Occupational Hygiene 2007; 51(6): 563-9

Author: Wang C., Liang J, Zhang C., Bi Y., Shi X., Shi Q.

Affiliation: Department of Toxicology, School of Public Health, Wuhan University, DongHu Road 115, Wuhan 430071, People's Republic of China.

Abstract: Objective of this study was to investigate the effect of ascorbic acid [vitamin C (VC)] on liver damage parameters in the lead-exposed mice, when given in combination with thiamine [vitamin B1 (VB(1))] at different concentrations. Sixty-six male mice were randomly assigned into 11 groups (n = 6). The results show that compared with the Group I, sub-chronic lead ingestion (Group II) resulted in a significant decrease of Hb, GSH-P(X), SOD in blood and GSH level in liver cells; lead exposure induced also a significant increase in DNA damage and apoptosis of liver cells (P < 0.05). Supplementation with VC and VB(1), however, reversed these effects. The best effective combination was VC (420 mg kg(-1) bw) and VB(1) (10 mg kg(-1) bw), followed by the combination of VC (420 mg kg(-1) bw) and VB(1) (30 mg kg(-1) bw). But no reversion was shown in the combination of the highest combination of VC (1260 mg kg(-1)) and VB(1) (90 mg kg(-1)). These findings strongly indicated that combination of VC and VB(1) can lessen the damage to liver cells from oxidative stress induce by lead, but the antioxidant effects are dependent on their concentrations.

The Potential Role of Combined Anti-Oxidants Against Cadmium Toxicity on Liver of Rats

Source: Toxicology and Industrial Health 2007; 23(7): 393-401.

Author: Koyuturk M., Yanardag R., Bolkent S., Tunali S.

Affiliation: Department of Histology and Embryology, Faculty of Medicine, Istanbul Science University, 34394-Esentepe, Istanbul, Turkey.

Abstract: Cadmium (Cd), a widely distributed toxic trace metal, has been shown to accumulate in liver after long- and short-term exposure. Cd (2 mg/kg/day CdCl2) was intraperitoneally given to rats for eight days. Vitamin C (250 mg/kg/day) + vitamin E (250 mg/kg/day) + sodium selenate (0.25 mg/kg/day) were given to rats by oral means. The animals were treated by anti-oxidants one hour prior to treatment with Cd every day. Anti-oxidants treatment increased cell proliferation. In the animals administered with Cd, an increase in serum aspartate (AST) and alanine (ALT) aminotransferases, liver glutathione (GSH) and lipid peroxidation (LPO) levels were observed. On the other hand, in the rats treated with anti-oxidants and Cd, serum AST and ALT, liver glutathione and LPO levels decreased. These results suggest that combined anti-oxidants treatment might be useful in protection of liver against Cd toxicity.

Effect of Vitamin C on Liver and Kidney Functions in Normal and Diabetic Rats

Source: Annals of the New York Academy of Science 2006; 1084: 371-90.

Author: Al-Shamsi M., Amin A., Adeghate E.

Affiliation: Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al Ain, United Arab Emirates.

Abstract: In diabetes, the oxidative stress is increased because of the deficiency in the antioxidant defense. The intake of antioxidants, such as vitamin C, may reduce the oxidative stress associated with diabetes and hence help to restore the antioxidant defense system. The aim of this article was to investigate the effect of different doses of vitamin C on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Biochemical analysis was used to study the effect of this vitamin on the biochemical parameters of normal and diabetic rats. Liver and kidney enzymes were elevated after the onset of diabetes. Moderate doses of vitamin C significantly (P < 0.0008) reduced plasma gamma-glutamyl level in diabetic rats. Moreover, vitamin C significantly (P < 0.01) reduced the blood urea nitrogen level of diabetic rats. The plasma level of electrolytes, such as calcium and sodium, also changed significantly (P < 0.00001) after oral administration of vitamin C. Antioxidants, such as vitamin C, may ameliorate the biochemical parameters of diabetic rats.

Antioxidants Vitamin E and C Attenuate Hepatic Fibrosis in Biliary-Obstructed Rats

Source: World J Gastroenterol., 2006 November 14; 12(42): pp.6835-41.

Author: Soylu A.R, Aydogdu N., Basaran U.N., Altaner S., Tarcin O., Gedik N., Umit H., Tezel A., Dokmeci G., Baloglu H., Ture M., Kutlu K., Kaymak K.

Affiliation: Division of Gatroenterology, Trakya University, Turkey.

Abstract: Aim of this study was to investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats. Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vit C, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vit E C, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. ed to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). The results show that each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% +/- 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05). The study concludes that each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

Relationship Between Antioxidant Capacity [Including Vitamin C] and Oxidative Stress in Children with Acute Hepatitis A

Source: World Journal of Gastroenterology 2006; 12(38): 6212-5.

Author: Cemek M., Dede S., Bayiroglu F., Caksen H., Cemek F., Mert N.

Affiliation: Faculty of Science, Afyon Kocatepe University, Afyon, Turkey.

Abstract: The aim of this study was to investigate children with acute hepatitis A. Whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum beta-carotene, retinol, vitamin E and vitamin C levels were studied in 19 (10 females, 9 males) children with acute hepatitis A and in 29 (13 females, 16 males) healthy control subjects. The results show that there was a statistically significant difference between patients and controls for all parameters (P < 0.05). Lipid peroxidation marker MDA was significantly elevated (P < 0.001), while antioxidants beta-carotene, retinol and GSH were significantly decreased (all P < 0.001) in patients compared to healthy subjects. In addition, alpha-tocopherol and ascorbic acid levels were significantly lower in patients when compared to age and sex matched controls (P < 0.05, P < 0.01, respectively). This study shows that hepatitis A virus induces oxidative stress in children with hepatitis A. This finding could be taken into consideration to improve the therapeutic approach in acute hepatitis A.

Vitamin C and vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in Choline Deficient Diet Fed Rats

Source: Nutrition Journal 2003; 2: 9.

Author: Oliveira CP, Gayotto LC, Tatai C, Della Nina BI, Lima ES, Abdalla DS, Lopasso FP, Laurindo FR, Carrilho FJ.

Affiliation: Department of Gastroenterology, Medical School, University of São Paulo, São Paulo, Brazil.

Abstract: Vitamin C and vitamin E are known to react with reactive oxygen species (ROS) blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in Nonalcoholic Fatty Liver Disease (NAFLD) is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E) in its prevention. Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6) - (200 mg/day), vitamin C (n = 6) (30 mg/Kg/day) or vehicle orally. The study concludes that vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet, while vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

Vitamin D

Nutritional Status of Patients with Biliary Atresia and Autoimmune Hepatitis Related to Serum Levels of Vitamins A, D and E

Source: Arquivos de gastroenterologia 2009; 46(1): 62-8.

Author: Saron M.L., Godoy H.T., Hessel G.

Affiliation: Department of Pediatrics, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Abstract: The aim of this study was to evaluate the nutritional status of pediatric-age patients with autoimmune hepatitis and biliary atresia related to serum levels of vitamins A, D and E and the disease severity. This controlled transverse study, evaluated the patients with autoimmune hepatitis and biliary atresia and a reference group paired by sex and age. The patients underwent anthropometric evaluation, alimentary inquiry and determination of serum levels of vitamins A, D and E by high performance liquid chromatography. The study concludes that patients with biliary atresia and cholestasis presented the highest nutritional injury. The patients with biliary atresia and autoimmune hepatitis presented lower serum levels of vitamins A, D and E that in control group. There is a directly proportional correlation between vitamin serum levels, mainly vitamin E, and all anthropometric variables of biliary atresia and autoimmune hepatitis groups.

Vitamin D Status in Gastrointestinal and Liver Disease

Source: Current Opinion in Gastroenterology 2008; 24(2): 176-83.

Author: Pappa H.M., Bern E., Kamin D., Grand R.J.

Affiliation: Division of Gastroenterology and Nutrition, Department of Medicine, and General Clinical Research Center, Children's Hospital Boston, Boston, Massachusetts, USA.

Abstract: The purpose of this review is to report on the vitamin D status and its relationship with bone health in individuals with gastrointestinal and liver disorders. In addition, recommendations regarding replacement and maintenance of optimal vitamin D stores, as well as the state of knowledge regarding its effect on the disease through its actions on the immune system, have been reviewed. The scientific community has revised upward the serum levels of vitamin D considered optimal, and doses of vitamin D much larger than those currently recommended may be needed to maintain these levels, especially in individuals with gastrointestinal and liver disorders. Hypovitaminosis D is prevalent among individuals with gastrointestinal and liver disease. Although replacement and supplementation guidelines have not been well defined, practitioners should aim for a serum 25-hydroxyvitamin D level of at least 32 ng/ml. The contribution of vitamin D to the bone health of these individuals and its role in altering disease course through its actions on the immune system remain to be elucidated.

Vitamin D and Parathyroid Hormone in Outpatients with Noncholestatic Chronic Liver Disease

Source: Clinical Gastroenterology and Hepatology 2007; 5(4): 513-20.

Author: Fisher L., Fisher A.

Affiliation: Department of Gastroenterology, Canberra Hospital, ACT, Australia.

Abstract: The liver plays a central role in vitamin D metabolism. The aim of this study was to determine the prevalence and type of vitamin D-parathyroid hormone (PTH) disturbance in ambulatory patients with noncholestatic chronic liver disease (CLD) and its relationship with disease severity and liver function. The study involved 100 consecutive outpatients (63 men, 37 women; mean age, 49.0 +/- 12.1 [SD] y) with noncholestatic CLD caused by alcohol (n = 40), hepatitis C (n = 38), hepatitis B (n = 12), autoimmune hepatitis (n = 4), hemochromatosis (n = 4), and nonalcoholic steatohepatitis (n = 2); 51 patients had cirrhosis. Serum concentrations of 25-hydroxyvitamin D (25[OH]D), PTH, calcium, phosphate, magnesium, creatinine, and liver function tests were determined. The study concludes that vitamin D inadequacy is common in noncholestatic CLD and correlates with disease severity, but secondary hyperparathyroidism is relatively infrequent. Management of CLD should include assessment of vitamin D status in all patients and replacement when necessary.

Vitamin D Replacement for Cirrhosis-Related Bone Disease

Source: Nature Clinical Practice. Gastroenterology & Hepatology 2006; 3(12): 689-99.

Author: Crawford B.A., Labio E.D., Strasser S.I., McCaughan G.W.

Affiliation: Royal Prince Alfred Hospital and Concord General Repatriation Hospital, and a Senior Clinical Lecturer in the Faculty of Medicine at the University of Sydney, Australia.

Abstract: About 66% of patients with moderately severe cirrhosis and 96% of patients awaiting liver transplantation have vitamin D deficiency. Studies have shown a strong correlation between vitamin D deficiency and bone density, particularly in the hip. Previous studies of vitamin D therapy in cirrhosis-related bone disease have had major design flaws. Most reports and guidelines on the treatment of hepatic bone disease have concluded that vitamin D deficiency does not have a significant pathogenetic role in the development of osteoporosis in cirrhosis, and that there is no evidence for a therapeutic effect of vitamin D supplementation. Conversely, it is generally recommended that patients with cirrhosis and low bone density should receive calcium and vitamin D supplementation; yet there is a paucity of reliable data on the optimal doses to use, as well as a lack of clearly demonstrated benefit. This study suggest that clinical trials of vitamin D therapy in these patients with liver disease are warranted. As low-dose oral supplementation often will not normalize vitamin D levels or suppress parathyroid hormone activity in cirrhotic patients, high-dose, parenteral vitamin D might be preferable, but further long-term studies are required to assess the benefits and safety of this approach.

"Oral vitamin D replacement is effective in chronic liver disease"

Source: Gastroenterol Clin Biol 2010;34(11): 618-20

Author: Rode A, Nicoll A, et al

Affiliation: Royal Melbourne Hospital, Grattan St, Parkville, VIC, 3050, Melbourne, Australia

Abstract: In a study involving 158 outpatients with chronic liver disease, results indicate a high prevalence of poor vitamin D status in this population, and potential for improvement of vitamin D status, with vitamin D supplementation. The authors of this study conclude, "Vitamin D deficiency improves with oral vitamin D supplementation and levels fall without supplementation. Chronic liver disease patients are at very high risk of vitamin D deficiency regardless of etiology or severity."

Vitamin E

Carbon Tetrachloride-Induced Liver Disease in Rats: the Potential Effect of Supplement Oils with Vitamins E and C on the Nutritional Status

Source: German Medical Science 2009; 7: Doc05.

Author: Ismail R.S., El-Megeid A.A., Abdel-Moemin A.R.

Affiliation: Nutrition and Food Science Department, Faculty of Home Economics, Helwan University, Cairo, Egypt.

Abstract: The aim of the present investigation was to study the effects of olive oil (OO), corn oil (CO), and flaxseed oil (FO), with or without supplementation of vitamins E and C, on food intake, body weight gain %, liver weight to body weight %, total lipids, liver functions, and liver histology in male rats intoxicated with carbon tetrachloride (CCl(4)). Forty-two rats were divided into two main groups. The first main group was fed on basal diet (BD) as a negative control group (NC). The second main group received subcutaneous injections of CCl(4) in paraffin oil (50% v/v 2 ml/kg) twice a week to induce chronic damage in the liver. The group was then divided into six subgroups, three of which were fed on 4% unsupplemented oils (CO, FO, and OO) as positive control for the three oils used. The rest of the groups were fed on 4% of the same oils supplemented with vitamins E and C. The most effective treatment was observed with oils supplemented with vitamins E and C. Hierarchically FO achieved the best results compared to other additives, followed by OO and finally CO showing the least effective treatment among the observed groups.

Protective Effects of Glutamine Dipeptide and Alpha-Tocopherol Against Ischemia-Reperfusion Injury in the Isolated Rat Liver

Source: Clinical Nutrition 2009; 28(3): 331-7.

Author: Schuster H., Blanc M.C., Bonnefont-Rousselot D., Nakib S., Le Tourneau A., Furst P., Cynober L., De Bandt J.P.

Affiliation: Laboratory of Nutrition Biology EA 2498, Paris Descartes University, France.

Abstract: The aim of this study was to investigate the effects of glutamine, either alone or combined with vitamin E, against I/R in the isolated perfused rat liver. METHODS: Four groups of 8 livers from male Sprague-Dawley rats were isolated and submitted to a 45-min no-flow ischemia and reperfusion in the presence of alanine 2 mM, alanine 2 mM plus vitamin E 150 microM, Alanyl-Glutamine (AlaGln) 2 mM, or AlaGln 2 mM plus vitamin E 150 microM. Six non-perfused livers were studied in parallel. Liver function, metabolic parameters, oxidative stress and inflammatory parameters have been studied. The study concludes that both glutamine, by attenuating inflammatory response, and vitamin E, via its antioxidative properties, showed complementary protective effects against I/R-induced hepatic injury. These data emphasize the potential benefit of combining glutamine and vitamin E supplementation in hepatic I/R injury.

Nutritional Status of Patients with Biliary Atresia and Autoimmune Hepatitis Related to Serum Levels of Vitamins A, D and E

Source: Arquivos de gastroenterologia 2009; 46(1): 62-8.

Author: Saron M.L., Godoy H.T., Hessel G.

Affiliation: Department of Pediatrics, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Abstract: The objective of this study was to evaluate the nutritional status of pediatric-age patients with autoimmune hepatitis and biliary atresia related to serum levels of vitamins A, D and E and the disease severity. This controlled transverse study, evaluated the patients with autoimmune hepatitis and biliary atresia and a reference group paired by sex and age. The patients underwent anthropometric evaluation, alimentary inquiry and determination of serum levels of vitamins A, D and E by high performance liquid chromatography. The results show that the highest nutritional deficit was observed in patients with biliary atresia, mainly with cholestasis. The serum levels of vitamins A and E for the reference group changed as a function of age. The serum levels of vitamins A, D and E were higher in reference group than in patients with biliary atresia and autoimmune hepatitis together or separately. The study concludes that patients with biliary atresia and cholestasis presented the highest nutritional injury. The patients with biliary atresia and autoimmune hepatitis presented lower serum levels of vitamins A, D and E that in control group. There is a directly proportional correlation between vitamin serum levels, mainly vitamin E, and all anthropometric variables of biliary atresia and autoimmune hepatitis groups.

Vitamin E Treatment for Children with Chronic Hepatitis B: a Randomized Placebo Controlled Trial

Source: World Journal of Gastroenterology 2008; 14(47): 7208-13.

Author: Gerner P., Posselt H.G., Krahl A., Ballauff A., Innerhofer A., Binder C., Wenzl T.G., Zense M., Hector A., Dockter G., Adam R., Neubert J., Classen M., van Gemmern R., Wirth S.

Affiliation: Children's Hospital, Duisburg-Essen University, Klinik 2, Essen 45122, Germany.

Abstract: The aim of this study was to evaluate the safety and efficacy of vitamin E in children with chronic hepatitis B. Patients with chronic hepatitis B, positive for hepatitis Be antigen (HBeAg), to receive either Vitamin E or placebo once daily for 6 months in a 3:1 ratio were randomly assigned and in double-blind manner. The primary end point was HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum hepatitis B virus DNA, and the appearance of antibodies against HBeAg 12 mo after therapy. The study concludes that there is only a tendency that vitamin E may promote HBeAg seroconversion. Therefore larger studies are needed to clarify the role of antioxidants in the therapy of chronic hepatitis B.

Treatment with Silybin-Vitamin E-Phospholipid Complex in Patients with Hepatitis C Infection

Source: Journal of Medical Virology 2008; 80(11): 1900-6.

Author: Falasca K., Ucciferri C., Mancino P., Vitacolonna E., De Tullio D., Pizzigallo E., Conti P., Vecchiet J.

Affiliation: Clinic of Infectious Diseases, Department of Medicine and Science of Aging, G. d'Annunzio University, Chieti-Pescara, Italy.

Abstract: The aim of this study was to evaluate the hepatoprotective and anti-inflammatory effects of silybin-phospholipids and vitamin E complex (SPV complex), by determining cytokine patterns and various markers of liver disease. Forty Caucasian patients with chronic HCV infection were recruited and divided into two groups: 30 were treated with SPV complex for 3 months, while the other 10 did not receive any treatment. Ten other subjects without HCV infection but with staeatosic diagnosis were recruited and treated with SPV complex. Biochemical and hepatic principal parameters were investigated at 0 (T0) and 3 months (T3). The data suggest that the SPV complex exerts hepatoprotective, anti-inflammatory and antifibrotic effects. This new compound may therefore be useful in clinical practice in patients with chronic hepatitis C who cannot undergo conventional antiviral therapy.

Effects of Dietary Vitamin E, C and Soybean Oil Supplementation on Antioxidant Enzyme Activities in Liver and Muscles of Rats

Source: Food and Chemical Toxicology 2008; 46(10): 3290-4.

Author: Shireen K.F., Pace R.D., Mahboob M., Khan A.T.

Affiliation: Department of Food and Nutritional Sciences, Tuskegee University, Tuskegee, Alabama, USA.

Abstract: The effect of elevated levels of dietary vitamin E, C and a combination of vitamin E and C (E&C) with soybean oil on activities of antioxidant (AOE) enzymes important in the protection against lipid peroxidation was studied in male rats fed with vitamin C (12 mg/g), vitamin E (3.68 mg/g) or E&C (3.68 mg/kg+12 mg/g) supplemented diets for 28 days. Catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity in liver, pectoralis major (PM) and sartorius (S) muscles was increased significantly in rats fed with dietary vitamin C, E separately, and vitamin C&E combination, except, superoxide dismutase (SOD), which showed no alterations. These results clearly indicated that vitamin E&C separately and E&C together increased AOE activity in liver, PM and S muscle of rats. However, vitamin E and C combination enhanced AOE activity more significantly and our findings suggest the possible role of vitamin C&E and their combination in reducing the risk of chronic diseases related to oxidative stress.

Vitamin K

Prevalence of Subclinical Vitamin K Deficiency in Cholestatic Liver Disease

Source: Journal of Pediatric Gastroenterology and Nutrition 2009; 49(1): 78-84.

Author: Strople J., Lovell G., Heubi J.

Affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Memorial Hospital, Chicago, IL 60614, USA.

Abstract: This study investigated the frequency of vitamin K deficiency in children and adults with cholestatic liver disease by determining plasma protein induced in vitamin K absence II (PIVKA-II), and assessed the relation between plasma PIVKA-II levels and markers of cholestasis, measured PT, international normalized ratio (INR), serum undercarboxylated osteocalcin (ucOC), serum vitamins A and E, and serum 25-hydroxyvitamin D levels. PATIENTS AND METHODS: Blood was collected from patients with cholestatic liver disease for liver biochemistries, PT, INR, bile acids, 25-hydroxyvitamin D, vitamin A, vitamin E, ucOC, and PIVKA-II. The study concludes that despite vitamin K supplementation, elevation of plasma PIVKA-II suggesting ongoing vitamin K deficiency is common in cholestatic liver disease. Better strategies for vitamin K supplementation and dosing guidelines are needed.

Prevalence of Vitamin K and Vitamin D Deficiency in Patients with Hepatobiliary and Pancreatic Disorders

Source: Nutrition Research 2009; 29(9): 676-83.

Author: Fisher L., Byrnes E., Fisher A.A.

Affiliation: Department of Gastroenterology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.

Abstract: Little is known about the role of fat-soluble vitamins K and D in liver function and bone metabolism in biliary and pancreatic diseases associated with cholestasis and/or fat malabsorption. The aim of this study was to determine vitamin K of bone, vitamin D and parathyroid hormone status in patients with biliary and pancreatic disorders. In 90 consecutive patients (mean +/- SD age, 65.5 +/- 17.7 years; 45 females) undergoing endoscopic retrograde cholangiopancreatography (68 with choledocholithiasis, 14 with other benign condition, and 8 with cholangiopancreatic cancers) fasting concentrations of carboxylated (cOC) and undercarboxylated osteocalcin (ucOC), 25-hydroxyvitamin D, calcium, phosphorus, magnesium, prothrombin time, liver function tests, lipase, and creatinine were measured. Vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was found in 45.6% of patients and elevated parathyroid hormone levels in 27.8%. This study demonstrates that vitamin K and vitamin D deficiencies are common in patients undergoing endoscopic retrograde cholangiopancreatography. Liver dysfunction is associated with and predictive of vitamin K deficiency of bone and decreased production of osteocalcin, indicating the need for appropriate supplementation.

Zinc

High Incidence of Zinc Deficiency Among Filipino Children with Compensated and Decompensated Liver Disease

Source: Journal of Gastroenterology and Hepatology 2009 October 9. [Epub ahead of print]

Author: Umusig-Quitain P., Gregorio G.V.

Affiliation: Department of Pediatrics, University of the Philippines, Philippine General Hospital, Manila, Philippines.

Abstract: The role of zinc in the nutrition and growth of children with chronic liver disease is poorly defined. The present study determined the serum zinc levels of children with compensated liver disease (CLD) and decompensated liver disease (DLD) and compared this with healthy children. Zinc levels were also correlated with the severity of liver disease as measured by Child-Pugh scores. The study comprised of 60 children 0-10 years of age with chronic liver disease, defined as CLD (n = 30) if the Child-Pugh score was < 6, and DLD (n = 30) if the Child-Pugh score was >/= 6. Thirty healthy children 0-10 years served as controls. Serum zinc levels were measured by atomic absorption spectrometry. The study concludes that children with chronic liver disease, whether in a compensated or decompensated state, had lower serum zinc levels compared with the healthy controls. As the severity of liver disease worsened, the zinc levels decreased. The study suggests that zinc supplementation should constitute part of the micronutrient intake of children with chronic liver disease.

Low Plasma Zinc Concentrations in Pediatric Patients with Cirrhosis

Source: Jornal de pediatria 2009; 85(4): 359-64.

Author: Schneider A.C., Pinto R.B., Froehlich P.E., Hammes T.O., da Silveira T.R.

Affiliation: Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Abstract: The aim of this study was to determine plasma zinc concentrations in children and adolescents with cirrhosis and to investigate the association between these results and dietary zinc intake, anthropometric data, and severity of liver disease. Plasma zinc concentration was assessed by atomic absorption spectrophotometry in 30 children and adolescents with cirrhosis (105.0+/-60.0 months; 22 girls) and 27 without liver disease (122.3+/-47.3 months, 14 girls). Dietary zinc data were evaluated by 3-day food intake records. Anthropometry measures included height, weight, skinfold thickness, brachial circumference, and upper arm muscle size. Severity of liver disease was classified according to the Child-Pugh, MELD, and PELD criteria. The study concludes that the prevalence of hypozincemia was 43% for patients with cirrhosis. Although low plasma zinc concentration was associated with more severe liver disease, it was present even in some Child-Pugh A patients. Therefore, zinc supplementation should be considered for cirrhotic children.

Protective Effects of Selenium (Se) and Zinc (Zn) on Cadmium (Cd) Toxicity in the Liver of the Rat: Effects on the Oxidative Stress

Source: Ecotoxicology and Environmental Safety 2009 July; 72(5): 1559-64.

Author: Jihen el H., Imed M., Fatima H., Abdelhamid K.

Affiliation: Departement de Biophysique, Faculte de Medecine de Monastir, Unite de Recherche, Elements Traces, Radicaux Libres, Antioxydants, Pathologies Humaines et Environnement, Tunisie.

Abstract: Cadmium (Cd) is a very harmful environmental pollutant that transfers between various levels of the food chain. To study the protective effect of Se and Zn on Cd-induced oxidative stress in livers, male rats received either, tap water, Cd, Cd+Zn, Cd+Se or Cd+Zn+Se in their drinking water, for 35 days. The activities of total superoxide dismutase (SOD), copper, zinc-superoxide dismutase (CuZn SOD), glutathione peroxidase (GPx) and catalase (CAT), malondialdehyde (MDA) level and the ratio of CuZn SOD to GPx activity, were determined in the liver. Exposure to Cd lowered total SOD, CuZn SOD, GPx and CAT activities, while it increased MDA level and the ratio of CuZn SOD to GPx activity, in the organ studied. With Se or Zn administration during exposure to Cd, only partial corrective effects on Cd-induced oxidative stress in the liver have been observed, while Se and Zn together assured a more efficient protection of the organ against the observed oxidative stress.

Efficacy of Zinc Administration in Patients with Hepatitis C Virus-Related Chronic Liver Disease

Source: Scandinavian Journal of Gastroenterology 2007; 42(9): 1078-87.

Author: Himoto T., Hosomi N., Nakai S., Deguchi A., Kinekawa F., Matsuki M., Yachida M., Masaki T., Kurokochi K., Watanabe S., Senda S., Kuriyama S.

Affiliation: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan.

Abstract: Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease (CLD). The study therefore examined the effects of zinc administration on inflammatory activity and fibrosis in the liver of patients with HCV-related CLD.  Polaprezinc, a complex of zinc and l-carnosine, was administrated at 225 mg/day for 6 months to 14 patients with HCV-related CLD, in addition to their ongoing prescriptions. Peripheral blood cell counts, liver-related biochemical parameters, serological markers for liver fibrosis, HCV-RNA loads, and serum levels of zinc and ferritin were evaluated before and after zinc administration. The results show that serum zinc concentrations were positively correlated with hepatic reserve before zinc supplementation. A significant increase in serum zinc level was observed after zinc supplementation (64+/-15 versus 78+/-26 mg/dl, p=0.0156). The findings suggest that polaprezinc exerts an anti-inflammatory effect on the liver in patients with HCV-related CLD by reducing iron overload.