Liver Wellbeing

Curcumin

Curcumin, an extract of the Indian spice turmeric, is well researched for its health properties.
It has been shown to prevent hepatocellular carcinoma (HCC) through apoptosis [1,2] and, during an HCC in vitro study, 5-Fu chemotherapy and curcumin resulted in significant additional anti-cancer effects [3].
Similarly, combination therapy using curcumin has resulted in a reduction in tumour cell production and an increase in cell death of tumour cells in-vitro. [4].

References

1. Chuang SE, Kuo ML, Hsu CH, et al. Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis 2000; 21:331–335.
2. [Darvesh AS, Aggarwal BB, Bishayee A. Curcumin and liver cancer: a review. Curr Pharm Biotechnol. 2012 Jan;13(1):218-28].
3. Zhu R, Wu X Xiao Y et al. Synergetic Effect of SLN-Curcumin and LDH-5-Fu on SMMC-7721 Liver Cancer Cell Line. Cancer Biother Radiopharm 2013;28(8):579-87
4. Notarbartolo M, Poma P, Perri D et al. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 2005;224:53–65.

Curcumin in other liver diseases

Hepatitis

An in vitro study showed that curcumin decreases the hepatitis C gene expression [1]. It may therefore be potentially useful as an anti-hepatitis C agent in humans [1]. Another study found that curcumin inhibits hepatitis C liver cell entry, independently of the person’s genotype, by affecting membrane fluidity, impairing the virus binding and fusion [2].
Hepatitis B also infects the liver and uses its cell host for gene expression and propagation. One in vitro study showed that the combination of Lamivudine and curcumin treatments suppresses hepatitis B expression by up to 75% when compared to non-treated cells. Curcumin also inhibits hepatitis B gene expression and replication [3,4].
These early study results suggest that curcumin may work together with current hepatitis B treatments, and that this combination may result in a better suppression of the virus, reducing progression to cirrhosis and HCC.

References

1. Kim K, Kim KH, Kim HY et al. Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway. FEBS Letters. 2010;584(4):707–712.
2. Anggakusuma, Colpitts CC, Schang LM et al. Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells. Gut. 2014;63(7):1137-49.
3. Rechtman MM, Har-Noy O, Bar-Yishay I, et al. Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1α [FEBS Lett. 584, (2010), 2485-2490] FEBS Letters. 2010;584(11):2485–2490.
4. Rechtman MM, Har-Noy O, Bar-Yishay I, et al. Erratum to Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1α [FEBS Lett. 584, (2010), 2485-2490] FEBS Letters. 2010;584(14):p. 3239.

Green Tea

Green Tea is well studied and evidence from both in vivo systems and animal models suggests that green tea catechins such as epigallocatechin-3-gallate (EGCG) are likely to prevent fat accumulating in the liver. They do this by decreasing intestinal lipid and carbohydrate absorption, decreasing adipose lipolysis and stimulating hepatic b-oxidation and thermogenesis by improving insulin sensitivity. Catechins are also likely to prevent the progression from liver steatosis to non-alcoholic steatohepatitis (NASH) and then cirrhosis, through their anti-oxidant and anti-inflammatory properties [1]. Green tea polyphenols, especially EGCG, are therefore thought to prevent development of liver cancer.
One study looked at 215 hepatocellular carcinoma (HCC) patients compared to 415 controls. Those who drank green tea for longer than 30 years were at the lowest risk. Other favourable effects reported were possible delayed entry of hepatitis B and C viruses into cells and potential effects on polymorphism of targets for anti-viral therapy [2]. Another clinical trial showed that the daily intake of six green tea polyphenol tablets containing 474 mg of polyphenols significantly reduces HAI-induced oxidative stress in HCC patients while the anti-oxidative potentials of the patients remain constant [3].
Green Tea may therefore help protect against liver cancer and is important for those at high risk.

References

1. C. Masterjohn, Bruno S. The therapeutic potential of green tea in Non-alcoholic fatty liver disease. Nutrition reviews, 2012;70(1):41-56.
2. Li Y, Chang SC, Goldstein BY et al. Green tea consumption, inflammation and the risk of primary hepatocellular carcinoma in a Chinese population Cancer Epidemiol. 2011;35(4):362-8.
3. Baba Y, Sonoda JI, Hayashi S et al. Reduction of oxidative stress in liver cancer patients by oral green tea polyphenol tablets during hepatic arterial infusion chemotherapy. Exp Ther Med. 2012;4(3):452-458.

Lycopene

Lycopene is an antioxidant pigment found in fruit such as tomatoes and watermelon and it has been studied in relation to hepatocellular carcinoma (HCC) and found to have beneficial properties.
In a human case control study of 84 cases and 375 controls, low plasma levels of lycopene were found to be a risk factor for alcohol-induced HCC [1].
During HCC, a mouse study looked at the effect of lycopene in liver cancer spreading to the lungs. It found significant inhibition of cancer cell growth in the lycopene-supplemented mice [2].
Lycopene may benefit those with liver damage.

References

1. Yu M-W, Chiu Y-H., Chiang Y-C, et al. Plasma carotenoids, glutathione S-transferase M1 andT1 genetic polymorphisms, and risk of hepatocellular carcinoma: Independent and interactive effects. Am. J. Epidemiol. 1999; 149: 621–629.
2. Chin-Shiu-Huang, Jiunn Wang Liao and Miao-Lin Hu (2008). Lycopene inhibits experimental metastasis of Human hepatoma SK-Hep-1 Cells in Athymic Mice, Journal of Nutrition;138:538-43.

Lycopene in other liver diseases

Hepatitis

In regard to cancer risk, non-alcoholic steatohepatitis (NASH) patients have been shown to have significantly reduced plasma lycopene levels [1], suggesting the potential interactions between low lycopene status and the development of liver diseases [1].
In one animal trial, tomato extract supplementation was more protective against high fat diet-induced hepatic inflammation than lycopene alone [2]. Another study showed at high risk of developing HCC following a high fat diet had lower levels of hepatic inflammation and total plasma cholesterol when they were given a tomato extract which contained lycopene [3]. In obese animals, also at risk of HCC by following a high fat diet, supplementing the diet with the lycopene metabolite Apo-10’-lycopenic acid reduced tumour formation and liver inflammation [4].
One human clinical trial examined a group at high risk of liver cancer and randomised the 24 patients to receive a mixture of phytochemicals, of which lycopene was one component. They were then compared to 46 controls. The patients were followed for 2.5 years and the cumulative incidence of liver cancer in the treated group was much lower [5].

References

1. Erhardt A., Stahl W., Sies H., Lirussi F., Donner A., Haussinger D. Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH) Eur. J. Med. Res. 2011;16:76–78.
2. Wang Y, Ausman LM, Greenberg AS et al. Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats. Int. J. Cancer. 2010; 126: 1788–1796.
3. Melendez-Martinez AJ,et al (2013). Effect of tomato extract supplementation against high-fat diet-induced hepatic lesions. Hepatobiliary Surg Nutr;2(4):198-208.
4. Ip BC,et al (2013). Lycopene metabolite, apo-10′-lycopenoic acid, inhibits diethylnitrosamine-initiated, high fat diet-promoted hepatic inflammation and tumorigenesis in mice. Cancer Prev Res (Phila);6(12):1304-16.
5. Nishion H. Phyotchemicals in hepatocellular cancer prevention. Nutr Cancer. 2009:61:789-91.

Vitamin E

Vitamin E has been studied in relation to liver disease. When the liver is diseased and bile salts are unable to reach the intestine for digestion, malabsorption of fat occurs [1]. When fat is not broken down properly, stools become pale, yellow, loose, greasy, foul smelling or frothy and floating –‘steatorrhoea’ [1]. As fat contains vitamins, including Vitamin E, patients with liver disease may become deficient in this vitamin. Patients with non-alcoholic-steatohepatitis (NASH) have been found to have reduced plasma levels of vitamin E [2].
Vitamin E is an antioxidant that protects against toxic liver injury in animals [3]. It reduces the production of tumour growth factor (TGFβ) [3,4] and reduces the activity of hepatic stellate cells [5]. Vitamin E has already been shown to improve [6] or stabilise [7] hepatic fibrosis scores in NASH.
A trial in hepatitis patients gave those in the active treatment group a daily antioxidant supplementation (vitamin E 800 mg, C 500 mg and zinc 40 mg) for six months. The supplements protected patients against the oxidative effects of the hepatitis C [8]. In 69 hepatitis B patients, serum vitamin E, as well as other antioxidants, was found to be lower in concentration and oxidative stress was found to be higher, than in 20 healthy controls [9]. In a randomised controlled trial, investigators evaluated 51 patients with alcoholic hepatitis. Twenty-five patients received daily supplementation with 1000 mg of vitamin E and 26 took a placebo for three months. Patients showed improvement in serum hyaluronic acid levels [10].

References

1. Grant JP, Chapman G, Russell MK. Malabsorption associated with surgical procedures and it’s treatment. Nutr Clin Pract 1996; 11: 43-52.
2. Erhardt A., Stahl W., Sies H., Lirussi F., Donner A., Haussinger D. Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH) Eur. J. Med. Res. 2011;16:76–78.
3. Parola M, Leonarduzzi G, Biasi F, Albano E, Biocca ME, Poli G, Dianzani MU. Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis. Hepatology. 1992;16:1014–1021.
4. Parola M, Muraca R, Dianzani I, Barrera G, Leonarduzzi G, Bendinelli P, Piccoletti R, Poli G. Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. FEBS Lett. 1992;308:267–270.
5. Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A. Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001;15:1667–1672.
6. Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003;98:2485–2490.
7. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–1685.
8. Farias MS, Budni P, Ribeiro CM et al. Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients. Gastroenterol Hepatol. 2012;35(6):386-94.
9.Tasdelen Fisgin N, Aydin BK, Sarikaya H, et al. Oxidative stress and antioxidant defense in patients with chronic hepatitis B. Clin Lab. 2012;58(3-4):273-80.
10. Mezey E, Potter JJ, Rennie-Tankersley L, Caballeria J, Pares A. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol. 2004;40:40–46.

Thiamine

Studies have found that people at risk of liver cancer are often deficient in the water-soluble B1 vitamin thiamine. One study found levels of thiamine deficiency to be similarly low in hepatitis C patients and alcohol-related cirrhosis patients [1]. Administering thiamine to patients with liver disease is standard medical practice due to the high risk of deficiency in these patients. Another study found thiamine may help treat hepatitis B, as it was found to significantly reduce the liver enzyme, aminotransferase, and reduce hepatitis B DNA to undetectable levels [2]. In vitro, the antioxidant effects of thiamine have been shown to inhibit lipid peroxidation and free radical oxidisation in liver cells [3]. In an animal study of Wilson’s disease, where copper accumulates in the liver, thiamine was found to delay the occurrence of or reduce the rate of incidence of liver cancer [4].
Thiamine is therefore an important part of holistic care for preventing and treating liver diseases.

Reference

1. Lévy S, Hervé C, Delacoux E et al. Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases. Dig Dis Sci. 2002 Mar; 47(3): 543-8.
2. Wallace AE, Weeks WB. Thiamine treatment of chronic hepatitis B infection. Am J Gastroenterol. 2001; 96(3): 864-8.
3. Lukienko PI, Mel’nichenko NG, Zverinskii IV
 et al. Antioxidant properties of thiamine. Bulletin of Experimental Biology and Medicine. 2000; 130(9): 874–876.
4. Sheline CT. Thiamine Supplementation Attenuated Hepatocellular Carcinoma in the Atp7b Mouse Model of Wilson’s Disease. Anticancer Res. Oct 2011; 31(10): 3395–3399.

For extended reading, you can download examinations of the relationship between diet, food supplements and health conditions here