Avoiding the Insidious Assassin Claiming Human Livers

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Avoiding the Insidious Assassin Claiming Human Livers
Aug 18, 2021

Silent killer – this is a title assigned to several deadly cancers including primary liver cancer. Liver cancer is the third deadliest cancer worldwide1. This silent killer has claimed many lives including that of Legendary Hong Kong actor Ng Man-tat2, Chinese musician Zhao Yingjun, Singaporean veteran wine retailer Don Tay3 and Danish author Hans Christian Andersen4 to name a few.

Who is most at-risk of primary liver cancer?

How can "fishbones" (yes, fishbones) be used to assess individual susceptibility to liver cancer?

Can TCM treasure Ganoderma Lucidum (lingzhi) guard against liver cancer?

All will be revealed as you read on!

Some Statistics - Who is Most At-Risk?

80% of global liver cancer cases occur in Asia; China alone accounts for 55% of liver cancer diagnoses5. Why does Asia have such a high incidence of liver cancer? This is because Asian countries have higher rates of hepatitis B infections5 – a highly contagious virus that causes liver inflammation. Gentlemen do take note: Incidence of primary liver cancer tends to be three to four times higher in men compared to women5,6.

Long-term survival and successful treatment is higher when liver cancer is detected early.  Unfortunately, as symptoms seldom appear until the cancer has advanced, liver cancer is often diagnosed late. Only 20% of primary liver cancer cases are diagnosed at early stages when curative treatment is possible.


Using "Fishbones" to Assess Susceptibility – How at-risk are you?

Primary liver cancer is a unique cancer because its root cause is known in over three quarters of all cases. Although the hepatitis B virus is the primary cause, primary liver cancer can be caused by numerous co-existing risk factors or risk-enhancing conditions. Awareness of the risk factors of primary liver cancer can help us better understand our own susceptibility to the cancer, allowing early adoption of preventative and surveillance efforts.

For a convenient at-a-glance depiction of the most common risk factors of liver cancer, we created an Ishikawa diagram (also known as a fishbone diagram):

Common risk factors of primary liver cancer - a fishbone diagram

The primary cause of liver cancer cases (90%) is attributed to chronic viral infection with hepatitis B or C.
  • Primary infection with hepatitis B accounts for over 75% of global liver cancer cases5; hepatitis C is a major cause of liver cancer in Western countries, Africa and Japan6.
  • Hepatitis B is transmitted from mother to new-born or via sexual transmission; Hepatitis C is transmitted from contaminated needles, injected drugs and/or blood supplies.

Obesity & Diabetes:

  • The synergism between obesity and diabetes are purported to exacerbate non-alcoholic fatty liver disease which can lead to development of liver cancer.
  • Diabetics have a 2-4 fold increased risk of liver cancer.

Chronic Liver Diseases:

Non-alcoholic fatty liver disease (NAFLD) is a term that encompasses a variety of liver conditions characterised by ≥5% of liver fat accumulation (that is not caused by excessive alcohol consumption, viral hepatitis, or other chronic liver diseases).

  • NAFLD can range from readily reversible simple steatosis to the more severe non-alcoholic steatohepatitis (NASH).
  • NASH may progress rapidly to advanced liver fibrosis/cirrhosis which increases the risk of progression to liver cancer.
  • Recent studies have revealed a concerning 35% to 50% of NAFLD cases can progress to liver cancer without cirrhosis7.

Liver Cirrhosis, regardless of cause, is a major risk factor for liver cancer and is present in 80-90% of liver cancer cases.

  • 70%-90% of HBV-related liver cancer mutates from cirrhotic livers.
  • Hepatitis C-induced liver cirrhosis increases liver cancer risk 17-fold.
  • Alcohol is considered a co-carcinogen because it induces cirrhosis which increases risk of viral infections and enhances activation of carcinogens.

Excessive alcohol intake:

  • Although alcohol does not have a carcinogenic effect per se, prolonged excessive intake is a well-established risk factor of liver cancer.
  • Excessive alcohol consumption (i.e., >50–70 g/day) leads to formation of scar tissue in the liver (cirrhosis) which is a major risk factor of liver cancer.
  • Alcohol consumption above 60g per day coupled with hepatitis C infection doubles risk of liver cancer.

Long-term anabolic steroid use:

  • A serious complication of long-term androgenic or anabolic steroid use is the development of liver tumours.
  • Tumours may be detected within two years of steroid use but are more commonly found after five to 15 years of steroid use8.

Male gender:

  • Men are approximately 3 times more at risk of developing liver cancer; Men in the Asia-Pacific region have a 4-fold risk.
  • Added exposure to other risk factors (e.g. alcohol, smoking, obesity) are suspected to contribute to this gender-related incidence5.

Inherited conditions:

  • Inherited genetic and metabolic disorders (e.g. hemochromatosis, Wilson's disease) can cause liver damage and trigger early liver cirrhosis which increases risk of liver cancer9,10.

Aflatoxin consumption:

  • Aflatoxin is a poisonous hepatocarcinogenic substance produced in a weedy mould that affects certain crops grown in humid areas e.g. peanuts, grains, corn, cassava, and soy beans.
  • Aflatoxins are believed to induce DNA mutations – such as in tumour suppressor gene p53 – downregulation of p53 gene is present in 30-60% of primary liver cancer cases in Asia5,6.

Exposure to environmental carcinogens:

  • Individuals who have been exposed to certain environmental carcinogenic chemicals have moderately high risk of primary liver cancer.
  • Some chemicals that have known associations with liver cancer include arsenic, vinyl chloride, organic solvents and hydrocarbons (e.g. trichloroethylene, tetrachloroethylene, polychlorinated biphenyls), certain pesticides (e.g. DDT – an insecticide that has been banned in many developed countries)11.

Lingzhi and Liver Cancer

Noteworthily, numerous studies have been conducted on the natural cancer-preventing effects of Ganoderma Lucidum. Scientists have revealed that Ganoderma Lucidum triterpenoids suppresses cancer cell growth and trigger apoptosis of cancer cells – an upcoming potential therapy or complement to conventional chemotherapy agents12–15.

An In Vitro Study on Ganoderma Lucidum Spores Oil and Human Liver Cancer Cells

Effect of Ganoderma Lucidum (lingzhi) Spores oil on migration ability of human hepatocelluar carcinoma (HepG2) cells

An informative study conducted an in vitro test to investigate how Ganoderma Lucidum Spores Oil affects proliferation of human HepG2 hepatoma cells16. Scientists treated human HepG2 (liver cancer) cells with different concentrations of Ganoderma Lucidum Spores Oil for 24 and 48 hours. Their main findings:

  • Ganoderma Lucidum Spores Oil inhibited proliferation of HepG2 cells in a dose-dependent manner.
  • Different concentrations of Spores Oil prevented infiltration and migration ability of HepG2 cells – higher concentrations of Spores oil had higher inhibition effects.
  • Ganoderma Lucidum Spores oil induced apoptosis of HepG2 cells.

Altogether these in vitro findings suggests that Ganoderma Lucidum Spores Oil can regulate expression of apoptosis-inducing genes in hepatocellular carcinoma cells – which inhibits proliferation and promotes apoptosis of liver cancer cells16.

Treating Human Liver Cancer cells with Ergosterol Peroxide

Ganoderma Lucidum is rich in triterpenoids, containing over 150 types of triterpenoids – scientists have found over 50 triterpenoids that exclusive to the fungus17. Ergosterol peroxide is a bioactive compound naturally found within Ganoderma Lucidum Spores Oil. This compound has been shown to inhibit tumour growth by cutting off blood supply to the tumour and triggering cancer cell death.

In another study, ergosterol peroxide was tested to induce cell death, reduce cell progression and growth, and inhibit cell migration and survival of human liver cancer cells18. Similar to the in vitro study above, the underlying anti-tumour mechanisms of ergosterol peroxide was attributed to its ability to regulate important genes associated with tumour growth and cancer cell death18.

  • Ganoderma Lucidum Spores Oil is extracted from Ganoderma Lucidum Spores Powder using Supercritical CO2 extraction.
  • It takes 1 kilogram of Spores Powder to produce less than 50 grams of Spores Oil.
  • This highly concentrated oil is 70 times more effective than Spores Powder.
  • Premium quality Ganoderma Lucidum Spores Oil should contain over 25% of triterpenoids per 100g of Spores Oil.

The Big Question

Can we avoid the insidious assassin that claims human livers and lives? Be aware, prevent early, screen accordingly.

  1. World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Published 2021.
  2. Siu P. Legendary Hong Kong actor Ng Man-tat dies of liver cancer at 70. South China Morning Post. https://www.scmp.com/news/hong-kong/society/article/3123442/legendary-hong-kong-actor-ng-man-tat-dies-liver-cancer-70. Published February 27, 2021.
  3. Quek E. Bacchus owner was “nicest wine merchant in Singapore.” The Straits Times. https://www.straitstimes.com/life/food/bacchus-owner-was-nicest-wine-merchant-in-singapore. Published July 14, 2021.
  4. Biography.com Editors. Hans Christian Andersen Biography. A&E Television Networks. https://www.biography.com/writer/hans-christian-andersen. Published 2020.
  5. Boyle DA. Hepatocellular carcinoma: Implications for Asia-Pacific Oncology Nurses. Asia-Pacific J Oncol Nurs. 2017;4(2):98. doi:10.4103/2347-5625.204497
  6. Zhu RX, Seto W-K, Lai C-L, Yuen M-F. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region. Gut Liver. 2016;10(3). doi:10.5009/gnl15257
  7. Perumpail BJ, Khan MA, Yoo ER, Cholankeril G, Kim D, Ahmed A. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(47):8263-8276. doi:10.3748/wjg.v23.i47.8263
  8. Bethesda (MD). LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.ncbi.nlm.nih.gov/books/NBK548931/. Published 2020.
  9. Scorza M, Elce A, Zarrilli F, Liguori R, Amato F, Castaldo G. Genetic Diseases That Predispose to Early Liver Cirrhosis. Int J Hepatol. 2014;2014:1-11. doi:10.1155/2014/713754
  10. Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: A study in the SEER-medicare database. Hepatology. 2011;54(2):463-471. doi:10.1002/hep.24397
  11. Uccello M, Malaguarnera G, Corriere T, Biondi A, Basile F, Malaguarnera M. Risk of Hepatocellular Carcinoma in Workers Exposed to Chemicals. Hepat Mon. 2012;12(10). doi:10.5812/hepatmon.5943
  12. Patlolla J, Rao C. Triterpenoids for Cancer Prevention and Treatment: Current Status and Future Prospects. Curr Pharm Biotechnol. 2012;13(1):147-155. doi:10.2174/138920112798868719
  13. Y. Radwan FF. Apoptotic and Immune Restoration Effects of Ganoderic Acids Define a New Prospective for Complementary Treatment of Cancer. J Clin Cell Immunol. 2012;01(S3). doi:10.4172/2155-9899.S3-004
  14. Li X, Xie Y, Yang BB. Characterizing novel anti-oncogenic triterpenoids from ganoderma. Cell Cycle. 2018;17(5):527-528. doi:10.1080/15384101.2017.1315493
  15. Cao F-R, Feng L, Ye L-H, et al. Ganoderic Acid A Metabolites and Their Metabolic Kinetics. Front Pharmacol. 2017;8. doi:10.3389/fphar.2017.00101
  16. SUN L, HUA C, HOU Y. Effect of glossy ganoderma spore oil on human hepatoma cell line HepG2. J Pract Oncol. 2011;(2):128-133. https://en.cnki.com.cn/Article_en/CJFDTotal-SYZZ201102010.htm.
  17. Wachtel-Galor S, Yuen J, Buswell JA, Benzie IFF. Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom. In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. Boca Raton (FL): CRC Press/Taylor & Francis; 2011.
  18. Li X, Wu Q, Bu M, et al. Ergosterol peroxide activates Foxo3-mediated cell death signaling by inhibiting AKT and c-Myc in human hepatocellular carcinoma cells. Oncotarget. 2016;7(23):33948-33959. doi:10.18632/oncotarget.8608

Disclaimer: This article is intended for educational enlightenment and is not designed to diagnose, treat, or cure. Every individual is unique – if you have any health concerns, do discuss them with a medical or health professional.

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