The increase in incidence of Liver cancer cases has astonished everyone. Since 1980, the incidence of liver cancer has tripled and in between 2006 and 2015, the total number of people diagnosed with Liver Cancer increased by approximately 3% annually. Moreover, men are about 3 times more prone to this disease as compared to women. This year, it has been estimated that 42,030 adults with 29,480 men and 12,550 women in the United States will be diagnosed with primary liver cancer. This data clearly suggests that men are about 3 times more likely than women to be diagnosed with the disease.

It is also estimated that 31,780 people including 21,600 men and 10,180 women will die from these disease this year. In fact, Liver cancer is the 5th most common cause of cancer death in men and in women, it is the 7th most common cause if cancer death among women. Moreover, the overall death rate has more than doubled from 1980 to 2016. Although, Liver cancer is more prominent in sub – Saharan Africa and South – East Asia. Furthermore, the general 5 – year survival rate of people suffering from Liver cancer is 18%. Elaborating on the survival rate even further, it has been found that 44% people who are diagnosed at an early stage, the 5 – year survival rate is 31%. If the cancer has spread to surrounding tissues or organs and/or the regional lymph nodes, the 5 – year survival rate is 11%. If the cancer has spread to a distant part of the body, the 5 – year survival rate is 2%. Henceforth, it can be concluded that Liver Cancer is one the deadliest cancers.

Also, a disease Non – Alcoholic fatty liver disease (NAFLD) is defined as the accumulation of excessive fat in the liver in the absence of excessive drinking of alcohol and any secondary cause. This disease can progress slowly from simple Non – Alcoholic Steatosis (NAS) to Non – Alcoholic Steatohepatitis (NASH) and subsequently to hepatitis fibrosis, cirrhosis of liver and cancer. At present, there is no specific test which can predict progression of NAS to NASH. 

Fig. 1: Stages of Liver Cancer: Liver is very intolerant towards fat. Over 5% fat as shown in the 3rd image of liver is already a very fatty liver.

DeltaGold Tocotrienol against Liver Cancer

Although, researchers have kindled some hope by discovering Annatto based Tocotrienols (DeltaGold – Eannatto) which has been observed to inhibit certain anti – cancer activities against Liver cancer like Apoptosis, Anti – Angiogenesis, Anti – Cell Proliferation, and so on. Several studies on Annatto based Tocotrienols (DeltaGold – Eannatto) have been conducted which have further showed the anti – cancer effects of DeltaGold. One study, “Gamma-Tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line” was conducted to observe the effects of Tocotrienol on liver cancer. In the study, it was observed that Tocotrienol inhibited anti-proliferative abilities against liver cancer cells.  In another study related to fatty liver, “Tocotrienols for normalization of hepatic echogenic response in nonalcoholic fatty liver: a randomized placebo – controlled clinical trial” showed hepatoprotective effects of Tocotrienols in hypercholesterolomic adults with Non – Alcoholic fatty liver disease (NAFLD).

Most research in the past 50 – 60 years has been focused on Tocopherols and 50% of all the research in last 30 years has been done on Tocotrienols in last 5 years. Half of the Tocotrienol research ever published has been published in last 10 years as shown in Fig. 1. Each day it is becoming increasingly understood that Tocotienols (especially Eannatto – DeltaGold) are the right form of Vitamin E. Well in excess of 100 studies and clinical trials have shown the surprising benefits of Tocotrienols – without any known side effects.

Fig. 2: In the graph, as you can see, R & D on Tocotrienol has increased exponentially over the years in all fields while research on Tocopherols has decreased. Whether it is cancer, Cardiovascular diseases (CVD), Diabetes, Anti – Oxidant activities or others, in all fields research on Tocotrienol has not only gained pace but quant as well.

So why Tocotrienol?

Fig. 3: In the study conducted by Dr. Qureshi, he saw that at 250 mg of Tocotrienols, the endogenous anti-oxidant, TAS (represented with grey colour) increased, while the C-reactive protein (CRP) dropped by 40%, oxidized fat (MDA) dropped by 34% and Total Anti-oxidant increased by 22%.
Fig. 4: In a study, it was observed in mice cells, that Delta – Tocotrienol inhibited the formation of blood vessels in cancer cells (Anti – Angiogenesis) while Tocopherol completely failed on such grounds. Delta-Tocotrienol was also observed to induce apoptosis in the mice cancer cells.
Fig. 5: About 1% of cancer cells are Cancer Stem Cells (CSC) which keep circulating in your body even after nailing the cancer through chemo. It has been observed that Gamma – Tocotrienol and Delta – Tocotrienol, both specifically target CSC.

Study 1 – Gamma-Tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line.

This study was conducted to determine the Anti – proliferative effects of Gamma-Tocotrienol (DeltaGold – Eannatto) treatment on differential protein expression in HepG2 cells. Under this study, HepG2 cells were treated with 70 μM Gamma-Tocotrienol (DeltaGold – Eannatto)  for 48 hours and differentially expressed protein spots were determined by two-dimensional electrophoresis (2DE), identified by MALDI-TOF mass spectrometer (MS) and validated by quantitative real-time polymerase chain reaction (qRT-PCR).

It was observed that Gamma-Tocotrienol (DeltaGold – Eannatto) treatment on HepG2 cells showed a total of 5 differentially expressed proteins which when compared to their respective untreated cells where three proteins were down – regulated and two proteins were up – regulated. One of these up – regulated proteins was identified as peroxiredoxin – 4 (Prx4) and validation by qRT – PCR however showed decreased expression of Prx4 mRNA in HepG2 cells following GTT treatment. 

Study 2 – Tocotrienols for normalization of hepatic echogenic response in nonalcoholic fatty liver: a randomized placebo – controlled clinical trial.

Non – Alcoholic fatty liver disease (NAFLD) is one of the commonest liver disorders. Obesity, oxidative stress, insulin resistance and lipid peroxidation have been identified amongst the possible hits leading to the onset and progression of this disease. Nutritional evaluation of NAFLD patients have shown a lower – than – recommended intake of Vitamin E. Vitamin E consists of 8 isoforms, 4 Tocopherols and 4 Tocotrienols, Alpha – Tocopherols have een widely investigated in liver diseases, whereas no previous clinical trial has investigated Tocotrienols for NAFLD. The objective of the study was to determine the effects of mixed Tocotrienols, in normalizing the hepatic echogenic response in hypercholerterolaemic patients with ultrasound – proven NAFLD.

87 untreated hypercholesterolaemic adults with ultrasound – proven Non – Alcoholic fatty liver disease (NAFLD) were enrolled and randomized into control group (n = 44) and Tocotrienols group (n = 43). The treatment, either mixed Tocotrienols 200 mg twice daily or placebo, had a 1 – year duration.

Normalization of hepatic echogenic response, being the trial primary aim, was used in sample size calculations. The data were assessed according to treat principle as primary outcome. Per protocol analysis was also carried out as secondary outcome measurement.

30 and 34 participants concluded the study in the Tocotrienols and placebo group respectively. Alpha – Tocopherol levels were within the normal range for all subjects. As primary outcome, the normalization of hepatic echogenic response was significantly higher for the Tocotrienols treated group compared to the placebo group in the intention of treat analysis (P = 0.039; 95% CI = 0.896 – 6.488). As secondary objective, the per protocol assessment also showed significant rate of remission (P = 0.014; 95% CI = 1.117 – 9.456). Worsening of Non – Alcoholic fatty liver disease (NAFLD) grade was recorded in two patients in the placebo group, but none in the group treated with Tocotrienols. No adverse events were reported for both groups. This was the first clinical trial that showed the hepatoprotective effects of Tocotrienols in hypercholesterolemic adults with Non – Alcoholic fatty liver disease (NAFLD).

Summary

Dosage

Why Tocotrienol and Not Tocopherol?

Fig. 6: The 2nd pie chart represents Palm Tocotrienol rich fraction with 32% Alpha – Tocopherol which was given to people and when the Alpha – Tocopherol was removed then it was represented by the 1st pie chart with 0.3% Alpha – Tocopherol which was then given to people. In the graph, the hollow bar represents the Tocotrienol with Tocopherol which reduced the concentrations of Alpha, Gamma and Delta Tocotrienol in the body but when Tocopherol was removed from the dosage (Solid grey bars in graph), the concentrations of Alpha, Gamma and Delta – Tocotrienol significantly increased.

References

https://doi.org/10.1016/j.phrs.2018.02.017

www.nutraceuticalsworld.com

https://www.ncbi.nlm.nih.gov/pubmed/25886747

https://www.cancer.net/cancer-types/liver-cancer/statistics

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877967/