Latest Research Studies – Hepatitis C

Hepatitis C is a liver disease caused by the hepatitis C virus. The virus can cause both acute and chronic hepatitis, ranging in severity from a mild illness lasting a few weeks to serious, lifelong illness. The hepatitis C virus is a blood – bone virus and the most common modes of infection are through exposure to small quantities of blood. This may happen through injection drug use, unsafe injection practices, unsafe health care, and the transfusion of unscreened blood and blood products. A significant number of those who are chronically infected will develop cirrhosis or liver cancer.

Approximately 399,000 people die each year from hepatitis C, mostly from liver cirrhosis and hepatocellular carcinoma. Antiviral medicines can cure about 95% of people with hepatitis C infection, thereby reducing the risk of death from liver cancer and cirrhosis, but access to diagnosis and treatment is low. There is no vaccinecurrently for Hepatitis C although research in this area is ongoing.

Hepatitis C virus (HCV) causes both acute and chronic infections. Acute HCV infection is usually asymptomatic, and is rarely associated with life – threatening disease. About 15 – 45% of infected persons spontaneously clear the virus within 6 months of the infection without any treatment. The remaining 60 – 80% of persons might develop chronic HCV infection. Of those with chronic HCV infection, the risk of cirrhosis of the liver lies between 15 – 30% within 20 years.

Hepatitis C is found to be present all around the world and the most affected regions include WHO Eastern Mediterranean and European Regions, with the prevalence of 2.3% and 1.5% respectively. Prevalence of HCV infection in other WHO regions varies from 0.5% to 1%. Depending on the country, Hepatitis C infection can be concentrated in certain populations and/or in general populations. It has been estimated that in 2015 itself, there were 1.75 million new HCV infections (globally, 23.7 new HCV infections per 100,000 people).

In the pursuit to fight Hepatitis C, researchers have discovered Tocotrienol  which is supposed to exhibit anti-Hepatitis C virus activities. Several studies have been conducted over Annatto based Tocotrienol (DeltaGold – Eannatto). Several studies have been conducted on Tocotrienol for its effects against Hepatitis C like, ‘Delta – Tocotrienol feeding modulates gene expression of EIF2, m TOR, protein ubiquitination through multiple – signaling pathways in chronic hepatitis C patients’ where the effects of Delta-Tocotrienol in the suppression of chronic Hepatitis C were observed.

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. 1: 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.

Study 1 – Delta – Tocotrienol feeding modulates gene expression of EIF2, m TOR, protein ubiquitination through multiple – signaling pathways in chronic hepatitis C patients.

Delta – Tocotrienol is a naturally occurring proteasome inhibitor, which has the capacity to inhibit proliferation and induce apoptosis in several cancer cells obtained from several organs of humans, and other cancer cell lines. Moreover, results of plasma total mRNAs after Delta – Tocotrienol feeding to Hepatitis C patients, revealed significant inhibition in the expression of pro – inflammatory cytokines (TNF – Alpha, VCAM1, proteasome subunits) and induction in the expression of ICAM1 and IFN – Gamma after post – treatment. This down – regulation of proteasome subunits leads to autophagy, apoptosis of immune cells and several genes. The present study describes RNA – sequence analysis of plasma total mRNAs obtained from Delta – Tocotrienol treatment of Hepatitis C patients on gene expression regulated by proteasome.

Pooled specimens of plasma total mRNAs of pre – dose versus post – dose of Delta – Tocotrienol treatment of hepatitis C patients were submitted to RNA – sequence analyses. The data based on more than 1 and 8 – fold expression changes of 2136 genes were uploaded into “Ingenuity Pathway Analyses (IPA)” for core analysis, which describes possible canonical pathways, upstream regulators, diseases and functional metabolic networks.

The IPA of “molecules” indicated fold change in gene expression of 953 molecules, which covered several of biological biomarkers. Out of these, gene expressions of 220 related to present study, 12 were up regulated, and 208 down – regulated after Delta – Tocotrienol  (DeltaGold – Eannatto)treatment. The gene expression of transcription regulators (ceramide synthase 3 and Mohawk homeobox) were up – regulated, and gene expression of 208 molecules were down – regulated, involved in several biological functions (HSP90AB1. PSMC3, CYB5R4, NDUFB1, CYP2R1, TNFRF1B, VEGFA, GPR65, PIAS1, SFPQ, GPS2, EIF3F, GTPBP8, EIF4A1, HSPA14, TLR8. TUSSC2). IPA of “casual network” indicated gene regulators (676), in which 76 down – regulated (26 s proteasomes, interleukin cytokines, and PPAR – ligand – PPA – Teinoic acid – RXRa, PPAR Gamma – ligand – PPAR Gamma – Retinoic acid – RARa, IL – 21, IL – 23) with significant P – values. The IPA of “diseases and functions” regulators (85) were involved with cAMP, STAT2, 26S proteasome, CSF1, IFN Gamma, LDL, TGFA, and microRNA – 155 – 5p, miR – 223, miR – 21 – 5p. The IPA of “upstream analysis” (934) showed 57 up – regulated (mainly 38 microRNAs) and 64 gene regulators were down – regulated (IL – 2, IL – 5, IL – 6, IL – 12, IL – 13, IL – 15, IL – 17, IL – 18, IL – 21, IL – 24, IL – 27, IL – 32), interferon Beta – 1a, interferon Gamma, TNF – Alpha, STAT2, NOX1, prostaglandin J2, NF – kB, 1kB, TCF3, and also miRNA – 15, miRNA – 15, miRNA – 124, miRNA – 218 – SP with significant activation of Z – Score (P<0.05).

This is first report describing RNA – sequence analysis of Delta – Tocotrienol (DeltaGold – Eannatto)treated plasma total mRNAs obtained from chronic hepatitis C patients, that acts via multiple – signaling pathways without any side – effects. These studies may lead to development of novel classes of drugs for treatment of chronic hepatitis C patients.

Summary

The above study was conducted on 12 Hepatitis C patients with 500 mg dose of Delta – Tocotrienol (DeltaGold – Eannatto) for 6 months.

So why Tocotrienol?

  • Antioxidants, especially Tocotrienol was observed to exhibit anti-cancer activity against breast cancer cells by lowering inflammation and oxidative stress as shown in Fig. 2.

Fig. 2: 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%.

  • Viral Load, was decreased by Delta – Tocotrienol (DeltaGold – Eannatto)
  • Infection and Progression of Hepatitis C Virus (HCV) was reduced by Delta –Tocotrienol(DeltaGold – Eannatto).
  • Cell Proliferation is the process by which immune cells copy their DNA and divide into two immune cells during mitosis and rapidly multiply into more immune cells of Hepatitis C is down regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Proliferation of mononuclear leukocytes was also down regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Free Radical Scavenging which leads to oxidation of cells is also down – regulated by Delta – Tocotrienol (DeltaGold – Eannatto) .
  • Endocrine System disorder is also down regulated by Delta Tocotrienol (DeltaGold – Eannatto).
  • Diabetes Melitus was also down – regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Monilization of Ca2+ was also down – regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Replication of Virus which lead to the spread of the disease was also down regulated by Delta – Tocotrienol(DeltaGold – Eannatto).
  • HIV infection was also down regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Replication of Influenza virus was also down regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Apoptosis or programmed cell death is the process of elimination and death of infected cells. Tocotrienol induces apoptosis in infected cells by increasing endoplasmic reticulum stress and autophagy thus helping in killing infected cells. Cell death and survival of was up regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Necrosis of malignant tumor was up regulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Gene expression was upregulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Organismal Death was upregulated by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Cancer stem cell death has been observed by the action of Tocotrienols especially Delta – Tocotrienols (DeltaGold – Eannatto). Even after chemotherapies, radiation and surgeries, there are stem cells of those cancerous tissues left revolving in your body which can lead to your cancer coming back. Henceforth, their death is very necessary and Tocotrienols have been observed to kill cancer stem cells.

Fig. 3: 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.

  • Tumor nutrition can also be obstructed by Tocotrienol as they may well work on dual antitumor mechanisms that include the removal of the vital nutrient to tumor lifeline.

Dosage

  • Under the study, 500 mg/day of Delta –Tocotrienols (DeltaGold – Eannatto) were used to treat Hepatitis C liver cells and no adverse effects were observed and the death of Hepatitis C cells and virus was witnessed.

Why Tocotrienol and Not Tocopherol?

  • Tocotrienol the unappreciated Vitamin E: Since several decades, the majority of research has been focused on alpha-tocopherol whereas only 3% of the study has been conducted on Tocotrienol. However clinical studies have significantly proven that Tocotrienols display stronger anti-oxidant, anti-inflammatory, and chemopreventive activities than Tocopherol based Vitamin E.
  • Small structure and less molecular weight: The higher anti-oxidant activity of Tocotrienols is due to their small structure and less molecular weight which assist in their integration of the cell, unlike Tocopherols.
  • Tocopherol in your food: The amount of antioxidants like Tocopherols required by your body is already present in our daily diet so we won’t get any benefit from Tocopherol supplementation.
  • Tocopherol, the enemy of Tocotrienol: Tocopherol interferes with the functioning of Tocotrienol as it attenuates cancer inhibition, inhibits absorption, reduces adipose storage, and compromises cholesterol and triglyceride reduction.
  • Tocotrienol, the protector of State: Tocotrienol has more mobility than Tocopherol due to its small structure so it can cover a larger area and target more cells.
  • Absorption: As compared to Tocopherols, Tocotrienols absorb better in the body and Tocopherols have been observed to prevent absorption of Tocotrienols.

Fig. 4: 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:

  • Tocotrienols: Latest Cancer Research in Vitamin E by Barrie Tan, Ph.D., and Anne M.Trias, MS.
  • Tocotrienols: The Promising Analogues of Vitamin E for Cancer Therapeutics

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

  • World Health Organisation: Hepatitis C

               https://www.who.int/news-room/fact-sheets/detail/hepatitis-c

  • Delta – Tocotrienol feeding modulates gene expression of EIF2, m TOR, protein ubiquitination through multiple – signaling pathways in chronic hepatitis C patients by AsafA. Qureshi, Dilshad A. Khan, ShahidMushtaq, Shui Qing Ye, Min Xiong and Nilofer Qureshi.

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