The Study – Non Alcoholic Fatty Liver Disease (NAFLD)

Non – Alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic disease worldwide. It won’t be wrong to say that right now, there is a worldwide epidemic of Non – Alcoholic fatty liver disease (NAFLD). Asia is itself a very large, heterogeneous area with substantial variation in socioeconomic status and prevalence obesity. Non – Alcoholic fatty liver disease (NAFLD) prevalence in Asia is increasing and is associated with poor outcomes including hepatocellular carcinoma and death. Speaking of the western world, 20 – 30% of the general population in the western world suffer from Non – Alcoholic fatty liver disease (NAFLD). The prevalence is increased in Type – 2 diabetes mellitus which is around 70% and morbid obesity is around 90%. This correlates with the rising incidence of obesity and metabolic syndrome in the western world.

In the USA, the National Health and Nutrition Examination Surveys from 2009 – 2010 showed obesity rates of 35.5% among men and 35.8% among women while in Asia, similar prevalence of Non – Alcoholic fatty liver disease (NAFLD) has been found in the range of 15% to 30% in the general population and over 50% in patients with diabetes and metabolic syndrome. In the general population of US, the prevalence of NASH is about 3% but could be more than 25% in obese individuals.

Non – Alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the western world. 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 hepatoma. 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.

In the pursuit to fight Non – Alcoholic fatty liver disease (NAFLD), researchers have discovered Tocotrienol  which is supposed to exhibit anti – NAFLD activities. Several studies have been conducted over Annatto based Tocotrienol (DeltaGold – Eannatto).  Several studies have been conducted on Tocotrienol for its effects againstNon – Alcoholic fatty liver disease (NAFLD) like “Tocotrienols for normalization of hepatic echogenic response in nonalcoholic fatty liver: a randomized placebo – controlled clinical trial” in which 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.

Study 1 – 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 – provenNon – 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 withNon – Alcoholic fatty liver disease (NAFLD).

Study 2

Non – Alcoholic Fatty Liver Disease happens when there is too much fat stored in the liver cells which is usually caused by wrong dieting habits. Nonalcoholic steatohepatitis (NASH) is more serious form of the disease indicated by liver inflammation and fibrosis. NASH can turn to cirrhosis and liver failure.

A randomized, double – blind, placebo – controlled study was conducted in 71 patients having ultrasound – proven fatty liver disease. They were given either 300 mg of Tocotrienols twice a day or a placebo for 12 weeks. After 12 weeks, Tocotrienols showed a greater effect than the placebo by enhancing liver function. Significant improvements were also shown in stress reduction related to the liver. CRP and MDA – both markers of inflammation and fat oxidation – decreased by 18% and 14% after three months, respectively. Tocotrienols were considered a safe natural aid for excess inflammation and free radicals in patients with NAFLD.

In addition, a significant decrease of fat in the blood showed reduced inflammation that was consistent with the results of previous clinical trials conducted with DeltaGold for people with an excess of cholesterol in their blood and liver, The fatty liver index score (a measure of fat in liver storage) decreased by 11%.

What made this study even more remarkable, especially for the patients, is that the Tocotrienol – supplemented group lost an average of 9.7 pounds, with a resultant decrease in BMI and waistline. What this means for you is that when your liver is less “fatty”, it can better filter out the (environmental) toxins in your body and break down fats and make proteins, allowing it to more efficiently and effectively perform its over five hundred biological functions. With a better functioning liver your overall health will improve.

Summary

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. 3.

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%.

  • Weight loss was observed by the action of Delta – Tocotrienol (DeltaGold – Eannatto). A loss of 9.7 lbs in weight was observed in the patients suffering from diabetes and Non – Alcoholic Fatty Liver Disease.
  • Body Mass Index (BMI) was made better by the effect of Delta – Tocotrienol (DeltaGold – Eannatto). Like BMI from 30.7 was bought to the value 29.9 in 3 months.
  • Triglycerides were reduced by the effect of Delta – Tocotrienol (DeltaGold – Eannatto)by a whopping 9.9% in just 3 months!
  • Liver Enzymes like Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) were lowered by 15.6% and 14.6% respectively by the action of Delta – Tocotrienol (DeltaGold – Eannatto). Lowering of ALT and AST is very necessary for the treatment ofNon – Alcoholic Fatty Liver Disease.
  • C – Reactive Protein (hsCRP) was oxidizedand lowered by 18% in 3 months by Delta – Tocotrienol (DeltaGold – Eannatto)which is also very necessary for the treatment of Non – Alcoholic Fatty Liver Disease.
  • MDA was also reduced by 14.3% in 3 months by Delta – Tocotrienol (DeltaGold – Eannatto).
  • Fatty liver index was also reduced by a whopping 11.1% by Delta – Tocotrienol (DeltaGold – Eannatto)which was the most spectacular feature of DeltaGold during the treatment of the diseases.
  • Angiogenesis which is the process of formation of blood vessels in cancer cells like in the case of liver cancer when NAFLD reaches its extreme stage is suppressed by Delta – Tocotrienol (DeltaGold – Eannatto).

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.

  • Apoptosis is the programmed cell death which leads to the death of liver cancer cells. Delta – Tocotrienol (DeltaGold – Eannatto)induces apoptosis in liver cancer cells by increasing endoplasmic reticulum stress and autophagy thus helping in killing cancer cells.
  • Cell Proliferation is the process by which cancer cells copy their DNA and divide into more cancer cells during mitosis thus lead to spreading cancer. According to several kinds of research, it has been observed Delta – Tocotrienol (DeltaGold – Eannatto). suppress the proliferation of liver cancer cells.
  • Anti-Tumor effects on breast cancer have been observed by all kinds of Tocotrienols isoforms.
  • Annatto-Tocotrienol which comprises of 90% of Delta-Tocotrienol and 10% of Gamma-Tocotrienol reportedly delayed the development of mammary tumor and reduced the number and size of the tumor via enhancing both apoptosis and senescent-like growth arrest in transgenic mice.
  • 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 thus preventing further damage to liver again.

Fig. 4: 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.

Dosage

  • In the studies it was observed that 150 mg of Delta – Tocotrienols (DeltaGold – Eannatto) was optimum for a normal person while those suffering from Non – Alcoholic Fatty Liver Disease (NAFLD) were given 250 – 300 mg twice a day which makes around 500 – 600 mg per day.
  • Substances that complement Tocotrienol for Non – Alcoholic Fatty Liver Disease (NAFLD)includeCoQ10, Omega – 3, Methionine, Glutathione.

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. 5: 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: The Promising Analogues of Vitamin Efor Cancer Therapeutics

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

  • Annato: Delivering Tocotrienols from Amazonia, by Barrie Tan, Founder, &Anne Trias, Product Director

www.nutraceuticalsworld.com

  • Tocotrienols for normalization of hepatic echogenic response in nonalcoholic fatty liver: a randomized placebo – controlled clinical trial by Enrico Magosso, MukhtarAlam Ansari, YogheshwaranGopalan, Ibrahim LutfiShuaib, Jia – Woei Wong, Nurzalina Abdul Karim Khan, Mohamed Rizal Abu Bakar, Bee – Hong Ng, and Kah – Hay Yuen.

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

  • The Lancet: Gastroenterology and Hepatology
  • Prevalence, incidence, and outcome of non – alcoholic fatty liver disease in Asia, 1999 – 2019: A systematic review and meta – analysis.

https://www.thelancet.com/journals/langas/article/PIIS2468-1253(19)30039-1/fulltext

  • The Truth About Vitamin E: The Secret to Thriving with Annatto Tocotrienols by Dr. Barrie Tan.

Note:

1.       To read studies in detail, follow the references and links given.

2.     The dosages given must not be taken as the advice of a medical practitioner. Consult your physician for the optimum dosage to be consumed.

Search

Latest