Vitamin E Tocotrienol Supplement Delays Progression of Advanced Liver Disease

13/02/2012 21:41:00

COLUMBUS, Ohio – New research conducted at The Ohio State University’s Wexner Medical Center suggests an alternate form of natural vitamin E delays the progression of disease in patients awaiting liver transplantation, the only definitive therapy that reduces a patient’s morbidity, mortality and improves their quality of life.

The study shows, for the first time, successful delivery of the vitamin – administered orally – to vital human organs such as the brain, heart, liver, skin and fatty tissue.
Researchers at Ohio State’s Wexner Medical Center initially sought to measure levels of vitamin E tocopherol (TCP) and vitamin E tocotrienol (TE) in tissue and vital organs of patients with end stage liver disease. The data displayed a significant increase in TE levels in the bloodstream and tissue of study participants who received daily oral supplements of TE.

“This work is the first to show oral supplements of tocotrienol are being transported to the vital organs of patients,” says Chandan K. Sen, associate dean for translational and applied research in The Ohio State University College of Medicine. “This is exciting evidence for patients at high risk for stroke because our previous work identified low levels of TE to be protective against stroke-induced damage to the brain. Findings of this current research are equally excited for patients on the liver transplant list as it increases their chances of receiving a new liver, and therefore survival.”

Earlier research published by Dr. Sen and colleagues at Ohio State’s Medical Center proved tocotrienol a safe and neuroprotective nutrient, which minimizes stroke-related damage to the brain. “We also showed in previous studies that TE can be part of a regular diet and keeps the brain enriched and better prepared to defend itself,” added Sen, also vice chair for research in Ohio State's Department of Surgery.
For this recent study, published in the February issue of Journal of Nutrition, researchers studied blood and tissue samples from 80 participants. One cohort involved healthy patients who received oral TE or TCP supplements. Vitamin E levels found in tissue were measured in healthy participants after 12 weeks of receiving oral supplementation. Healthy adult participants were selected for this study because they could receive oral supplements for a designated period of time, whereas the other cohort was bound by surgery schedules.
In another cohort, adult surgical patients were randomized and received daily oral supplements of either TE or TCP. Concentration levels of both vitamin E sources were measured in vital organs, including: cardiac muscle from heart transplant patients with end stage heart failure; liver from transplant patients with end stage liver disease; abdominal fatty tissue from morbidly obese patients undergoing reconstructive plastic surgery; and brain tissue from epileptic patients.

The results showed oral supplementation of tocotrienol significantly increased the levels of the nutrient found in blood, skin, fatty tissue, the brain, cardiac muscle and the liver. Tocotrienol was delivered to the human brains of study participants at levels found to be neuroprotective in earlier stroke-related research.

Oral administration of tocotrienol also lowered the model for end stage liver disease (MELD) score in 50 percent of the patients who received TE supplements, while only 20 percent of patients who received TCP supplements experienced a reduction in their MELD score. MELD score refers to a clinical scoring system used to determine the severity of chronic liver disease and assess the priority and need for liver transplant allocation.

The tocotrienol form of vitamin E is available as a nutritional supplement in American supermarkets. One of the richest and healthiest food sources for TE is palm oil, which contains an abundance of the nutrient. It contains zero tans fat content and is also a popular component of a typical Southeast Asian diet. Other foods containing TE include rice, bran, oat, barley, and wheat germ.

Sen says he and colleagues are planning a much larger Phase II clinical trial testing the safety and effectiveness of tocotrienol against stroke and end stage liver disease in humans.

Along with Sen, other Ohio State researchers involved in the study were Viren Patel, Cameron Rink, Gayle M.Gordillo, Savita Khanna, Urmila Gnyawali, Sashwati Roy, Bassel Shneker, Kasturi Ganesh, Gary Phillips, J. Layne Moore, Atom Sarkar, Robert Kirkpatrick, Elmahdi A. Elkhammas, Emily Klatte, Michael Miller, Michael S. Firstenberg and E. Antonio Chiocca. Kalanithi Nesaretnam, from the Malaysian Palm Oil Board’s Food Technology and Nutrition Unit, also participated in the research.

The research was supported by a grant awarded by the National Institutes of Health. In addition, the Malaysian Palm Oil Board – an institution of Government of Malaysia – funded the study.

Source

Vitamin E Tocotrienol Supplement Delays Progression of Advanced Liver Disease

By Staff Editor
Feb 13, 2012 - 2:00:01 PM

(HealthNewsDigest.com) - COLUMBUS, Ohio – New research conducted at The Ohio State University’s Wexner Medical Center suggests an alternate form of natural vitamin E delays the progression of disease in patients awaiting liver transplantation, the only definitive therapy that reduces a patient’s morbidity, mortality and improves their quality of life. The study shows, for the first time, successful delivery of the vitamin – administered orally – to vital human organs such as the brain, heart, liver, skin and fatty tissue.

Researchers at Ohio State’s Wexner Medical Center initially sought to measure levels of vitamin E tocopherol (TCP) and vitamin E tocotrienol (TE) in tissue and vital organs of patients with end stage liver disease. The data displayed a significant increase in TE levels in the bloodstream and tissue of study participants who received daily oral supplements of TE.

“This work is the first to show oral supplements of tocotrienol are being transported to the vital organs of patients,” says Chandan K. Sen, associate dean for translational and applied research in The Ohio State University College of Medicine. “This is exciting evidence for patients at high risk for stroke because our previous work identified low levels of TE to be protective against stroke-induced damage to the brain. Findings of this current research are equally excited for patients on the liver transplant list as it increases their chances of receiving a new liver, and therefore survival.”

Earlier research published by Dr. Sen and colleagues at Ohio State’s Medical Center proved tocotrienol a safe and neuroprotective nutrient, which minimizes stroke-related damage to the brain. “We also showed in previous studies that TE can be part of a regular diet and keeps the brain enriched and better prepared to defend itself,” added Sen, also vice chair for research in Ohio State's Department of Surgery.

For this recent study, published in the February issue of Journal of Nutrition, researchers studied blood and tissue samples from 80 participants. One cohort involved healthy patients who received oral TE or TCP supplements. Vitamin E levels found in tissue were measured in healthy participants after 12 weeks of receiving oral supplementation. Healthy adult participants were selected for this study because they could receive oral supplements for a designated period of time, whereas the other cohort was bound by surgery schedules.

In another cohort, adult surgical patients were randomized and received daily oral supplements of either TE or TCP. Concentration levels of both vitamin E sources were measured in vital organs, including: cardiac muscle from heart transplant patients with end stage heart failure; liver from transplant patients with end stage liver disease; abdominal fatty tissue from morbidly obese patients undergoing reconstructive plastic surgery; and brain tissue from epileptic patients.

The results showed oral supplementation of tocotrienol significantly increased the levels of the nutrient found in blood, skin, fatty tissue, the brain, cardiac muscle and the liver. Tocotrienol was delivered to the human brains of study participants at levels found to be neuroprotective in earlier stroke-related research.

Oral administration of tocotrienol also lowered the model for end stage liver disease (MELD) score in 50 percent of the patients who received TE supplements, while only 20 percent of patients who received TCP supplements experienced a reduction in their MELD score. MELD score refers to a clinical scoring system used to determine the severity of chronic liver disease and assess the priority and need for liver transplant allocation.

The tocotrienol form of vitamin E is available as a nutritional supplement in American supermarkets. One of the richest and healthiest food sources for TE is palm oil, which contains an abundance of the nutrient. It contains zero tans fat content and is also a popular component of a typical Southeast Asian diet. Other foods containing TE include rice, bran, oat, barley, and wheat germ.

Sen says he and colleagues are planning a much larger Phase II clinical trial testing the safety and effectiveness of tocotrienol against stroke and end stage liver disease in humans.

Along with Sen, other Ohio State researchers involved in the study were Viren Patel, Cameron Rink, Gayle M.Gordillo, Savita Khanna, Urmila Gnyawali, Sashwati Roy, Bassel Shneker, Kasturi Ganesh, Gary Phillips, J. Layne Moore, Atom Sarkar, Robert Kirkpatrick, Elmahdi A. Elkhammas, Emily Klatte, Michael Miller, Michael S. Firstenberg and E. Antonio Chiocca. Kalanithi Nesaretnam, from the Malaysian Palm Oil Board’s Food Technology and Nutrition Unit, also participated in the research.

The research was supported by a grant awarded by the National Institutes of Health. In addition, the Malaysian Palm Oil Board – an institution of Government of Malaysia – funded the study.

Source

Milk thistle, vitamin E and fish oil fats can prevent and reverse fatty liver disease

Friday, November 19, 2010 by: John Phillip, citizen journalist

(NaturalNews) As many as 1 in 3 Americans are living with a ticking bomb known as nonalcoholic fatty liver disease (NAFLD). The condition is virtually symptomless until the liver becomes inflamed or scarred from decades of dietary abuse. The vast majority of NAFLD is caused by poor dietary choices that increase dangerous blood fat levels. As a consequence, fat is deposited in the liver cells where it triggers inflammation and the release of chemical messengers known as adipokines as the liver attempts to repair itself. Left unchecked, NAFLD can progress to cirrhosis and liver failure. Emerging research provides powerful nutritional options that can dramatically lower the risk of developing fatty liver disease.

Understanding the Cause of Nonalcoholic Fatty Liver Disease

Many chronic conditions are known to initiate and progress due to inflammation within our body, and fatty liver disease is no exception. The liver is responsible for metabolizing cholesterol and influences how fat is either burned for energy or stored for future use. An increasing burden is placed on the organ as we eat excess calories from sugar, refined carbohydrates and hydrogenated fats. Fat metabolism is disrupted as high levels of blood fats become stored in the liver. Eventually this leads to a decline in liver function and finally to total organ failure and death.

Study Supports the Antioxidant Power of Vitamin E

Natural nutrients that are known to exert strong antioxidant and anti-inflammatory properties have proven more effective than any pharmaceutical in the prevention and treatment of NAFLD. Researchers from the Virginia Commonwealth University Medical Center compared the effect of vitamin E and the drug Actos on lowering liver enzymes that are associated with advancement of liver disease. They found that the insulin-sensitizing drug had no effect while vitamin E (800 IU per day) was shown to provide significantly lowered enzyme markers and to improve scarring.

Fish Oil Fatty Acids Improve Blood Lipids, Improve Liver Function

EPA and DHA Omega-3 fats have gained notoriety for their ability to positively regulate cholesterol ratios and lower triglycerides. Research published in the British Medical Journal found that supplementing with 1,000 mg of Omega-3 fats per day markedly decreased serum markers of liver cell damage, triglyceride levels and glucose. Any natural therapy that helps the body eliminate triglycerides and lower blood sugar levels will lower the underlying risk factors for NAFLD.

Milk Thistle Shown to Directly Target the Liver

The active compound in milk thistle, known as silymarin, is a potent antioxidant and anti-inflammatory agent that directly impacts liver function. Researchers have discovered that milk thistle inhibits the release of cytokines from the liver that normally increases with fatty liver inflammation. This action allows the liver to begin the natural healing process while reducing fat accumulation and reducing blood markers associated with liver damage.

Vitamin E, Omega-3 fats and milk thistle each help to restore normal liver function for the millions of men, women and children that suffer the silent effects of fatty liver disease. Including all three of these powerful natural nutrients in your daily disease-fighting arsenal will provide a multi-modal defense against NAFLD.

Article References:
http://pmj.bmj.com/content/82/967/3...
http://www.nature.com/ajg/journal/v...
http://hepatmon.com/view/?id=425

About the author

John Phillip is a Health Researcher and Author who writes regularly on the cutting edge use of diet, lifestyle modifications and targeted supplementation to enhance and improve the quality and length of life. John is the author of 'Your Healthy Weight Loss Plan', a comprehensive EBook explaining how to use Diet, Exercise, Mind and Targeted Supplementation to achieve your weight loss goal. Visit My Optimal Health Resource to continue reading the latest health news updates, and to download your Free 48 page copy of 'Your Healthy Weight Loss Plan'.

Source

Metformin, Vitamin E Do Not Significantly Improve NAFLD in Children

Bob Roehr

November 4, 2010 (Boston, Massachusetts) — The first randomized controlled trial to use histology as a measure for treating nonalcoholic fatty liver disease (NAFLD) in children has found that neither metformin nor vitamin E provide a statistically significant sustained reduction in alanine transaminase (ALT) levels, the primary end point of the study, compared with placebo.

Results of the TONIC study by the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network, presented here at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting, by Joel Lavine, MD, from the Department of Gastroenterology, Hepatology, and Nutrition at Columbia University in New York City, "reinforce the PIVENS [trial] findings in adults with NASH."

The rise of childhood obesity has helped make NAFLD the most common cause of chronic liver disease in American children. "NASH-related cirrhosis has been described in children as early as 7 years," and it is also a risk factor for metabolic syndrome, Dr. Lavine said. There is no established pharmacologic treatment for NAFLD or NASH in children, in part because no pediatric study of liver disease has ever used histology as an end point.

The researchers enrolled 173 children 8 to 17 years of age with biopsy-confirmed NAFLD and elevated serum alanine aminotransferase (ALT > 60 U/L). Diabetes, cirrhosis, significant alcohol use, ALT above 400 U/L, and a recent pharmaceutical course of therapy for fatty liver disease were exclusionary factors. Most of the 229 children screened but not enrolled had insufficiently high ALT levels to meet the entry criteria.

Patients were randomized in a 1:1:1 manner to receive 400 IU of the natural form of vitamin E twice a day (58 subjects), 500 mg of metformin in gel capsules twice a day (57 subjects), or placebo (58 subjects) for 96 weeks, with 24 weeks of follow-up to ascertain durability. They also were counseled on diet and lifestyle changes to improve their health.

The primary end point was a sustained reduction in ALT to either below 40 IU/L or below 50% from baseline ALT from weeks 48 to 96. In light of the 2 separate interventions being evaluated in the study, the floor for statistical significance was established as P < .025.

Dr. Lavine said that "ALT [levels] decreased in all 3 groups," primarily because of changes in diet and exercise. The vitamin E group showed an early (week 24) statistically significant sharp decline in ALT levels, "but by the time 96 weeks came around, they all converged, to a decline of about 40 IU/L."

There was a sustained 25.9% reduction in serum ALT levels in the vitamin E group, a 15.8% reduction in the metformin group, and a 17.2% reduction in the placebo group. The decline seen with vitamin E, compared with placebo, was just shy of significance (P = .26); with metformin, the significance was more distant (P = .83).

There were statistically significant improvements in hepatocellular ballooning: 44%, 44%, and 21% in the vitamin E, metformin, and placebo groups, respectively. Improvement was also seen in patients with NASH or borderline NASH at baseline: 58% in the vitamin E group and 28% in the placebo group (P = .006). There was no significant impact on fibrosis or inflammation with either intervention.

"There also was no change in insulin resistance, which was somewhat surprising in light of the fact that metformin is used to treat type 2 diabetes in children," said Dr. Lavine.

Diet and activity questionnaires were administered at baseline and at weeks 48 and 96. Analysis of the way changes in these parameters affected metabolic responses will be published in the future.

One audience member noted the significant improvement on all measures in the placebo group, and wondered if that might not mask some of the contributions of vitamin E and metformin.

Dr. Lavine would not speculate on that. He added: "I think that lifestyle advice works in the context of having frequent follow-up and the amount of attention these children received, and the investment by their families in making considerable changes in terms of the type of foods they were eating and activities they pursued." But such an intense intervention probably is not possible to implement on a broader population basis.

Ronald J. Sokol, MD, from the University of Colorado in Aurora, praised the study for its completeness. He was surprised by the ALT data that showed a convergence of all 3 groups at the end of the study. He wondered if there are follow-on data.

Dr. Lavine responded that "this is not a durable response. ALT will rise again once vitamin E and placebo are discontinued, but it doesn't rise back to its baseline. That is probably because of the adoption and maintenance of lifestyle changes."

The study was totally supported by the National Institutes of Health. Dr. Lavine has disclosed no relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract 110. Presented November 1, 2010.

Source

Also See: AASLD: Vitamin E Resolves NASH in Children

AASLD: Vitamin E Resolves NASH in Children

By Kristina Fiore , Staff Writer, MedPage Today
Published: November 02, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

BOSTON -- Vitamin E may help resolve nonalcoholic steatohepatitis (NASH) in children -- although it won't lower alanine aminotransferase (ALT) levels, researchers reported here.

Although the 96-week randomized trial involving nearly 200 children missed its primary endpoint of lowering ALT, only vitamin E -- compared with metformin and placebo -- had significant effects on several histologic parameters, according to Joel Lavine, MD, of Columbia University, and colleagues.

"Vitamin E use should be supported for children with NASH," Lavine said during an oral presentation at the annual meeting of the American Association for the Study of Liver Diseases.

Similar findings were reported for adults last April, in which the PIVENS trial, published in the New England Journal of Medicine, found vitamin E significantly improved a composite of four histological features of NASH compared with placebo.

In that trial, pioglitazone (Actos) also improved these histologic features, but not significantly compared with placebo.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in American children, yet no pharmacologic therapy has yet been established.

So the researchers conducted a randomized, placebo-controlled trial among 173 children (ages 8 to 17) from eight centers in the NASH Clinical Research Network to see whether vitamin E or metformin would mitigate fatty liver disease.

The kids were randomized to 500 mg of metformin twice a day, 400 IU of vitamin E twice a day, or placebo. The mean age was 13, boys made up the majority of the population (80%); they were largely Hispanic and most were obese with a body mass index (BMI) in the 33 to 34 range, Lavine said.

They had biopsy-confirmed NAFLD, as well as an ALT over 60 at baseline. Those with diabetes, cirrhosis, or significant alcohol use were excluded.

All of the children in the trial were also given standard care, including advice on lifestyle modification.

Children had regular clinic visits during the 96-week trial, and were followed for an additional 24 weeks to assess treatment durability.

The primary endpoint was reduction in ALT, while the secondary endpoints looked at histological changes.

The researchers found that ALT decreased in all three groups -- most likely because they were all receiving the standard of care, which is education on diet and exercise, Lavine said.

There was a more rapid decline in those levels for children on vitamin E, but the data converged by the end of the trial (25.9% achieved a reduction with vitamin E, 15.8% with metformin, and 17.2% with placebo).

The results did not change after controlling for factors such as age, gender, and ethnicity, Lavine said.

Yet when the researchers looked at histological factors, they found that both vitamin E and metformin improved hepatocellular ballooning compared with placebo (44% and 44% versus 21%, P=0.006).

But only vitamin E significantly improved NAFLD scores compared with placebo (P=0.02).

In the subset of children with NASH at baseline, vitamin E significantly increased resolution of NASH on the 96 week liver biopsy compared with placebo (58% vs 28% P=0.006).

However, neither vitamin E nor metformin improved liver fibrosis, lobular formation, or portal inflammation scores.

There were equal changes in body weight across groups, with the children gaining a mean 13 kg (28.6 lbs) over the 96 weeks of the study -- despite the exercise and diet advice provided.

Lavine and colleagues concluded that while neither vitamin E nor metformin was superior to placebo for sustained ALT reduction, vitamin E improved several histologic markers for children with NASH.

He added that further work needs to be done with regard to the effects of the exercise and dietary intervention used in the trial.

Lavine concluded that the results "reinforce the PIVENS findings that vitamin E improved NASH in adults."

Arun Sanyal, MD, of Virginia Commonwealth University Medical Center in Richmond and president of the AASLD, said that fatty liver disease "is a very scary disease in children," since it is also an emerging risk factor for diabetes and coronary artery disease.

Sanyal, who was also an investigator in the adult PIVENS trial, said the improvement in steatohepatitis seen with vitamin E "is a small step forward in a very important area."

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, as well as the National Institute of Child Health & Human Development.

Vitamin E was provided by Pharmavite.

The researchers reported no conflicts of interest.

Primary source: American Association for the Study of Liver Disease

Source reference:
Lavine JE, et al "Vitamin E, metformin, or placebo treatment of nonalcoholic fatty liver disease in children" AASLD 2010; Abstract 110.

Source

Integrative Medicine: Weight loss and vitamin E two liver-disease fighters

Published: Sunday, Jul. 11, 2010 - 12:00 am

Liver disease is a huge problem worldwide, and one of the contributors is the epidemic of obesity. Persistent obesity often leads to fat deposits and inflammation in the liver, and unchecked inflammation ultimately produces scarring and even cirrhosis.

Perhaps you've thought of cirrhosis of the liver as a drinker's disease; in fact, obesity is now a common cause of cirrhosis. More than 20 percent of all liver disease in the United States is now attributed to non-alcoholic fatty liver disease, also known as NAFLD.

So how do we treat inflammation in the liver when it's caused by fat? The most obvious answer is to lose weight, but for many people this is difficult. Thus, scientists have looked for ways to reduce inflammation in the liver before scarring sets in.

A recently published study in the New England Journal of Medicine suggests that high-dose vitamin E might be one answer.

In this well-designed, two-year study, researchers randomized 247 non-diabetic adults with NAFLD to receive one of three treatments: pioglitazone (an expensive drug used to reduce insulin resistance); vitamin E, 800 units per day; or a placebo. Liver tissue was examined at the beginning and end of the study to look for changes in inflammation and scarring.

The scientists found that both vitamin E and pioglitazone reduced fatty changes and inflammation in the liver, but vitamin E seemed to work better than pioglitazone, and only vitamin E produced significant improvements in scarring. In fact, 43 percent of the patients getting the vitamin E showed benefit. In addition, those people taking the pioglitazone gained weight during this study.

There are no good treatments for NAFLD other than weight loss; based on this study, some researchers believe that everyone with NAFLD should be treated with vitamin E. Vitamin E in high doses like this is probably safe, though there have been some studies suggesting that it may increase the risk of bleeding.

If you have or are at risk of fatty liver disease, first and foremost, we strongly encourage you to do whatever it takes to eat a healthier diet and lose weight. Reducing your intake of animal food and processed food is a great way to start; the website NutritionMD.org is an excellent source of healthy nutrition information and recipes.

If you are overweight or obese, we encourage you to speak with your doctor about your risk of liver disease, and to see if vitamin E supplementation might be right for you.

Read more

Source