Showing posts with label vitamin E. Show all posts
Showing posts with label vitamin E. Show all posts

Friday, April 6, 2018

Older Americans Are Hooked On Vitamins Despite Scarce Evidence They Work

Older Americans Are Hooked On Vitamins Despite Scarce Evidence They Work
By Liz Szabo April 4, 2018
When she was a young physician, Dr. Martha Gulati noticed that many of her mentors were prescribing vitamin E and folic acid to patients. Preliminary studies in the early 1990s had linked both supplements to a lower risk of heart disease.

She urged her father to pop the pills as well: “Dad, you should be on these vitamins, because every cardiologist is taking them or putting their patients on [them],” recalled Gulati, now chief of cardiology for the University of Arizona College of Medicine-Phoenix.

But just a few years later, she found herself reversing course, after rigorous clinical trials found neither vitamin E nor folic acid supplements did anything to protect the heart. Even worse, studies linked high-dose vitamin E to a higher risk of heart failure, prostate cancer and death from any cause.

“‘You might want to stop taking [these],’” Gulati told her father.

More than half of Americans take vitamin supplements, including 68 percent of those age 65 and older, according to a 2013 Gallup poll. Among older adults, 29 percent take four or more supplements of any kind, according to a Journal of Nutrition study published in 2017.

Often, preliminary studies fuel irrational exuberance about a promising dietary supplement, leading millions of people to buy in to the trend. Many never stop. They continue even though more rigorous studies — which can take many years to complete — almost never find that vitamins prevent disease, and in some cases cause harm.

“The enthusiasm does tend to outpace the evidence,” said Dr. JoAnn Manson, chief of preventive medicine at Boston’s Brigham and Women’s Hospital.

There’s no conclusive evidence that dietary supplements prevent chronic disease in the average American, Manson said. And while a handful of vitamin and mineral studies have had positive results, those findings haven’t been strong enough to recommend supplements to the general U.S. public, she said.

The National Institutes of Health has spent more than $2.4 billion since 1999 studying vitamins and minerals. Yet for “all the research we’ve done, we don’t have much to show for it,” said Dr. Barnett Kramer, director of cancer prevention at the National Cancer Institute.

In Search Of The Magic Bullet
A big part of the problem, Kramer said, could be that much nutrition research has been based on faulty assumptions, including the notion that people need more vitamins and minerals than a typical diet provides; that megadoses are always safe; and that scientists can boil down the benefits of vegetables like broccoli into a daily pill.

Vitamin-rich foods can cure diseases related to vitamin deficiency. Oranges and limes were famously shown to prevent scurvy in vitamin-deprived 18th-century sailors. And research has long shown that populations that eat a lot of fruits and vegetables tend to be healthier than others.

But when researchers tried to deliver the key ingredients of a healthy diet in a capsule, Kramer said, those efforts nearly always failed.

It’s possible that the chemicals in the fruits and vegetables on your plate work together in ways that scientists don’t fully understand — and which can’t be replicated in a tablet, said Marjorie McCullough, strategic director of nutritional epidemiology for the American Cancer Society.

More important, perhaps, is that most Americans get plenty of the essentials, anyway. Although the Western diet has a lot of problems — too much sodium, sugar, saturated fat and calories, in general — it’s not short on vitamins, said Alice Lichtenstein, a professor at the Friedman School of Nutrition Science and Policy at Tufts University.

And although there are more than 90,000 dietary supplements from which to choose, federal health agencies and advisers still recommend that Americans meet their nutritional needs with food, especially fruits and vegetables.

Also, American food is highly fortified — with vitamin D in milk, iodine in salt, B vitamins in flour, even calcium in some brands of orange juice.

Without even realizing it, someone who eats a typical lunch or breakfast “is essentially eating a multivitamin,” said journalist Catherine Price, author of “Vitamania: How Vitamins Revolutionized the Way We Think About Food.”

That can make studying vitamins even more complicated, Price said. Researchers may have trouble finding a true control group, with no exposure to supplemental vitamins. If everyone in a study is consuming fortified food, vitamins may appear less effective.

The body naturally regulates the levels of many nutrients, such as vitamin C and many B vitamins, Kramer said, by excreting what it doesn’t need in urine. He added: “It’s hard to avoid getting the full range of vitamins.”

Not all experts agree. Dr. Walter Willett, a professor at the Harvard T.H. Chan School of Public Health, says it’s reasonable to take a daily multivitamin “for insurance.” Willett said that clinical trials underestimate supplements’ true benefits because they aren’t long enough, often lasting five to 10 years. It could take decades to notice a lower rate of cancer or heart disease in vitamin takers, he said.

Vitamin Users Start Out Healthier
For Charlsa Bentley, 67, keeping up with the latest nutrition research can be frustrating. She stopped taking calcium, for example, after studies found it doesn’t protect against bone fractures. Additional studies suggest that calcium supplements increase the risk of kidney stones and heart disease.

“I faithfully chewed those calcium supplements, and then a study said they didn’t do any good at all,” said Bentley, from Austin, Texas. “It’s hard to know what’s effective and what’s not.”

Bentley still takes five supplements a day: a multivitamin to prevent dry eyes, magnesium to prevent cramps while exercising, red yeast rice to prevent diabetes, coenzyme Q10 for overall health and vitamin D based on her doctor’s recommendation.

Like many people who take dietary supplements, Bentley also exercises regularly — playing tennis three to four times a week — and watches what she eats.

People who take vitamins tend to be healthier, wealthier and better educated than those who don’t, Kramer said. They are probably less likely to succumb to heart disease or cancer, whether they take supplements or not. That can skew research results, making vitamin pills seem more effective than they really are.

Faulty Assumptions
Preliminary findings can also lead researchers to the wrong conclusions.

For example, scientists have long observed that people with high levels of an amino acid called homocysteine are more likely to have heart attacks. Because folic acid can lower homocysteine levels, researchers once hoped that folic acid supplements would prevent heart attacks and strokes.

In a series of clinical trials, folic acid pills lowered homocysteine levels but had no overall benefit for heart disease, Lichtenstein said.

Studies of fish oil also may have led researchers astray.

When studies of large populations showed that people who eat lots of seafood had fewer heart attacks, many assumed that the benefits came from the omega-3 fatty acids in fish oil, Lichtenstein said.

Rigorous studies have failed to show that fish oil supplements prevent heart attacks. A clinical trial of fish oil pills and vitamin D, whose results are expected to be released within the year, may provide clearer questions about whether they prevent disease.

But it’s possible the benefits of sardines and salmon have nothing to do with fish oil, Lichtenstein said. People who have fish for dinner may be healthier due to what they don’t eat, such as meatloaf and cheeseburgers.

“Eating fish is probably a good thing, but we haven’t been able to show that taking fish oil [supplements] does anything for you,” said Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic Foundation.

Too Much Of A Good Thing?
Taking megadoses of vitamins and minerals, using amounts that people could never consume through food alone, could be even more problematic.

“There’s something appealing about taking a natural product, even if you’re taking it in a way that is totally unnatural,” Price said.

Early studies, for example, suggested that beta carotene, a substance found in carrots, might help prevent cancer.

In the tiny amounts provided by fruits and vegetables, beta carotene and similar substances appear to protect the body from a process called oxidation, which damages healthy cells, said Dr. Edgar Miller, a professor of medicine at Johns Hopkins School of Medicine.

Experts were shocked when two large, well-designed studies in the 1990s found that beta carotene pills actually increased lung cancer rates. Likewise, a clinical trial published in 2011 found that vitamin E, also an antioxidant, increased the risk of prostate cancer in men by 17 percent. Such studies reminded researchers that oxidation isn’t all bad; it helps kill bacteria and malignant cells, wiping them out before they can grow into tumors, Miller said.

“Vitamins are not inert,” said Dr. Eric Klein, a prostate cancer expert at the Cleveland Clinic who led the vitamin E study. “They are biologically active agents. We have to think of them in the same way as drugs. If you take too high a dose of them, they cause side effects.”

Gulati, the physician in Phoenix, said her early experience with recommending supplements to her father taught her to be more cautious. She said she’s waiting for the results of large studies — such as the trial of fish oil and vitamin D — to guide her advice on vitamins and supplements.

“We should be responsible physicians,” she said, “and wait for the data.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Thursday, February 8, 2018

Clinical studies investigating the effect of vitamin E therapy in patients with NASH

Clinical Liver Disease
View issue TOC
Volume 11, Issue 1
January 2018
Pages 16–21

Clinical studies investigating the effect of vitamin E therapy in patients with NASH
Sebastian Larion M.D.,Sandeep Khurana M.B.B.S.

First published: 31 January 2018
DOI: 10.1002/cld.687

Watch a video presentation of this article
Full Text

Nonalcoholic steatohepatitis (NASH) is the inflammatory sequelae of fatty liver disease that is characterized histologically by steatosis with ballooning degeneration and lobular hepatitis. NASH and particularly fibrosis development are significantly associated with increased all-cause and liver-related mortality.[1, 2] By 2030, NASH is projected to affect more than 27 million patients in the United States and be attributed to 10.9% of all patient deaths.[3] Despite this major public health burden, no U.S. Food and Drug Administration–approved medications exist for the specific treatment of NASH, identifying an unmet need for a further understanding of disease-causing processes.

Friday, July 5, 2013

Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis

Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis

Alimentary Pharmacology & Therapeutics

J. H. Hoofnagle1,*, M. L. Van Natta2, D. E. Kleiner3, J. M. Clark2, K. V. Kowdley4, R. Loomba5, B. A. Neuschwander-Tetri6, A. J. Sanyal7, J. Tonascia2, the Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN)
Article first published online: 29 MAY 2013 DOI: 10.1111/apt.12352

Volume 38, Issue 2, pages 134–143, July 2013

Discussion Only

Full Text Available @ Alimentary Pharmacology & Therapeutics

Non-alcoholic fatty liver disease has become the most common cause of liver test abnormalities adults in the Western world and is estimated to affect up to 30% of the adult population.[17-19] This condition is also increasing in frequency among children and adolescents.[20] NAFLD is often benign and nonprogressive and associated with few, if any, symptoms. On the other hand, a proportion of patients with NAFLD develop progressive liver disease that can result in cirrhosis, end-stage liver disease, need for liver transplantation, hepatocellular carcinoma and death.[21-25] Patients with progressive disease usually have NASH on liver biopsy with the typical findings of centrizonal (zone 3) cellular injury (also called ballooning degeneration), inflammation, and fibrosis in addition to steatosis.[22] The separation of simple steatosis from NASH non-invasively can be difficult and is not predicted by serum aminotransferase levels, thus leading to the need for liver biopsy to decide upon interventions.[26, 27] These findings suggest that serum ALT and AST are unreliable markers for the degree of activity or severity, stage or degree of fibrosis and ultimate progression of NASH to end-stage liver disease.
In this secondary analysis of the PIVENS trial, however, serum ALT levels, if elevated at baseline, were found to have reasonable reliability in detecting improvement in the underlying liver disease, at least as assessed by liver biopsy and a validated histological scoring system. Over 80% of patients treated with vitamin E whose serum ALT levels fell to 40 U/L or less and by at least 30% of baseline had histological improvement. Importantly, none of these patients had evidence of worsening. In contrast, patients who did not achieve this degree of improvement in serum liver biochemical tests were less likely to show histological improvement and a significant proportion worsened.
This reanalysis of the PIVENS trial also showed the important and confounding effects of weight change on serum ALT levels as well as histological features of disease. Indeed, in patients who lost weight (using a cut point of only 2 kg over a 2-year period), the proportion of patients with histological improvement was similar in vitamin E and placebo groups (71% vs. 64%), although the quantitative degree of improvement in NAS score was greater with vitamin E than placebo (−2.8 vs. −1.9 points). Perhaps more strikingly, patients who gained weight were less likely to improve with vitamin E therapy, and those receiving placebo were likely to worsen. Weight gain was indeed associated with significant worsening of hepatic fibrosis in the placebo-treated patients. In contrast, patients who received placebo and who lost or did not gain weight and those who received vitamin E were unlikely to demonstrate progression of fibrosis scores over the 2-year period of this study whether or not ALT levels improved. These results provide strong and evidence-based support for dietary recommendations in patients with NASH. A first priority should be weight loss. But, perhaps more important is strict avoidance of further weight gain, which is closely associated with worsening of fibrosis, a surrogate, but convincing marker for disease progression.
The demonstration that vitamin E resulted in decreases in ALT levels and histological improvements in NASH was shown in the initial publication of the PIVENS trial [13] and was reinforced by several features in this study. First, there was a rapid and statistically significant decline in ALT levels in the vitamin E-, but not placebo-treated patients. The proportion of patients with an ALT response was three or more times higher in the vitamin E than placebo group, both at 24 weeks (39% vs. 7%) and 96 weeks (48% vs. 16%). Improvements in ALT levels were associated with improvements in histology scores and this was most evident in the vitamin E-treated subjects. Finally, discontinuation of vitamin E was followed by a prompt relapse and loss of the ALT response in 42% of patients.
Shortcomings of this post hoc analysis include the small sample size of the controlled study, which was adequate to assess the primary endpoint, but was somewhat limited for extensive secondary analyses. In addition, the definitions of ALT and histological responses were made a priori with only limited analysis of the dataset. However, both definitions are based upon clinical understanding of NAFLD and were easy to apply. The numbers of patients in the study were too few to attempt to generate statistically based algorithms for defining an ALT or histological responses; however, in preliminary analyses, modification of the criteria, such as dropping the requirement for a 30% decline in ALT from baseline, decreasing the criteria for an ALT response from ≤40 to ≤30 U/L, and using AST rather than ALT values did not improve the area under the curve in predicting histological responses (Table S1). Finally, this study was carried out in nondiabetic patients and the findings may not be applicable to patients with diabetes, who typically have more severe disease. Furthermore, only half of patients (48%) responded to vitamin E therapy and most relapsed when it was stopped.
In summary, these results show that vitamin E therapy is associated with improvements in serum aminotransferase levels, and that decreases of ALT values into the normal range (to ≤40 U/L and by 30% of baseline) are usually associated with histological improvement in disease activity (steatosis, inflammation, cell injury). Weight loss can also achieve these endpoints, but importantly weight gain has definite negative implications for the natural history and outcome of this common and increasingly important form of liver disease. The effects of vitamin E and weight loss on both ALT and histological responses were separate and independent, so that even patients who lost weight benefitted from vitamin E therapy.

Clinical Trial Number: NCT00063622.

Wednesday, July 18, 2012

Vitamin E either from supplement or diet may lower liver cancer risk

Vitamin E may lower liver cancer risk

High consumption of vitamin E either from diet or vitamin supplements may lower the risk of liver cancer, according to a study published July 17 in the Journal of the National Cancer Institute.

Vitamin E is a fat-soluble vitamin which is considered an antioxidant and numerous experimental studies have suggested that vitamin E may prevent DNA damage.

Liver cancer is the third most common cause of cancer mortality in the world, the fifth most common cancer found in men and the seventh most common in women. Approximately 85 percent of liver cancers occur in developing nations, with 54 percent in China alone.

To determine the relationship between vitamin E intake and liver cancer risk, Wei Zhang, M.D., MPH., Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, and colleagues analyzed data from a total of 132,837 individuals in China who were enrolled in the Shanghai Women's Health Study (SWHS) from 1997-2000 or the Shanghai Men's Health Study (SMHS) from 2002-2006, two population-based cohort studies jointly conducted by the Shanghai Cancer Institute and Vanderbilt University.

Using validated food-frequency questionnaires, the researchers conducted in-person interviews to gather data on study participants' dietary habits. Participants were asked how often they ate some of the most commonly consumed foods in urban Shanghai and whether they took vitamin supplements.
The investigators then compared liver cancer risk among participants who had high intake of vitamin E with those who had low intake.

The analysis included 267 liver cancer patients (118 women and 149 men) who were diagnosed between two years after study enrollment and an average of 10.9 (SWHS) or 5.5 (SMHS) years of follow-up. Vitamin E intake from diet and vitamin E supplement use were both associated with a lower risk of liver cancer. This association was consistent among participants with and without self-reported liver disease or a family history of liver cancer.

"We found a clear, inverse dose-response relation between vitamin E intake and liver cancer risk," the authors write, noting a small difference between men and women in the risk estimate, which is likely attributable to fewer liver cancer cases having occurred among male participants due to the shorter follow-up period.

"Overall, the take home message is that high intake of vitamin E either from diet or supplements was related to lower risk of liver cancer in middle-aged or older people from China," said Xiao Ou Shu, M.D., Ph.D., professor of Medicine at the Vanderbilt Epidemiology Center.

Conversely, participants who had the highest vitamin C intake from supplements and who had a family history of liver cancer or self-reported liver disease were more likely to develop liver cancer.

There was no link to liver cancer among participants who had the highest levels of vitamin C or other vitamins from food.


Other investigators involved with the study included Honglan Li, M.D., M.Ph., Jing Gao, M.D., Yong-Bing Xiang, M.D., M.Ph., and Yu-Tang Gao, M.D., Shanghai Cancer Institute; Gong Yang, M.D., MPH, Hui Cai, M.D., Ph.D., and Wei Zheng, M.D., Ph.D., Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center; and Bu-Tian Ji, M.D., Dr.PH, National Cancer Institute.
Funding for the study was supported by grants from the National Cancer Institute, a division of the National Institutes of Health (R37 CA070867 and R01 CA082729), the State Key Project Specialized for Infectious Diseases of China (2008ZX10002-015 and 2012ZX10002008-002), and a training grant from the Fogarty International Center (D43 TW008313).

Wednesday, December 21, 2011

Scientists identify an innate function of vitamin E

Scientists identify an innate function of vitamin E
Posted on December 20, 2011 by Toni Baker

AUGUSTA, Ga. – It’s rubbed on the skin to reduce signs of aging and consumed by athletes to improve endurance but scientists now have the first evidence of one of vitamin E’s normal body functions.

The powerful antioxidant found in most foods helps repair tears in the plasma membranes that protect cells from outside forces and screen what enters and exits, Georgia Health Sciences University researchers report in the journal Nature Communications.

Everyday activities such as eating and exercise can tear the plasma membrane and the new research shows that vitamin E is essential to repair. Without repair of muscle cells, for example, muscles eventually waste away and die in a process similar to what occurs in muscular dystrophy. Muscle weakness also is a common complaint in diabetes, another condition associated with inadequate plasma membrane repair.

“Without any special effort we consume vitamin E every day and we don’t even know what it does in our bodies,” said Dr. Paul McNeil, GHSU cell biologist and the study’s corresponding author. He now feels confident about at least one of its jobs.

Century-old animal studies linked vitamin E deficiency to muscle problems but how that happens remained a mystery until now, McNeil said. His understanding that a lack of membrane repair caused muscle wasting and death prompted McNeil to look at vitamin E.

Vitamin E appears to aid repair in several ways. As an antioxidant, it helps eliminate destructive byproducts from the body’s use of oxygen that impede repair. Because it’s lipid-soluble, vitamin E can actually insert itself into the membrane to prevent free radicals from attacking. It also can help keep phospholipids, a major membrane component, compliant so they can better repair after a tear.

For example, exercise causes the cell powerhouse, the mitochondria, to burn a lot more oxygen than normal. “As an unavoidable consequence you produce reactive oxygen species,” McNeil said. The physical force of exercise tears the membrane. Vitamin E enables adequate plasma membrane repair despite the oxidant challenge and keeps the situation in check.

When he mimicked what happens with exercise by using hydrogen peroxide to produce free radicals, he found that tears in skeletal muscle cells would not heal unless pretreated with vitamin E.

Next steps, which will be aided by two recent National Institutes of Health grants, include examining membrane repair in vitamin E-deficient animals.

McNeil also wants to further examine membrane repair failure in diabetes. Former GHSU graduate student Dr. Amber C. Howard showed in a recent paper in the journal Diabetes that cells taken from animal models of types 1 and 2 diabetes have faulty repair mechanisms. Howard found high glucose was a culprit by soaking cells in a high-glucose solution for eight to 12 weeks, during which time they developed a repair defect. It’s also well documented that reactive oxygen species levels are elevated in diabetes.

The Nature Communications paper showed that vitamin E treatment in an animal model of diabetes restored some membrane repair ability. Also, an analogue of the most biologically active form of vitamin E significantly reversed membrane repair deficits caused by high glucose and increased cell survival after tearing cells in culture.

Now McNeil wants to know if he can prevent the development of advanced glycation end products – a sugar that high glucose adds to proteins that his lab has shown can also impede membrane repair – in the animal models of diabetes. The researchers have a drug that at least in cultured animal cells, prevents repair defects from advanced glycation end products.

Howard, first author on the Nature Communications paper, is an instructor at Husson University in Bangor, Maine. McNeil is a faculty member in GHSU’s Medical College of Georgia and College of Graduate Studies.

Also See:
AASLD:Video/Vitamin E Resolves NASH*non alcoholic steatohepatitis in Children

Tuesday, May 3, 2011

Hepatitis C; Beta Carotene

Published in the Cochrane Database of Systematic Reviews March 2011 Issue is data showing that Beta-carotene, vitamin A, vitamin C, and vitamin E could not be recommended for treatment of liver diseases.

In the review treatment with antioxidant supplements of alcoholic, autoimmune, hepatitis B or hepatitis C virus liver diseases, or liver cirrhosis was assessed. The review includes 20 randomised clinical trials. In total, 1225 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. The low number of randomised participants increases the risk of random errors ('play of chance'). Trial quality was low and accordingly the risk of systematic errors ('bias') was high. The authors concluded no evidence to support or refute antioxidant supplements in patients with liver disease. In addition antioxidant supplements may increase liver enzyme activity.

Today the UC Berkeley Wellness Letter discusses the claims and benefits of Beta Carotene.

Beta Carotene
Beta carotene is one of several carotenoids, natural plant pigments found in deeply colored fruits and vegetables. Others include alpha carotene, lutein, lycopene, and zeaxanthin. Beta carotene and some other carotenoids are "provitamin A carotenoids," meaning that the body can convert them into vitamin A. Beta carotene is also an antioxidant; thus it may help deactivate free radicals, unstable molecules that are by-products of cells "burning" oxygen for energy. Free radicals can damage the basic structure of cells and thus lead to chronic diseases (notably cancer and heart disease) and accelerate the aging process. There is no daily recommended intake, or safe upper level.

Claims, purported benefits: Prevents cancer and heart disease; boosts immunity, supports good vision.
Bottom line: Some good research—mostly involving beta carotene from the diet—suggests that beta carotene could lower the risk of cancer and possibly other diseases. Thus, some nutrition experts once recommended beta carotene pills. Then came two first-rate studies showing that beta carotene supplements could cause serious harm, at least in smokers. The CARET study (full name: Beta Carotene and Retinol Efficacy Trial) tested beta carotene and vitamin A supplements in people at high risk for lung cancer—smokers, former smokers, and asbestos-industry workers. The study was halted when it became clear that those taking beta carotene (not even a high dose—just 30 milligrams a day) actually had a higher rate of lung cancer and higher mortality rate than those taking a placebo.

Don't assume that beta carotene or other antioxidants in supplement form are beneficial, or even harmless. Don’t take beta carotene pills, particularly if you’ve ever been a smoker. Beta carotene is plentiful in vegetables and fruits, and is safe and beneficial when consumed from such foods.

Tuesday, November 2, 2010

AASLD:Video/Vitamin E Resolves NASH*non alcoholic steatohepatitis in Children

AASLD: Vitamin E Resolves NASH in Children
By Kristina Fiore , Staff Writer, MedPage TodayPublished: November 02, 2010Reviewed 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 DiseaseSource reference:Lavine JE, et al "Vitamin E, metformin, or placebo treatment of nonalcoholic fatty liver disease in children"
AASLD 2010; Abstract 110

Monday, October 11, 2010

Fatty Liver Disease, Genotype 3, Vitamin E and HCV

Fatty Liver Disease, Genotype 3, Vitamin E and HCV
Fatty Liver disease in HCV has been proven to be caused directly from the virus. Genotype 3 patients are known to have a higher rate of fatty liver then other genotypes. Previously both genotype 2 and 3 were treated with the same treatment duration with the assumption both were the easier genotype to treat. Currently the data has shown that genotype 3 patients have a higher incidence of fatty liver and possibly the two genotypes may require different treatment protocols.
Treating with telaprevir alone (as shown below in this post) or monotherapy was not as potent against genotype 3 as it is in genotype 2. However, treating with Telaprevir showed the best results in combined therapy with interferon and ribavirin Only time will tell how genotype 3 will fair with the new drugs coming down the pipeline, and both boceprevir and telaprevir should soon be FDA approved.
However until all the data is in there are other drugs making their way through clinical trials .
RG7128 in phase one.
RG7128 in April of this year was presented at the "45th Annual Meeting of the European Association for the Study of the Liver (EASL)" in Vienna, Austria.
The Link
The Study
LB10. Antiviral Activity Of The HCV Nucleoside Polymerase Inhibitor R7128 In HCV Genotype 2 And 3 Prior Non-Responders: Interim Results Of R7128 1500mg BID With PEG-IFN And Ribavirin For 28 Days.
E. J. Gane; M. Rodriguez-Torres; D. R. Nelson; I. M. Jacobson; J. G. McHutchison; L. Jeffers; A. Beard; S. Walker; N. Shulman; W. Symonds; E. Albanis; M. M. Berrey

Historically, HCV genotype (GT) 2 and 3 prior non-responders have demonstrated poor response rates to re-treatment with PEG-IFN/RBV (SOC).
No direct-acting antiviral agent in development has shown significant activity in individuals infected with HCV GT 2/3.
R7128 is a potent nucleoside analog inhibitor of HCV polymerase, with activity against HCV GT 2/3 in vitro. When administered at doses of 1000-1500mg BID in combination with SOC for 28 days in treatment-naïve, HCV+ GT 1 patients, R7128 delivered an 85-88% rapid virologic response (RVR).
This study was designed to evaluate R7128 with 180µg PEG-IFN and 1000-1200mg RBV for 28 days in patients with HCV GT 2 or 3.

25 patients (20 active/5 placebo) with genotype 2 (n=10) or genotype 3 (n=15) who had not previously achieved a sustained virologic response (SVR) with interferon-based therapy were enrolled.
Patients received R7128 1500mg BID or placebo along with PEG-IFN/RBV for 28 days, followed by PEG-IFN/RBV alone for a minimum of 20 weeks. All patients were non-cirrhotic and all had been previously treated with at least 12 weeks of interferon-based therapy.
Antiviral Activity
· 90% RVR was demonstrated in this cohort of treatment failure HCV GT 2 or 3 patients with R7128 + SOC .
· Prior treatment response had no impact upon R7128 + SOC response, RVR was 60% in SOC prior relaspers
· The antiviral activity observed with R7128 + SOC was maintained across genotype 2 and 3; and consistent with in vitro data
· Compared to prior therapy, the addition of R7128 resulted in a more rapid decline in plasma HCV RNA, based upon those subjects with available prior treatment histories
· HCV RNA values in the SOC alone group declined with a -3.7 log 10 change from baseline compared to -5.0 in the R7128 cohort
· A mean 5.0 log 10 decline in plasma HCV RNA was demonstrated following 28 days of combination therapy with R7128 + SOC in HCV genotype 2 or 3 infected subjects
· Compared to prior treatment responses, R7128 provided additional antiviral activity in these subjects
· R7128 was generally well-tolerated and demonstrated no evidence of acute target organ toxicity
· Serum ALT levels normalized during R7128 therapy in 54% of subjects with elevated ALT at baseline
· Pharmacokinetic data demonstrate that the ‘new’ formulation results in slightly higher plasma exposures compared to the previous formulation.
· R7128 has provided positive proof-of-concept that a direct acting antiviral can deliver additional antiviral potency in an HCV genotype 2 or 3 treatment failure population with an RVR of 90%. Longer term data is needed to determine adequate length of treatment in this population.
· As predicted by in vitro data, R7128 demonstrated similar potency against HCV genotype 2 or 3 compared to a previous study of R7128 again genotype 1 HCV
· The absence of virologic breakthrough reinforces the implications from monotherapy studies that nucleo0side polymerase inhibitors have a high genetic barrier to resistance
· The safety and efficacy of this combination study support further development of R7128 in combination with the standard of care (pegylated interferon and ribavirin) in this difficult to rreat, HCV genotype 2/3 non-responder population and provides appropriate potency and safety to progress to Phase 2b studies to explore optimal treatment duration in HCV genotype 2 or 3 treatment-naive patients.
Clinical Phase Phase I RG7128
lDrug Name RG7128 (Polymerase Inhibitor)
Drug Category RG7227 (ITMN-191) (Danoprevir) Protease Inhibitor
Comments: AASLD 2009:

Comments: AASLD 2009: Results from 13 days of treatment with RG7128 & RG7227: 63% (5 out of 8) genotype 1 treatment-naive patients were HCV RNA negative (less then 15 IU/mL) and 25% (2 out of 8) of null responders were HCV RNA negative (less then 15 IU/mL). The drugs were well-tolerated; no treatment discontinuations due to side effects.
Special Presentation
, k
On November 17 2009, InterMune announced that an independent data monitoring committee recommended the company stop testing the therapy in the RG7227 900 milligram dosage given once every 12 hours after three patients had elevated levels of ALT, a liver enzyme.
EASL 2010: A small study using ritonavir (100 mg) to boost danoprevir (200 mg) both given twice a day achieved 100% undetectable HCV RNA after 15 days and was generally well-tolerated. Based on these findings an additional two study arms of prior complete non-responders will be retreated with danoprevir, ritronavir, PEG/RBV for 12 weeks. A larger study titled INFORM-3 is being planned that will include ritonavir.
Since then Roche has bought full rights to the drug and other drugs from Intermune.
Roche buys full rights to danoprevir from InterMune
Agreement reinforces Roche’s leadership in the fight against hepatitis C
"The latest news is that Danoprevir is a second generation protease inhibitor for hepatitis C that has shown promising efficacy in pre-clinical and early clinical development. Following co-development between Roche and InterMune since 2006, Roche now assumes sole ownership of danoprevir. This results in increased flexibility to develop and market its portfolio of drugs against hepatitis C, which also includes Pegasys (40 kDa pegylated interferon alfa 2a, the current standard of care) and RG7128, a nucleosidic polymerase inhibitor which has shown a promising resistance profile."
Information/links related to geno 3 treatment and fatty liver disease.
Also the study on Vitamin E and fatty liver disease.


Steatosis is a condition characterised by the build up of fat within the liver, sometimes triggering inflammation of the liver. It is also known as fatty liver. It is only recently that the significance and relationship of steatosis to HCV has begun to be understood.
There are two different forms of steatosis (Fatty Liver) that may be found in people with HCV: Metabolic steatosis and HCV-induced steatosis
. .
Metabolic steatosis can result from obesity, raised blood fat levels (hyperlipidemia), insulin resistance and type II diabetes and is similar to the type of fatty infiltration caused by excessive alcohol consumption and that is also found in Non-Alcoholic Fatty Liver (NASH).
Metabolic steatosis is not triggered by the hepatitis C virus; however the combination of this form of steatosis and the presence of HCV can lead to a more rapid progression of scarring or fibrosis.
HCV-induced steatosis is fatty infiltration that is directly caused by the presence of the virus. It is possible for people with HCV to have both forms of steatosis simultaneously.
Genotypes and Fatty Liver Disease:
Although it seems that all genotypes can trigger steatosis, the risk of developing steatosis is significantly higher for people with genotype 3. There is a complex reaction between the genotype 3 virus and liver cells that is not seen in other genotypes that makes this group at much higher risk of developing the condition. Around 40% of people with hepatitis C have steatosis, compared to about 14% to 31% of the general population. However, 60% - 80% of people with genotype 3 have moderate or severe steatosis.
Hepatitis C virus genotypes 2 and 3 are both responsive to antiviral treatment, they have been regarded as similar. However, recent evidence has shown there may be differences between these two genotypes with regard to their clinical features and possibly responses to combined interferon and ribavirin therapy.
As demonstrated in recent studies considering rapid virologic response (RVR) as a criterion for shortening treatment from the standard 24 weeks to 12 or 16 weeks in patients with genotype 2 or 3, the reason for lower response in genotype 3 versus genotype 2 patients may be a lower response rate in patients without an RVR. As a consequence, treatment longer than the currently recommended 24 weeks may be required for patients with genotype 3 but not for those with genotype 2 in the absence of an RVR. Whether this lower sensitivity to treatment in a subgroup of patients with genotype 3 may be attributed to viral heterogeneity or other associated cofactors is not yet known
Genotype 3 patients, SVR rates were lower overall :
G3 telaprevir alone: SVR 50%;
G3 telaprevir/pegylated interferon/ribavirin: SVR 67%;
G3 pegylated interferon/ribavirin: SVR 44%.
Therapy response to interferon-based regimen in patients with HCV genotype 3 infection is negatively affected by increasing age, suggesting that elderly patients (> 50 years old) with genotype 3 infection may need longer duration of therapy."
Steatosis and HCV treatment
There is increasing evidence that steatosis can reduce the effects of treatment.
Some retrospective studies have shown that people with steatosis were less likely to achieve a sustained virologic response (SVR) even when taking into account other factors that might induce steatosis.
One study found that sustained virologic response rates were 18-32% lower in people with steatosis compared to people without steatosis after adjusting for other co-factors that affect treatment such as genotype, fibrosis score, and viral load level. /
Diet and Excercise: A recent study found that HCV patients who participated in a diet and exercise program for three months lowered their grade of steatosis and, remarkably, their fibrosis score.
The Study
In this study we show that, besides alcohol consumption, an unbalanced diet is an important factor of hepatitis C evolution and nonresponse to antiviral treatment. Specific nutritional education and severe alcohol restrictions might, synergistically, improve the response to antiviral therapy
. /,
Many people with steatosis experience no symptoms.
Symptoms that people do experience are non-specific and liver enzymes levels are not necessarily raised. As with fibrosis, the definitive way to diagnose steatosis is a liver biopsy.
Vitamin E appears to be more effective in treating obesity-associated chronic liver disease than a prescription drug, U.S. researchers found.......
Vitamin E, diabetes drug may reverse fatty liver disease
In a notable research, scientists claim to have found that vitamin E pills may help treat chronic liver disease.
Vitamin E, diabetes drug may reverse fatty liver disease
In a notable research, scientists claim to have found that vitamin E pills may help treat chronic liver disease.'
The research conducted by Virginia Commonwealth University (VCU), U.S., and funded by National Institutes of Health and Takeda Pharmaceutical revealed that vitamin E tablets could reverse nonalcoholic fatty liver disease --steatohepatitis.
Project scientist, Patricia Robuck, National Institute of Diabetes and Digestive and Kidney Diseases was quoted by Los Angeles Times as saying, “This is an important landmark in the search for effective treatmentsfor (the disease).”
How Many People In The Study
How Long Was The Study ?
A 96-week study including 247 adults in their mid-40s, suffering from steatohepatitis (Fatty Liver)
None of them were diabetics or excessive drinkers, but all were obese.
Assigned To Three Groups For Two Years
' .
For the study, the subjects were randomly assigned three varied treatments for two years wherein they were given certain amount of medication on a daily basis.
The First Group
The first group was given 800 International Units (IU) of vitamin E
The Second Group
The second group was given 30 milligrams of the diabetes drug pioglitazone(an insulin-sensitizer)'
Third Group
The third group was administered a *placebo treatment instead of medication. (*Placebo dummy medication
All Had A Liver Biopsy After Treatment
All the subjects underwent a liver biopsy at the commencement and finishing of the trial such that the researchers could arrive at comparative results. .
The Big Reveal
First Group; Results of liver tissue characteristics during liver biopsies revealed that 43 percent of the vitamin E group had improved significantly.
Second Group; 34 percent of the group given the diabetes drug pioglitazone showed improvements
Third Group; 19 percent improvement was shown of those given placebo treatment.'
Furthermore, the biopsy data revealed that vitamin E considerably reduced liver inflammation, fat accumulation and presence of dying ‘ballooning cells’ that appear in fatty liver tissue.
The Second Group (diabetes drug pioglitazone) was found to improve insulin signaling, which helps diabetics metabolize sugar. However, it could also diminish the amount of fat in the liver, the researchers added.
“This confirms a long-term benefit for pioglitazone and gives an alternative option in the form of vitamin E,” Kenneth Cusi, endocrinologist, University of Texas Health Science Center was quoted in ScienceNews as saying.
Robuck cautioned that vitamin E should only be taken under a doctor’s supervision. He was cited in Business Week as saying, “The trial included only a relatively healthy population with no diabetes and no cardiovascular disease.
For those people, it can be an important treatment.”Arun Sanyal, MD, VCU stressed on further research and told ScienceNews, “It’s too early to recommend (vitamin E) as a panacea for fatty liver disease.”

The study appears in New England Journal of Medicine.

Friday, October 1, 2010

HCV/Vitamin E Repairs Liver Injury

Hepatitis C and Vitamins

If you have hepatitis C, vitamins (such as vitamins A and K) may actually make your liver disease worse. People with hepatitis C should not take supplements of vitamin K and should avoid doses of vitamin D that are greater than 2,000 IU.
At high doses, vitamin E can thin the blood, so people with hepatitis C should not take doses greater than 400 IU. It's important to avoid high doses of these -- and other -- vitamins if you have hepatitis C. Vitamins in large doses can cause additional harm to the liver.

Vitamin E is an antioxidant responsible for proper functioning of the immune system and for maintaining healthy eyes and skin. It is actually a group of fat soluble compounds known as tocopherols (i.e., alpha tocopherol and gamma tocopherol). Gamma tocopherol accounts for approximately 75% of dietary vitamin E.

Vitamin E rich foods include nuts, cereals, beans, eggs, cold-pressed oils, and assorted fruits and vegetables. Because vitamin E is a fat soluble vitamin, it requires the presence of fat for proper absorption. Daily dietary intake of the recommended daily allowance (RDA) of vitamin E is recommended for optimum health.

Vitamin E is absorbed by the gastrointestinal system and stored in tissues and organs throughout the body. Certain health conditions may cause vitamin E depletion, including liver disease, celiac disease, and cystic fibrosis. Patients with end-stage renal disease (kidney failure) who are undergoing chronic dialysis treatment may be at risk for vitamin E deficiency. These patients frequently receive intravenous infusions of iron supplements which can act against vitamin E.

Vitamin E deficiency can cause fatigue, concentration problems, weakened immune system, anemia, and low thyroid levels. It may also cause vision problems and irritability. Low serum (or blood) levels of vitamin E have also been linked to major depression.

General use
Vitamin E is necessary for optimal immune system functioning, healthy eyes, and cell protection throughout the body. It has also been linked to the prevention of a number of diseases.

The therapeutic benefits of vitamin E include:
Cancer prevention. Vitamin E is a known antioxidant, and has been associated with a reduced risk of gastrointestinal, cervical, prostate, lung, and possibly breast cancer.

Immune system protection.

Various studies have shown that vitamin E supplementation, particularly in elderly patients, boosts immune system function. Older patients have demonstrated improved immune response, increased resistance to infections, and higher antibody production. Vitamin E has also been used with some success to slow disease progression in HIV-positive patients.
Eye disease prevention. Clinical studies on vitamin E have shown that supplementation significantly reduces the risk for cataracts and for macular degeneration, particularly among women.

Memory loss prevention. Vitamin E deficiency has been linked to poor performance on memory tests in some elderly individuals.

Alzheimer's disease treatment.

In a study performed at Columbia University, researchers found that Alzheimer's patients who took daily supplements of vitamin E maintained normal functioning longer than patients who took a placebo.

Liver disease treatment.

Vitamin E may protect the liver against disease.
Diabetes treatment. Vitamin E may help diabetic patients process insulin more effectively.
Pain relief. Vitamin E acts as both an anti-inflammatory and analgesic (or pain reliever).

Studies have indicated it may be useful for treatment of arthritis pain in some individuals.
Parkinson's disease prevention.

Other benefits of vitamin E are less clear cut, and have been called into question with conflicting study results or because of a lack of controlled studies to support them,

Vitamin E Repairs Liver Injury
By Maureen Williams

(June 3, 2010)—

Alcohol is not the only danger our livers face day to day: insulin resistance, a common condition in which blood sugar isn’t used properly in the body, can trigger a condition known as nonalcoholic fatty liver disease. First evidenced by fat deposits forming in liver cells, severe cases cause inflammation and scarring, called steatohepatitis, which can eventually progress to cirrhosis and liver failure.Taking steps to improve insulin sensitivity and the way the body uses carbohydrates can help reverse the damaging effects of nonalcoholic steatohepatitis, and now a new study has found that vitamin E supplements may reduce fatty deposits and inflammation in people with this disease as well.Rescuing the liverThe study, published in the New England Journal of Medicine, included 247 people with nonalcoholic steatohepatitis.

They were randomly assigned to receive 800 IU of vitamin E per day, 30 mg of a medication used to increase insulin sensitivity (pioglitazone) per day, or placebo for 96 weeks. They underwent liver biopsies at the beginning and end of the trial and were monitored for 24 weeks after the end of treatment.

The findings were as follows:

• Steatohepatitis improved in both the vitamin E and medication groups compared with placebo, but the difference between medication and placebo was not statistically significant.

• Medication and supplement reduced fatty deposits and inflammation in both treatment groups compared with placebo.

• Liver function tests improved in both treatment groups.

• Insulin resistance improved only in the medication group, but this group also experienced an average weight gain of 4.7 kg (10.3 pounds) that was not lost after stopping the medication.Repairing the liver with vitamin E

Although the exact cause of nonalcoholic steatohepatitis is not fully understood, insulin resistance and obesity clearly play a role.

The primary finding of this study—“vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes” —suggests that oxidative damage might also contribute to liver cell injury in people with this condition.

Taking steps to improve metabolism and to reduce cell damage caused by unstable compounds in the environment may be the best way to reverse nonalcoholic steatohepatitis:

• Stick to a low-glycemic-load diet. This type of diet has the best effect on blood sugar control, insulin sensitivity, and weight loss. Researchers have found that people with steatohepatitis can reduce liver injury through diet and weight loss.

• Exercise regularly. Physical activity improves insulin sensitivity and carbohydrate metabolism, and facilitates weight loss.

• Aim for gradual weight loss (about 1 to 2 pounds per week). There is some evidence that rapid weight loss may actually worsen fatty liver disease.

• Eat foods high in vitamin E, especially nuts and seeds. Not only are these the richest sources of vitamin E, they also have low glycemic loads and protect against cardiovascular disease.

• Consider adding a vitamin E supplement. Add 800 IU of vitamin E per day to help protect your liver.

(NEJM 2010;18:1675–85)Maureen Williams, ND, received her bachelor’s degree from the University of Pennsylvania and her Doctorate of Naturopathic Medicine from Bastyr University in Seattle, WA. She has a private practice on Cortes Island in British Columbia, Canada, and has done extensive work with traditional herbal medicine in Guatemala and Honduras. Dr. Williams is a regular contributor to Healthnotes Newswire.Copyright © 2010 Aisle7. All rights reserved. Republication or redistribution of the Aisle7® content is expressly prohibited without the prior written consent of Aisle7. Healthnotes Newswire is for educational or informational purposes only, and is not intended to diagnose or provide treatment for any condition. If you have any concerns about your own health, you should always consult with a healthcare professional. Aisle7 shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.