Showing posts with label Complementary and Alternative Medicine. Show all posts
Showing posts with label Complementary and Alternative Medicine. Show all posts

Monday, November 13, 2017

Ex-naturopath blowing the whistle on industry

Today on Health Report, a radio program based in Australia, Norman Swan interviewed ex-naturopathic doctor Britt Hermes.

Hermes became a critic of naturopathy and alternative medicine after discovering unethical practices in the field of naturopathic medicine. Early on Hermes learned her boss was importing a drug to treat cancer patients, a drug not FDA approved to treat cancer or any disease and in clinical trials was shown to cause bone marrow toxicity and liver failure.

Complementary medicine is discussed in this interview.

Listen here -

Britt Hermes
Naturopathic Diaries
Britt Hermes can also be found at Forbes, Science 2.0, KevinMD and Science-Based Medicine.

Tuesday, April 7, 2015

States ask U.S. Congress to launch inquiry of herbal supplements

States ask U.S. Congress to launch inquiry of herbal supplements
NEW YORK | By Karen Freifeld

NEW YORK (Reuters) - A group of 14 state attorneys general on Thursday asked the U.S. Congress to investigate the herbal supplements industry after a New York probe of the products turned up ingredients that were not listed on labels and raised safety concerns.

The group, led by New York Attorney General Eric Schneiderman and Indiana Attorney General Greg Zoeller, also asked Congress to consider giving the U.S. Food and Drug Administration more oversight of herbal supplements.

"We believe the safety and efficacy of these supplements is a matter of deep public concern across the country," the attorneys general said in the letter, urging "swift action."

Continue reading...
(Reporting By Karen Freifeld; Editing by David Gregorio)

Thursday, February 26, 2015

Herbal products and adverse effects on the liver

Herbal products and adverse effects on the liver

The most recent issue of the Gastroenterology reviews adverse effects and mechanisms.

Herbal products have been used for centuries among indigenous people to treat symptoms and illnesses.

Recently, their use in Western countries has grown significantly, rivaling that of prescription medications.
News image

Dr Leonard Seeff and colleagues from Pennsylvania, USA report that herbal products are used mainly for weight loss, and bodybuilding purposes but also to improve well-being and symptoms of chronic diseases.
Many people believe that because they are natural, they must be effective and safe.

However, these beliefs are erroneous.
Highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant
The researchers noted that few herbal products have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary.

The research team found that current highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant.

The team observed that herbal products are no safer than conventional drugs, and have caused liver injury severe enough to require transplantation or cause death.

Furthermore, their efficacy, safety, and claims are not assessed by regulatory agencies, and there is uncertainty about their reported and unreported contents.

Dr Seeff's team concludes, "We review the history of commonly used herbal products, as well as their purported efficacies and mechanisms and their adverse effects."

Gastroenterol 2015(148): 3: 517–532.e3
26 February 2015

Monday, January 5, 2015

Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases.

Ann Hepatol. 2015 Jan-Feb;14(1):7-19.

Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases.

Teschke R1, Zhang L2, Long H3, Schwarzenboeck A1, Schmidt-Taenzer W1, Genthner A1, Wolff A4, Frenzel C5, Schulze J6, Eickhoff A1.

Author information
1Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Medical Faculty of the Goethe University Frankfurt/ Main, Germany. 2Center for Drug Reevaluation, China Food and Drug Administration, Beijing, China.
3Department of Internal Medicine, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. 4Department of Internal Medicine II, Division of Gastroenterology, Hepatology and Infectious Diseases, Friedrich Schiller University Jena, Germany. 5Department of Medicine I, University Medical Center Hamburg Eppendorf, Germany. 6Institute of Industrial, Environmental and Social Medicine, Medical Faculty of the Goethe University Frankfurt/Main, Germany.

Abstract Only
Download Full Text 

Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal Traditional Chinese Medicine (TCM), we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury. 

The search focused primarily on English-language case reports, case series, and clinical reviews. We identified reported hepatotoxicity cases in 77 relevant publications with 57 different herbs and herbal mixtures of TCM, which were further analyzed for causality by the Council for International Organizations of Medical Sciences (CIOMS) scale, positive reexposure test results, or both. 

Causality was established for 28/57 different herbs or herbal mixtures, 
Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao. 

In conclusion, this compilation of liver injury cases establishes causality for 28/57 different Traditional Chinese Medicine (TCM) herbs and herbal mixtures, aiding diagnosis for physicians who care for patients with liver disease possibly related to herbal Traditional Chinese Medicine (TCM).

Open Access - Download Full Text 

Friday, September 26, 2014

Liver injury from herbals and dietary supplements may be rising in some parts of US

Liver injury from herbals and dietary supplements may be rising in some parts of US

Last Updated: 2014-09-22

By Will Boggs MD

NEW YORK (Reuters Health) - Liver injury from herbal medicines and dietary supplements appears to be on the rise in some parts of the country, according to data from the U.S. Drug-Induced Liver Injury Network (DILIN).

"More research is needed to identify more accurately what supplements, or ingredients thereof, cause liver injury and why," Dr. Victor J. Navarro from Einstein Medical Center in Philadelphia told Reuters Health by email. "Also, regulators must take note that current regulation of dietary supplements leans more toward protection of the manufacturer than the consumer."

About half of the U.S. adult population say they use herbals and dietary supplements, and there have been recent cases of life-threatening hepatotoxicity associated with the use of at least one of them (OxyElite Pro).

Dr. Navarro and colleagues examined the burden and characteristics of liver damage attributed to these products in the DILIN and compared the injuries with those caused by conventional medications. They excluded all cases related to acetaminophen, which account for the vast majority of medication-induced liver injuries.

The researchers defined liver injury as jaundice or coagulopathy in the presence of liver enzyme abnormalities or elevations of ALT or AST above five times the upper limit of normal or elevations of alkaline phosphatase above two times the upper limit of normal on two consecutive measurements at least 24 hours apart.

As for causality, medications were considered individually, whereas all herbals and dietary supplements taken by any patient were grouped together and adjudicated as a single agent, even if several were taken concurrently.

Ultimately, the analysis included 839 patients whose "definite," "very likely," or "probable" liver injuries were reported in the 10 years between 2004 and 2013. Most of these injuries (85%) were attributed to medications, and the rest were chalked up to herbals or dietary supplements.

The researchers divided those taking herbals and supplements into two groups based on whether they took the substances for bodybuilding purposes (45/130) or not (85/130).

During the first two years, cases attributed to herbals and dietary supplements accounted for 7% (eight cases) of the non-acetaminophen liver injuries. By the end of the study period, they accounted for 20% (63 cases in three years).

Liver transplantation was required more commonly in the nonbodybuilding supplements group (13%, 12 cases) than in the medications group (3%, 21 cases).

Based on the DILIN severity score, people taking herbals and dietary supplements had more severe cases than did those on conventional medications, the researchers report in Hepatology, online August 25.

The 130 patients in the herbals and dietary supplements group reported taking a total of 217 products, with only a minority of those products having a single ingredient and with 10% (bodybuilding) to 13% (nonbodybuilding) of the products containing more than 20 ingredients.

"Contrary to widespread belief, this study demonstrates that herbals and dietary supplement products are not always safe," the researchers conclude. "Indeed, our data suggest that, relative to conventional medication-induced hepatotoxicity, liver injury from herbal and dietary supplements not only occurs, but also may be increasing in frequency over time in the populations surrounding the DILIN centers and, probably, in the United States as a whole."

"The DILIN is not a population-based study, and although there was an increasing proportion of disease attributable to herbals and dietary supplements during the study, it cannot be concluded that the problem is actually on the rise in the United States," they add.

"Ask patients if they use supplements and always suspect them to be a cause for any unusual presentation, liver disease or otherwise," Dr. Navarro concluded.

How can patients protect themselves from supplement-related liver injury? "First, discuss their use with a qualified physician who understands their specific medical history and has knowledge of their other medications," Dr. Navarro suggested. "Second, if they choose to use supplements, they should stay within the labeled recommendations. Last, they should report any new symptoms to their doctor."

Dr. Rolf Teschke from Goethe University Frankfurt/Main in Germany, who studies medication-related liver toxicity, said most herbals and dietary supplements carry some risk of liver toxicity.

The risk is small but unpredictable, he told Reuters Health by email, and may be related to genetic susceptibility.

"Physicians often are confronted with patients who have increased liver values of primarily unknown etiology," Dr. Teschke said. "Apart from questioning regarding synthetic drugs as possible cause, the use of herbals and dietary supplements should be excluded by thorough investigation and repetitive questionings, since they are considered as natural and thereby perceived erroneously as safe."

He also criticized DILIN's causality assessments for not being quantitative.

"Other experts in the field worldwide prefer the use of the scale of CIOMS (Council for International Organizations of Medical Sciences), which is liver specific, structured, and quantitative based on specific items which are individually scored by -3 to +3 points, while the sum of the individual scores provides the respective causality grading," Dr. Teschke said. "The CIOMS scale can easily be applied already at the bedside of the patient, with results quickly available without the time-consuming expert-based procedure."

"Herbal and dietary supplements commonly are mixtures of multiple ingredients which prevent a clear causality assessment to one single ingredient," Dr. Teschke said. "The DILIN method is not prepared assessing various comedicated compounds, as opposed to the CIOMS scale, which facilitates such assessment."


Hepatology 2014.

Wednesday, August 20, 2014

Experts denounce clinical trials of unscientific, 'alternative' medicines

Experts denounce clinical trials of unscientific, 'alternative' medicines

Experts writing in the Cell Press journal Trends in Molecular Medicine on August 20th call for an end to clinical trials of "highly implausible treatments" such as homeopathy and reiki. Over the last two decades, such complementary and alternative medicine (CAM) treatments have been embraced in medical academia despite budget constraints and the fact that they rest on dubious science, they say.
The writers, David Gorski of Wayne State University School of Medicine and Steven Novella of Yale University, argue that, in these cases, the medical establishment is essentially testing whether magic works. Gorski and Novella are both editors for Science-Based Medicine, an organization and blog dedicated to exploring the complicated relationship between science and medicine.

"We hope this will be the first of many opportunities to discuss in the peer-reviewed literature the perils and pitfalls of doing clinical trials on treatment modalities that have already been refuted by basic science," said Gorski. "The two key examples in the article, homeopathy and reiki, are about as close to impossible from basic science considerations alone as you can imagine. Homeopathy involves diluting substances away to nothing and beyond, while reiki is in essence faith healing that substitutes Eastern mysticism for Christian beliefs, as can be demonstrated by substituting the word 'god' for the 'universal source' that reiki masters claim to be able to tap into to channel their 'healing energy' into patients."

"Studying highly implausible treatments is a losing proposition," Novella added. "Such studies are unlikely to demonstrate benefit, and proponents are unlikely to stop using the treatment when the study is negative. Such research only serves to lend legitimacy to otherwise dubious practices."
What is needed, say Gorski and Novella, is science-based medicine rather than evidence-based medicine. Biologically plausible treatments should advance to randomized clinical trials only when there is sufficient preclinical evidence to justify the effort, time, and expense, as well as the use of human subjects.

"Somehow this idea has sprung up that to be a 'holistic' doctor you have to embrace pseudoscience like homeopathy, reiki, traditional Chinese medicine, and the like, but that's a false dichotomy," Gorski said. "If the medical system is currently too impersonal and patients are rushed through office visits because a doctor has to see more and more patients to cover his salary and expenses, then the answer is to find a way to fix those problems, not to embrace quackery. 'Integrating' pseudoscience with science-based medicine isn't going to make science-based medicine better. One of our bloggers, Mark Crislip, has a fantastic saying for this: 'If you mix cow pie with apple pie, it does not make the cow pie taste better; it makes the apple pie worse.' With CAM or 'integrative medicine,' that's exactly what we're doing, and these clinical trials of magic are just more examples of it."

Gorski and Novella call on patients to exercise their critical thinking skills when it comes to evaluating the evidence for or against any kind of treatment, whether it is deemed "alternative" or not. "Critical thinking will help patients learn to recognize when a course of treatment is not supported by data or to tell when a health claim from any practitioner is just too good to be true," Gorski said.

Trends in Molecular Medicine - Full Text Article
Clinical trials of integrative medicine: testing whether magic works?

A commonly assumed paradigm in evidence-based medicine: Bench to bedside: findings in basic science progress through cell culture and in vitro studies, then to animal models, then to clinical trials. Clinical trials in turn consist of preliminary Phase I/II trials, followed by larger randomized Phase III trials. Although it is true that each stage can ‘cross-pollinate’ other stages, it is generally assumed that treatments do not reach the clinical trial stage without having passed through the first three stages and demonstrated promise, and thus prior plausibility, in preclinical experiments. Clinical trials of complementary and alternative medicine (CAM) upend this paradigm, with treatments that have little or no prior plausibility based on preclinical experimentation being tested prematurely in clinical trials.

Full Text Article

Friday, August 8, 2014

Watch: Drug-Induced Liver Injury

Drug-Induced Liver Injury

As summer heats up, so do I. Now, where did I put that trashy romance novel? You too?

In any event, whatever your pleasure, check out ....

Clinical Liver Disease Special Summer Issue: Drug-Induced Liver Injury

Clinical Liver Disease (CLD) is a great starting point for anyone interested in learning more about hepatitis C and liver disease. The journal is a product of the AASLD and published every two months. Topics in the July issue include; liver injury caused by dietary supplements, acetaminophen overdose, and drug-induced liver injury in Chinese herbal medicine, to name a few.

The reader will find articles with full-text audio, and other interactive content for a pleasant viewing and listening experience.

Although, unlike my novel "Valley Of Love Under The Bridge To Nowhere" the journal is void of any real romance, no heart-pounding sizzle or fantasy, only facts, not even a swoon.

I did however have a romantic moment with Dr. Maddukuri, after viewing his video with Dr. Bonkovsky. The good doctors summarize their May 2014 publication; Herbal and dietary supplement hepatotoxicity.

After finishing the video, I was rather surprised at myself. In the end, a very distinguished Dr. Bonkovsky won my heart, I was moved when he inquired about liver injury, and green tea extracts. Its the little things that matter.

Tonight, while drinking iced coffee, and reading Fifty Shades of Grey, I will let myself fondly remember Dr. Bonkovsky.

Herbal and dietary supplements (HDS) include vitamins, minerals, herbs or other plant materials, and some can cause hepatotoxicity. HDS hepatotoxicity has risen almost threefold over the past decade, read more to learn what to look for....

Clinical Liver Disease
Special Issue: Drug-Induced Liver Injury (DILI)
Volume 4, Issue 1, pages 1–3, July 2014
Begin here....

Until next time, stay healthy.

Saturday, July 5, 2014

Dietary Supplements—A Poorly Regulated Danger

Dietary Supplements—A Poorly Regulated Danger 99740351Posted in: Nutrition

In a CNN Opinion piece, David S. Seres, MD, emphasizes the need for scientific evaluation of dietary supplements. In addition to vitamins and herbs, says Dr. Seres, supplements can include hormones and other pharmacologically active ingredients that can alter the efficacy and safety of medications and affect the body’s physiologic functions.

This year marks the 20th anniversary of the passage of one of the most skillful pieces of legislation ever to undermine the health of Americans: The Dietary Supplement Health and Educational Act of 1994. The result was to remove from regulation by the Food and Drug Administration any substances labeled as a dietary supplement.
Supplement companies claim that FDA regulation would unfairly deprive the public of access to potentially beneficial substances. Dr. Seres says the companies cite inappropriate data to support their claims and dismiss any evidence to the contrary. Yet most people—scientists and nonscientists alike—are unaware of the weaknesses in the scientific data on supplements.

It is time, says Dr. Seres, to reassess the regulation of dietary supplements, consider our priorities in how funding is granted for nutrition research, reeducate nutrition experts as well as the public, and be honest about our inability to offer definitive, safe, and effective nutritional recommendations.

Dr. Seres is an associate professor of medicine at the Institute of Human Nutrition at Columbia University Medical Center. He is also a Public Voice Fellow with the Op-Ed Project.

Read the full CNN Opinion piece here.

Of Interest:
Linking Herbal Supplements with Liver Injury
FDA UPDATE - Sometimes Drugs and the Liver Don't Mix

Monday, June 30, 2014

Common Herbal Supplement Can Cause Dangerous Interactions with Prescription Drugs

Good morning folks, over at Newswise, researchers at Wake Forest Baptist Medical Center reported ‘natural’ treatments like St. John’s wort can interact with other medications reducing effectiveness and cause treatment failure.

On a side note, according to SOVALDI's packet insert, found here,  St. John’s wort also has the potential to interact with our newly approved HCV drug SOVALDI:
Drugs that are potent P-gp inducers in the intestine (e.g., rifampin or St. John's wort) may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect of SOVALDI and thus should not be used with SOVALDI 


Common Herbal Supplement Can Cause Dangerous Interactions with Prescription Drugs

Newswise — WINSTON-SALEM, N.C. – June 30, 2014 – St. John’s wort, the leading complementary and alternative treatment for depression in the United States, can be dangerous when taken with many commonly prescribed drugs, according to a study by researchers at Wake Forest Baptist Medical Center.

The researchers reported that the herbal supplement can reduce the concentration of numerous drugs in the body, including oral contraceptive, blood thinners, cancer chemotherapy and blood pressure medications, resulting in impaired effectiveness and treatment failure.

“Patients may have a false sense of safety with so-called ‘natural’ treatments like St. John’s wort,” said Sarah Taylor, M.D., assistant professor of dermatology at Wake Forest Baptist and lead author of the study. “And it is crucial for physicians to know the dangers of ‘natural’ treatments and to communicate the risks to patients effectively.”

The study is published in the current online issue of The Journal of Alternative and Complementary Medicine.

To determine how often S. John’s wort (SJW) was being prescribed or taken with other medications, the team conducted a retrospective analysis of nationally representative data collected by the National Ambulatory Medical Care Survey from 1993 to 2010. The research team found the use of SJW in potentially harmful combinations in 28 percent of the cases reviewed.

Possible drug interactions can include serotonin syndrome, a potentially fatal condition that causes high levels of the chemical serotonin to accumulate in your body, heart disease due to impaired efficacy of blood pressure medications or unplanned pregnancy due to contraceptive failure, Taylor said.

Limitations of the study are that only medications recorded by the physician were analyzed. However, she said the rate of SJW interactions may actually be underestimated because the database did not include patients who were using SJW but did not tell their doctor.

“Labeling requirements for helpful supplements such as St. John’s wort need to provide appropriate cautions and risk information,” Taylor said, adding that France has banned the use of St. John’s wort products and several other countries, including Japan, the United Kingdom, and Canada, are in the process of including drug-herb interaction warnings on St. John’s wort products.

“Doctors also need to be trained to always ask if the patient is taking any supplements, vitamins, minerals or herbs, especially before prescribing any of the common drugs that might interact with St. John’s wort.”

Co-authors are Steven Feldman, M.D., and Scott Davis, M.A., of Wake Forest Baptist.
Funding was provided by the Center for Dermatology Research at Wake Forest Baptist.

Related:Linking Herbal Supplements with Liver Injury

Thursday, June 26, 2014

Linking Herbal Supplements with Liver Injury

Linking Herbal Supplements with Liver Injury

Despite the perceived safety of herbal and dietary supplements, they can cause serious liver injury. In the July issue of Clinical Gastroenterology and Hepatology, Simona Rossi and Victor J. Navarro discuss the scope, use, and regulation of herbal and dietary supplements, as well as the diagnosis of herbal and dietary supplement-induced liver injury.

Patients take dietary supplements for many reasons, including anxiety, obesity, diabetes, rheumatoid arthritis, cancer, cardiovascular disease, and pain.

Almost a quarter of patients enrolled in a long-term hepatitis C treatment trial reported using herbal and dietary supplements.

Rossi and Navarro explain that the ease of access to these supplements allows consumers to assume that they are safe and can be used without consequences. Most patients do not divulge use of dietary supplements to health care providers.

However, in the US National Health and Nutrition Examination Survey, 52% of respondents reported using a dietary supplement, and other surveys have reported even higher use. In some Asian and African countries, up to 80% of the population use herbal supplements as their primary means of medical care.

Rossi and Navarro discuss the incidences of injury caused by different supplements in different countries. These range from 1%–2% of cases of liver injury in Spain (with antibiotics being among the most common class implicated) to Singapore, where 71% of cases of drug-related liver injury have been attributed to medicinal herbs—many adulterated with active drugs.

The authors discuss preliminary findings from the US Drug-Induced Liver Injury Network (DILIN) showing that herbal and dietary supplements are responsible for an increasing proportion of hepatotoxicity cases.

Rossi and Navarro discuss the US Dietary Supplement Health and Education Act of 1994, in which manufacturers are required to attest to a product’s safety, but give no authority to the Food and Drug Administration (FDA) to approve the supplements before marketing. Routine analysis of products’ contents by the FDA is performed on only a random basis.

They present strategies for diagnosis of herbal and dietary supplement–induced liver injury, and the process for linking a drug or dietary supplement to liver injury. Products and ingredients associated with hepatotoxicity include weight loss supplements (Hydroxycut, Herbalife/green tea, and usnic acid), joint health supplements (flavocoxid- and glucosamine-based supplements), and bodybuilding supplements.

Attributing liver injury to any specific ingredient in herbal and dietary supplements is the single greatest challenge to clinicians and researchers interested in liver injury. Rossi and Navarro explain that even detailed chemical analyses of products, which are expensive and complex, do not always identify the agents responsible for injury. The authors propose using chemical analyses to identify ingredients common to products implicated in injury; proposed culprits could then be tested in formal toxicologic analyses.

Nonetheless, Rossi and Navarro state that a better understanding of the epidemiology of supplement-induced liver injury is needed, to identify the scope of the problem and the groups most affected, as well as to develop management and prevention strategies. Without more accurate estimates of the overall use of herbal and dietary supplements and more complete reporting of adverse events, it is impossible to determine disease prevalence and incidence.


Saturday, February 15, 2014

2014 - Complementary and alternative medications in hepatitis C infection

Complementary and alternative medications in hepatitis C infection

Good afternoon folks, welcome to another edition of Weekend Reading.

On this fine Saturday a couple review articles evaluating the safety and efficacy of treating HCV using complementary and alternative medicine is our topic.

Sadly, we know not everyone can tolerate the currently available treatments, nor does everyone respond. Recently, two oral agents simeprevir and sofosbuvir were FDA approved, improving cure rates with shorter treatment duration and for some people even without interferon.

Over the last few years with grave desperation we have witnessed an era where new agents are rapidly being developed to eradicate this serious disease. Possibly Gilead's combination pill - consisting of both agents sovaldi and ledipasvir, may hold great promise. Gilead's clinical trials seem encouraging, for example in one trial deemed ION 2 that included 440 treatment-experience or difficult to treat genotype one patients, (88) with cirrhosis; SVR rates were at 93.6 percent after 12 weeks of therapy - while the cure rate rose to 99.1 percent with 24 weeks of treatment.

Last week Gilead filed for U.S. approval of Ledipasvir/Sofosbuvir Fixed-Dose Combination Tablet for Genotype 1 Hepatitis C

Again, not everyone who needs HCV treatment will be cured, and not everyone who needs treatment will be treated, thus complementary and alternative medications will be part of the equation aimed at trying to control symptoms or in some aspect manage HCV, especially in developing countries.

Complementary Health Approaches
Previously, The National Institutes of Health reported many people living with the virus try complementary approaches to manage HCV, such as massage, deep breathing exercises, meditation, progressive relaxation, and yoga, others use complementary and alternative medications, especially dietary supplements. Although these alternative options may offer therapeutic benefits, no complementary or alternative medications has been shown to be effective against the hepatitis C virus.

Review Articles
The first article provided below; "Complementary and alternative medications in hepatitis C infection," published in World J Hepatol, 2014 January, offers a look at the therapeutic potential of complementary and alternative medications (CAM), and drug interactions between medical and complementary treatments, including drug-CAM interactions which may lead to a reduced therapeutic effect when used with HCV oral drugs simeprevir and sofosbuvir.

A second review article; Management of chronic hepatitis C in patients with contraindications to anti-viral therapy, published this year in Alimentary Pharmacology & Therapeutics, provides information on alternative treatments for people who cannot tolerate or decide against interferon-based treatments. In the article researchers reported on life interventions which were associated with biochemical improvement, and treatments that had anti-inflammatory and/or anti-fibrotic effects. However, they found other alternatives such as (ribavirin monotherapy, amantadine, silibinin, vitamin supplementation, etc.) did not have any beneficial effect or need to be tested in larger clinical studies, view the full article, here.

Complementary and alternative medications in hepatitis C infection

World J Hepatol 2014 January 27; 6(1): 9-16
Published online 2014 January 27. doi: 10.4254/wjh.v6.i1.9.

Dina L Halegoua-De Marzio and Jonathan M Fenkel. Dina L Halegoua-De Marzio, Jonathan M Fenkel, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States Author contributions: Halegoua-De Marzio DL and Fenkel JM both outlined, researched the topics wrote, and wrote the manuscript.

Chronic hepatitis C (CHC) infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Until recently, the only treatments available were pegylated interferon and ribavirin, which traditionally were not very effective and have considerable side effects. For this reason, interest in complementary and alternative medications (CAM) in the management of hepatitis C has been investigated. Some CAM has demonstrated therapeutic potential in chronic hepatitis C treatment. Unfortunately, some CAM has been shown to have the potential to cause drug-induced liver injury. This article will review and evaluate many of the natural molecules that interact with the hepatitis C virus (HCV) life cycle and discuss their potential use and safety in HCV therapy, as well as highlight some important interactions between medical and complementary treatments.

Core tip: Over the last 10 years there has been a substantial increase in reports of natural compounds displaying anti-viral activity against hepatitis C. At this time, there is no firm evidence supporting complementary and alternative medications for hepatitis C virus infection. Due to a limited number of trials and small numbers of subjects included in them, it is not possible to fully evaluate the risk of adverse events connected with the use of these products.

Hepatitis C virus (HCV) infection affects an estimated 180 million people globally and is a leading cause of chronic hepatitis, cirrhosis, and liver cancer[1,2]. To prevent the complications of chronic hepatitis C (CHC), the goal of therapy is complete viral eradication. For the past decade, a combination of pegylated interferon-α (peg-IFN) and ribavirin was used to treat CHC with disappointing viral eradication rates. These rates were particularly suboptimal in patients with genotype 1 HCV, which is responsible for approximately 60% of worldwide infections[3]. Sustained virological response (SVR) rates for genotype 1 HCV are approximately 40% following 48 wk of peg-IFN/ribavirin and are even lower in patients with HIV co-infection, high baseline viral load, advanced fibrosis, or those of African descent[4-7].

The life cycle of HCV can be divided into three major steps: (1) entry of the virus into its target cells by receptor-mediated endocytosis; (2) cytoplasmic and membrane-associated replication of the RNA genome; and (3) assembly and release of the progeny virions[8]. In recent years, there has been improvement in SVR rates with the development and approval of the first HCV-specific direct-acting antiviral agents (DAAs), namely boceprevir and telaprevir[9,10]. In contrast to the non-specific antiviral activity of peg-IFN and ribavirin, DAA are designed to inhibit viral proteins involved in the HCV life cycle. Still, the first DAAs require coadministration with peg-IFN and ribavirin, and many patients remain intolerant to treatment-associated side effects, including fevers, influenza-like symptoms, headache, cytopenias, fatigue, anorexia, rash, and depressive symptoms.

CAM is being used increasingly across the globe for many chronic diseases[11,12]. The Cochrane Library included nearly 50 systematic reviews of complementary medicine interventions as of 2003[13]. Many people turn to CAM when conventional medicine fails, or they believe strongly in its effectiveness. During the last few years, a substantial increase of reports on natural compounds displaying an anti-HCV activity has been published. There is data that some of these medicinal herbs might have therapeutic potential in CHC, or may alleviate side effects of conventional therapy[13]. CAM use is common among people with CHC. A survey of 1145 participants in the National Institutes of Health (NIH)-supported HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial found that 23% of the participants used herbal products[14]. Although sometimes thought by the public to be safer then conventional therapy, there are many reports about liver toxicity and other adverse events from some herbal products[11,15].

The aim of this review is to evaluate the efficacy and safety of treating HCV infection using complementary and alternative medicine.


An extract of the milk thistle plant, silymarin (Silybum marianum), has been used to treat chronic liver disease since the time of the ancient Greeks[16]. Owing to its purported hepatoprotective properties, it is the most commonly used herbal product by individuals with chronic liver disease in the United States[16,17]. A recent publication from the HALT-C study group indicated that 33% of patients with CHC and cirrhosis reported current or past use of silymarin[14]. A follow-up study found silymarin use among CHC patients was associated with reduced progression from fibrosis to cirrhosis, but had no impact on clinical outcomes[16].

The major active component of silymarin, silibinin (a mixture of the two diastereoisomers silybin A and silybin B), is thought to be responsible for silymarin’s hepatoprotective properties[18]. Silymarin appears to inhibit HCV infection at two or more different levels: (1) it inhibits HCV replication in cell culture; and (2) it displays anti-inflammatory and immunomodulatory actions that may contribute to its hepatoprotective effect[19,20]. The inhibition of HCV replication has been attributed to inhibitory action on the NS5B RNA-dependent RNA polymerase.

Clinical studies that have evaluated milk thistle for a variety of liver diseases have yielded inconsistent results and low bioavailability of oral silymarin components[21]. Studies with IV silibinin have shown substantial antiviral effect against HCV in liver transplant recipients, and even in nonresponders with good safety outcomes[22-24]. Although oral administration of silymarin is not effective for the treatment of HCV, intravenous silibinin formulation may represent a future potential therapeutic option.

Green tea extract
Green tea, made from the unfermented leaves of Camellia sinensis, is comprised of several polyphenolic compounds called catechins, and can be concentrated into a green tea extract (GTE). Epigallocatechin-3-gallate (EGCG) is the most abundant and potent catechin contained within GTE, comprising typically approximately 40% of the total polyphenol content[25]. EGCG is a potent inhibitor of HCV entry in primary human hepatocytes independent of the genotype, by blocking virus attachment. This novel inhibitor may provide a new approach to prevent HCV infection, especially in the setting of liver transplantation of chronically infected HCV patients[26,27]. Beyond its antiviral effect on HCV, EGCG may have potential use as a chemopreventative agent for hepatocellular cancer as EGCG may inhibit cancer cell growth. This mechanism of action is thought to be due to tyrosine kinase inhibition and modulation of target gene expression associated with induction of apoptosis and cell cycle arrest in cancer cells[28-34].

GTE is a common ingredient in several dietary supplements, some of which have been withdrawn from the market due to safety concerns. An example of this is Exolise (Arkopharma, France), a weight loss supplement containing high EGCG levels that was withdrawn from the market in April 2003 due to 13 cases of attributable liver injury[35]. Between 1966 and 2008, 216 case reports of toxicity with green tea extracts were identified by the United States Pharmacopeia, of which 34 were concerning for liver toxicity[36]. Recent animal studies with high doses of GTE and EGCG have described dose-dependent hepatotoxicity resulting in severe morbidity and mortality[37]. However, chronic moderate to high dose daily GTE and EGCG use in healthy human volunteers, and selected patients with cirrhosis, was safe and did not impair liver function[38-40]. Although GTE may be very useful in further treatment of CHC and prevention of HCC, its hepatotoxic potential must be acknowledged and monitored carefully in future studies.


HCV associates with β-lipoproteins [very low density lipoprotein (vLDL) and low-density lipoprotein (LDL)] circulating in blood[41]. In addition, HCV replication can be up-regulated by fatty acids and inhibited by statins; this suggests an interaction between HCV, cholesterol, and lipid metabolism[42]. Recent research has found that of HCV secretion is dependent on both apolipoprotein B (ApoB) expression and vLDL assembly in a chromosomally integrated complementary DNA (cDNA) model of HCV secretion[43].

Naringenin is the predominant flavanone present in the grapefruit and is responsible for its bitter taste. Naringenin has been shown to reduce cholesterol levels both in vitro and in vivo[44,45]. Furthermore, naringenin inhibits ApoB secretion by reducing the activity and the expression of the microsomal triglyceride transfer protein (MTP) and the acyl-coenzyme A cholesterol acyltransferase 2 (ACAT)[44,46]. Due to the close link between HCV assembly/secretion and lipoprotein metabolism, there has been extensive study on the impact of naringenin on the secretion of HCV particles[43]. A dose-dependent decrease of core protein, HCV-positive strand RNA, infectious particles, and ApoB has been observed in the supernatant of infected primary hepatocytes in culture after naringenin treatment[43]. Overall, naringenin blocked the assembly of intracellular infectious viral particles without affecting intracellular levels of the viral RNA or protein. Although still at the cell culture phase, naringenin may offer new insight into a promising and novel HCV therapeutic target.

Glycyrrhizin, a natural compound extracted from the roots of Glycyrrhiza glabra, has been used for more than 20 years as a treatment for chronic hepatitis[47]. It has been used for many centuries in traditional Chinese medicine as an anti-allergic agent. Because of its sweet taste it is also used as a food additive, for example in beverages and licorice[48]. In an attempt to use glycyrrhizin as a treatment for “allergic” hepatitis it was found to lower the transaminases. In a study by Suzuki et al[49] in 1977, plasma transaminases activity improved significantly with glycyrrhizin in patients with chronic liver disease compared to a placebo group.

The mechanism by which glycyrrhizin improves the biochemistry and histology in liver disease is unknown. It is thought to have anti-inflammatory, antioxidant and immunomodulatory activities. Due to this there has been much interest in use of glycyrrhizin in CHC. In the only randomized clinical trial of glycyrrhizin, ALT levels declined modestly during treatment, compared with placebo, but this was not sustained after cessation of treatment and there was no significant effect on HCV RNA levels[50]. In the another trial, statistically significant differences in liver enzyme levels, but not viral loads, between treatment groups were identified during treatment, however, again no sustained response occurred at follow-up[51]. Use of glycyrrhizin is not without side effects. It has been found to cause pseudo-aldosteronism, manifested by sodium retention, hypokalemia and hypertension[52]. Cardiac arrhythmia and acute rhabdomyolysis due to severe hypokalemia caused by excess licorice consumption have also been reported[52-54].

Oxymatrine is the major alkaloid extract from the root of sophora flavescens, a deciduous shrub native to China, Japan, South Korea and Russia. It is reported to have antiviral activity against HCV in cell cultures and in animal studies[55-57]. Clinical studies have shown that oxymatrine has some hepatoprotective activity in alcohol toxicity and hepatitis B infection, but not carbon tetrachloride, acetaminophen or cadmium chloride-induced acute hepatitis[58,59].

Oxymatrine is considered to be an antifibrotic, likely through inhibition of lipid peroxidation[60-62]. In a study of HCV-infected subjects randomized subjects to receive either an intramuscular injection of oxymatrine 600 mg/d or other support products such as oral vitamins 47% of the treated cases had complete HCV viral suppression after 3 mo, compared with only 5% in the control group[61]. No serious adverse events were reported. The treated group had significantly more ALT normalizations than the control group in the first 2 mo, but this improvement waned by the end of the third month of treatment. While treatment with oxymatrine holds promise, it is difficult to draw conclusions from the small studies currently available.

Traditional chinese herbal medications
The primary goal of Chinese traditional medicine is to create wholeness and harmony within a person, allowing the mind/body/spirit to heal itself. There have been several randomized clinical trials of traditional Chinese medicine in the treatment of hepatitis C, however, the methodological quality of these studies is generally considered poor[63-70].

In two trials of herbal formulations in combination with interferon-alfa, there was a trend toward greater clearance of HCV RNA and ALT normalization with the combination treatment compared with patients receiving monotherapy[63,64]. In the only placebo-controlled trial of solo therapy with traditional Chinese medicine, a significant reduction in ALT levels during treatment occurred, though no virologic effect was identified[69]. Detailed descriptions of adverse events were not provided for most of these trials. The safety of these medicines is unclear due to the individualized nature of many of the herbal compounds involved, the large number of different herbs in each formulation, and the relatively small number of subjects within each clinical trial.

Vitamin D
The traditional role of Vitamin D (Vit D) was thought to be based upon its interaction in calcium homeostasis, via regulation of intestinal calcium absorption and of bone health. However, over the last several years Vit D has been shown to have a much more complex role in many other host functions, including its interaction with chronic hepatitis C. 25-OH Vit D is made in the liver via cytochrome P450 (CYP27A1) activated hydroxylation of Vit D, brought into the body either by intestinal absorption or endogenous synthesis through sun-exposed skin. It is then converted to 1.25 OH Vit D (calcitriol) in the kidneys, the most active form, where it becomes available to bind to Vit D receptors throughout the body[71,72].

A growing body of clinical evidence has demonstrated an increased prevalence of Vit D deficiency in patients with CHC. As such, Vit D supplementation has been proposed as an adjunct to current standard regimens for treatment of hepatitis C[72]. One study found that mean 25-OH Vit D serum levels were significantly lower in CHC (25 μg/L) than in the controls (43 μg/L)[73]. Importantly, low Vit D has been linked to increased fibrosis and impaired sustained virologic response (SVR) in IFN-based therapy[71].

One clinical trial demonstrated that the addition of Vit D to the standard IFN plus ribavirin treatment significantly increased SVR in patients with genotype 1 CHC[74]. Regarding the underlying molecular mechanisms, an in vitro study showed that Vit D remarkably inhibits HCV production in Huh7.5 hepatoma cells[75]. These cells express Vit D hydroxylases and can eventually generate calcitriol. Notably, treatment with calcitriol resulted in HCV inhibition through induction of IFN-beta. Overall, 25-OH Vit D levels appear to be an important prognostic marker in helping determine the likelihood of SVR. 25-OH Vit D levels should be checked routinely before HCV treatment and supplementation provided to deficient patients, in an effort to enhance treatment response.

Antioxidants are one of the most common dietary supplements taken by patients with CHC[14]. The use of these supplements is based on the fact that oxidative stress has been attributed to both host inflammatory processes and induction by viral proteins. By increasing antioxidants, one may be able to decrease oxidative stress and therefore decrease liver injury[76]. Existence of oxidative stress in CHC is well documented, as oxidized protein and nucleic acid markers are increased and antioxidant levels are decreased[77-80]. Studies have shown levels of oxidative stress markers to correlate with disease severity, HCV RNA, iron overload, and insulin sensitivity[78,79]. Oxidative stress has also been shown to be an early event in carcinogenesis and is a risk factor for development of HCC in patients with chronic HCV[81].

Multiple trials have shown antioxidants, such as Vitamin E and N-acetyl cysteine, only lead to small reductions in ALT after chronic administration in some instances[82-93]. Further, the decrease in ALT levels in most studies is marginal and is not sustained after stopping the treatment, raising the question of their clinical significance. No study has shown an improvement in outcome. In addition, no study has shown clear benefit of antioxidants as adjuvant to interferon based therapy of HCV. At the doses studied, these antioxidants appear to be well-tolerated, with no specific adverse events reported in any of the trials. However, very large oral doses of N-acetyl cysteine are commonly associated with nausea and vomiting and intravenous administration of N-acetyl cysteine can result in anaphylactoid reactions, which may be more common in patients with chronic liver disease[94]. Therefore, evidence supporting use of antioxidants as useful therapeutic agents in CHC is lacking.


Drug-related hepatotoxicity is a serious health problem, with broad implications for patients, healthcare providers, the pharmaceutical industry and governmental regulatory agencies. The Drug Induced Liver Injury Network (DILIN), a federally funded consortium of 12 centers in the United States, recently reported the preliminary results of its prospective study[94]. Dietary supplements were implicated in 9% of reported DILI cases. This may be potentially related to increasing use of herbal or dietary supplements in the US population. The importance of these supplements as a cause of DILI is further underscored by a retrospective Japanese study, in which 10% of 879 cases of single agent DILI from 1997 to 2006 were attributed to dietary supplements and 7% to Chinese herbal drugs[95]. 

Telaprevir, Boceprevir, Simeprevir and Sofosbuvir
Another major area of awareness when patients are considering using CAM is whether or not drug-CAM interactions may exist that could impact the medical therapy. This issue is becoming even more complicated with the addition of new medications for the treatment of CHC infection such as simeprevir and sofosbuvir approved for use in the U.S. in December 2013. St. John’s wort (Hypericum perforatum), a common CAM used for the treatment of depression, is an inducer of cytochrome P450 3A4[99].

This cytochrome is also the primary metabolizer of many medications, including the HCV protease inhibitors: telaprevir, boceprevir, and simeprevir. Additionally, St. John’s wort is a potent intestinal P-gp inducer and may lead to a reduced therapeutic effect of the HCV nucleotide polymerase inhibitor sofosbuvir[100]. Concomitant use of St. John’s wort and these HCV treatments is contraindicated and can lead to treatment failure by reducing blood concentrations. Additionally, concomitant use of milk thistle use is contraindicated with simeprevir. This combination may increase levels of simeprevir by milk thistle CYP3A inhibition leading to possible toxicity[101] (Table 1). Garlic extracts, grapefruit juice, and germander also have cytochrome P450 3A4 interactions[102].

Many human studies have shown improvements in subjective symptoms and liver biochemistries in HCV patients with CAM, but there is no convincing data to suggest a definite histological and/or virologic improvement with any of the herbal agents currently available. Vit D seems to have the best available data as adjunctive therapy to antiviral medications in patients with Vit D deficiency. Poorly designed studies, heterogeneous patient populations, lack of standardized preparations, and poorly defined nonobjective end points may partly explain the conflicting reports in the literature.

The safety profiles of the interventions discussed within this review are encouraging at the doses studied. However, the long-term safety for use in the treatment of hepatitis C, either alone or in combination with conventional medicines, has not been established. Comparative and placebo-controlled trials suggest that patients experience no more adverse events with these interventions than with placebo or comparative medications, although short-term clinical trials are not designed to detect rare or delayed adverse events. Physicians need to be cognizant of known or occult use of CAM by their patients because hepatotoxicity and drug interactions may occur with many herbal medications, and may occur more frequently in patients with chronic liver disease.

There is an undoubted need for further research into the treatment of hepatitis C, and this review has identified several promising compounds, including Vit D, silymarin, oxymatrine, naringenin, and GTE. Some or all of these may be integral components of future HCV management.

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