Can Food Or Herbs Interact With Conventional Medical Treatments?

Can food or herbs interact with conventional medical treatments?
Most consumers assume that herbs and botanical products in dietary supplements are safe, however they are not regulated by the FDA, in addition these products can interact with prescription drugs, over-the-counter drugs, and other dietary supplements. Because milk thistle is the most commonly used herbal supplement in the United States for liver problems, we explore how this herb may cause potential interactions when used with conventional medications, including direct-acting antivirals (DAAs) for the treatment of hepatitis C infection. Finally, with several experimental studies suggesting that silymarin may have beneļ¬cial effects in chronic liver diseases, particularly in nonalcoholic steatohepatitis (NASH), an overview of data is offered as well.

If you are new to the world of hepatitis C or liver disease, you may find this summary of key research about herb-drug interactions and safety information beneficial. However, if you are a savvy patient, you may find this post repetitive, no doubt you have done your homework, good for you!

Green Tea & CYP3A4
Green-tea (Camellia sinensis) is a popular botanical beverage and has become the raw material for extracts used in various beverages, food products, and dietary supplements.

We begin with a review article investigating possible herb-drug interactions between herbals and prescription medications, published in the British Journal of Clinical Pharmacology.

Researchers found a number of herbal products that may affect the properties of prescription drugs, leading to alterations in the drugs' effectiveness as well as potentially dangerous side effects. For instance, green tea products may interfere with the action of an enzyme called CYP3A4, mainly found in the liver and small intestine, and used to help break down medications. When the enzyme is blocked, a medication enters the blood and stays in the body longer, resulting in the potential to raise drug levels, causing serious side effects. When the enzyme is lowered it may reduce a drugs overall therapeutic effect. The study pointed out a patient who complained of extreme leg cramps after consuming green tea while taking blood pressure medication - amlodipine, and a medication used to lower cholesterol - simvastatin. Researchers noted this interaction was attributed to an increase levels of simvastatin lactone due to inhibitory effect of green tea on the enzyme CYP3A4.

In the journal Hepatology, published: 27 September 2016, researchers investigated 700 cases of liver damage reported to the Drug Induced Liver Injury Network (DILIN), with around 130 linked to dietary supplements. Although the study is not new, it clearly shows the dangers of induced liver injury from herbal and dietary supplements. A contributing factor is green tea extract (GTE), and a large number of products advertised as weight loss agents contain GTE. An article by Lauren Cooper, available online at Consumers Reports detailed the Hepatology study. Cooper writes: products listing green tea extract—either as a single ingredient or as part of a blend—contributed to liver damage in 24 of the 130 cases linked to dietary supplements, reported. Cooper explains; These supplements are not the beverage made from brewing tea leaves in hot water. Instead, they are pills containing concentrated amounts of particular compounds found in green tea. For more information about the study read the complete article, here.

In 2017, Health Canada ordered a more explicit warning on labels of green tea extract products over concerns about the risk of liver injury. In 2003, France and Spain banned a green tea extract called Exolise, after it was linked to liver damage.

Herbal assault: liver toxicity of herbal and dietary supplements
Finally, an editorial published in the March 2018 issue of The Lancet Gastroenterology & Hepatology, warned that patients are more at risk for sever herbal and dietary supplement-induced liver injury outcomes; died or required liver transplantation, than liver injury from conventional medications.

Excerpt
New evidence is also emerging that the type of liver injury caused by herbal and dietary supplements might be particularly dangerous. In a report from the Spanish DILI registry, most cases of herbal and dietary supplement-induced liver injury reported between 1994 and 2016 had a hepatocellular pattern with very high alanine aminotransferase values—features associated with increased risk of severe outcomes. Indeed, a greater proportion of patients with liver injury attributed to supplement use died or required liver transplantation compared with cases attributed to anabolic steroid use or conventional medications. In a prospective registry study from the USA, higher transplantation rates and lower survival—but no difference in type of liver injury—were reported among patients with liver injury caused by so-called complementary and alternative medications compared with that of patients with prescription drug-related liver injury.....

Grapefruit & CYP3A4
Grapefruit juice is a classic example of food–drug interaction, seville oranges, limes, and pomelos, produce drug interactions similar to grapefruit by inhibiting intestinal CYP-3A4.

These interactions depend on juice volume and may change among different drugs. However, research has shown one whole grapefruit, or a glass of grapefruit juice; is enough to cause increased drug levels. Its not always beneficial taking medications and grapefruit products hours apart, even 72 hours later the juice can still have an effect, leaving elevated concentrations of the medication in the body.

Short List: Medications That Interact With Grapefruit
Some medications that interact with grapefruit include; statin drugs to lower cholesterol, such as Zocor (simvastatin) and Lipitor (atorvastatin), drugs that treat high blood pressure - Procardia and Adalat CC (both nifedipine, organ-transplant rejection drugs, for example Sandimmune and Neoral (both cyclosporine), anti-anxiety drugs, for instance buspirone, corticosteroids that treat Crohn’s disease or ulcerative colitis, which include Entocort EC and Uceris (both budesonide), drugs that treat abnormal heart rhythms - Pacerone and Nexterone (both amiodarone), and antihistamines -  Allegra (fexofenadine), for a list of additional drugs, click here.

Milk Thistle & HCV
Before the FDA approval of interferon-free oral therapies to treat the hepatitis C virus (HCV), milk thistle was commonly used by people living with the virus. Milk thistle taken orally does not appear to have any beneficial or toxic effects on the liver and it does not significantly alter HCV RNA levels (viral load). No dietary supplement has been shown to be effective for hepatitis C or its complications. Patients who continue to take milk thistle should be warned about the gastrointestinal and hypoglycemic side effects, and the potential for drug-drug interactions.

Ask the Doctors: Potential benefits of milk thistle need further study in humans 
This month Tulsa World, published an article with an overview of Milk Thistle, written by Robert Ashley, M.D., an internist at the University of California, Los Angeles. The good doctor answered the following question;

Dear Doctor: What are the pros and cons of taking milk thistle?
Dear Reader: Let’s begin with some background on this purple-flowered plant that most people in this country think of as an invasive weed. It’s a member of the thistle family, so-named for the sharp projections upon the leaves and stems. Although it originated in Europe, milk thistle (Silybum marianum) has made its way to many parts of the world, including the hills of Southern California, where I’ve pricked my legs on it many times while hiking. Nuisance or not, however, the seeds of the plant have been used for medicinal purposes for more than 1,000 years. That’s because they contain silymarin, a mixture....

Milk thistle & botanical products containing St. John's wort and Ginkgo
Milk Thistle, also known as Silybum marianum may significantly slow down the activity of the liver enzyme CYP3A4, raising the potential for drug-herb interactions. According to a 2008 study, people with HCV - rather they had cirrhosis or not - that used relatively small concentrations of milk thistle significantly slowed down the activity of the enzyme CYP3A4 by 50% to 100%. Botanical products containing St. John's wort and Ginkgo had the greatest number of documented interactions with prescribed drugs.

Milk Thistle & HCV Therapy
In order to avoid any unforeseen interactions, patients should discuss any herbal and dietary supplements they are taking before starting hepatitis C treatment. Check out this list of medications that interact with HCV agents, available online in the journal Clinical Liver Disease; Drug‐drug interactions in hepatitis C virus treatment: Do they really matter? published 30 November 2017.

Milk Thistle - St. John's Wort & Simeprevir Containing Regimens
Taking drugs that are moderate or strong inducers - or inhibitors of CYP3A - with simeprevir containing regimens *Olysio/Sovaldi FDA approved in 2014, may significantly increase the potential to either amplify or weaken the action of simeprevir, resulting in reduced therapeutic effect or adverse reactions. See prescribing information.

St. John's Wort & HCV Therapy
St. John's Wort (SJW) had been identified as an inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), and shown to increase the metabolism of the following HCV drugs, resulting in decrease drug concentrations and reduction in efficacy; Vosevi, Mavyret, Epclusa, Zepatier, Viekira Pak, Technivie, Harvoni, Daklinza, Olysio, and Sovaldi.

Milk Thistle & Fatty Liver Disease - An Update
In the United States, fatty liver disease is reaching epidemic proportions, in particular a more serious form referred to as Nonalcoholic steatohepatitis (NASH) is predicted to become the leading cause of liver transplants by 2020. The following study investigated the efficacy of silymarin (the extract from the seeds of the plant Silybum marianum, also called milk thistle) in patients with NASH.

A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis
In a 2017 randomized, double-blind, placebo-controlled trial, published in Clinical Gastroenterology and Hepatology, the efficacy of silymarin in patients with nonalcoholic steatohepatitis (NASH) was reported to improve fibrosis. I highly suggest you read an overview of the study, with commentary by Atif Zaman, MD, MPH, available online over at NEJM Journal Watch.

Excerpt:
This small but well-designed and well-executed randomized study demonstrated that 48 weeks of silymarin therapy was not more effective in achieving global histologic improvement in NASH compared with placebo. However, significant fibrosis improvement was noted in the silymarin group, possibly reflecting the antifibrotic effect of silymarin. As degree of fibrosis has been shown to be the key driver of morbidity and mortality among NASH patients, further studies of silymarin alone or in combination with other candidate NASH drugs are warranted, especially as silymarin appears to be safe and well tolerated.

Full-Text @ Clinical Gastroenterology and Hepatology

Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR
This particular study may be of interest to people with HCV, according to data published Mar 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals.

Recommended Reading
In January of this year, AASLD updated practice guidelines for both the "Diagnosis and Management of NAFLD" and "Treatment of Hepatocellular Carcinoma"

Which supplements can cause liver toxicity?
To help aid your decision-making process, here is a list of dietary supplements that may cause damage to the liver, found online at consumerlab.com.

National Institutes of Health
NIH has fact sheets on dietary supplements at ods.od.nih.gov/factsheets/list-all/. NIH also recently launched an online Dietary Supplement Label Database at www.dsld.nlm.nih.gov. This free database lets you look up the ingredients of thousands of dietary supplements. It includes information from the label on dosage, health claims, potential interactions with other medicines or supplements and cautions.

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