Liver damage from supplements

The FDA also reviews the data gathered at each phase to ensure safety before approving the next phase of testing. Then, at the end of phase three, all of the clinical data about the drug are submitted to the FDA for their review. In addition, before the drug can be approved, the FDA brings in an independent panel of experts to review all of the data and materials. Finally, after the drug has received FDA approval and can be prescribed, physicians are obliged to report any instances of possible adverse drug reactions to the FDA sponsored MedWatch program. This last type of monitoring is referred to as post-marketing surveillance.

Ironically, consumers, physicians, and the pharmaceutical industry have sometimes criticized this rigorous evaluation process for drugs. These critics claim that the process causes unnecessary delays in the release of potentially life-saving cures. I feel, however, that these procedures are necessary to safeguard the health of the public. Indeed, despite this demanding process, we still occasionally hear of previously unrecognized, terrible adverse reactions to drugs that already have been approved by the FDA. The diabetic drug, troglitazone (Rezulin), comes to mind.

Troglitazone was considered a novel medication for the treatment of adult onset diabetes. It was not until after the drug had received FDA approval and was in wide use that it became apparent that troglitazone could cause severe liver injury and death. (This tragic story actually came to light through the persistence of an investigative reporter at the LA Times.) The drug has since been removed from the market, but it reminds us that we must be vigilant when taking any medication or supplement.

Back to the dietary health supplements. More research, including clinical studies, is needed on the effectiveness and safety of dietary supplements. As a matter of fact, I am not aware of published data in peer-reviewed medical journals from Phase 1 or Phase 2 studies on these supplements. Nor do I know of randomized controlled trials that have been conducted on dietary supplements to show safety, let alone effectiveness.

On the other hand, it is important to recognize that few manufacturers of health supplements have the resources (money) to carry out valid RCTs because these trials are extremely expensive to run. Moreover, at present, no federal funding for the FDA is available to actively study and monitor the adverse events associated with these supplements. Nevertheless, more regulation of dietary supplements is needed and should be instituted. In this regard, a White House Commission on Complementary and Alternative Medicine (CAM) recently released its somewhat controversial report after two years of study. The good news is that the report called for more funding for valid scientific research on the benefits and hazards of CAM, including dietary supplements.

As a final note, I would like to caution our readers. A drug is a drug, whether it is a medication or a dietary supplement. Moreover, any drug can interact with another drug and result in a serious adverse event. For example ginkgo biloba, which is an herbal product touted to improve memory, can react with ibuprofen (Motrin) to cause severe internal bleeding. Don’t go by what is said in an advertisement about a drug or dietary supplement. Rather, look critically at the data about the product. When you see your physicians, let them know about all drugs you are taking, including supplements. In your interest, they should know this. In fact, I have learned to ask, not just once but several times, whether my patients are taking any dietary supplements, especially herbal products. If you don’t feel well, stop the supplement immediately and consult a physician. Don’t withhold information from your physician about your supplements.

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Many Popular Dietary Supplements Can Yield Dangerous Liver Results

Athletes often use over-the-counter products to help lose weight or improve their energy and performance levels.

However, the vast majority of herbal and dietary supplements (HDS) never undergo formal efficacy or safety tests because their manufacturing, production and content are not closely regulated by the Food and Drug Administration, says Robert Fontana, M.D., University of Michigan’s medical director of liver transplantation, and Ammar Hassan, M.D., a U-M hepatology fellowship graduate, who have explored several over-the-counter HDS products linked to liver injury.

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As the number of HDS products available in the United States continues to grow, more than 80,000 commercial products are available to consumers, with nearly 50 percent of adults reporting regular use of at least one kind of supplement. Many adverse effects are linked to consuming HDS products, including hepatotoxicity, or chemically induced liver damage, according to the Drug-Induced Liver Injury Network.

Fontana and Hassan explored several popular over-the-counter HDS products linked to liver injury in a recent article in Seminars in Liver Disease. Here is a rundown:

Bodybuilding supplement hepatotoxicity

The majority of bodybuilding HDS products that lead to liver injury appear to contain androgenic anabolic steroids (AAS) or are contaminated with these and other chemicals.

AAS are synthetic derivatives of testosterone. Some medical conditions require the use of AAS products, including primary male hypogonadism and hereditary angioneurotic edema, but athletes use many of these steroids without medical supervision for their performance-enhancing and muscle-building properties.

SEE ALSO: Troubling Trends in Drug-Induced Liver Damage

“The use of these products is very common among amateur and professional athletes, including many active-duty military personnel,” Fontana says. “Data suggests that 69 percent of these individuals use at least one HDS product, while 22 percent report using more than three a day.”

These products are often purchased at health food stores or online in bulk. Over the past two decades, a significant increase in the incidence of liver injury related to the illicit use of AAS has been reported.

“Bodybuilding supplements that contain AAS can lead to liver damage, including severe cholestatic hepatitis, which can take months to resolve,” Fontana says. “Additionally, various multi-ingredient nutritional supplements taken to enhance energy, increase performance and facilitate weight loss can lead to potentially severe, or even fatal, liver damage.”

Non-bodybuilding supplement hepatotoxicity

Some of the most frequently used non-bodybuilding supplements associated with hepatotoxicity include green tea extract and multi-ingredient nutritional supplements that contain both botanicals and other compounds. These products include familiar names like Hydroxycut, Oxy ELITE Pro and LipoKinetix.

Green tea extract, or GTE, is derived from unfermented leaves of the Chinese tea tree, Camellia sinensis. One of the active ingredients in GTE is epigallocatechin gallate, which is a catechin, or a compound that is abundant in teas, cocoa products and certain berries. It boasts purported weight-loss properties by stopping fat-causing lipogenic enzymes.

While the public tends to view HDS products as safer than most conventional medications because they are derived from plants and other “natural sources,” this is not always the case, Fontana says.

“Various animal studies have shown the hepatotoxic (and possibly deadly) potential of GTE,” he says. “Extreme levels of GTE will lead to elevated aminotransferase (enzymes) in mice that significantly reduce their survival rates.”

Further, the Drug-Induced Liver Injury Network reported a study in which six patients who took GTE-containing Slimquick weight-loss products suffered hepatocellular injury, while four of the six were also severely jaundiced. Additionally, three patients from this group were hospitalized, and one had to have a liver transplant.

Hydroxycut hepatotoxicity

The first reported incidents of hepatotoxicity attributed to ephedra-containing Hydroxycut involved 12 patients in the U.S. who developed severe hepatitis after consuming supplements. Of the patients, 75 percent were female, with a mean age of 38.

It took an average of just eight weeks for an individual to develop hepatocellular injury after taking Hydroxycut.

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Eight of these patients recovered from their liver damage, while three underwent liver transplantation, Fontana says. One patient died before transplantation.

At least 17 additional cases of Hydroxycut-associated liver injury have been reported with similar phenotypes of liver injury and outcomes. And in 2004, the FDA banned the sale of supplements containing ephedra.

In May 2009, the FDA published a warning about Hydroxycut-related hepatotoxicity, resulting in withdrawal of 14 Hydroxycut products from the market.

“Without regulations like standardized chemical analyses and product manufacturing guidelines, it is nearly impossible to determine the exact chemical makeups for these types of supplements,” Fontana says. “And that just adds another element of danger to consuming them.”

Fontana has received research grants from AbbVie, Gilead Sciences and Bristol-Myers Squibb. He also provides consulting services for Alnylam Pharmaceuticals.

PMC

G&H How common is supplement-induced liver injury in the United States?

VN That is a difficult question to answer because the true number of people who sustain liver injury is not known. Not all people with liver injury go to a doctor, and among those who do go, not all are ill enough to be identified by the doctor. Many times, the doctor might not even ask the proper questions to determine whether a patient has been taking supplements. Therefore, it is unclear how often supplement-induced liver injury actually occurs. What is known is that more than half of US adults use some type of supplement and that the use of supplements is likely on the rise, based upon the number of supplements being sold and the amount of money being spent on them. Doctors have also recently been noting that, in their experiences, more and more patients are presenting with liver disease or injury from supplements. Thus, we can make the assumption that liver injury from supplements is becoming more common.

G&H Which supplements seem to be associated with liver injury?

VN Right now, the supplements most likely to cause liver injury are thought to be those that improve one’s physical performance, endurance, and appearance. An example is bodybuilding supplements, which are most commonly used by young men. The other most likely cause of supplement-induced liver injury involves over-the-counter weight-loss supplements. There are currently numerous supplements that fit this category; there is no one particular supplement that is especially injurious.

We are trying to understand whether there is one particular ingredient of these supplements that might be causing injury, but not even that much is known. It is suspected that there might be several injurious ingredients that are more likely to be present in, for example, weight-loss supplements. One such ingredient may be green tea extract, which refers to an extract of the plant, not the green tea that people drink. In very high doses, it is possible that green tea extract may cause liver injury. In addition, it has been suspected that bodybuilding and performance-enhancing supplements may be tainted or may contain anabolic steroids, many of which are illegal and should not be present in those products.

G&H Are any traditional herbal medicines associated with liver injury?

VN There might be. It is challenging to answer this question because liver injury is fairly rare and traditional herbal medicines are often dispensed from herbal practitioners without a label; thus, it is not clear what is actually contained in these products. My colleagues and I are currently in the process of conducting research examining what is included in common herbal products to determine what might be the cause of liver injury, but we do not know yet.

G&H What are the possible mechanisms behind supplement-induced liver injury?

VN Liver injury is probably an idiosyncratic (ie, unpredictable) phenomenon. It might have something to do with the dose that people take; people may be taking too high of a dose because there is no governmental or research control on what exact dose should be taken. It might be the way that people take these supplements. For example, if people take certain types of supplements when they are fasting, there might be an increased chance of causing injury. It might be that there is a genetic predisposition to liver damage from some supplements. Patients who experience liver injury from appearance- or performance-enhancing supplements tend to be young men who almost always present in the same way (with very severe jaundice and itching) and who all improve several months after discontinuation of the supplement. The pattern is so consistent that there has been some speculation that there might be a genetic predisposition for this type of liver injury. However, if there is, it has not yet been found.

G&H How can liver injury be diagnosed?

VN The first step is that providers have to understand that the possibility of liver injury exists, and that is usually because the patient presents with jaundice or has elevated liver injury test results and does not feel well. Whenever a patient presents with suspected liver injury or damage, it is important to obtain a careful history and find out whether he or she has been taking any supplements. Next, providers have to make sure that the patient’s symptoms are not caused by anything other than supplements. There are many causes of liver injury, such as viruses, gallstones, and alcohol, so providers have to exclude all of these causes when examining patients. By excluding other causes in a patient with a history of supplement use, providers can make a diagnosis of medication- or supplement-induced liver injury with greater confidence. A liver biopsy is not necessary to make the diagnosis, although it can reveal the severity of the injury.

G&H How should these patients be managed?

VN There is no specific treatment for liver injury caused by supplements except to stop the injurious supplement and watch the patient.

It is also important to keep in mind that some forms of supplement-induced injury can look just like treatable causes of liver disease, and vice versa. A good example is autoimmune liver disease, in which the immune system, for reasons that are unclear, causes inflammation in the liver. Another possibility is that medications can trigger the immune system to cause injury in the liver. These patients can be treated with corticosteroids, which can help attenuate the degree of liver disease.

G&H Is it always necessary to completely stop use of the injurious supplement?

VN If there is suspicion that a supplement is causing the injury, then use of that supplement should be completely stopped and should not be restarted because it is not exactly known why people develop liver injury. If the injury is actually triggered by an immune reaction, for example, then even a smaller exposure can cause a more severe reaction.

G&H Can injury to the liver usually be reversed?

VN Most people do recover; it is very rare that a person who develops severe liver injury does not get better. In particular, liver injury from appearance- and performance-enhancing supplements is almost always, if not always, recoverable. People do not die from this type of liver injury, although there may be a very prolonged period of illness with jaundice, itching (a common symptom of liver injury), and missing work.

However, clinicians should be particularly cautious when managing the subset of patients who have severe jaundice (ie, high bilirubin levels) as well as very elevated liver injury test results, indicating the presence of a large amount of inflammation in the liver. The combination of high bilirubin levels and liver injury test results induced by medications, which may also be true for supplement-induced liver injury, may indicate that the patients are at risk for becoming very sick, even to the point of needing a liver transplant or dying from the liver injury.

G&H How does supplement-induced liver injury compare with medication-induced liver injury?

VN Probably the most important difference is that the outcome of supplement-induced liver injury can be more severe than medication-induced liver injury. In our research, my colleagues and I have found that patients who had supplement-induced liver injury were more likely to need liver transplantation than patients who had liver injury from medications.

G&H Are there any regulations surrounding herbal and dietary supplements?

VN The regulatory framework for herbal and dietary supplements is the Dietary Supplement Health and Education Act, which was written in 1994 and has undergone several amendments since then. In essence, the law states that a manufacturer does not need to prove that the product it is selling is safe in animals or humans. However, although safety does not have to be proven, the manufacturer must say that the supplement is safe. Also, the manufacturer is restricted in the claims that it can make; it is not allowed to say that a supplement can cure or treat disease.

In addition, if a manufacturer becomes aware of a severe reaction to its supplement, the manufacturer is supposed to report it. The manufacturer is also supposed to truthfully portray on the supplement’s label what is actually included in the product. However, there have been many examples in which it is clear that what was in the product was not on the label, and vice versa. Thus, these regulations are imperfect. They are not designed to prove the safety of the products in humans, and in many circumstances, most of these products have never been tested in humans. Therefore, it is unclear whether the supplements even have the capacity to cause injury of the liver or other organs, for that matter.

G&H Are there any databases of liver injury induced by supplements?

VN My colleagues and I are currently compiling a research database through the Drug-Induced Liver Injury Network (DILIN). There are also databases that are maintained by the government, for example the Office of Dietary Supplements, which has an extensive database of supplements and some toxicities. However, I believe that the DILIN is the only database that focuses on banking cases of liver injury from supplements. The DILIN has shown us that there is an increase of liver injury cases among its study group and that the proportion of these cases that are caused by supplements is also increasing. We suspect that the majority of cases are occurring because of either appearance- and performance-enhancing supplements or weight-loss supplements, and it appears that their use is becoming more prevalent.

G&H Do you have any advice for doctors managing patients who are interested in taking supplements or who may have liver injury?

VN Doctors should always ask patients during office visits whether they are taking, or thinking of taking, supplements and, if they are, should state the importance of not exceeding the dosage listed on the label. It is unclear whether the label actually has any rationale behind it for dosing, but exceeding the dose makes no sense and might put the patient in harm’s way.

In addition, doctors should keep in mind that most vitamins and minerals or multivitamins are safe when used as directed. However, once manufacturers start adding multitudes of ingredients and then bringing in natural products such as herbs (perhaps in high concentrations, which in and of itself is difficult to judge because of the lack of standards for appropriate concentrations of herbals in a supplement), the product may become unsafe. Also, it is important that providers remember that dietary supplements are intended to supplement the diet. That means that there should be some deficiency that the supplements are treating or improving. However, most supplements, particularly performance-enhancing and weight-loss supplements, do not follow this guideline. It is important that providers keep in mind that supplements are not required to be tested for safety in humans. The public has the perception that all supplements are safe, and the vast majority are; it is the rare patient who becomes ill.

G&H What are the next steps in research in this area?

VN My colleagues and I are trying to develop a better understanding of the actual culprits of liver injury. We are collecting products that we think cause injury to patients and are digging deep into the products to analyze them chemically and determine whether there are common patterns or types of ingredients that might be the actual causes of liver injury.

Turmeric supplements are popular these days, but for one woman in Arizona, taking a turmeric supplement may have triggered an uncommon liver problem, according to a new report of the case.

What’s more, the link between the woman’s liver problem and her turmeric supplement use wasn’t identified by her doctors — but rather by the woman herself, after she consulted the internet.

Until the woman brought it up, her doctors weren’t aware that she was taking a turmeric supplement, and the case underscores the need for doctors and patients to communicate about the supplements that patients are taking, the report’s authors said.

The report, by researchers at the University of Arizona, was published Sept. 10 in the journal BMJ Case Reports.

Turmeric as a supplement

Turmeric is perhaps best-known as a spice in curry powder, but some studies suggest that it has anti-inflammatory properties. Early research suggests that turmeric may help with certain conditions, such as osteoarthritis and rheumatoid arthritis, but more research is needed on its benefits, according to the National Institutes of Health (NIH).

In the new case, the 71-year-old woman started taking turmeric supplements after she read a news article about a study in animals that suggested turmeric may help prevent stroke. She was also taking 20 other medicines and supplements. Her health care providers knew about most of these medicines and supplements, but not the turmeric.

About eight months after she started the turmeric supplements, a blood test showed elevated levels of liver enzymes — a sign of liver problems, the report said.

Further tests revealed the woman had a condition called autoimmune hepatitis, in which the body’s immune system attacks the liver, causing inflammation and liver damage, according to the NIH.

After her diagnosis, the woman was monitored closely without receiving specific treatment. But three months later, she told her doctor she had stopped taking turmeric, after she read on the internet about a possible link to liver problems.

This was the first time the woman had told her doctors about the turmeric supplement. And her suspicion about its tie to her liver problems may have been right — after she stopped taking the turmeric supplement, her doctors noticed a rapid decrease in her levels of liver enzymes, the report said.

It’s known that in about 10 to 15 percent of people with autoimmune hepatitis, the condition is triggered by drugs or supplements, the report said. In these cases, the condition is called drug-induced autoimmune hepatitis. It’s unclear how drugs or supplements trigger drug-induced autoimmune hepatitis, but it’s thought that in some cases, the breakdown of drugs may lead to the formation of molecules that trigger an immune reaction, according to the NIH.

When the authors of the new report reviewed 35 previous studies of turmeric supplements in people, they found that about 5 percent of participants in those studies experienced liver problems tied to the supplements. It may be that some patients, such as older adults or those who consume alcohol, are more prone to these problems tied to supplements.

Still, the authors said that it’s unclear whether turmeric compounds were indeed responsible for the liver problems in the woman’s case. A sample of the product was not available to test, but it could be that contaminants in the product, rather than the turmeric itself, triggered the condition, the report said. Or, it may be that the combination of turmeric and other medicines and supplements that the woman was taking led to the condition.

Still, the new case “highlights the importance of discussing DS use,” particularly among older patients, who may be taking multiple drugs and are also at greater risk of liver problems, the report said.

The NIH recommends that patients tell their health care providers, including their doctors, pharmacists and dietitians, about which dietary supplements they are taking so that they can discuss what’s best for the patients’ overall health.

Original article on Live Science.

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Your liver is constantly working to filter hundreds of toxins found in your diet and environment. On top of that, your liver also helps to break down your food and provide energy to your other organs.

To help your liver function efficiently, make sure you have essential vitamins and nutrients in your diet. When you cannot get an adequate amount from your diet, you can consider taking supplements.

Here are a few vitamins and minerals you need for a healthy liver.

Vitamin A and iron

Vitamin A and iron deficiencies are among the most common nutritional deficiencies worldwide, according to a study published in the 2000 issue of Nutrition. Vitamin A may lower iron levels and lead to anemia, and low iron may lead to decrease vitamin A levels in the liver. Supplementing vitamin A along with iron resolves iron deficiency anemia better than either iron or vitamin A alone.

Although vitamin A has several benefits to offer someone with liver disease, it can be toxic to the liver in high dosages. For example, iron may promote the formation of scar tissue in the liver. Therefore, those with chronic liver disease – and especially those with cirrhosis – should take multivitamins without iron unless their physician has determined that they are iron deficient.

(Read also: Vitamin D deficiency is widely overestimated, doctors warn)

Vitamin D

According to researchers from the University of Tennessee in Memphis, more than 90 percent of individuals with chronic liver diseases have some degree of vitamin D deficiency. The researchers agreed that severe vitamin D deficiency was more common among those with cirrhosis – an advanced form of liver disease that can lead to liver cancer. However, excess vitamin D, which usually occurs from taking too many supplements, can cause poor appetite, nausea and vomiting; elevated calcium in the blood; and impaired growth.

Vitamin E

Again, vitamin E has several benefits to offer someone with liver diseases, but it can be hazardous if taken in excess. In doses over 1,200 IU per day, vitamin E can thin the blood and cause bleeding.

Vitamin B12

Vitamin B12 is the only B-complex vitamin and water-soluble vitamin that can be stored in the liver, where it can remain for years, notes the University of Maryland Medical Center. As a rule, however, water-soluble vitamins are not stored and must be consumed daily to maintain levels sufficient for optimal health.

A good diet and adding in supplements can provide the body a wide range of antioxidants and assistance in liver detoxification. However, those with chronic liver disease should be aware of the quantity of vitamin E, vitamin A and iron. By knowing what to look for and choosing an appropriate multivitamin, managing chronic liver disease will be one step easier. (kes)

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‘The food supplement that ruined my liver’

Image copyright Jim McCants

Jim McCants took green tea capsules in a drive to get healthy in middle age. His doctors now say they left him needing an urgent liver transplant, writes the BBC’s Tristan Quinn.

It should have been one of the happiest days of his life. But Jim McCants looks back on his youngest son’s high school graduation with mixed emotions. As he sat down next to his wife Cathleen in the university auditorium, just outside Dallas, Texas, she turned to look at him.

It was shocking partly because Jim, then 50, had been working on improving his lifestyle and losing weight, focusing on eating more healthily and taking regular exercise.

“My dad had a heart attack at aged 59 and he did not make it,” says Jim. “There’s a lot that he missed out on with us and I was determined to do what I can to take care of myself as best I can, so that I don’t miss out.”

But soon after his son’s graduation, Jim was admitted to hospital with a suspected liver injury.

Image copyright Jim McCants Image caption Jim, his son and his wife, at his son’s graduation

Trying to identify the cause of Jim’s liver injury, those treating him ruled out alcohol.

“For the last 30 years I drank maybe a six-pack of beer a year, no wine. So alcohol was not a big part of my life,” Jim says.

They also ruled out prescription drugs – he wasn’t taking any at the time – and smoking, something he had never done.

“Then my hepatologist drilled in to, ‘What about any over-the-counter supplements?'” says Jim.

Find out more

Watch the BBC Two Horizon programme Vitamin pills: Miracle or Myth? online (UK viewers only)

BBC Food: Can a vitamin pill a day keep the doctor away?

As part of his mid-life health kick, Jim had started taking a green tea supplement because he had heard it might have cardiac benefits. These supplements have grown in popularity in recent years, often breathlessly promoted online for their antioxidant benefits, and their supposed ability to aid weight loss and prevent cancer.

“I felt fine then,” remembers Jim, who lives in Prosper, north of Dallas. “I was walking or running 30-to-60 minutes, five or six days a week.” He was working as a finance manager but hoped to retrain as a physician assistant. “I was taking two or three classes at a time at nights and at weekends,” he recalls.

He had been taking the green tea supplement for two to three months when he became ill. According to Jim’s medical record this is the presumed cause of his liver injury. “It was shocking because I’d only heard about the benefits,” remembers Jim. “I’d not heard about any problems.”

After his admission to hospital, Jim went into a “holding pattern”, waiting for the results of a series of blood tests to establish the seriousness of his liver injury. Then, about three weeks after his wife had first noticed he looked ill, one of his liver doctors delivered the news he had been fearing: “She said you need a liver transplant. This has to happen fast. You have days – you don’t have a week.”

Jim was stunned.

“I was thinking this looks very bleak for me. It really crystallises what’s important in life. I wasn’t there thinking about projects at work. I was thinking of different people that were important to me for different reasons.”

Image copyright Getty Images

What is it about green tea supplements that might cause harm at certain doses to some people? Scientists do not know for certain. Because green tea has been drunk for thousands of years, supplements consisting of its concentrated form are regulated in the US and Europe as foods, not medicines. That means that specific safety testing has not been required, so the scientific picture of how green tea supplements might affect our health is incomplete.

“If you are drinking modest amounts of green tea you’re very safe,” says Prof Herbert Bonkovsky, director of liver services at Wake Forest University School of Medicine in North Carolina, who has been tracking injuries linked to green tea supplements for nearly 20 years. “The greater risk comes in people who are taking these more concentrated extracts.”

Concern has focused on a potentially toxic ingredient called Epigallocatechin-3-gallate or EGCG, the most abundant of the naturally occurring compounds with antioxidant properties in green tea, called catechins. There are likely to be a number of factors that might make an individual susceptible to harm from EGCG including genetics, and the way supplements are used.

“Usually people are taking these green tea extracts trying to lose weight, so they’re often not eating,” Dr Bonkovsky explains. “We know from animal studies that fasted animals absorb a much higher percentage of the catechins than do fat animals. There may well be other factors of other drugs, other chemicals, use of alcohol that are also important as modifying factors.”

Antioxidants

Antioxidants are a group of vitamins and other compounds that for many have taken on miraculous properties, helping to drive the global market for supplements of all kinds, now worth more than £100bn per year.

Antioxidants ward off “free radicals”, molecules produced in our cells as they turn oxygen and food into energy. Just as oxygen and water corrode iron, too many free radicals can damage our cells.

In the 1950s, Prof Denham Harman theorised that free radicals drove the process by which the body ages and could lead to disease.

But some scientists now believe that free radicals at certain levels may be beneficial for human health, and argue that the orthodox view of the last half century that antioxidants are an unalloyed good is outdated.

While millions of people take green tea supplements safely, at least 80 cases of liver injury linked to green tea supplements have been reported around the world, ranging from lassitude and jaundice to cases requiring liver transplants. Those harmed after taking green tea pills have included teenagers, like 17-year-old Madeline Papineau from Ontario, Canada who developed liver and kidney injury, and an 81-year-old woman diagnosed with toxic acute hepatitis.

A recent investigation by the European Food Safety Authority into the safety of green tea concluded that catechins from green tea drinks are “generally safe”, but when taken as supplements catechin doses at or above 800mg per day “may pose health concerns”. The EFSA could not identify a safe dose on the basis of available data and called for more research to be carried out.

The day after Jim was told he needed a liver transplant, amazingly he was told a suitable liver had been found. “I was elated. The phone call that there was a match gave me hope that there would be something positive on the other side of this for me,” he says.

The liver transplant saved Jim’s life. But four years later he still has serious health problems including kidney disease that may require dialysis and a transplant in the future. He sees his liver and kidney doctors twice a year, and lives with chronic abdominal pain.

“My life before was pretty active. And now it’s much more sedentary and I struggle with fatigue,” he says.

It’s a “tremendous blessing”, as he puts it, that his managers allow him to work from home. “I may need a lie down for 20 or 30 minutes during the day. I’m able to just let my manager know I’m going offline, I’ll be back.”

Jim is pursuing a lawsuit against the American firm Vitacost, which sold the green tea supplement he took. “I’m hoping that they make the decision to put a very strong warning label on the product, on the website, let people know before they buy it,” he says.

Vitacost did not want to comment on the legal case, but said: “We take the safety of our Vitacost brand supplements very seriously and stand behind the quality of our products.”

Four years on, Jim reflects on how his life and that of his family changed after he took a green tea supplement.

“I didn’t expect harm. I expected that I might waste my money, I may take these and they don’t do a bit of good. I can accept that risk,” he says. “But the risk that it could cause my liver to fail, that’s a risk that’s too high for somebody to take.”

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Storage of vitamins and minerals

The liver acts as a storage site for some vitamins, minerals and glucose. These provide a vital source of energy for the body which the liver transforms into glycogen for more efficient storage (see ‘metabolism’). The liver stores vitamins and minerals for the times when they may be lacking in the diet. It can store enough vitamin A and vitamin B12 for four years, and enough vitamin D for four months.

Vitamins

Vitamins are a group of organic compounds that act as catalysts in various chemical reactions. The vitamins trigger these reactions and speed them up. A compound becomes classified as a vitamin when a lack of it causes disease.

Contrary to popular belief, vitamins do not directly provide energy. As catalysts, vitamins are required for the release of energy from protein, fat and carbohydrates. They are essential for normal growth and development and particularly important for the healthy functioning of red blood cells, hormones, genetic materials and the nervous system.

The liver stores vitamin A, D, E, K and B12. The first four of these are all fat soluble. This means that the bile secreted during digestion is essential for absorbing them so that the body can use them. If bile production is compromised by liver damage, the proper absorption of these vitamins may be affected.

When taking multivitamins it is important to make sure the recommended doses of fat soluble vitamins are not exceeded. If this occurs, it might result in liver damage.

Minerals

The liver also stores iron and copper. Copper is essential as a vital link in many of the body’s different chemical reactions and in the formation of protein within the liver. It also plays a role in using up the body’s iron stores, whenever they are needed.

Page: The liver and metabolism

The word metabolism originated from the Greek word ‘to change’. In relation to the liver, it refers to the processing of food digested by the stomach and intestine for its many uses by the body.

We get our energy and build our cells and tissues using the energy given off from the breakdown of three major classes of nutrients.

These are carbohydrates (simple and complex sugar), lipids (various fats and oils) and proteins (large molecules found in plant and animal tissues made up of amino acids). The liver plays an essential role in the breaking down of all of these types of nutrients and converting them into substances essential to the body. This process is called metabolism.

Carbohydrate metabolism

Glucose (or blood sugar) is made when carbohydrates are broken down. It is an essential energy source for all cells. Although we often eat at irregular intervals, the energy supplied to the body’s cells remains constant. The liver plays a crucial role in this process. If more glucose is absorbed than the body needs at that moment, the excess is turned into a substance called glycogen. This is then taken up by the liver for easier storage.

When blood concentrations of glucose begin to drop and the body needs to generate more energy and heat, the liver converts the glycogen back into glucose. It is then released back into the blood for transport to all other tissues.

The liver’s glycogen stores are limited. But when the supply of glycogen begins to run out the liver cells begin to produce glucose out of amino acids and other carbohydrates.

If the synthesis and storage of glucose is reduced by liver damage, the blood sugar levels may be affected. This can lead to insufficient amounts of energy reaching the muscles and the brain. This can then result in fatigue, a general sense of feeling unwell or slowed thinking and memory recall.

Fat metabolism

Fats or lipids are broken down in the liver for use as energy. They are then moved to fat tissue. More than 90% of body energy is stored here and is the main source of fuel storage for the body.

Fats are insoluble in blood and water and so the liver produces special, fat-carrying proteins called lipoproteins. These lipoproteins circulate in the blood, carrying essential fatty acids between the liver and body tissues.

The liver stores very little fat for its own use. Chronic hepatitis C can lead to an accumulation of fatty deposits in the liver. This condition is called ‘steatosis’ (Link to page). It is thought to be linked to increased fibrosis progression and advanced liver damage. It can also cause a decreased response to treatment for hepatitis C.

The lipoproteins also transport cholesterol. Although cholesterol has a certain ‘unhealthy’ reputation, it is still essential for the correct functioning of the body. It is used to make bile salts, to synthesise vitamin D, to make sex hormones, to make other hormones for the immune system and in dealing with stress. Cholesterol is also vital for the health of nerve cells and for the brain.

Cholesterol only becomes a problem when it builds up in the body in places it should not be. A healthy liver ensures that it is transported to tissues where it is needed and away from the tissues where it is not needed and may cause damage.

If the liver is not functioning properly or is over-burdened by cholesterol, fatty deposits containing cholesterol build up in the lining of arteries. These deposits can cause an obstruction to the blood flow and can also lead to heart attacks. They can also lead to a build-up of cholesterol in bile which can result in the formation of gallstones.

Liver injury due to herbal and dietary supplements: A review of individual ingredients

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Doctors believe a health supplement is to blame for a 23-year-old Texas woman’s sudden, acute liver failure.

Emily Goss said that in the weeks leading up to Thanksgiving, she had each day been taking about four pills containing an herbal supplement meant to support hormonal balance, weight management and fertility.

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But when she started noticing the whites of her eyes turning yellow, and some abdominal pains and fatigue, she stopped. Within weeks, she was rushed to Methodist Hospital in Dallas, where she was placed on the liver transplant list, which saw her receive a new organ on Christmas Day, NBC DFW reported.

“I have my life because someone gave me their liver and I’m just so thankful,” she told the news station.

Goss’ doctor, Jeffrey Weinstein, who is medical director of Liver Transplantation and Hepatobiliary Services at the hospital, said that while the herbal supplements may be marketed as healthy additions to a diet, they are often unregulated by the FDA.

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“I view them all as drugs and I view them all as chemicals, so there should be good caution into how you use them and why you use them,” he told NBC DFW.

Goss’ case is not the first documented instance of supplements causing damage to the liver and other internal organs. While doctors believe a biopsy of her liver may reveal which ingredient caused so much damage, it is estimated that herbal and dietary supplements-induced liver injury now accounts for 20 percent of cases of hepatotoxicity in the U.S.

“Currently, however, the majority of HDS-associated liver injur are due to multi-ingredient nutritional supplements, and the component responsible for the toxicity is usually unknown or can only be suspected,” according to a 2016 study published in the U.S. National Library of Medicine National Institutes of Health.

Health professionals have called for more regulation in the supplement industry, as well as more oversight and safety measures.

It was not clear how long Goss had been taking the supplements before she noticed her symptoms.

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