HISTORY AND BACKGROUND OF HERBALIFE

HERBALIFE SIDE EFFECTS

History and Background Information:
Herbalife is a health supplement MLM (multi-level marketing) company with a weight loss emphasis. It was founded in 1980 by 24-year-old Mark Hughes. Net sales in 2006 were over $1.9 Billion dollars with over a million distributors worldwide. It was created—by a ninth grade dropout and juvenile delinquent —who decided to create his own MLM after being a distributor for two other weight loss MLM companies that went out of business.

According to a 1985 issue of the Herbalife Journal, Hughes started Herbalife because his own mother was 30 pounds overweight and died (when he was only 19 years old) by overdosing on diet pills and unwise dieting practices. Her death left him with a “fervent desire to find a product that would enhance and build health while allowing an individual to take weight off sensibly and safely…”

In actuality, the autopsy report shows that Hughes’ mother died of an overdose of Darvon, a narcotic. Although 5-foot-6-inches tall, she was a mere 105 pounds at death—hardly 30 pounds overweight.

There are reports that Hughes traveled to China to study herbal medicine although he had no formal medical or nutrition training. According to the Herbalife literature:

During [Hughes] search, he had met Richard Marconi, PhD, with whom he shared his dream …. After a lot of research and testing, Herbalife Slim and Trim was born.

Actually the truth is only after he met Richard Marconi and formed the company did Marconi sign up for a mail order PhD program to add more credibility to the company. The many statements Herbalife representatives have made about extensive testing and research have been shown to be false in later court trials.

Hughes started the company by selling Herbalife products out of the trunk of his car because he couldn’t afford a storefront. According to one former Herbalife employee, Hughes was able to make the company immensely successful because of his incredible charisma; he was loved and admired by his distributors. He led hundreds of sales rallies -- resembling religious evangelical gatherings -- drawing people both to the products and the prospect of getting rich selling them. His pitches are still broadcast on Herbalife's Web site.

Troubled Past For Herbalife
In 1982, the FDA sent Herbalife a Notice of Adverse Findings, which rebuked Herbalife for labeling claims that their products were effective for treating many diseases, dissolving and removing tumors, rejuvenating, increasing circulation, and producing mental alertness.

Safety Concerns
A 1984, FDA Talk Paper notes that the FDA had received many complaints about side effects that had occurred during the use of Herbalife products and had stopped when use of the products was stopped. Company literature given to Herbalife distributors at the time stated that “up to 25% of product users will have adverse effects” but claims that this is evidence of the body's improving itself. Several suits were filed by people who alleged that the products had harmed them. Some of these suits were settled out of court with substantial payment, but the amounts have not been disclosed, and the case records are sealed.

The hearing also brought to light a study done by Herbalife of 428 users of its products. About 40% had experienced headache, constipation, diarrhea, nausea, lightheadedness, palpitations, and/or other transient symptoms that might be attributable to Herbalife products. The occurrence of side effects came as no surprise, because several ingredients in Herbalife products were potent laxatives and one product (N.R.G.) contained guarana, which is high in caffeine.

Research and Testing
By 1985, Senate hearings grilled Hughes about the "research and testing" done prior to marketing Herbalife's products. Hughes said, "We have a lot of scientific data on the herbs," but it was ascertained that no actual testing of Herbalife products had taken place. Marconi told a CNN interviewer, "We employed hundreds … even thousands of PhDs in the research program for our products." But when asked who they were, he replied, "Why, the research papers that are published and printed that we have access to on our computer."

In March 1985, the California Attorney General had charged Herbalife with:
1) Violating California's consumer protection laws.
2) Making illegal claims in the company handbook that various herbal ingredients were effective against more than 70 diseases and conditions.
3) The suit also charged that Herbalife had been operating an illegal pyramid scheme.
The case was settled in 1986 when Hughes and the company agreed to pay $850,000 and to abide by a long list of court-ordered restrictions on claims and marketing practices.

Questionable Ingredients
Concern about the side effects of Herbalife weight loss products has grown, however, after the FDA attributed a 1998 cardiac arrest suffered by a 28- year-old woman to a Herbalife ephedrine product, Original Green. Ephedrine, a chemical cousin of amphetamines that increases blood pressure and heart rate, has been linked by the FDA to hundreds of adverse reactions and dozens of deaths.

Ephedrine, (also known as Ephedra, Ma Huang) was a key ingredient that made the Herbalife products so successful for weight loss. Ephedrine is essentially speed and will shut off your appetite completely—allowing you to subsist on one meal a day. But it shuts down your appetite at a price:

Possible Side Effects of Ephedra

• nausea
• headache; dizziness
• irritation of the stomach; diarrhea
• anxiety; psychosis
• kidney stones
• tremors
• dry mouth
• irregular or rapid heart rhythms; heart damage
• high blood pressure
• restlessness; nervousness; sleeping problems
• decreased appetite
• flushing; sweating
• increased urination

Beware of These Ingredients in the Shakes

Soy Protein: The problem with soy is that it can cause harmful effect on your endocrine system and also most soy is now genetically modified which can have a wide range of negative effects including DNA damage.

Fructose: The second ingredient in this product is fructose which means that the shake is mostly sugar. Fructose is worse than sucrose (table sugar) because it does not make you feel full like table sugar so you end up consuming more, and it causes increased risk of weight gain and bad cholesterol.

Ferrous fumarate: This is iron and should not be taken by men or post-menopausal women as it can result in above normal levels and have a toxic effect.

Vegetable oil preparation: Sunflower oil tends to be highly processed which can caused it to go rancid easily unless special care is taken in the processing and it is kept in the dark and refrigerated. It is also high in omega-6 fatty acids which most people get far too much of.

Sucralose (Splenda) and Acesufame-k: I wrote an entire book on the dangers of artificial sweeteners called Sweet Deception. The biggest scam with artificial sweeteners is that they actually cause you to be hungrier and cause weight gain instead of weight loss. Splenda has been shown to have harmful effects in lab animals and in humans from spontaneous abortions, rashes, pain, to digestive disturbances. Avoid at all costs. Ace-k is a cousin of Aspartame (Nutrasweet), a notorious neurotoxin.

On the other hand, many of the other Herbalife products we looked at did not contain any ingredients that appeared to be harmful although we cannot comment on their efficacy.

Health Evangelist Dies of Alcohol Abuse

Unfortunately in 2000, Mark Hughes died at the tender age of 44. Herbalife reported Hughes had an “accidental death from mixing anti-depressants with an alcohol overdose.”

But the autopsy report showed that Hughes died after a 4-day drinking binge combined with an anti-depressant and possible a narcotic overdose. In addition to alcohol abuse, Hughes smoked 6-8 cigars a day.

My Comments on the Company History:

My intention in including this history is not to gossip. But I do have concerns about the mistruths that have been told about Herbalife’s history, research, testing, and credentials. If someone owns a health company, s/he better be a health expert or have a team of health experts from the beginning. S/he also needs to walk his talk and set an example of being healthy which includes living a healthy lifestyle and being addiction free.

As far as Herbalife’s trouble for making health claims, it seems Herbalife in the early years was out of line with many of their claims (curing cancer and dissolving tumors are big FDA no-nos). However, I also think it’s a crime that the FDA has a gag order in effect and that no supplements are allowed to make health claims—only pharmaceutical drugs can make health claims. In my opinion, any natural product should be able to make a claim as long as there is double blind research that can prove the claim and if the company offers a money back guarantee to mitigate consumer risk.

About the Herbalife Diet Program

The diet program involves asking you to drink two protein drinks and to eat only one actual meal per day. The shakes are only 180 calories and a typical meal is 400-600 calories so we feel that the program is too low in calories to be considered healthy. The World Health Organization considers any caloric intake below 2,200 calories to be starvation. Low calorie diets usually result in rebound and binge eating as your body tries to compensate for the starvation. Low calorie diets will also slow down your metabolism—the rate at which you burn calories and fat.

There is quite a strong emphasis on exercise within some of the written materials. The exercise emphasis has increased since the arrival of CEO Michael O. Johnson in 2003. He came from a 17-year career at Disney, and is a triathlete.

Its company spreadsheet reports nearly zero dollars in research and development, meaning that there is little done to affirm that the items in the supplements actually do what they’re supposed to do. Almost all of its manufacturing is outsourced, including to a factory in China. Its advisory board consists of paid physicians and no nutritionists (allopathic physicians receive very little nutrition training in medical school, as they are too busy memorizing drugs).

The dietary recommendations are to eat one balanced meal per day with lots of phytonutrient-rich vegetables and fruits. You can also customize your protein intake to suit your individual needs. The rest of your meals are protein drinks. Dieters must take “activator” capsules and a multivitamin with each meal.

Praise For The Herbalife Weight Loss Program

There are hundreds of thousands of zealous distributors who rave about Herbalife products and who can attest to how Herbalife has helped them lose weight or get healthier. Furthermore, Herbalife provides a potentially lucrative business opportunity to those who want a home based business in the trillion dollar health industry. As with any MLM, only a small fraction of the distributors develop the know-how and diligence to become successful. For the pros and cons of being a distributor click here http://answers.google.com/answers/threadview?id=302284

 Criticism of the Herbalife Weight Loss Program

This diet does nothing to mimic what real life is like and relies heavily on the use of supplements and protein powders at a cost of up to five dollars a day. Once you achieve your ideal weight, Herbalife recommends maintenance, which consists of one shake a day. This just isn’t realistic, and you will likely gain the weight right back again as soon as you stop the diet.

The diet is very expensive and is much too low in fat and carbohydrates unless you load up on the fat and carbs during your one meal per day. Two scoops (or 25 grams) of the protein shake contain only 1 gram of fat and 13 grams of carbohydrates. If you need to snack, the program will be happy to sell you their own version of a protein bar, which is also very expensive.

Other Herbalife Supplements

The other part of the program includes supplements such as Total Control which contains green tea and cacao, both of which “stimulate your metabolism” basically through a high caffeine intake. You can get the same thing out of a cup of tea or coffee for a lot less. Total Control costs $27 for 90 capsules.

The Cell Activator supplement claims to contain antioxidants and lists ingredients including inositol, chorella, Shitake mushrooms, L-glutamine, Cayenne pepper, Dried Rhodiola root, dried Reishi mushroom extract, and dried pine bark extract. It also contains many of the acids found in the Krebs cycle—an energy cycle found in every cell. Inositol is a B vitamin, while Chorella is a blue-green algae. It is supposed to “support” your cells as you lose weight. Cell Activator costs around $34 for 90 capsules.

While many of these ingredients are high in antioxidants and may be helpful from an overall health perspective, antioxidants have not been shown to have a strong impact on weight loss. If you are going to spend money on a supplement, we suggest investing in an antioxidant-rich multi-vitamin, as vitamin and mineral deficiencies can lead to food cravings and overeating.

There are also other supplements you can add to the regimen, including Cell-U-Loss, which is supposed to reduce the appearance of dimpled skin and help with water weight gain. Cell-U-Loss contains couch grass, hydrangea, short bushu extract, dried corn silk and dried uva ursi extracts. The company does not guarantee that the products have been manufactured without animal testing.

Conclusion Herbalife is one of the most successful multi-level marketing companies of all time. Its weight loss program does not emphasize natural lifestyle changes but sells protein shakes and supplements as a solution for weight loss. There are ingredients in the protein shakes that are unhealthy and should be avoided. Does the program work? Millions of distributors and customers claim it does. There is something to be said for this. Unfortunately, when people go off the Herbalife program, it seems inevitable that weight gain will follow when they resume their old ways of eating.

WIKIPEDIA ABOUT HERBALIFE INTERNATIONAL

Herbalife

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Herbalife International

Type	Public
Traded as	NYSE: HLF
Industry	Nutrition & Skin Care products
Founded	Los Angeles, California (1980)
Founder(s)	Mark Hughes
Headquarters	L.A. Live Los Angeles, California, United States
Key people	Michael O. Johnson (CEO) Des Walsh (President) Richard P. Goudis (COO) John DeSimone (CFO)
Products	Weight management, nutritional supplements, personal care, sports nutrition.
Revenue	US$3.454 billion (2011)[1]
Operating income	US$562.270 million (2011)[1]
Net income	US$412.578 million (2011)[1]
Total assets	US$1.446 billion (2011)[1]
Total equity	US$560.188 million (2011)[1]
Employees	5,100 (31 Dec 2011)[1]
Website	www.herbalife.com

Coordinates: 33.857195°N 118.291855°W
Herbalife International (NYSE: HLF) is a global nutrition, weight management and skin-care company. The company was founded in 1980 and it employs around 5,000 people worldwide. Herbalife reported net sales of US$3.45 billion in 2011 with a retail sales turn over of US$5.1 billion with an increase of US$1.1 billion retail sales on 2010.^[2] Though incorporated in the Cayman Islands,^[1] its corporate headquarters are in Los Angeles, California, United States.^[3]
The company distributes its products in 84 countries (As of July 2012) through a network of approximately 2.7 million independent distributors,^[1] some of whom earn profit on product sales and additional commission from a multi-level marketing (MLM) compensation structure.

Contents 1 History 2 Products 3 Efficacy of Herbalife products for weight loss 3.1 The study of Treyzon et al. 3.2 The Lee study 3.3 Flechtner-Mors et al. 4 Adverse effects 5 Herbalife and liver disease 6 Business model 7 Sponsorships 7.1 Sports 7.2 Media 8 Criticism 9 Charity 10 See also 11 References 12 External links

History

In February 1980, Mark Hughes began selling the original Herbalife weight management product from the trunk of his car. Hughes often stated that the genesis of his product and program stemmed from the weight loss concerns of his mother Joanne, whose premature death he attributed to an eating disorder and an unhealthy approach to weight loss. His goal was to change the nutritional habits of the world.
His first product was a protein shake designed to help people manage their weight. He structured his company using a direct-selling, multi-level marketing model which attracted thousands of distributors (Herbalife Independent Distributors) who sold its products door-to-door or through word-of-mouth, without relying on commercial distribution in retail stores.
The company's slogan, "Lose Weight Now, Ask Me How", became a marketing theme for distributors, featuring heavily on badges, flyers and posters. Early methods to recruit distributors included seminars, which would feature distributors giving health and weight loss testimonials on the Herbalife products and a keynote address by Hughes. By 1982 Herbalife had reached US$2 million in sales and had expanded into Canada.
In 1985, the California Attorney General sued the company for making inflated claims about the efficacy of its products. The company settled the suit for $850,000 without admitting wrongdoing.^[4] In 1986 Herbalife became a publicly traded company on the NASDAQ, and in 1996 Herbalife reached US$1 billion in annual sales.
Mark Hughes died at age 44.^[5] The Los Angeles County Coroner autopsy results ruled that the entrepreneur had died of an accidental overdose of alcohol and doxepin, an anti-depressant.^[6] The company continued to grow after his death and in 2002 was acquired by Whitney and Co LLC and Golden Gate Capital for US$685 million, who took the company private again.^[7]
In April 2003, Michael O. Johnson joined Herbalife as CEO following a 17-year career with The Walt Disney Company, most recently as president of Walt Disney International.^[4] On 16 December 2004, the company had an initial public offering on the NYSE of 14,500,000 common shares at $14/share. 2004 net sales were reported as $1.3 billion. In April 2005, the company celebrated its 25th anniversary with a four-day event attended by 35,000 Herbalife Independent Distributors from around the world. In August 2005, Dr. Steve Henig joined the company as Chief Scientific Officer, responsible for product research and development. In 2008, President and COO Greg Probert resigned after it was reported that he had not completed the degree requirements for the MBA he claimed on his resume.^[8]

Products

Herbalife's product range includes protein shakes, protein snacks, nutrition, energy and fitness supplements and personal care products.^[9] The Formula 1 protein shake, a soy-based meal-replacement shake, is the company's number one product and was one of the first products sold by the company. The range also includes products for heart health, digestive health, skin care, and the new 24 sports line released in 2011. Some products are vegetarian, kosher, allergen free^[10] or halal, and Herbalife provides testimonials and advice from health professionals as part of their product marketing.
According to the 2009 Form 10-K, many of its weight management, nutritional and personal care products are manufactured by third party manufacturing companies, with the exception of products distributed in and sourced from China, where they have their own manufacturing facility, and several products are produced in its manufacturing facility in Lake Forest, California (renovated 2011^[11]). Herbalife is currently making modifications to its recently acquired manufacturing facility in order to increase capability and capacity, and upon completion of these modifications, expect to increase self manufacturing.^[12]:16
In October 2010, Herbalife held a ground-breaking ceremony in Changsha, Hunan Province, China for its botanical extraction facility for its inner and outer nutrition products. The new facility is expected to open in the second half of 2011. The new extraction facility will purchase botanicals directly from farms in Hunan province, China and other regions, perform extraction and other conversion processes and then send these processed raw materials directly to Herbalife's manufacturing facilities in Suzhou, China and Lake Forest, California, or to its third party manufacturers throughout the world. The new extraction plant will produce botanical extracts, including teas, guarana, chamomile, broccoli and bilberry, among others, for use in many of its products.^[13]

Efficacy of Herbalife products for weight loss

Three clinical studies have been completed of the effect of different Herbalife products on weight loss.

The study of Treyzon et al.

Treyzon et al compared a protein supplement (Performance Protein Powder, Herbalife Intl., Los Angeles) with a similar tasting carbohydrate placebo. The two treatments showed significant differences in their effects on the primary outcome of body weight. Effects on body mass index, waist circumference or fat free mass were also significantly different. Subjects on the high protein powder lost significantly more fat mass, 1.01 kg, P=0.05.^[14] As this was a secondary analysis these findings should be interpreted with caution and regarded as exploratory until confirmed in independent studies.

The Lee study

Lee et al used a similar design but a differently named protein powder (ShapeWorks Formula 3, Herbalife). Lee et al. found no significant difference in the effect of this protein powder on fat mass compared with placebo. Effects on other body weight and composition outcomes also did not differ significantly between the Herbalife protein powder and placebo. In a subgroup analysis, among subjects with dietary compliance ≥ 70%, the high-protein treatment was more effective than the control treatment in reducing body fat.^[15] As this was a secondary analysis these findings should be interpreted with caution and regarded as exploratory until confirmed in independent studies.

Flechtner-Mors et al.

Flechtner-Mors et al instructed 110 obese persons to cut their calories by about 50%.^[16]
Fifty-five persons made up the high protein group and received Herbalife meal replacement shakes, Performance Protein Powder and protein bars. The other 55 made up the conventional diet group, and received diet instructions only. After 12 months, 24 subjects in the protein group had dropped out, as opposed to 12 in the conventional group. For the dropouts, weight at 3 months instead of 12 months was used for calculating the effect of treatment. Mean weight loss at 12 months was 8.96 kg (19.76 lb) in the protein (Herbalife) group and 6.41 kg (14.13 lb) in the conventional group, a difference of 2.55 kg (5.63 lb). The authors concluded that a protein-enriched diet may have advantages for the management of the adverse effects of obesity on health.^[17]
The study was criticised by Busetto et al.^[18] because the interpretation of the results was complicated by the high dropout rate, and also by the provision of shakes and bars to the Protein (Herbalife) group only. When subjects receive special weight loss products, they may stick better to their diet, independent of what weight loss products are given. In addition, the mean weight loss was small in both groups — less than 9 kg (20 lb) over the course of a year in the protein group and even less in the conventional group.
By and large, these studies do not provide convincing evidence that Herbalife products produce more weight loss than other products or than a proper placebo.^{[citation needed]}

Adverse effects

Some of the original Herbalife weight loss products contained the active ingredient Ma Huang or Sida cordifolia, two herbs containing ephedra, an appetite suppressant. Herbalife stopped using ephedrine in its products in 2002 after several U.S. states banned supplements containing botanical sources of ephedrine alkaloids.^[19]:15[20] The U.S. Food and Drug Administration banned supplements containing ephedra in 2004.^[21]
In May 2008, the Fraud Discovery Institute, which claims to be a consumer watchdog organization, reported that laboratory test results of Herbalife products showed lead levels in excess of limits established by law in California under Proposition 65.^[22][23] The Fraud Discovery Institute was founded by Barry Minkow, who served seven years in jail for stock fraud,^[24] and since disclosed that his company was profiting from the allegations by shorting Herbalife stock.^[25] Herbalife responded stating its products met federal FDA requirements^[26][27] and released independent laboratory tests it said proved the products did not exceed Proposition 65 limits.^[25]
On May 10, 2008 a suit was filed on behalf of a woman who developed lead-related liver complaints that she claimed were a reaction to a combination of Herbalife products.^[24][28] The suit was filed by lawyer Christopher Grell, cofounder of the Dietary Supplement Safety Committee and an associate of Barry Minkow.^[24] On June 17, 2008, the suit was expanded to add distributors who had supplied the woman with the Herbalife products, with Grell launching a website to offer persons who believe they were harmed by Herbalife products the chance of redress.^[29] In August 2008, Minkow retracted all accusations against Herbalife and removed any mention of the company from his web site.^[30]
In 2011, Minkow started serving a 5-year federal prison sentence for securities fraud after pleading guilty to one count of conspiring to damage Lennar Corp. by attacking the Miami-based home builder in reports he acknowledged were filled with falsehoods..^[31]

Herbalife and liver disease

In 2004 Israel's Health Minister began an investigation against Herbalife's products after four persons using Herbalife's products were found to have liver problems.^[32]
Herbalife's products were accused of containing toxic ingredients such as Qua-qua, Kompri, and Kraska. The products were sent to the Bio-Medical Research Design LTD (B.R.D) laboratory, to a private laboratory in the United States of America, and to Israel's Forensic research laboratory. The company issued a press release stating that the Israeli government, and scientists working with Herbalife, were unable to establish a link between the product and the eight cases of liver damage. Herbalife withdrew the product, which was only marketed in Israel.^[33] Herbalife's SEC 10-Q filings state that the Israeli Ministry of Health did not establish a causal relationship between the product and liver ailments. The Israeli Ministry of Health advises individuals with compromised liver function to avoid dietary supplements.^[34] In 2009, an Israeli woman sued Herbalife International and Herbalife Israel, claiming that her liver damage resulted from the use of Herbalife products.^[35]
Scientific studies in 2007 by doctors at the University Hospital of Bern in Switzerland and the Liver Unit of the Hadassah-Hebrew University Medical Center in Israel found an association between consumption of Herbalife products and hepatitis.^[32][36] In response, the Spanish Ministry of Health issued an alert asking for caution in consuming Herbalife products.^[37] Herbalife has stated they are cooperating fully with Spanish authorities.^[38]
By 2011, hospitals in Israel, Spain, Switzerland, Iceland, Argentina and the United States had reported liver damage in a number of patients, part of whom had used Herbalife products.^{[32][36][39][40][41][42][43][44][45][improper synthesis?]} Some patients recovered after they had stopped taking the products, in others the disease continued, and two patients died. Several authors considered it plausible that Herbalife products were the cause of the observed liver disease. Herbalife employees claim there is no definitive proof that Herbalife products cause hepatoxicity or other liver problems.^[46]

Business model

Herbalife is a multi-level marketing (sometimes called MLM or network marketing) company. In addition to profits from product sales, Herbalife distributors can earn additional commissions from sales by their 'downline' distributors. Supporters of MLM contend this is a fair compensation system, while critics contend that it is similar to a pyramid scheme.^[47] Critics also argue that the company does not make enough effort to curb abuses by individual distributors, though Herbalife has consistently denied such allegations.^[48] Herbalife is a member of the Direct Selling Association in most countries in which it operates.
In its filings with the U.S. Securities and Exchange Commission (SEC), company management note problems with inappropriate business practices in the past, their subsequent long-lasting effects and the need to avoid any repetition. Company management considers the number and retention of distributors a key parameter and tracks it closely in financial reports. By January of each year, sales leaders are required to requalify. In February of each year, they remove from the rank of sales leaders those individuals who did not satisfy the sales leader qualification requirements during the preceding 12 months. For the latest 12-month requalification period ending January 2011, approximately 48.9 percent of the eligible sales leaders requalified, reflecting an improvement from 43 percent in 2009.^[49] The company was cited as one of the most profitable companies in Los Angeles County.^[50]
A 2004 settlement resolved a class action suit on behalf of 8,700 former and current distributors that accused the company and distributors of "essentially running a pyramid scheme." A total of $6 million was to be paid out, with defendants not admitting guilt.
In a California class action suit filed on February 17, 2005, Minton v. Herbalife International, et al., the plaintiff is "challenging the marketing practices of certain Herbalife International independent distributors and Herbalife International under various state laws prohibiting "endless chain schemes", insufficient disclosure in assisted marketing plans, unfair and deceptive business practices, and fraud and deceit".^[51]
In a West Virginia class action suit filed on July 16, 2003, Mey v. Herbalife International, Inc., et al., the plaintiffs allege that some "telemarketing practices of certain Herbalife International distributors violate the Telephone Consumer Protection Act, or TCPA, and seeks to hold Herbalife International vicariously liable for the practices of these distributors. More specifically, the plaintiffs' complaint alleges that several of Herbalife International's distributors used pre-recorded telephone messages and autodialers to contact prospective customers in violation of the TCPA's prohibition of such practices". Herbalife management insisted they have meritorious defenses in both cases and that in the West Virginia case, any such distributor actions also went against Herbalife's own policies. Management also contends that any adverse legal outcomes Herbalife might suffer would not significantly affect their financial condition, particularly since they have already set aside an amount that they "believe represents the likely outcome of the resolution of these disputes".^[51] The case was resolved with Herbalife and its distributors paying $7 million into a fund for class members part of the suit.^[52]:42 Herbalife International did not acknowledge wrongdoing, or admit culpability for the actions of its distributors.
As of April 2008, a series of commercials featuring a large red animated fox advertising home-based business opportunities have been running on American television. The advertisements typically feature a series of testimonials from actors playing individuals who have made sums of money between US$5,000 and US$15,000 per month as a result of participating in an undescribed business program. The advertisements direct viewers to a website that allows them to purchase a "success kit". The kit also provides no information about how the business opportunity works.
These advertisements have been found to be run by independent Herbalife distributors, as a method of recruiting new 'downline' distributors.^[53] While it is not illegal, critics of this type of advertising prefer advertisers to be up front about their company associations.
==========================

GREEN TEA (CAMELLIA SINESIS) SIDE EFFECT

GREEN TEA (CAMELLIA SINESIS)

OVERVIEW
Green Tea

 

Introduction

Green tea is a popular and commonly consumed drink and its extract is found in many herbals and dietary supplements (HDS). Green tea extract and concentrated infusions of green tea have been implicated in many cases of clinically apparent acute liver injury, including instances of acute liver failure and death.

 

Background

Both green tea and black tea are produced from the leaves of the Chinese tea tree Camellia sinensis. Green tea, unlike black tea, is unfermented, which helps to preserve its antioxidant polyphenolic catechols. Green tea has long been believed to have health restoring properties and its ingredients to have antioxidant activity. For this reason, extracts of green tea have been used as an herbal medication alone and in combination with other herbals and dietary supplements which are advertised to improve health, prevent cancer and heart disease, decrease serum lipid levels, promote weight loss, decrease periodontal disease and treat clostridial diarrhea. Green tea extract is listed in more than 100 over-the-counter herbal preparations, but is not approved for any specific medical indication and is not strictly regulated by the FDA. The multiple polyphenols in green tea are believed to be the active components responsible for its purported chemoprotective, antiproliferative and antioxidant properties. The mechanism by which green tea may have such effects has not been elucidated. Human clinical studies demonstrate that single doses of up to 1.6 grams of green tea extract are well tolerated. The maximum tolerated dose in humans is reported to be 9.9 grams per day; a dose equivalent to 24 cups of green tea. Side effects of high doses of green tea extract are usually mild and include headache, dizziness and nausea. The safety and tolerability of long-term use of green tea extracts has not been well defined.

 

Hepatotoxicity

Drinking green tea has not been associated with liver injury or serum aminotransferase elevations; indeed cross sectional studies suggest that heavy use of green tea is associated with lower serum ALT and AST values. Nevertheless, case series and a systematic review by the United States Pharmacopeia illustrate evidence for the potential for green tea extract to cause hepatotoxicity. The prevalence of green tea extract-induced liver injury is not known, but is probably low in comparison to the wide-scale use of these products. Liver injury typically arises within 3 months, with latency to onset of symptoms ranging from 10 days to 7 months. The majority of cases present with an acute hepatitis-like syndrome and a markedly hepatocellular pattern of serum enzyme elevations. Most patients recover rapidly upon stopping the extract or HDS, although fatal instances of acute liver failure have been described. Biopsy findings show necrosis, inflammation, and eosinophils in a pattern resembling acute hepatitis. Immunoallergic and autoimmune features are usually absent. A small number of similar cases have also been described after drinking green tea “infusions” rather than taking oral preparations of extracts of green tea.

The most prominent regulatory action against green tea containing products concerned Exolise, a weight loss product which was withdrawn from Spain and France in 2003. Also, green tea is an ingredient in other supplements including most weight loss agents such as Herbalife and Hydroxycut products, many of which have been implicated in causing clinically apparent acute liver injury.

 

Mechanism of Injury

Preclinical and human data implicate the catechin component of green tea as the culprit of hepatotoxicity. Approximately 10% of the green tea extract is composed of catechins; of these, epigallocatechin-3-gallate (EGCG) is present in highest concentration. There is great variability in the concentration of green tea extract and EGCG among marketed products, which may explain while some products have been strongly implicated in hepatotoxicity. Exposure of rat hepatocytes to EGCG has been shown to induce mitochondrial toxicity and generation of reactive oxygen species. The association of liver injury with higher doses of green tea (as in extracts) suggests a component of direct hepatotoxicity, perhaps in the context of some degree of host susceptibility exacerbated by environmental features such as obesity, fasting or glutathionine depletion.

 

Outcome and Management

Given the wide spread consumption of green tea and its extract in various HDS, liver injury from green tea is rare. Patients who present with acute liver injury particularly with a hepatocellular pattern without an obvious cause should be asked about the use of HDS and green tea extract and should be advised to stop all herbal medications. In typical cases, recovery is expected in one to two months. As in any case of drug induced liver injury, the presentation with or development of abnormal liver function (abnormal mentation indicating encephalopathy), prolongation of the prothrombin time or elevation of the INR, and a depressed albumin, should prompt referral to be considered for liver transplantation. Patients who developed acute liver injury attributable to green tea extract should be cautioned about reexposure and avoidance of HDS that might include green tea.

 

Drug Class: Herbals and Dietary Supplements

 

Top of page

Case Report
Green Tea

 

Case 1. 37 year old woman with acute hepatitis after using weight loss supplement.
[Modified from: Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann Intern Med 2006; 144: 68-71. PubMed Citation]

A 37 year old woman developed nausea, abdominal pain and jaundice 4 months after starting a weight-loss supplement called The Right Approach Complex (Pharmanex, Provo, Utah), the major component of which was green tea extract. She denied history of liver disease, alcohol use, and risk factors for viral hepatitis. On examination, she was jaundiced but had no fever or rash. Laboratory tests showed marked elevations in serum aminotransferase levels (~20 times ULN), with minimal increases in alkaline phosphatase and serum bilirubin of 11.7 mg/dL (Table). Tests for hepatitis A, B and C were negative as were autoantibodies, except for antinuclear antibody which was weakly positive (1:40, speckled pattern). Liver biopsy revealed marked interface necrosis and inflammation and mild lobular inflammation. Cholecystectomy and intraoperative cholangiography were performed. The patient began to improve rapidly and was discharged after two weeks in the hospital. One month later, liver tests had improved significantly. One year later, she was again admitted with a one week history of abdominal pain and jaundice. She admitted to resuming The Right Approach Complex one month earlier, but stopped taking it one week before presentation when she developed dysphagia. On admission, she was jaundiced. She again improved rapidly and six months later all liver tests were normal.

 

Key Points

 

Medication:	The Right Choice (383.3 mg C. sinensis extract per 3 capsules)
Pattern:	Hepatocellular
Severity:	3+
Latency:	4 Months initially, 1 month on reexposure
Recovery:	1 Month
Other medications:	None mentioned

 

Laboratory Values

 

Time After Starting	Time After Stopping	ALT (U/L)	AST (U/L)	Alk P (U/L)	Bilirubin (mg/dL)	Other
0		Started The Right Approach (~1 gram of green tea extract daily)
4 months	0	1788	1783	238	11.7	Liver biopsy
5 months	~1 month	92	79		1.9
Time After Restarting	Time After Stopping Again	Restarted The Right Approach 1 year later
4 weeks	0	1131	977	165	11.7	INR: 1.3
5 weeks	1 week	877	816	165	2.9
9 weeks	5 weeks	69	80		1.2
7 months	6 months	25	27	85	1.0
Normal Values		<40	<40	<114	<1.2

Comment

This case demonstrates the typical acute viral hepatitis-like presentation of green tea hepatotoxicity with jaundice, accompanied by marked elevations in serum aminotransferase levels and minimal increases in alkaline phosphatase. Recurrence with a similar pattern of liver injury upon reexposure to the same product provided strong evidence for a causal association. Green tea extract was the major ingredient of the supplement and its other components have not been reported to cause liver injury (calcium, chromium, magnolia extract, epimedium extract, banaba leaf extract, β-sitosterol and vanadium). 

Case 2. 27 year old man with hepatitis attributed to Hydroxycut.
[Modified from: Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement Hydroxycut. Ann Intern Med 2005; 142: 477-8. PubMed Citation]

A 27 year old man developed fatigue and jaundice 4 to 5 weeks after starting Hydroxycut (9 tablets per day) for weight loss. He denied previous liver disease, alcohol abuse, recent travel or risk factors for viral hepatitis, and was not taking any other medications or herbal preparations. Laboratory tests showed marked elevations in serum aminotransferase levels (ALT 3131 U/L, AST 1808 U/L), with minimal increases in alkaline phosphatase (171 U/L) (Table). Liver tests worsened for a day and then rapidly improved.

 

Key Points

 

Medication:	Hydroxycut (1.8 grams C. sinensis extract per day)
Pattern:	Hepatocellular (R=54)
Severity:	3+ (Jaundice, hospitalization)
Latency:	4-5 Weeks
Recovery:	1-2 Months
Other medications:	None

 

Laboratory Values

 

Time After Starting	Time After Stopping	ALT (U/L)	Alk P (U/L)	Bilirubin (mg/dL)	Other
	Started Hydroxycut (1.86 g green tea extract daily)
5 weeks	0	3131	171	7.8	Admission
	2 days	3962			Peak values
9 weeks	4 weeks	304		1.3
Normal Values		<40	<150	<1.2

Comment

Green tea hepatotoxicity typically presents with jaundice and an acute viral hepatitis-like syndrome, and a markedly hepatocellular pattern of serum enzyme elevations and rapid improvement upon stopping. Hydroxycut contains high concentrations of green tea extract, although formulations frequently change. Because Hydroxycut, like many dietary supplements, is a brand of many products with many ingredients, it is difficult to implicate a specific ingredient of the product as the cause for liver injury. Other listed components of Hydroxycut included calcium, chromium, potassium Garcinia cambogia, Gymnema sylvestre leaf extract, glucomannan, α-lipoic acid, willow bark extract, L-carnitine, caffeine, guarana extract, gelatin, silica and cellulose.

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SUMMARY & LABELING
Green Tea

 

REPRESENTATIVE TRADE NAMES
Green Tea – Generic

DRUG CLASS
Herbals and Dietary Supplements

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CHEMICAL FORMULA AND STRUCTURE
Green Tea

 

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Green Tea	ID: CJ12600000	Herbal Mixture	Not Applicable

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REFERENCES
Green Tea

 

References Last Updated: 20 February 2012

1. Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4. (Expert review of hepatotoxicity published in 1999; Chinese herbal medications are discussed, but not green tea extract specifically).

2. Liu LU, Schiano TD. Hepatotoxicity of herbal medicines, vitamins and natural hepatotoxins. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 733-54. (Review of hepatotoxicity of herbal and dietary supplements published in 2007; mentions case reports of acute liver failure and case series of mixed cholestatic liver injury usually resolving within 4 months attributed to green tea extracts).

3. No authors listed. Green tea. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 414-22. (Compilation of short monographs on herbal medications and dietary supplements).

4. Imai K, Nakachi K. Cross-sectional study of effects of drinking green tea on cardiovascular and liver diseases. BMJ 1995; 310: 693-6. PubMed Citation  (In a population-based survey of 1371 Japanese men, drinking >10 cups of green tea daily was associated with lower total cholesterol and triglycerides levels, increased HDL and lower ALT [19 vs 24 U/L] and AST [23 vs 25 U/L] values).

5. Larrey D. Hepatotoxicity of herbal remedies. J Hepatol 1997; 52: 97-103. PubMed Citation  (Review of hepatotoxicity of herbals focusing upon pyrrolizidine alkaloids, germander and Chinese herbal medications, green tea was not mentioned).

6. Gavilan JC, Bermudez FJ, Saigado F, Pena D. [Phytotherapy and hepatitis]. Rev Clin Exp 1999; 199: 693-4. Spanish. PubMed Citation  (19 year old woman developed jaundice 14 weeks after starting herbal tea and 8 weeks after starting capsules of green tea [bilirubin 11 mg/dL, ALT 1110 U/L], with severe recurrence 3 years later within 3-4 weeks of restarting the capsules).

7. Stickel F, Egerer G, Seitz HK. Hepatotoxicity of botanicals. Public Health Nutr 2000; 3: 113-24. PubMed Citation  (Review of hepatotoxicity of herbals focusing upon Chinese herbals, germander, pyrrolizidine alkaloids, chaparral; no mention of green tea extracts).

8. Seddick M, Lucidarme D, Creusy C, Filoche B. [Is Exolise hepatotoxic?] Gastroenterol Clin Biol 2001; 25: 834-835. French. PubMed Citation  (50 year old woman developed jaundice 2 months after starting Exolise®, a green tea extract containing commercial herbal product [bilirubin 7.5 mg/dL, ALT 40 times ULN, Alk P 1.5 times ULN], resolving within 2 months of stopping).

9. Chantre P, Lairon D. Recent findings of green tea extract AR25(Exolise) and its activity for the treatment of obesity. Phytomedicine 2002; 9: 3-8. PubMed Citation  (Green tea extract AR25 [Exolise®] is an 80% ethanol extract of green tea standardized to 25% catechins, primarily epigallocatechin gallate and caffeine, but also others; it inhibits gastric and pancreatic lipase in vitro and stimulates thermogenesis; in an open label study, 70 obese patients lost an average of 4.6% of body weight over a 6 month period; serum ALT elevations occurred in one patient but no details given).

10. Haller CA, Dyer JE, Ko R, Olson KR. Making a diagnosis of herbal-related toxic hepatitis. West J Med 2002; 176; 39-44. PubMed Citation  (Two cases demonstrating the difficulties of identifying the toxic component of herbals: 42 year old woman developed fatigue 10 weeks after starting 3 herbal medications [bilirubin 1.2 mg/dL, ALT 3386 U/L, Alk P 100 U/L], ultimately attributed to Jin Bu Huan; 39 year old woman developed acute liver failure after taking multiple herbals [bilirubin 42.7 mg/dL, ALT 349 U/L, INR 3.9] believed to be due to chaparral).

11. Thiolet C, Mennecier D, Bredin C, Moulin O, Rimlinger H, Nizou C, Vergeau B, Farret O. [Acute cytolysis induced by Chinese tea]. Gastroenterol Clin Biol 2002; 26: 939-40. French. PubMed Citation  (39 year old woman developed fatigue 4 months after starting biweekly “infusions of Oolong tea fine tonic” [ALT peak 45 times and Alk P 3.5 times ULN, bilirubin not given], resolving within 8 weeks of stopping).

12. Pedrós C, Cereza G, García N, Laporte JR. [Liver toxicity of Camellia sinensis dried ethanolic extract.] Med Clin(Barc). 2003; 121: 598-9. PubMed Citation  (4 reports of liver injury due to Exolise® led to its withdrawal in Spain; women, ages 29 to 69 years, onset 15-45 days after starting herbal with hepatocellular injury [bilirubin 18-19 mg/L, ALT 4-40 times ULN, Alk P 1.5-2 times ULN], resolving in 3 subjects with follow up information).

13. Vial T, Bernard G, Lewden B, Dumortier J, Descotes J. [Acute hepatitis due to Exolise, a Camellia sinensis-derived drug.] Gastroenterol Clin Biol. 2003; 27: 1166-7. PubMed Citation  (46 year old woman developed jaundice 12 weeks after starting Exolise® [bilirubin 29.1 mg/dL, ALT 75 times and Alk P 2 times ULN], with rapid recovery and recurrence on reexposure).

14. Pittler MH, Ernest E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther 2003; 18: 451-71. PubMed Citation  (Systematic review of published cases of hepatotoxicity due to herbal medications listing 52 case reports or case series, most common agents being celandine [3], chaparral [3], germander [8], Jin Bu Huan [3], kava [1], Ma Huang [3], pennyroyal [1], skullcap [2], Chinese herbs [9], valerian [1]; green tea not specifically listed or mentioned).

15. Estes JD, Stolpman D, Olyaei A, Corless CL, Ham JM, Schwartz JM, Orloff SL. High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure. Arch Surg 2003; 138: 852-8. PubMed Citation  (Among 20 patients undergoing liver transplantation for acute liver failure at two U.S. transplant centers during 2001-2, 10 were attributed to herbals, but none to green tea extract).

16. Lenz TL, Hamilton WR. Supplemental products used for weight loss. J Am Pharm Assoc 2004; 44: 59-67. PubMed Citation  (At least 50 herbal and dietary supplements have been promoted for weight loss, but none have strong clinical evidence of efficacy and several are toxic [ephedra and green tea]).

17. Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. PubMed Citation  (Among ~50,000 liver transplants reported to UNOS between 1990 and 2002, 270 [0.5%] were done for drug-induced acute liver failure, 7 [5%] for herbal medications, including 1 attributed to kava and 1 to chaparral tea; green tea was not specifically mentioned).

18. García-Morán S, Sáez-Royuela F, Gento E, López Morante A, Arias L. [Acute hepatitis associated with Camellia tea and Orthosiphon stamineus ingestion]. Gastroenterol Hepatol 2004; 27: 559-60. Spanish. PubMed Citation  (25 year old woman developed jaundice 2 months after starting green tea extract [bilirubin 19.9 mg/dL, ALT 2398 U/L, Alk P 164 U/L], resolving in 2 months).

19. Duenas Sadornil C, Fabregas Puigtio S, Durandez R. [Hepatitis due to Camelia sinensis] Med Clin(Barc) 2004; 122: 677-8. PubMed Citation  (35 year old woman developed jaundice 5 weeks after starting Exolise® [18.9 mg/dL, ALT 1558 U/L, Alk P 430 U/L], resolving in 2 months: same case as in Pedros [2003]).

20. Peyrin-Biroulet L, Petitpain N, Kalt P, Ancel D, Petit-Laurent F, Trechot P, Barraud H, Bronowicki JP. [Probable hepatoxicity from epigallocatecol gallate used for phytotherapy]. Gastroenterol Clin Biol 2004; 28: 404-6. French. PubMed Citation  (50 year old woman developed jaundice 15 days after starting Minifit [epigallocatechin gallate], with bilirubin 4.7 mg/dL, ALT 54 times ULN, resolving in 2 months, patient had a similar event a year earlier).

21. Schmidt M, Schmitz HJ, Baumgart A, Guédon D, Netsch MI, Kreuter MH, Schmidlin CB, Schrenk D. Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture. Food Chem Toxicol 2005; 43: 307-14. PubMed Citation  (Green tea extracts were toxic to isolated rat hepatocytes in vitro, the active toxic component being epigallocatechin gallate, the major catechin in green tea).

22. Andrade RJ, Lucena MI, Fernández MC, Pelaez G, Pachkoria K, García-Ruiz E, García-Muñoz B, et al.; Spanish Group for the Study of Drug-Induced Liver Disease. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology 2005; 129: 512-21. PubMed Citation  (Reports of drug-induced liver injury to a Spanish network found 570 cases, herbal medications accounted for 9 cases).

23. Gloro R, Hourmand-Ollivier I, Mosquet B, Mosquet L, Rousselot P, Salamé E, Piquet MA, Dao T. Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea. Eur J Gastroenterol Hepatol 2005; 17: 1135-7. PubMed Citation  (48 year old woman developed jaundice 2 months after starting Exolise [bilirubin 26.3 mg/dL, ALT 102 times ULN, Alk P normal, prothrombin index 12%], with progressive liver failure requiring transplantation).

24. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement Hydroxycut. Ann Intern Med 2005; 142: 477-8. PubMed Citation  (27 and 30 year old men developed jaundice 2 and 5 weeks after starting Hydroxycut [bilirubin 7.8 and 7.8 mg/dL, ALT 3131 and 45 U/L, Alk P 171 and 530 U/L], resolving in 1-2 months: Case 2).

25. Porcel JM, Bielsa S, Madronero AB. Hepatotoxicity associated with green tea extracts. [Electronic letter]. Accessed by www.annals.org on June 3 2005.  (53 year old woman developed jaundice 2 weeks after stopping a 2-week course of a green tea extract [bilirubin 5.3 mg/dL, ALT 927 U/L, Alk P 187 U/L], resolving in 5 weeks).

26. Abu el Wafa Y, Benavente Fernández A, Talavera Fabuel A, Pérez Ramos MA, Ramos-Clemente JI. [Acute hepatitis induced by Camellia sinensis(green tea)] Ann Med Intern 2005; 22: 298-9. Spanish. PubMed Citation  (35 year old woman developed jaundice 10 days after starting Exolise® for obesity [bilirubin 19.5 mg/dL, ALT 2885, Alk P 182 U/L], resolving within 2 months).

27. Bonkovsky HL. Hepatotoxicity associated with supplements containing Chinese green tea(Camellia sinensis). Ann Intern Med 2006; 144: 68-71. PubMed Citation  (37 year old woman developed jaundice 4 months after starting “The Right Approach Complex” [which contains green tea extract] for weight loss [bilirubin 11.7 mg/dL, ALT 1788 U/L, Alk P 238 U/L], with resolution in 1 month and recurrence within 1 month of restarting the product: Case 1).

28. Martinez-Sierra C, Herrera PRULM. [Acute hepatitis after ingestion of green tea]. Med Clin(Barc) 2006; 27: 119. Spanish. PubMed Citation  (26 year old woman developed jaundice 4 months after starting weekly green tea “infusions” [bilirubin 6.5 mg/dL, ALT 3314, Alk P not mentioned], with recurrence within 2 weeks of restarting the drink [bilirubin 19 mg/dL, ALT 1750, Alk P 240] and resolving in 2 months upon stopping).

29. Galati G, Lin A, Sultan AM, O'Brien PJ. Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med 2006; 40: 570-80. PubMed Citation  (In vitro study of toxicity of green tea phenolic acids on rat hepatocytes, the most toxic component to mitochondrial membrane potential was epigallocatechin-3-gallate, which is the major component of green tea and is detoxified by glutathione).

30. Javaid A, Bonkovsky HL. Hepatotoxicity due to extracts of Chinese green tea(Camellia sinensis): a growing concern. J Hepatol 2006; 45: 334-5. PubMed Citation  (Letter in response to editorial by Stickel [2005] describing a 46 year old woman who developed jaundice 7 months after starting green tea extracts [bilirubin 12.3 rising to 29.5 mg/dL, ALT 1100 U/L, Alk P 194 U/L]; scant information and no follow up provided).

31. Jimenez-Saenz M, Martinez-Sanchez M del C. Acute hepatitis associated with the use of green tea infusions. J Hepatol 2006; 44: 616-7. PubMed Citation  (45 year old man drinking 6 cups of marketed green tea “infusions” daily for 4 months developed jaundice [bilirubin 7 mg/dL, ALT 1613 U/L, Alk P 310 U/L], resolving in 2 months and recurring within 1 month of restarting).

32. Molinari M, Watt KD, Kruszyna T, Nelson R, Walsh M, Huang WY, Nashan B, Peltekian K. Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl 2006; 12: 1892-5. PubMed Citation  (44 year old woman developed jaundice 4 months after starting green tea extract [720 mg/day] for weight loss [bilirubin 13.1 rising to 43.2 mg/dL, ALT 3583 U/L, GGT 112 U/L], undergoing liver transplantation 17 days after admission; patient was also on progesterone injections for contraception).

33. Jimenez-Saenz M, Martinez-Sanchez C. Green tea extracts and acute liver failure: the need for caution in their use and diagnostic assessment. Liver Transpl 2007; 13: 1067. PubMed Citation  (Letter in response to Molinari [2006] indicating that progesterone may have contributed to the injury and describing a 22 year old woman who developed jaundice 2 weeks after starting progesterone [bilirubin 13.5 mg/dL ALT 1584 U/L], with resolution on stopping).

34. Federico A, Tiso A, Loguercio C. A case of hepatotoxicity caused by green tea. Free Radic Biol Med 2007; 43: 474. PubMed Citation  (51 year old woman was found to have abnormal liver enzymes during the 5 years that she drank green tea daily, which normalized when she stopped and became abnormal again when she restarted [ALT 4-5 times ULN, Alk P 1.5-2 times ULN]).

35. Bjornsson E, Olsson R. Serious adverse liver reactions associated with herbal weight-loss supplements. J Hepatol 2007; 47: 295-7. PubMed Citation  (5 cases of liver injury from green tea containing herbal [Cuur] reported to Swedish Adverse Drug Reactions Advisory Committee over 2 years; 4 women and 1 man, ages 35 to 64 years, taking product for 5 to 20 weeks, 4 with jaundice [bilirubin 1-25 times ULN, ALT 25-95 times ULN, Alk P 1.4-8.3 times ULN], all resolved within 5-12 weeks, 4 received prednisone).

36. Jones FJ, Andrews AH. Acute liver injury associated with the herbal supplement hydroxycut in a soldier deployed to Iraq. Am J Gastroenterol 2007; 102: 2357-8. PubMed Citation  (19 year old male US Army soldier in Iraq developed jaundice 4 months after starting Hydroxycut for weight loss [bilirubin 11.7 mg/dL, ALT 1143 U/L, Alk P 153 U/L], resolving in 4 months of stopping).

37. Elinav E, Pinsker G, Safadi R, Pappo O, Bromberg M, Anis E, Keinan-Boker L, et al. Association between consumption of Herbalife nutritional supplements and acute hepatotoxicity. J Hepatol 2007; 47: 514-20. PubMed Citation  (12 cases of hepatotoxicity attributed to Herbalife products in Israel, 11 women, 1 man, ages 32 to 78 years, onset after 2 to 35 months [mean peak bilirubin 9.1 mg/dL, ALT 1481 U/L, Alk P 282 U/L], 1 with ANA resolving on recovery, 11 recovered, one died of hepatitis B reactivation, 3 positive rechallenges).

38. Schoepfer AM, Engel A, Fattinger K, Marbet UA, Criblez D, Reichen J, Zimmermann A, Oneta CM. Herbal does not mean innocuous: ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife products. J Hepatol 2007; 47: 521-6. PubMed Citation  (10 cases of hepatotoxicity due to Herbalife products in Switzerland; ages 30-69 years, 3 men and 7 women, with onset after 2 to 144 months, 9 with jaundice [bilirubin 0.4-28.2 mg/dL, ALT 4-50 times ULN, Alk P 1.1-6.5 times ULN], 2 with recurrence on rechallenge, 3 requiring liver transplant, 1 with sinusoidal obstruction syndrome, 1 with cirrhosis).

39. Stickel F. Slimming at all costs: Herbalife-induced liver injury. J Hepatol 2007; 47: 444-6. PubMed Citation  (Editorial in reference to Schoepfer [2007] and Elinay [2007] discussing the difficulties in assigning causality and identifying the toxic component, many patients take multiple herbal products and each including multiple components and possibly containing contaminants).

40. Duque JM, Ferreiro J, Salgueiro E, Manso G. [Hepatotoxicity associated with the consumption of herbal slimming products]. Med Clin(Barc) 2007; 128: 238-9. Spanish. PubMed Citation  (3 cases of hepatotoxicity attributed to Herbalife products, women ages 49-54 years, with onset of liver injury after 1, 6 and 36 months [bilirubin 0.7, 0.8, and 26.6 mg/dL, ALT 138, 505 and 1890 U/L, Alk P 112, 166 and 425 U/L], resolving in all 3 upon stopping).

41. Chao S, Anders M, Turbay M, Olaiz E, Mc Cormack L, Mastai R. [Toxic hepatitis by consumption Herbalife products a case report]. Acta Gastroenterol Latinoam 2008; 38: 274-7. Spanish. PubMed Citation  (63 year old woman developed jaundice and pruritus 2.5 months after starting Herbalife products [peak bilirubin 17.5 mg/dL, ALT 847 U/L, Alk P 3 times ULN], resolving within 5 months of stopping).

42. Manso G, López-Rivas L, Duque JM, Salgueiro E. Spanish reports of hepatotoxicity associated with Herbalife products. J Hepatol 2008; 49: 289-90; author reply 290-1. PubMed Citation  (Discussion of 4 cases of Herbalife hepatotoxicity from Spain [3 reported by Duque 2007], 2 occurring in sisters, suggesting a genetic propensity and an idiosyncratic drug reaction).

43. Ignarro L, Heber D, Henig YS, Bejar E. Herbalife nutritional products and liver injury revisited. J Hepatol 2008; 49: 291-3; author reply 293-4. PubMed Citation  (Comment on publications on Herbalife hepatotoxicity [Elinav and Schoepfer 2007] questioning whether their product was involved, as the product is used by millions).

44. Dara L, Hewett J, Lim JK. Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol 2008; 14: 6999-7004. PubMed Citation  (Two women ages 33 and 40 years with onset of symptoms 1 and 4 weeks after starting Hydroxycut [bilirubin 0.7 and 20.9 mg/dL, ALT 1150 and 934 U/L, Alk P 299 and 112 U/L], resolving rapidly; ingredients included green tea but not ephedra; review of liver injury due to weight loss supplements including Ma Huang, Lipokinetix, Kava, green tea, Shou Wu Pian, germander and usnic acid).

45. Vanstraelen S, Rahier J, Geubel AP. Jaundice as a misadventure of a green tea(camellia sinensis) lover: a case report. Acta Gastroenterol Belg 2008; 71: 409-12. PubMed Citation  (76 year old man who drank 6-7 “infusions” of green tea daily for years developed jaundice [bilirubin 16.7 mg/dL, ALT 646 U/L, Alk P 331 U/L], resolving within 10 weeks of stopping).

46. García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. [Liver injury induced by "natural remedies": an analysis of cases submitted to the Spanish Liver Toxicity Registry]. Rev Esp Enferm Dig 2008; 100: 688-95. Spanish. PubMed Citation  (Among 521 cases of drug-induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals, 3 due to green tea extracts: 23-27 year olds developed jaundice 5, 19 and 121 days after starting green tea [bilirubin 11.4-16.6 mg/dL, ALT 6-84 times ULN, Alk P 0.9-1.6 times ULN], resolving in 1.5-3 months).

47. Sarma DN, Barrett ML, Chavez ML, Gardiner P, Ko R, Mahady GB, Marles RJ, et al. Safety of green tea extracts: a systematic review by the US Pharmacopeia. Drug Saf 2008; 31: 469-84. PubMed Citation  (US Pharmacopoeia review of green tea hepatotoxicity identified 216 adverse event reports, including 34 of liver injury [8 published, others from Spanish, French, US, UK, Canadian and Australian safety reports], which were scored as probable in 7 and possible in 27; in most cases, there were multiple agents involved; the committee recommending taking green tea with meals).

48. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network(DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. PubMed Citation  (Among 300 cases of drug-induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications, green tea being prominently incriminated).

49. Verhelst X, Burvenich P, Van Sassenbroeck D, Gabriel C, Lootens M, Baert D. Acute hepatitis after treatment for hair loss with oral green tea extracts(Camellia Sinensis). Acta Gastro-Enterologica Belgica 2009; 72: 262-4. PubMed Citation  (41 year old woman developed jaundice 6 months after starting green tea containing herbal [bilirubin 13.6 mg/dL, ALT 2801 U/L, Alk P 251 U/L], with rapid resolution on stopping).

50. Shim M, Saab S. Severe hepatotoxicity due to Hydroxycut: a case report. Dig Dis Sci 2009; 54: 406-8. PubMed Citation  (28 year old man developed jaundice 3 months after starting Hydroxycut [containing green tea extract] for weight loss [bilirubin 18.1 mg/dL, ALT 2272 U/L, Alk P 152 U/L, ANA 1:40], with rapid improvement on stopping).

51. Schneider C, Segre T. Green tea: potential health benefits. Am Fam Physician 2009; 79: 591-4. PubMed Citation  (Review of health benefits of green tea, the medical evidence for benefit being of limited quality and often inconsistent).

52. Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 29: 373-82. PubMed Citation  (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; specific discussion of green tea, Hydroxycut, Herbalife and traditional Chinese herbal medicines).

53. Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, Mastrangelo S. Hepatotoxicity from green tea: a review of the literature and two published cases. Eur J Clin Pharmacol 2009; 65: 331-41. PubMed Citation  (Review of literature and addition of two cases from Italy: 81 year old woman developed jaundice 1 month after starting Epinerve® [epigallocatechin gallate] [bilirubin 21.8 mg/dL, ALT 2638 U/L], resolving in 3 months; and, 72 year old woman with jaundice 3 months after starting Epinerve® [bilirubin 18 mg/dL; ALT >700 U/L], resolving rapidly on stopping).

54. Amariles P, Angulo N, Agudelo-Agudelo J, Gaviria G. [Hepatitis associated with aqueous green tea infusions: a case study]. Farm Hosp 2009; 33: 289-91. Spanish. PubMed Citation  (43 year old woman taking green tea infusions for constipation for 8 months developed nausea [bilirubin 2.1 mg/dL, ALT 841 U/L, Alk P 100 U/L], with rapid recovery upon stopping).

55. Bergmann J, Schjott J. Hepatitis caused by Lotus-f3? Basic Clin Pharmacol Toxicol 2009; 104: 414-6. PubMed Citation  (51 year old woman with psoriasis on etanercept developed jaundice 3 weeks after starting a green tea extract containing herbal [bilirubin 17.5 mg/dL, ALT 1871 U/L, Alk P 342 U/L], with resolution within 6 weeks of stopping herbal and etanercept, which was later reintroduced without recurrence).

56. Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS. Hepatotoxicity of high oral dose(-)-epigallocatechin-3-gallate in mice. Food Chem Toxicol 2010; 48: 409-16. PubMed Citation  (In mice, high oral doses of epigallocatechin gallate cause ALT elevations and acute hepatic necrosis within 24 to 48 hours).

57. Sharma T, Wong L, Tsai N, Wong RD. Hydroxycut(®)(herbal weight loss supplement) induced hepatotoxicity: a case report and review of literature. Hawaii Med J 2010; 69: 188-90. PubMed Citation  (19 year old man developed fever, rash, fatigue and then jaundice 1 week after starting Hydroxycut [bilirubin 7.3 mg/dL, ALT 81 U/L, Alk P 298 U/L, protime 16.7 sec], biopsy showed scant necrosis, recovery within 14 weeks of stopping).

58. Rashid NN, Grant J. Hydroxycut hepatotoxicity. Med J Aust 2010; 192: 173-4. PubMed Citation  (23 year old woman developed jaundice approximately 8 weeks after starting Hydroxycut [bilirubin 6.6 mg/dL, ALT 2950 U/L, Alk P 121 U/L], resolving within 4 weeks of stopping).

59. Harvey KJ. Hydroxycut hepatotoxicity. Med J Aust 2010; 192: 669-70. PubMed Citation  (Letter in response to Rashid [2010] stating that Hydroxycut preparations in Australia continue to have the same ingredients that led to its withdrawal in the US, including green tea extract).

60. Chen GC, Ramanathan VS, Law D, Funchain P, Chen GC, French S, Shlopov B, et al. Acute liver injury induced by weight-loss herbal supplements. World J Hepatol 2010; 2: 410-5. PubMed Citation  (Three women, ages 31, 37 and 53 years, taking Hydroxycut or Herbalife for weight loss developed jaundice 3, 4 and 12 months after starting product [bilirubin 15.3, 29.9, and 18.2 mg/dL, ALT 1227, 2068 and 983 U/L, Alk P 268, 185 and 292 U/L], resolving within 2-3 months of stopping).

61. Fong TL, Klontz KC, Canas-Coto A, Casper SJ, Durazo FA, Davern TJ 2nd, Hayashi P, et al. Hepatotoxicity due to hydroxycut: a case series. Am J Gastroenterol 2010; 105: 1561-6. PubMed Citation  (Details of 17 cases of hepatotoxicity due to Hydroxycut in the United States between 2002-9: latency to onset ranged from 2 to 12 weeks with two outliers at 1 and 2 years, typical pattern of injury was hepatocellular, often severe, 4 were fatal or led to liver transplantation). 

62. Stickel F, Kessebohm K, Weimann R, Seitz HK. Review of liver injury associated with dietary supplements. Liver Int 2011; 31: 595-605. PubMed Citation.  (Review of current understanding of liver injury from herbals and dietary supplements, focusing upon Herbalife and Hydroxycut products, green tea, usnic acid, Noni juice, Chinese herbs, vitamin A and anabolic steroids).

63. Yellapu RK, Mittal V, Grewal P, Fiel M, Schiano T. Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review.  Can J Gastroenterol 2011 Mar; 25(3): 157-60. PubMed Citation.  (Ordered).

64. Thavanesan N. The putative effects of green tea on body fat: an evaluation of the evidence and a review of the potential mechanisms. Br J Nutr 2011; 106: 1297-309. PubMed Citation.  (Review of mechanisms of action of green tea in weight loss suggesting that multiple mechanisms are involved).

65. Appelhans K, Smith C, Bejar E, Henig YS. Revisiting acute liver injury associated with herbalife products. World J Hepatol 2011; 3: 275-7. PubMed Citation.  (Letter in response to Chen [2010] arguing that the two cases attributed to Herbalife products were inadequately documented).

66. Manso G, López-Rivas L, Salgueiro ME, Duque JM, Jimeno FJ, Andrade RJ, Lucena MI. Continuous reporting of new cases in Spain supports the relationship between Herbalife® products and liver injury. Pharmacoepidemiol Drug Saf 2011; 20: 1080-7. PubMed Citation.  (Update on cases of liver injury reported to the Spanish Pharmacovigilance Database between 2003-2010 identified 20 cases, 16 in women, mean age 45 years, 12 hospitalized, [bilirubin 0.6-33.3 mg/dL, ALT 88-3269 U/L, Alk P 112-1034 U/L], one developed cirrhosis, the others recovered; patients took 1 to 9 different Herbalife products and no single ingredient appeared common to most cases). 

67. Larrey D, Faure S. Herbal medicine hepatotoxicity: a new step with development
    of specific biomarkers. J Hepatol 2011; 54: 599-601. PubMed Citation.  (Editorial on the problem of hepatotoxicity of herbal medications, the difficulties of causality assessment, the variability of the products, possibly of contamination, lack of rigorous regulations and need for biomarkers for hepatic injury).

68. Stiefelhagen P. ["Doing something good" for the body? Definitely not! Liver damage caused by food supplements]. MMW Fortschr Med 2010 Oct 28; 152(43): 21. German. PubMed Citation. (Ordered).

69. Lobb A. Hepatoxicity associated with weight-loss supplements: a case for better post-marketing surveillance. World J Gastroenterol 2009; 15: 1786-7. PubMed Citation.   (Letter in response to Dara [2008] summarizing reports of liver injury attributed to hydroxycut and recommending more stringent regulations for HDS products in the United States).

70. Jóhannsson M, Ormarsdóttir S, Olafsson S. [Hepatotoxicity associated with the use of Herbalife]. Laeknabladid 2010; 96: 167-72. Icelandic. PubMed Citation.   (5 cases of liver injury attributed to Herbalife products from Iceland; 4 women and 1 man, ages 29-78 years with onset after 1 to 7 months of use [bilirubin 1.3-15.6 mg/dL, ALT 456-2637 U/L, Alk P 149-712 U/L], all recovered upon stopping). 

71. Appelhans K, Frankos V. Herbal medicine hepatotoxicity revisited. J Hepatol 2012; 56: 504-5. Reply by authors. PubMed PubMed Citation. (Letter in response to Larrey [2011] arguing that Herbalife products are carefully assessed for purity and and that the green tea extracts used have never been implicated in causing liver injury; authors reply that idiosyncratic liver injury occurs with many medications of proven purity).
    

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