FDA Deputy Commissioner Joshua Sharfstein, M.D.

FDA Principal Deputy Commissioner Joshua M. Sharfstein, M.D. gave the keynote speech to the Council for Responsible Nutrition Conference. Dr. Sharfstein expressed a willingness to work with supplement industry members and received a warm welcome from industry members in return.

Sharfstein filled in at the last minute when Commissioner Margaret Hamburg, M.D. was called before the Senate Committee on Health, Labor, Education and Pensions to testify at a hearing entitled “Keeping America’s Families Safe: Reforming the Food Safety System.”

Dr. Sharfstein started off by noting that FDA products account for $.20 of every $1.00 spent by Americans.  As to supplements, he revealed that he (like me) suffers from lactose intolerance and supplements with lactase enzyme.

Beyond the pleasantries, Sharfstein focused his speech on regulatory concerns with specific types of products and what FDA is doing currently to address these concerns.  Sharfstein pointed specifically to FDA successes in addressing products promoted for treating H1N1 flu, adulterated muscle enhancers containing anabolic steroids, and male enhancement supplements containing erectile dysfunction drug analogues.

Sharfstein also addressed suggestions that one way regulate adulterated supplements is through the NDI process.  Under DSHEA, ingredients that were in the food supply prior to October of 1994 are grandfathered in, but those that were not and require new dietary ingredient (NDI) applications.  However, as Sharfstein noted, there is no FDA recognized list of grandfathered supplement ingredients at present, and also many supplement products often contain undeclared ingredients which makes an approach that depends upon examining labels fundamentally flawed.  As a result, Sharfstein declared that new ingredient premarket verification is a priority for FDA.  With these and other challenges Sharfstein expressed a sincere willingness to work with industry to improve FDA response and regulatory strategies.

Sharfstein did receive several probing questions including a challenge regarding the FDA’s handling of the recent Hydroxycut recall, something we at NutriSupLaw have previously questioned several times.  The questioner noted that Hydroxycut was recalled based upon just 23 reports of liver disease out of over 20 million units of Hydroxycut sold, and asked Sharfstein for a the scientific basis of the FDA’s action.  The questioner also noted that the panel that raised concerns with Hydroxycut failed to identify a specific ingredient in the product that caused the problems, and there are many products still on the market today that contain those same ingredients.

To his credit, Sharfstein did not simply “toe the party line” on this issue in his response.  Instead he observed “I am getting the sense that there is a lack of understanding in this room about why the FDA did this,” and he went on to suggest that FDA reevaluate the matter and hold a conference call with industry to discuss it further.

Let’s see if FDA comes through and works with industry on these efforts.

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This is a tale of two types of weight-loss products and how the Food and Drug Administration had different responses to similar problems with them. The separate, but not equivalent treatment raises questions about how the FDA operates.

On Aug. 24, the FDA issued a statement about an ongoing safety review of orlistat based on reports of liver injury in people taking the weight-loss drug. It is marketed as the prescription drug Xenical and the over-the-counter medication Alli.

The FDA said it had received 32 reports of serious liver injury in patients taking orlistat between 1999 and 2008.  Of those cases, 27 required hospitalization and six resulted in liver failure.

Sound familiar? It should. On May 1, the FDA issued a warning about the danger of Hydroxycut based on 23 reported liver problems over seven years, including 16 hospitalizations. One person died in February 2007 after taking that weight-loss product.

That is where the stories diverge. For orlistat, the FDA is conducting a review because, “no definite association between liver injury and orlistat has been established at this time,” according to the release. “Consumers taking Xenical should continue to take it as prescribed, and those using over-the-counter Alli should continue to use the product as directed.”

In contrast, the FDA told consumers to stop immediately using Hydroxycut even though the agency acknowledged in a health hazard evaluation board report that “The Board does not know what ingredient(s) of Hydroxycut are responsible for producing liver toxicity. In addition, there is insufficient information to determine whether there is a dose-response effect between Hydroxycut ingestion and liver disease or whether its effects are cumulative over time.”

Despite a lack of direct evidence, the board concluded “that the ingestion of the dietary supplement, Hydroxycut, presents a severe potentially life-threatening hazard to some users.” The makers of Hydroxycut immediately ordered a recall.

What might the same health board members think about orlistat? It has caused liver injuries for a longer time period and has put more people in the hospital with similar ailments — jaundice and liver failure.

Does the FDA give greater weight to the patient death? If so, it seems to us that the product would have been recalled in 2007.

Is the difference the way the products are regulated? The FDA approved Xenical in 1999 and Alli in 2007. None of the ingredients in Hydroxycut were identified in the report as needing FDA review.

If the distinctions are not clear from a review of the facts, then what are we to expect the next time a weight-loss product is associated with health problems?

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Outside the industry, the viewpoints were more pragmatic. Scot Long, an exercise physiologist and professor from Mississippi, weighed in, writing: “Bottom line, do I think that Hydroxycut is an evil product? No. I think many people abused this product (taking too much) and some may have even had pre-existing medical conditions. Do I recommend it to my students, clients and friends? Of course not. I do think, however, that Iovate Health Sciences could have made a safer product. But it shouldn’t shoulder all the blame.”

Marion Nestle, author of “Food Politics,”  wrote in her San Francisco Chronicle column, “I freely concede that most supplement companies make reliable products, but without federal oversight how is anyone – even a store clerk – supposed to know which ones they are. Some clerks may know their business, but in my experience few think critically about the products they are selling and most appear to take the manufacturers’ words at face value.”

After a Hydroxycut recall article was posted on FitSugar.com, a commenter who goes by the name Mondaymoos offered this first-person experience : “I never took diet pills for the purpose of losing weight. Me, and a lot of other people in the military, used them as a tool to work 12 hour shifts and still go out and have a life afterwards without racking up massive calories in energy drinks and soda. Was it a healthy decision, probably not. Did it work? Definitely yes.”

Consumers seem to know that there are no magic diet pills and that abusing a product is probably harmful. Thus, rhetoric that casts the FDA — or a manufacturer — as hero or villain does not sway consumers. They would rather know the benefits and risks of a product, and make an informed choice based on that.

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The Food & Drug Administration issued on May 1 a consumer warning to stop using Hydroxycut, the heavily marketed weight-loss product. The agency said that “some Hydroxycut products are associated with a number of serious liver injuries” and announced that the maker was recalling all products.

Did the FDA properly react? The warning cited 23 serious health problems, including jaundice, liver damage, seizures and cardiovascular disorders. One person has died from liver failure since 2002 when the Center for Food Safety and Applied Nutrition first received reports about liver damage associated with intake of Hydroxycut.

Some people — for reasons not totally understood — had adverse reactions to Hydroxycut, according to a research report cited in the FDA warning. Sometimes the individuals required serious treatment for liver damage. Other times, the people regained normal health when they stopped taking the product.

Until 2004, Hydroxycut contained ephedra, a substance that the FDA banned after a study found more than 16,000 adverse events associated with its use in dietary supplements. According to a recent label, the main ingredients in Hydroxycut are now the minerals calcium, chromium and potassium, plus what the company calls Hydroxagen Plus and HydroxyTea. The former contains leaf and rind extracts and the latter is a combination of tea and ginger extracts.

None are banned substances. And the  health hazard evaluation board acknowledged in its report that it “does not know what ingredient(s) of Hydroxycut are responsible for producing liver toxicity. In addition, there is insufficient information to determine whether there is a dose-response effect between Hydroxycut ingestion and liver disease or whether its effects are cumulative over time.”

The board concluded, “Three lines of evidence derived from multiple disparate sources suggest it is very likely that exposure to Hydroxycut can cause idiosyncratic hepatotoxicity.”

Some definitions are in order. According to a 2007 article in Toxicological Sciences, “Idiosyncratic hepatotoxicity is a rare and unpredictable event of liver injury affecting generally less than 1 in 10,000 patients treated with certain drugs. However, it is a serious clinical problem as it accounts for 10% of all drug-induced liver failure cases.”

And citing a study published in May 2005 in the Nature Reviews Drug Discovery, the article said, “Idiosyncratic hepatotoxicities are currently the main cause for Food and Drug Administration-mandated warnings, restrictions of use or even withdrawals of drugs from the market.”

So, the FDA puts great weight on idiosyncratic hepatoxicity even though it is uncommon and difficult to predict in a population. Given the level of uncertainty, did the FDA have other options? After conducting a risk-benefit analysis, could the agency have told the makers of Hydroxycut to add a warning to immediately discontinue use and seek medical attention if certain symptoms present themselves? Why did an average of three cases per year — none this year and only three last year — justify a ban and recall?

Here’s a clue from the report, which references the Center for Food Safety and Applied Nutrition as CFSAN:  “In discussions in March and April of 2009 with hepatologists Tse-Ling Fong, M.D. of the University of Southern California and William Lee, M.D. of the University of Texas Southwestern Medical Center, CFSAN has become aware of these physicians’ case series of patients with severe liver disease associated with the use of Hydroxycut. Two cases from this series, representing additional cases to the ones reported to CFSAN, underwent liver transplantation following acute liver failure.”

Were the doctors two of the three sources? And were their case series the underlying reason for such swift and final FDA action? The answers are not here, but they are needed.

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The FDA has just announced a massive recall of the popular weight loss supplement, Hydroxycut.

According to the FDA press release dated today, FDA has received 23 reports of serious health problems ranging from jaundice and elevated liver enzymes, an indicator of potential liver injury, to liver damage requiring liver transplant. One death due to liver failure has been reported to the FDA. Other health problems reported include seizures; cardiovascular disorders; and rhabdomyolysis, a type of muscle damage that can lead to other serious health problems such as kidney failure.

Hydroxycut is manufactured and distributed by Iovate Health Sciences.  As of this writing, both the hydroxycut.com and iovate.com websites are effectively “down” with all information having been stripped from their home pages.  Expect recall notices to be posted there shortly.

A long list of products are included in the recall.  They are:

• Hydroxycut Regular Rapid Release Caplets
• Hydroxycut Caffeine-Free Rapid Release Caplets
• Hydroxycut Hardcore Liquid Caplets
• Hydroxycut Max Liquid Caplets
• Hydroxycut Regular Drink Packets
• Hydroxycut Caffeine-Free Drink Packets
• Hydroxycut Hardcore Drink Packets (Ignition Stix)
• Hydroxycut Max Drink Packets
• Hydroxycut Liquid Shots
• Hydroxycut Hardcore RTDs (Ready-to-Drink)
• Hydroxycut Max Aqua Shed
• Hydroxycut 24
• Hydroxycut Carb Control
• Hydroxycut Natural

According to FDA, one death due to liver failure has been reported.   If there is real causation behind this announcement then this could be one of the largest supplement liability issues ever.

Stay tuned for more news as we receive it.

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