Two Herbal Supplements Recalled Amid Rising Regulatory Concerns

The manufacturer of a promising and widely used herbal treatment for prostate cancer told consumers Friday to stop taking the product after California authorities determined it was contaminated with potentially harmful prescription drugs.

State health officials asked BotanicLab Inc. of Brea to recall PC SPES, the prostate cancer treatment, and another supplement, SPES, after finding they contained elements of the anxiety drug Xanax and the blood-thinning drug Coumadin. Both drugs are supposed to be taken under the supervision of a physician.

On Friday, the company posted a letter on its Web site asking consumers and distributors to return all unused PC SPES pills in their original containers for a refund. The letter did not mention SPES.

Meanwhile, the U.S. Food and Drug Administration announced it was launching an investigation based on California authorities’ findings.

PC SPES, taken by at least 10,000 American men, is one of the few herbal supplements to demonstrate substantial therapeutic effects. Studies on its positive effects have been published in respected medical journals and demand for the compound, whose effectiveness is still being studied, has grown dramatically.

The contamination underscores ongoing concern about the lack of regulation for supplements--particularly of manufacturing standards.

PC SPES appears to reduce the growth of prostate tumors. SPES is marketed as a supplement that can help boost the immune system. But little is known about the compounds they contain and how they work. The PC SPES ingredients are reishi, Baikal skullcap, rabdosia, dyer’s woad, mum, saw palmetto, San-Qui ginseng and Chinese licorice.

The state Department of Health Services announced Friday that its investigators, in tests of product samples at a Sacramento laboratory, had found warfarin in PC SPES, and alprazolam in SPES. Warfarin is marketed under the trade name Coumadin and alprazolam under the trade name Xanax.

Independently, researchers at UC San Francisco’s medical school confirmed to The Times that they had tested four different lots of PC SPES and found that all contained yet a third contaminant, diethylstilbestrol, or DES, a hormone that was once used to prevent miscarriages but later was banned when it was shown to cause birth defects in children and blood clots and other side effects among men.

1994 Law Limited FDA’s Authority

PC SPES, which had shown success in treating men whose prostate cancer did not respond to conventional therapies, had been undergoing clinical trial at UC San Francisco.

But Ray Wilson, a scientist with the state health department, said the trial was abruptly halted recently by Dr. Eric J. Small, who was heading the study, because of concerns about DES contamination.

The recall comes as concern is mounting among medical experts nationally over the lack of regulation of herbal supplements. Herbal remedies are classified as food supplements and, unlike prescription drugs, are not subject to regulation by the U.S. Food and Drug Administration.

The FDA once had authority to regulate dietary supplements and in 1989 did act swiftly to recall one such substance--L-tryptophan--which was ultimately linked to 37 deaths. But under a 1994 law, the supplement manufacturers were made responsible for ensuring the safety of a product and the accuracy of the labeling.

Federal officials can still intervene in the case of fraudulent marketing claims. And the FDA is required under the 1994 law to issue “good manufacturing practices” guidelines for the makers of supplements, although it has yet to do so.

On Friday, FDA officials warned consumers that the supplements PC SPES and SPES may pose serious health risks and are under investigation by the agency.

“In this case, the agency’s warning is due to the finding of the California state government that the ingredients in [the supplements] posed serious health risks,” FDA spokesman Jason Brodsky said. “We certainly are supportive of the company’s decision to recall the products.”

Brodsky declined to comment on the nature or scope of the FDA investigation, citing agency policy.

FDA officials said they are unaware of any consumer complaints of adverse reactions to the supplements. However, Brodsky cited a recent report in the New England Journal of Medicine about a serious reaction to PC SPES.

D.A. Fielded Complaints of PC SPES Side Effects

BotanicLab has not been shy about marketing PC SPEC, but the company has avoided media scrutiny and typically has refused requests by the media to speak to its scientists.

Although the state health department and FDA Web sites said both PC SPES and SPES were being recalled, the recall notice posted on BotanicLab’s Web site made no mention of the SPES recall.

No one at BotanicLab, a privately held company founded by patent-holder Sophie Chen, could be reached for comment Friday evening.

In a letter to customers, president John Chen said the company believes “further testing [of PC SPES] is necessary to confirm the material at issue is warfarin.” The letter said that the company was nonetheless recalling the product to be prudent.

“As we implement a new quality control process, further shipments of PC SPES may not be immediately available,” the letter said.

Wilson, the state health department scientist, said state investigators visited BotanicLabs’ Brea facility after receiving a report from a Southern California district attorney who had been fielding complaints of adverse effects from constituents who had taken PC SPES.

He said the reactions reported were consistent with those experienced by men who have been exposed to an estrogen product--swollen breasts, tender nipples, erectile dysfunction and a lowered sex drive.

Lea Brooks, a spokeswoman for the state health department, said officials there keep tabs on Web sites and chat rooms where dietary supplements are discussed. Officials became aware of persistent reports of DES contamination through consumers who had ordered laboratory tests and reported the results on the Internet.

“We went looking for DES in PC SPES, and we didn’t find it,” he said, explaining that the state’s tests may not have been sufficiently sensitive to detect the small quantities--3% or less--that UCSF detected.

Study Discovered Taint--and Benefit

The discovery of Xanax in SPES came by accident. Wilson said the department did not originally intended to test SPES but took samples along with PC SPES to the lab. Xanax was detected when the product was given a conventional test for prescription drugs.

The state also detected warfarin, or Coumadin, in PC SPES. Although BotanicLab officials suggested that the warfarin may have been naturally present in some of the herbs it uses, Wilson said state scientists were confident that it was a synthetic version of the drug.

The state health department and the manufacturer recommended that users of the supplements immediately halt their use. However, medical experts said this could lead to complications for the users of SPES, since drugs like Xanax are somewhat addictive and abruptly ending their use could result in withdrawal symptoms if usage had been heavy and prolonged. Because dietary supplements are generally not taken under the supervision of a doctor, doses and duration of use are often not carefully controlled.

A research assistant for UCSF researcher Small confirmed Friday that letters had recently been sent to study participants advising them that small amounts of DES had been discovered in the pills they were being given.

“Because of ongoing concerns about the contents of PC SPES, we recently decided to test each of the lots provided to us for the study by BotanicLab. We tested samples from all four lots used in the study. The laboratory tests revealed that each of the lots tested had small amounts of DES present,” the letter states.

The letter did have some good news for the cancer patients enrolled in the study: Preliminary data suggest that 45% of patients treated initially with PC SPES have had a 50% or greater reduction in their prostate-specific antigen levels, considered a marker for prostate cancer.

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Times staff writers Megan Garvey and Shari Roan contributed to this report.

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About PC SPES

* PC SPES is a centuries-old herbal remedy, a blend of eight herbs, that has shown striking results in treating patients with advanced prostate cancer.

* It is made by Brea-based BotanicLab and sold over the counter in capsule form.

* As of last year, it was used by an estimated 10,000 men and appears to reduce the signs of tumor growth in patients who have exhausted conventional treatments, including hormone therapy.

* It carries the risk of serious side effects, including breast tenderness and enlargement because of herbs that act like estrogen.

* As an over-the-counter supplement, it is not regulated by the U.S. Food and Drug Administration, although manufacturers are barred from claiming it cures disease.

* Federal and state health officials and the manufacturer urged patients to stop taking the drug Friday after it was found to contain the prescription drug warfarin, a blood-clotting agent marketed as Coumadin.

Source: Times file