New blog home, same old story: dietary supplement adulteration with prescription drugs

If you are new to this blog, you should know that our laboratory and collaborators work on all aspects of physiologically-active compounds from natural sources – plants, fungi, bacteria, marine organisms, etc.

So, I am equally interested in prescription drugs and herbal or non-botanical dietary supplements. There are still some products on the shelves of health food stores that can actually provide health benefits if manufactured properly and taken in high enough doses.

However.

A common practice by unscrupulous supplement manufacturers is to add prescription drugs, or close structural relatives, to their herbal product to make it appear to the consumer that their product has beneficial effects.

In the last two weeks, the US FDA MedWatch program has announced two voluntary product recalls for dietary supplements adulterated with undeclared prescription drugs.

Another in a long litany of erectile dysfunction products boosted with compounds like those found in Viagra or Cialis comes to us from Vialipro by Good Health, Inc.:

Good Health, Inc. is conducting a voluntary recall after an FDA lab analyses found that the product tested from certain batches of Vialipro contain Sulfoaildenafil, an analogue of Sildenafil, an FDA-approved drug used as treatment for male Erectile Dysfunction (ED) making this product an unapproved drug. The undeclared ingredient may pose a threat to the consumer because the interaction of the analogue with some prescription drugs (such as nitroglycerin) may lower blood pressure to dangerous levels. Consumers with diabetes, high blood pressure, high cholesterol, or heart disease often take other prescription drugs.

The Vialipro product website is dead as of the time of this writing.

Such practice with this product class is extremely sophomoric: the FDA has had a testing program running for several years to detect these compounds in male sexual enhancement products. The FDA hasn’t updated their consumer information page since February, 2009, but this guide lists a large number of herbal products identified since 2004 as having prescription, phosphodiesterase-5 inhibitors in them.

The practice is simply disingenuous and damages the reputation of botanical supplement manufacturers (and botanical researchers) who are trying to play by the rules and rigorously study these products.

Case two comes courtesy of J&H Besta Corporation and their Joyful Slim/Slim-30 “Natural Herb for Weight Loss”:

FDA lab analysis of this herb supplement was found to contain the undeclared drug, desmethyl sibutramine, an FDA-approved drug used as an appetite suppressant for weight loss. Sibutramine is known to substantially increase blood pressure and/or pulse rate in some patients and may present a significant risk for patients with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke.

The Joyful Slim website is still live (because they sell other products) but contains this ironic image:

A reason to shop from them is that they let you know about product recalls? Well, I guess that's a nice consumer feature. (From joyfulslim.com on 27 July 2010)

The FDA press releases to which I’ve linked (1, 2) contain information for the consumer on returning the products for refund and reporting any adverse reactions associated with product use.

This is cheating, my friends, and these are only the cases that are detected by the FDA. These incidents make me wonder just how many cases of reported dietary supplement efficacy are due to physiologically-active adulterants – the abundance of clinical trial failures of well-characterized, chemically-qualified herbal supplements may speak to this very issue.

Heavy metal-laden African morning sickness remedy now found in New York City

Just before Christmas, the US FDA issued a warning regarding a clay-based traditional West African remedy for morning sickness called Nzu or Calabar or Calabash clay. We discussed this topic here when the initial health warning came out from Texas.
The problem with the product is that it contains high levels of lead and arsenic that could be toxic to both fetus and mother.
And now the problem has expanded beyond Texas.
Scott Gavura at his excellent Science-Based Pharmacy blog tweeted earlier that the New York City Department of Health issued a similar warning today:

Calabash chalk.jpgFebruary 16, 2010 – A traditional morning sickness remedy, commonly known as calabash chalk, has been found to contain lead and arsenic, the Health Department warned today. The agency warns pregnant women not to use the product, which was recently found in local New York City stores selling African remedies. The Health Department was alerted to the potential hazard by the U.S. Food and Drug Administration. The chalk-like substance – also known as calabash clay, nzu, poto, calabar stone, mabele, argile or la craie – can be sold as large pellets or in blocks that resemble clay or mud. It is often packaged in clear plastic bags, with or without labeling. The remedy is used mainly by women from West African communities.

As shown above, the product looks like innocuous chalk. But the city is alerting both consumers and health care providers:

“Using calabash chalk is unhealthy for pregnant women and their unborn children,” said Nancy Clark, assistant commissioner for the Health Department’s Environmental Disease Prevention Bureau. “And the sale of these products is illegal.” Anyone who has used calabash chalk should call the Poison Control Center at 212-POISONS (764-7667). The Poison Control Center does not check immigration status, and its services are available in many languages. . .
. . .The Health Department is also alerting city healthcare providers about the use of calabash chalk. If you suspect you may have been poisoned, call the Poison Control Center at 212-POISONS (764-7667) or 212-VENENOS (836-3667) for Spanish speakers.

As we have quite a few readers in the New York City Tri-State area, please pass the word around, particularly if you work with colleagues who are from West African countries.

MuscleMaster.com “voluntarily” recalls 17 steroid-laden dietary supplements

It seems that bodybuilding supplement makers are challenging erectile dysfunction supplement makers to see who can recall the greatest number of products adulterated with undeclared, unapproved drugs.
In this case, an internet retailer of the following supplements has issued a voluntary recall of the following supplements sold between June 1, 2009 and November 17, 2009. The recall follows an FDA warning letter on detection of undeclared, synthetic anabolic steroids in these products:

  • Advanced Muscle Science Dienedrone, 60 caps
  • Advanced Muscle Science Liquidrone, 60 ml
  • Anabolic Formulation M1, 4AD, 60 caps
  • Anabolic Formulations 1, 4 AD, 60 caps
  • Anabolic Xtreme Hyperdrol X2
  • Anabolic Xtreme 3-AD, 90 caps
  • BCS Labs Testra-Flex, 90 caps
  • Competitive Edge Labs M-Drol, 90 Caps
  • Competitive Edge Labs P-Plex, 90 caps
  • Competitive Edge Labs X-Tren, 90 caps
  • 4Ever Fit D-Drol, 60 caps
  • Gaspari Novedex XT 60 Caps
  • Gaspari Halodrol Liquigels, 60 gels
  • iForce 1,4 AD BOLD 200, 60 Caps
  • iForce MethaDROL, 90 caps
  • iForce Dymethazine, 60 caps
  • Monster Caps, 60 caps

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Nzu: African morning sickness remedy in Texas contains lead and arsenic

The US FDA has released a statement based on finding from the Texas Department of State Health Services on December 23, 2009:

The Texas Department of State Health Services is warning consumers, especially pregnant or breastfeeding women, to avoid consuming a traditional product called “Nzu” because of the potential health risks from high levels of lead and arsenic.
Nzu, which is consumed as a traditional remedy for morning sickness, has been found by DSHS food inspectors at two African specialty stores – one in the Dallas area and one in Houston. It was also found at a distributor in Houston. The product generally resembles balls of clay or mud and also is called Calabash clay, Calabar stone, Mabele, Argile and La Craie.
Laboratory analysis by DSHS found high levels of lead and arsenic in this product.
Exposure to lead can result in a number of harmful effects, and a developing child is particularly at risk of effects on the brain and nervous system. Arsenic is a carcinogen, and excessive long-term exposure to it has been associated with a range of adverse health effects, including cancers of the urinary bladder, lung and skin.
The Nzu may be covered in a brown or white “dust” and is usually sold in small plastic bags with a handwritten label identifying it as “Nzu” or “Salted Nzu.”
Anyone who has been ingesting the product should contact their health care provider.
The source of the product in Texas is not yet known. Inspectors with DSHS are continuing to investigate.

Ingesting soil, particularly mineral-rich clay, is a practice called geophagy. Various kinds of earth have been a folk remedy common to many cultures, primarily for gastrointestinal complaints.
In fact, that is where the name “Terra Sigillata” is derived.
Terra Sigillata was a fatty clay harvested from the Greek isle of Lemnos and contained at least one component found in today’s Kaopectate diarrhea remedy. A special ceremony would be held to harvest the clay where it would be cut into planchets, embossed with an official seal, then dried and sold. Terra Sigillata stands in pharmacy history as the first trademarked medicine.
Geophagy is also why South Carolinians are sometimes called “sandlappers” and why this Nigerian remedy is often called “Calabash Clay” or “Calabash Chalk.” (Calabash is a coastal town right at the border between North and South Carolina. A style of spiced seafood, usually shrimp, is also known as Calabash.)
But as regards “nzu,” a warning similar to that in Texas came out in 2002 from the Northern Ireland Department of Health, Social Services, and Public Safety (PDF).
In trying to dig up some literature, I believe this may be the first time I have entered a search term in PubMed and come up with zero returns. A search for Calabash chalk comes up with a 2004 paper in Chemosphere for which I cannot obtain full text. The abstract is suggestive that samples were analyzed for several elements and environmental contaminants, with 40 mg/kg of lead being present as well as pesticides. I believe that I will have to consult my geology or Nigerian colleagues for more information on this as I anticipate there is far more literature available but perhaps in regional journals not abstracted by the US National Library of Medicine. I’m primarily curious as to where such samples might be taken from so as to have such high levels of Pb.
In the meantime, I’ll be interested to learn later what case(s) in Texas spurred the current FDA action but I hypothesize that it involved pre-natal, post-natal, or maternal neurological toxicity.

What is squalene?

Meet squalene:
Squalene515px.jpg
Squalene is a 30-carbon branched structure made from isoprene units in the production of cholesterol and other endogenous compounds such as glucocorticoids and sex steroids.
We all have squalene in our bodies. We NEED squalene. All mammals make squalene. Even fungi make squalene (for a compound called ergosterol that is required in their cell membranes).
So ubiquitous is squalene is that it is extracted commercially from shark liver oil. Squalene is intentionally added to cosmetics sold as “natural.”
Squalene is also a component of a vaccine adjuvant that has been used for over 10 years in Europe but is still pending approval in the US for use in the H1N1 flu vaccine.
In the context of immunology, an adjuvant is a chemical or combination of chemicals used to improve the immune response to vaccines.
But squalene is already in our bodies. We make the stuff. A vaccine with squalene will just be adding a little more squalene into our bodies.
Any questions?

Dietary supplement adulteration with prescription drugs: Is it really a problem of DSHEA?

ResearchBlogging.orgRebecca Skloot, journalist, University of Memphis writing professor, and author of the upcoming book, The Immortal Life of Henrietta Lacks (pre-order here), just brought to my attention this commentary by Dr Pieter Cohen in the New England Journal of Medicine entitled, “American Roulette — Contaminated Dietary Supplements.”
In the commentary, Dr Cohen remarks upon the epidemic of adulteration of herbal and non-herbal dietary supplements with undeclared prescription drugs or unapproved drugs:

In July 2009, the FDA expanded its alert to include 75 tainted weight-loss products that contain undeclared medications. Analyses by the FDA have found the stimulant sibutramine in weight-loss supplements at levels amounting to three times the maximum recommended daily dose. Several of the unapproved anorectic ingredients detected in dietary supplements have been linked to serious adverse events: rimonabant to suicide and fenproporex to both addiction and suicide. The inclusion of furosemide and other diuretics in some of these supplements may result in dehydration and hypokalemia; other contaminants, such as benzodiazepines and antidepressants, mask the side effects of stimulants while conferring an increased risk of dependence. Some weight-loss pills, including many from Brazil, combine multiple medications in a single formulation. . .
. . .Recently, unscrupulous manufacturers have made it more difficult for the FDA to detect undeclared ingredients by incorporating pharmaceutical analogues into their products. Analogues are created by modifying the original chemical structure of a compound — for example, by adding a hydroxyl group. It is suspected that these analogues are developed to evade detection by the FDA, making the products more difficult to regulate, and to reduce the risk of patent-infringement lawsuits. A recent analysis showed that more than half of 26 supplements marketed for the enhancement of sexual function contained analogues of phosphodiesterase type 5 inhibitors.

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FDA Public Health Advisory: Serious liver injury, pulmonary embolism with steroid-containing body-building supplements

American Cellular steroid products.jpgWe’ve spoken here every few months about so-called natural dietary supplements being adulterated with prescription drugs used for similar indications. The most common of these of late have been erectile dysfunction supplements which have been repeatedly found to contain the active compounds present in prescription E.D. products such as Viagra and Cialis.
The latest public health advisory from the US FDA concerns what appears to be a much more serious case of adulterations, this time with steroids in body-building supplements marketed as containing “steroid-like” compounds:

The FDA is notifying the public about new safety information concerning products marketed for body building and increasing muscle mass. The FDA has sent a Warning Letter to a manufacturer of body building supplements that claim to contain steroid-like ingredients, but in fact contain synthetic steroids. The products named in the Warning Letter are marketed by American Cellular Laboratories, Inc., and include “TREN-Xtreme,” “MASS Xtreme,” “ESTRO Xtreme,” “AH-89-Xtreme,” “HMG Xtreme,” “MMA-3 Xtreme,” “VNS-9 Xtreme,” and “TT-40-Xtreme.”
The FDA has received reports of serious adverse events associated with the use of these products and other similar products. Products like these are frequently marketed as alternatives to anabolic steroids for increasing muscle mass and strength and are sold both online and in retail stores. They are often promoted to athletes to improve sports performance and to aid in recovery from training and sporting events. Although products containing synthetic steroids are frequently marketed as dietary supplements, they are NOT dietary supplements, but instead are unapproved new drugs that have not been reviewed by the FDA for safety and effectiveness.
Adverse event reports received by the FDA for body building products that are labeled to contain steroids or steroid alternatives involve men (ages 22-55) and include cases of serious liver injury, stroke, kidney failure and pulmonary embolism (blockage of an artery in the lung). [emphasis mine]

Here is the consumer FAQ from FDA and here is the actual warning letter to the manufacturer. For those readers working in this research area, the warning letter lists the IUPAC names of the actual compounds found in each supplement.

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Locopops solves DSHEA dietary supplement labeling issue

In the United States, herbal and non-herbal dietary supplements can be sold without any assurance of safety or efficacy as a result of a hastily-passed, late-night, final-session piece of legislation put forth by Sen Orrin Hatch (R-Utah). (Aside: Utah has several large dietary supplement manufacturers.) This piece of legislation is named the Dietary Supplement Health and Education Act of 1994, or DSHEA. A FAQ for consumers is provided by the US Food and Drug Administration here.
An unusual aspect of the law is that supplement manufacturers can make a variety of wellness or structure-function claims as long as 1) they do not refer directly to disease treatment or prevention and 2) that the following statement appears somewhere on the label and in advertising:

“This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease”

This statement is lovingly referred to by my physician-blogger colleague, PalMD, as the Quack Miranda Warning. This disclaimer is usually printed in such small font on labels and websites as to be unreadable by people over 35 (the primary dietary supplement demographic) and we all know it is, well, – sensitive readers: please cover your eyes and ears – bullshit. These products are often available in pharmacies, right beside drugs with proven efficacy and known safety profiles. And even though people pay out-of-pocket for these remedies while complaining to the pharmacist about their $20 co-pays on prescription drugs, the industry racks up around $20-30 billion in sales.
So, it was with great mirth that I took this photograph last time the PharmKid and I were at our favorite purveyor of Mexican-style paletas, Locopops (2006 interview with founder, Summer Bicknell, here).
Locopops Cure wide 515px.jpg

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Weight loss supplements under Hydroxycut banner withdrawn: death, liver failure – where will this end?

FDA and the New York Times are reporting today 23 cases of adverse reactions to various Hydroxycut weight loss supplements. (FDA Consumer PDF here).
Above and beyond whether the stuff actually helps with weight loss, it is clear that the products contain some compound(s) that cause idiosyncratic cases of liver damage.

According to the law governing dietary supplements, the F.D.A. is empowered to act only in cases when it identifies a harmful or adulterated product that is already on sale.
“Part of the problem as you know is that F.D.A. looks at dietary supplements from a post-market perspective, so that an isolated incident is often difficult to follow,” Dr. Linda Katz, interim chief medical officer of the agency’s Center for Food Safety and Applied Nutrition, said Friday during a conference call with reporters.

And this is what gets my goat about the 1994 Dietary Supplement Health and Education Act (DSHEA) and something that the new FDA chief (and consumers) should really try to cultivate Congressional support to change:

In March, the federal General Accounting Office issued a report (77 page PDF) that criticized federal oversight of dietary supplements. The report, commissioned by the House Committee on Energy and Commerce, concluded that the F.D.A. had insufficient knowledge of the dietary supplement industry, insufficient resources dedicated to overseeing the industry, and insufficient ability to identify and recall problem products.

Enough already.

Selenium the cause of Lechuza Caracas polo horse deaths

Regular commenter and friend of Terra Sig, leigh (the path forward), let us know overnight that Florida State Veterinarian Dr Thomas J Holt officially confirmed that selenium overdose killed 21 Venezuelian polo horses in Wellington, Florida, on 19 April.
An attempt by an Ocala, Florida, compounding pharmacy to reproduce an equine dietary supplement called Biodyl resulted in a toxic dose of sodium selenite to be given to the horses. The pharmacy is cooperating fully with the FDA and other authorities but there is no official word as to whether the pharmacy made a calculation error or were given an improper formula by the requesting veterinarian.
We predicted that of the components of Biodyl, sodium selenite was the most likely culprit. It is required in microgram doses and even a 100-fold calculation error could have led to toxicity. A superb comment thread developed at our post with several members of the equine community weighing in as well as a discussion on the practice of compounding pharmacy.
For my money, the best news outlet coverage of the toxicology report comes from Andy Reid and Missy Diaz at the South Florida Sun-Sentinel. This report has the most details on the investigation and is the only one I could find this morning that indicates the magnitude of the selenium toxicity:

Toxicology results of the horses showed the animals had as much as 15 times the amount of selenium in their blood and as much as 20 times in their liver as normal, said veterinarian Dr. John Harvey, the executive associate dean of the University of Florida’s college of veterinary medicine.

The Sun-Sentinel also has the most complete coverage of other related events including video of a memorial service for the horses, a photo gallery, and references Twitter discussions of the case.