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Category → Dietary Supplements

How Do You Like Your Caffeine?

Inhaled or oral?

Natural or synthetic?

Two interesting reports came across the interwebs over the last couple of days.

Earlier this week, the US Food and Drug Administration issued a warning letter (press release) to makers of Aeroshot brand of inhaled caffeine. No, it’s not an asthma medicine (although oral theophylline is). It’s billed as a non-caloric caffeine delivery system, 100 mg per hit. That’s roughly the amount in two 12 fl oz/355 mL cans of Mountain Dew or one gulp more than a 8.4 fl oz/250 mL can of Red Bull energy drink. However, the company claims that only 15-25 mg are delivered – perhaps half the amount in a Coca-Cola.

The FDA has concerns about the dual promotion of the product for swallowing and inhalation, the relative safety of inhaled caffeine, and the potential for children and adolescents to use the product in combination with alcohol. The company’s FAQ specifically notes that the product is not marketed for use in children. Readers will recall that Four Loko caffeinated alcohol drinks were withdrawn from the market in late 2010 and replaced with alcohol-only versions.

From Zhang et al., doi:10.1021/ac203197d

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Intravenous Milk Thistle for Mushroom Poisoning

This intravenous form of milk thistle extract has been used for mushroom poisoning in Europe and is now in Phase II/III clinical trials in the US Credit: Madaus AG.

Apologies to readers for the radio silence – a heavier-than-usual load at the day job has been compounded by what I hope is not a prelude to a similar, serious bout of pneumonia I had almost two years ago.

In the meantime, I wanted to share with you a chemistry-relevant post I wrote for my monthly gig at Science-Based Medicine on 28 October 2011. The comments there evolved into a mouth-watering discussion of culinary mushrooms. Enjoy!


If you’ve been fortunate to live in the parts of the US that were soggier than usually as of late – or unfortunate enough to have had flooding from hurricanes and tropical storms – then you’ve be noticing a tremendous burst of mushrooms.

For mycologists – mushroom enthusiasts – there are two classic chestnuts: “There are old mushroom collectors and bold mushrooms collectors, but there are no old, bold mushroom collectors.”

Or, in a more concise Croatian proverb, “All mushrooms are edible, but some only once.”

As such, this is the time of year that emergency rooms and regional poison centers begin to see a burst in poisonings from mushroom ingestion, due primarily to amateur misidentification of the fruiting bodies.

Just this past week, Jason McClure at Medscape Oncology News (free reg req’d) wrote about the unusual bloom of mushrooms in the northeastern US and the concomitant bloom of mushroom poisonings this fall.

But “mushroom poisoning” is an imprecise diagnosis for the ER physician. The constellation of symptoms caused by toxic mushrooms is as diverse as the colors and shapes of these wonders of nature. From another Medscape article on emergency management of mushroom poisoning by Dr. Rania Habal from the Emergency Medicine department of NYU:

Mushrooms are best classified by the physiologic and clinical effects of their poisons. The traditional time-based classification of mushrooms into an early/low toxicity group and a delayed/high toxicity group may be inadequate. Additionally, many mushroom syndromes develop soon after ingestion. For example, most of the neurotoxic syndromes, the Coprinus syndrome (ie, concomitant ingestion of alcohol and coprine), the immunoallergic and immunohemolytic syndromes, and most of the GI intoxications occur within the first 6 hours after ingestion.

Ingestions most likely to require intensive medical care involve mushrooms that contain cytotoxic substances such as amatoxin, gyromitrin, and orellanine. Mushrooms that contain involutin may cause a life-threatening immune-mediated hemolysis with hemoglobinuria and renal failure. Inhalation of spores of Lycoperdon species may result in bronchoalveolitis and respiratory failure that requires mechanical ventilation.

Mushrooms that contain the GI irritants psilocybin, ibotenic acid, muscimol, and muscarine may cause critical illness in specific groups of people (eg, young persons, elderly persons). Hallucinogenic mushrooms may also result in major trauma and require care in an intensive care setting. Lastly, coprine-containing mushrooms cause severe illness only when combined with alcohol (ie, Coprinus syndrome).

Among the poisonous mushrooms, Amanita phalloides is perhaps the most deadly. If you’ve spent any time in a biochemical laboratory you will have learned of the primary toxin of the mushroom, α-amanitin. This potency of this toxin comes from its remarkably high affinity for RNA polymerase II, the primary RNA polymerase for making messages that are converted into proteins.

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Molecular Target for Thunder God Vine

This post appeared originally last Friday for my monthly gig at Science-Based Medicine.

ResearchBlogging.orgThunder god vine may not be a useful herbal medicine but the compounds isolated from it are fascinating – if not as medicines, then most certainly as laboratory tools. Nature Chemical Biology recently published an article where a research team from Johns Hopkins, the University of Colorado at Boulder, and Drew University in New Jersey, has determined the molecular mechanism of action of triptolide, an unusual triepoxide compound from the plant.

Tripterygium wilfordii Hook F, or thunder god vine, is known as lei gong teng in Chinese traditional medicine and has a history of use as an anti-inflammatory herb. As with many traditional medicines, usage patterns do not necessarily indicate scientific validity. In fact, a Cochrane review published just last month on herbal therapies for rheumatoid arthritis indicated that the efficacy of thunder god vine was mixed. More concerning is that the herb had significant adverse effects in some trials, from hair loss to one case of aplastic anemia.

Nevertheless, the herb’s components have been studied since the 1970s for since they also appears to kill tumor cells in culture with nanomolar potency and have immunosuppresant activity in animal models. The group of the late natural products chemist at the University of Virginia, S. Morris Kupchan, first identified the unusual structures of triptolide and tripdiolide from Tripterygium wilfordii as described in this 1972 paper from the Journal of the American Chemical Society. Cytotoxic activity toward tumor cells in culture was used to guide the chemical fractionation of extracts. The unusual presence of three consecutive epoxides in the structures of both compounds led Kupchan to hypothesize later in Science that they target leukemia cells by covalent binding to cellular targets involved in cellular growth.

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Herbal supplement interactions with prescription meds for “heart problems”

"Heart attack" (get it?). iStockphoto via CBS News

…or, “how to artificially inflate your readership.”

Yesterday, I saw tweets about a CBS News online article – or so I thought – about 30 herbal dietary supplements to avoid if one has “heart trouble.” What I found was a photo gallery site that I had to click on 20 times to obtain the information – an adaptation of this paper from Mayo Clinic Rochester and Scottsdale investigators in the Journal of the American College of Cardiology last February.

Most of the herbs listed were there because of their positive or negative interactions with the oral anticoagulant drug, warfarin. This list included typical, top-ranked supplements such as ginkgo, garlic, saw palmetto, green tea, and alfalfa. Granted, each page had a lovely photo of the plant or product and a brief description. The list also included herbs that acted via other mechanisms such as St. John’s wort, which can accelerate the metabolism of a wide variety of drugs (via CYP3A4 induction) and yohimbine, whose alpha-2 receptor antagonistic activity can modify the effects of prescription antihypertensive drugs.

The information actually appears quite valid and, from my knowledge of the literature, appears quite accurate. Of course, it doesn’t include original literature references since the gallery appears intended for a general readership.

But I found it vexing to have to click through 20 pages – also after being misled into clicking the only hyperlink in the frontpage of the photo gallery, CBS News’ “friends” at Health.com (link not provided here on purpose), thinking that it was the source of the “easy guide.”

Or maybe I’m just cranky because I have figured out a way to get you to click on my site here 20 consecutive times.

Reference:

Tachjian, A., Maria, V., & Jahangir, A. (2010) Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases. Journal of the American College of Cardiology, 55(6), 515-525. DOI: 10.1016/j.jacc.2009.07.074

Flurry of FDA action against aromatase inhibitor supplements

A bodybuilder with Grade I gynecomastia (left) and after symptom resolution. Source: Dr. Mordcai Blau, Wikimedia Commons

If you’ve ever met me, you’ll know that I’m not a bodybuilder. That’s why I was taken aback earlier this year when I learned that men are taking aromatase inhibitors – and not for breast cancer.

This education came to me when I was asked by a network news program to comment on a litany of drugs and supplements found in the possession of self-proclaimed guru James Arthur Ray following the Sedona sweat lodge deaths at one of his “Spiritual Warrior” retreats. Among the bodybuilding supplements and testosterone replacement drugs authorities found in his possession was anastrozole (Arimidex), for which he had a valid prescription.

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Bleachgate: UK and Kenyan press raising awareness of Miracle Mineral Solution

In July, the US FDA issued a warning to consumers about a dietary supplement product being sold worldwide under the name Miracle Mineral Solution or Supplement (MMS). Marketed as a cure for everything from HIV/AIDS and cancer to malaria and tuberculosis, the product is 28 percent sodium chlorite.  The consumer is instructed to mix the solution with a citrus juice, generating chlorine dioxide, and is encouraged to take 30 drops or more of the mixture. Worse, the consumer is told that if they begin vomiting, this is evidence that the product is “working.”

Martin Robbins, reporter for The Guardian, wrote last week about the story of “inventor” and promoter for the product, Jim Humble, in an article entitled, “The man who encourages the sick and dying to drink industrial bleach.” Therein, Martin also discusses the case of a teenage Crohn’s disease patient who was banned from a patient support forum for criticizing the remedy and trying to teach fellow patients about the truth behind the product.

Martin’s article has since gotten the attention of the Kenyan press as Humble claims to have tested the product in Malawi prisoners and up to 75,000 patients in Kenya and Uganda. Yesterday, a Sunday editorial from the Kenyan newspaper, The Nation, called for action from their Ministry of Health.

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Sharks don’t get cancer but do they get Salmonella poisoning???

This post appeared originally at the ScienceBlogs home of Terra Sigillata on 18 May 2007. I’m putting it up today to accompany a superb post by University of Hawai’i graduate student and science writer, Christie Wilcox, at Observations of a Nerd.

Actually, sharks do get cancer but a 15-year-old book by William Lane led people to think otherwise, launching investigation of shark cartilage as a source of antiangiogenic, anticancer compounds. While there is one promising shark cartilage extract (Neovastat) in clinical trials for multiple myeloma, most oral preparations on health food store shelves aren’t stabilized and characterized well-enough to guarantee stability of antiangiogenic compounds.

But it gets worse with this news today from FDA’s MedWatch program that illustrates once again the safety problems of some dietary supplements – shark cartilage may just not work; it might also give you Salmonella poisoning:

NBTY and FDA informed consumers and healthcare professionals of a nationwide recall of 3 lots of Shark Cartilage Capsules the company manufactured in 2004 and distributed to consumers through mail and internet orders, and retail stores throughout the United States. The product was recalled because of possible contamination with Salmonella, an organism that can cause serious and sometimes fatal infections in young children, frail or elderly people, and others with weakened immune systems. Healthy persons infected with Salmonella often experience fever, diarrhea, nausea, vomiting and abdominal pain. In rare circumstances, infection with Salmonella can result in the organism getting into the bloodstream and producing more severe illnesses such as arterial infections, endocarditis and arthritis. Customers can return the product back to the place of purchase for a full refund. Read the press release for specific names and lot numbers of the recalled product.

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