If your dietary supplement is advertised to work as well as a pharmaceutical, it may be adulterated with one

Recent news is that the US Department of Justice has taken action against some major manufacturers of dietary supplements – companies whose products are sold in retail outlets such as GNC and Vitamin Shoppe.  They are alleged to have intentionally adulterated their products with synthetic pharmaceutical drugs.

It has long been known that the less reputable supplement manufactures, the kind that sells things like “herbal viagra” over the internet, spike their products with pharmaceutical ingredients to make them effective.  They know, for example, that in terms of effectiveness, nothing natural can compete with Viagra.  So they add sildenafil (the active ingredient in Viagra), tadalafil (Cialis), or vardenafil (Levitra) to their products to make them actually work as well as their customers expect.  This, of course, can be dangerous for those purchasing these products because they have no idea what they will be consuming.  They are being dosed with an unknown amount of a potent drug that can cause serious side effects even when taken under the controlled conditions of a prescription medication.  The recent news about basketball star Lamar Odom’s near-fatal overdose on “herbal viagra” pills highlights this danger.

Even worse, in an attempt to outwit authorities that may be testing their products for those specific adulterants, supplement manufacturers are known to turn to untested, unapproved drugs instead.  There are many drug candidates with the same mechanism of action as Viagra (a class of drugs known as PDE5 inhibitors) that failed clinical trials or were dropped from development for various reasons (maybe toxicity, unacceptable side effects, etc) or never even advanced into clinical trials.  Examples include acetildenafil, aildenafil, and thiosildenafil.  Unscrupulous supplement manufacturers have been caught putting these in their products too.  A criminally dangerous behavior, indeed.

But now with the recent news from the DOJ, it seems that even some big names in the supplement industry are doing the same thing.  It is apparent that they believe what their critics have been saying all along: all-natural herbal ingredients just aren’t effective in the same way as FDA approved pharmaceutical drugs that have succeeded through scientifically vigorous clinical trials.  So to get their supplements to work as well as those pharmaceuticals, they have resorted to adding them to their own products.  Although the headliner is USP Labs, whose executives have been arrested and are facing criminal charges, there are over 100 manufacturers being targeted.  The problem appears to be widespread.

So, yes, if your dietary supplement is advertised to work as well as a pharmaceutical, it just may be adulterated with one.

No, crayons will not give your kids cancer

A good read about how the Environmental Working Group is using scare tactics to draw attention to a non-issue about crayons and cancer:

Color Them Stupid: Environmental Working Group Goes After Crayons

Periodic Table Battleship

This is a cute idea for kids:
Periodic Table Battleship

Methylhexanamine

Methylhexanamine (also called 1,3-dimethylamylamine or DMAA) is a stimulant drug invented in the 1940s that was once used as nasal decongestant.  Even though it was withdrawn decades ago as a pharmaceutical drug, it is used as an ingredient in some marketed “energy boosting” supplements.

Normally, synthetic pharmaceutical drugs cannot be used in dietary supplements, but it has been claimed that methylhexanamine is natural and can be found in the oil extracted from geraniums.  In the United States the FDA generally does not have the authority to regulate natural chemical compounds this way.

There is at least one scientific report suggesting that geranium oil does indeed contain trace amounts of methylhexanamine.  A more recent and more thorough study that used multiple research labs and multiple plants types from multiple sources failed to find even a trace of methylhexanamine in any sample.  Nevertheless, for many years, the FDA did not intervene because it was potentially natural.

So if a supplement claims to contain methylhexanamine because it uses geranium oil, then the consumer is getting only uselessly small amounts of it, if any.  And if a “natural” supplement does contain a pharmacologically useful amount, then it is surely adulterated with synthetic material produced in a laboratory.

In recent years, potential hazards associated with consumption of methylhexanamine-containing supplements have concerned the FDA enough for them to take action.  Elevated blood pressure, cardiovascular problems, shortness of breath, tightening of the chest, heart attacks, and even death have been reported.    So the FDA does not currently permit supplements that contain methylhexanamine to be sold in the United States.

This just goes to show that the regulatory scheme in the US where natural ingredients with pharmacological effects cannot be regulated the same way that synthetic ingredients are is unjustifiable.  It is predicated on the falsehood that anything natural is inherently safer than anything synthetic.  And unless you study at the Gwyneth Paltrow School of Toxicology (“I don’t think anything that is natural can be bad for you”, she reportedly said), you know that some of the world’s most dangerous substances come from plants and animals.  How many people suffered health problems (or even died!) because of a tenuous claim that methylhexanamine is natural?

An antiaging odd couple

A team of researchers, mostly from the Mayo Clinic and Scripps Research Institute, recently reported an interesting study.  They basically show that various cells that have stopped dividing (“senescent cells”) accumulate with age and that killing off those cells can extend the time that an animal remains healthy as it ages.

The researchers identified a combination of drugs that selectively killed these senescent cells.  When administered to mice, the drugs had the effect of “alleviating symptoms of frailty and extending healthspan”.  The drugs turned out to be an odd combination:  dasatinib, a drug used to treat cancer, and quercetin, a natural flavonol that is sold as a nutritional supplement.

As with much of journalism’s coverage of scientific work, the news reports are a bit exaggerated (or copied uncritically and essentially word-for-word from a glowing press release, such as in this Science Daily article).  The drugs used in the combination are probably far from being ideal drugs for this potential new use.  Dasatinib has the kinds of serious side effects that are tolerable when treating a potentially fatal disease, but wouldn’t be for someone who is essentially healthy.  Quercetin, like most flavonoids, is not that bioavailable with most of what is ingested getting quickly metabolized or excreted.

Whether this work will be “transformative”, as the authors claim, remains to be seen of course.  Extending the healthy life of a mouse is not necessarily going to translate to doing the same thing in a human.  Humans already have done a great deal to extend life expectancy and to maintain health into old age through various changes in society, lifestyle, and medicine.  To a certain extent, the system has already been optimized, so any further optimization will be increasingly more difficult.

But this is fascinating work that is certainly worth following up on.  No doubt these researchers already are, and probably others will join in looking to confirm and build upon these results.

The paper is published in the journal Aging Cell, which is open access, and can be obtained here: http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/abstract.

Can an old hallucinogen be a new antidepressant?

Ketamine is an anesthetic and sedative drug developed in the 1960s. It’s not widely used anymore, primarily because there are better options. Among its side effects are dissociative and hallucinogenic effects. Because of these effects, ketamine has also been used as recreational drug with the street name “Special K”.

Ketamine exerts its effects by modulating the neurotransmitter glutamate. Specifically, it blocks the function of a type of glutamate receptor in the brain called NMDA receptors.

In addition to its approved uses, ketamine has also been used off-label as an antidepressant, but its usefulness for this purpose is not well established. The only way to know for certain is to conduct well controlled clinical trials. It appears that Johnson & Johnson is trying to do exactly this (through its subsidiary Janssen). Like many organic molecules, ketamine can exist in either of two mirror images. Ketamine as used in medicine is an equal mixture of the two. J&J is investigating just one of them, named esketamine.

For a pharmaceutical company it is a bit of risk to take a drug that is abused recreationally into clinical trials. The path to regulatory approval won’t be easy. Although ketamine already has established medical uses and one might think that the existing approval for current uses would make approval for a new use simpler, but I’m not sure that’s going to be the case. Ketamine, when used as an anesthetic is given intravenously, but J&J is looking at nasal delivery. This could make a big difference. Intravenous drugs are generally given in a doctor’s office or hospital, while a nasal drug for depression will almost certainly be intended to be taken home by the patient where the potential for abuse is higher.

It will be interesting to see how this plays out.

First world war dysentery bug was penicillin-resistant

Here’s an interesting story about drug resistant bacteria from before the first antibacterial agents were discovered:

First world war dysentery bug was penicillin-resistant – New Scientist.

What drugs are being used experimentally to treat ebola?

With ebola in the news so much these days, I became curious which pharmaceutical drugs are being used to treat patients. I haven’t come across the information in any one place, just scattered among news articles and other sources. So I decided to put together a list myself. There aren’t any drugs approved specifically for treating ebola, but apparently several antiviral agents are being used experimentally. They are mostly drugs developed (or in development) primarily for treating other viruses.

• Brincidofovir (CMX001) – An experimental antiviral agent which is a prodrug of the approved HIV medication cidofovir (Vistide). It belongs to the class of drugs known as nucleoside analog. The first person with ebola in the United States, Thomas Duncan, received this drug.
• Favipiravir (T-705) – This is an antiviral agent that has activity against a variety of viruses. It is approved in Japan for use against influenza.
• Lamivudine – HIV drug used in Liberia
• ZMapp and ZMab – Related monoclonal antibodies. Both have been used in ebola patients in the United States and in Spain
• BCX4430 – Experimental broad-spectrum antiviral and nucleoside analog. The National Institute of Allergy and Infectious Diseases (NIAID) is funding additional research and drug production.
• TKM-Ebola – Has been used in one patient who was infected in Africa and brought to the United States. It is a combination of small interfering RNAs.
• JK-05 – Several news articles describe this as “an experimental anti-Ebola drug developed by the Chinese military” that is “already approved for emergency military use” and has been sent to Africa, but I can’t find anything specific about what exactly it is or whether it is actually being used yet during the current outbreak
• FGI-103, FGI-104, FGI-106 – I haven’t found any news references to these compounds currently being used experimentally during the current ebola outbreak, but there are animal studies reported in the corresponding Wikipedia articles

There are also vaccines such as VSV-EBOV under development.  These can’t be used to treat infected patients, but are instead intended to prevent the spread of the disease.

If I have missed any other drugs that have been mentioned in the news but aren’t on this list, please let me know and I’ll add them.

 

 

Forces that hold rapidly spinning near-Earth asteroid together discovered — ScienceDaily

Chemists are used to thinking about things on a very small scale. Sometimes, though, we think about how molecular interactions have tangible or visible effects on the properties of materials. But we don’t often think about how interactions between molecules can have much larger effects, like determining the fate of an entire astronomical object. Here’s story to remind chemists to think about the big picture:

Forces that hold rapidly spinning near-Earth asteroid together discovered — ScienceDaily

How do tick bites cause allergy to red meat?

I’ve seen reports of this in the news a few times lately:  some people can become allergic to red meat after being bitten by a tick.  (See here or here, for example.) We are not used to thinking about allergic reactions this way. We think of sensitization to an allergen due to repeated exposure to that allergen. Peanut allergies come from exposure to peanuts, for example. So why does exposure to a tick bite sometimes lead to becoming allergic to red meat?

The connection is a carbohydrate called galactose-alpha-1,3-galactose, or just “alpha-gal”. Alpha-gal is present in the tissues of mammals, with the exception of primates (including humans). When a tick bites an animal, some alpha-gal then gets into the tick. When the tick bites a human, the alpha-gal is transferred through the tick’s saliva into the individual who is bitten. The bite, or perhaps a component of the tick’s saliva, triggers an immune response that results in the alpha-gal being recognized as a foreign substance leading to sensitization to alpha-gal upon later exposures. Since alpha-gal is present in animals, particularly those from which we get red meat, an individual who has become sensitized to alpha-gal has an allergic reaction to eating red meat.

In the United States, the problem seems to be closely associated with only the Lone Star Tick, which has a limited range mostly in the Southeast. The problem doesn’t appear to be currently widespread.

For details on how the cancer drug cetuximab was the key to discovering the connection between tick bites and red meat allergy, the paper titled “The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose” makes a good read.