Chemicals and Toxins — What Is Safe?

One of the most common questions I get from SquintMom readers is along the lines of is item/substance/compound XYZ toxic? I’d like to go ahead and answer this once and for all: YES, it is.

Now let me explain what I mean, and how I can answer this very generic question in a catch-all way without specifying the item/substance/compound to which I refer. Because he said it so well that it doesn’t need rephrasing, I’ll quote the Renaissance-era botanist Philippus Aureolus Paracelsus, who said:

All substances are poisons; there is none that is not a poison. The right dose differentiates a poison from a remedy.

Phrased more generally, this is simply that any substance can be either safe or toxic; the dose (quantity) to which one is exposed is what makes the difference. I’ve mentioned in previous posts (like this one about oxybenzone in sunscreen) that the notoriously jumpy Environmental Working Group (EWG) systematically fails to recognize this particular principle; they have a tendency to vilify anything that proves toxic in any dose, under any conditions. This attitude, however well intentioned, leads us to some interesting places. Pause for a moment and check out the cautionary website DHMO.org. Note that the highly toxic dihydrogen monoxide (DHMO) is associated with cancer (it’s found in every tumor ever identified), has serious environmental impact (it’s a major greenhouse gas and overexposure is associated with thousands upon thousands of deaths every year), and, per the website:

[DHMO’s] basis is the highly reactive hydroxyl radical, a species shown to mutate DNA, denature proteins, disrupt cell membranes, and chemically alter critical neurotransmitters.

Sounds horrid, doesn’t it? No doubt we should ban it. Except that…DHMO.org is a joke website, and dihydrogen monoxide is the almost never-used, formal chemical name for water.

None of the information on DHMO.org is false, which is what makes it both amusing and apropos to this discussion. Water does, in fact, directly result in many deaths. Not only through “overexposure” via flooding and/or drowning, but also through overconsumption. For instance, in 2007, a radio station held a contest (“Hold your wee for a Wii”), the idea of which was to drink as much water as possible without a bathroom break; the caller who drank the most would win a coveted Wii game console. Contestant Jennifer Strange won (and then lost) by consuming more than 2 gallons of water in the space of less than an hour. She died shortly thereafter of hyponatremia, a condition in which there is an insufficient concentration of sodium in the body fluids to support life (sodium is critical to cellular function, neural conduction, muscular contraction, brain function, and so forth). This is not the only incident of water toxicity on record; similar cases have resulted from fraternity hazings, bizarre diet plans, and overconsumption of water during endurance sporting events like marathons.

On the other hand, there are substances that we typically consider highly toxic that are, in the right dose, of great medicinal utility. Clostridium botulinum is a species of bacteria that produces botulinum toxin, generally considered the deadliest substance on Earth. The average 150 pound man would have a 50:50 chance of survival if exposed to merely 341 ng (that’s less than a millionth of a gram) of pure botulinum toxin. Regardless, marketed under the trade name Botox, botulinum toxin is used for cosmetic purposes (wrinkle treatment and prevention). Of perhaps greater medical importance, it’s also used to ease the painful symptoms of temporomandibular joint syndrome (TMJ) and other spasmodic disorders, and mitigate the symptoms of diabetic neuropathy (damage to peripheral nerves, often in the feet, due to diabetes).

Further complicating matters, our perception that “natural” substances are somehow safer or better for us than “artificial” substances is misinformed. A simple example is the flavoring agents found in many foods. While the common perception is that natural flavors come from the food of which they taste (strawberry flavor, for instance, comes from strawberries), nothing could be further from the truth. In reality, natural and artificial flavors are generally identical chemicals, collected or produced in different ways.* Natural almond flavor, for instance, isn’t a mixture of “natural substances” that come from almonds. Instead, it’s a chemical called benzaldehyde that is extracted from peach pits. Artificial almond flavor is also benzaldehyde, but unlike natural almond flavor, the artificial stuff is made in the lab. Funnily enough, it’s possible to get benzaldehyde made in the lab much more pure than that extracted from peach pits. Further, the stuff that comes from peach pits — the natural almond flavor, remember — contains small amounts of deadly cyanide that occurs naturally in those same peach pits (one of many reasons it’s not wise to eat the pits of stone fruit).

*Eric Schlosser’s excellent book Fast Food Nation contains a very interesting chapter on this topic, for further reading.

Where does this leave us, in trying to avoid toxins? First, as a chemist, let me just say that the word toxin is very often misused in popular sources and conversation, and the word chemical is almost always misused. “Chemicals” are not bad things that cause harm and should be avoided. Instead, they are matter; they are what makes up the physical universe. Nothing that has mass and occupies space — nothing we touch, eat, drink, breathe — is not chemical. There’s no such thing as chemical-free bread, shampoo, or paint. Water is a chemical (and — let’s not forget — a toxic one at that). With regard to toxins, the word is used too often in a vague, handwaving sense on the Interwebs. I see pop-authors (who are generally trying to sell something) write about how Product X contains “toxins,” and should therefore be avoided, or Product Y (which they’re selling) contains no toxins.* I’m not sure what these folks mean when they say “toxins” (and since they rarely name said toxins, I’m not sure they know either); after all, let’s not forget that all substances are toxic in the right dose.

*Or worse yet, Product Y (which they’re selling) is a detoxifying agent. This is ridiculous; almost all humans (with the exception of a few with significant disease) are possessed of one of the most powerful detoxifying mechanisms known to man — a liver. Livers work really well, particularly when they’re left alone to do their job.

This is not to say that we should all go about our business with no concern whatsoever for the things we touch/eat/drink/breathe; it’s simply to say that we simultaneously worry too much and worry too little about “chemicals.” To take one particular example, a few scare-articles about bisphenol A (BPA) have some of us so worried (and confused) that we’re willing to shell out extra cash for BPA-free diaper wipe containers, toys, and even a bath toy organizer. In reality, if BPA has any effect at all in doses to which we’re routinely exposed (which has not yet been established), it would require significant physical contact with the compound to absorb it. Holding, playing with, or storing one’s bath toys in a BPA-containing item would not be a problem, particularly given that while the absorption rate of BPA through human skin hasn’t been thoroughly evaluated or established, it nevertheless appears to be significantly lower than the (already modest) rate of absorption through the skin of other animals (Marquet et al). Based upon the current research, might it be worth avoiding storing food in BPA-containing plastics? Possibly. This is because food might leech BPA out of the plastic in sufficient quantities to possibly have some effect on people (because we eat the food, which gives it an easy route into the system). Is it worth it to avoid all BPA in our houses, however? Simply, no. And on that note, it particularly amuses me to watch women with painted nails shopping for BPA-free toys for their daughters (also with painted nails), given that the exposure to potentially harmful substances (like toluene) is much greater when one physically paints said chemicals on one’s body.*

*For those who are curious, I do paint my nails, because I really don’t think this is that big a deal. But it’s certainly a more significant exposure to chemicals (ew! chemicals!) than touching a rubber ducky in the tub.

So, we worry too much. But we also worry too little. In our desire for the “natural” (whatever that means), we choose the cyanide-laced flavoring agent over the one made under strict conditions and control in the lab. We go to the natural foods store and buy herbs to treat our ailments — which are essentially unregulated for either safety or efficacy, and which may interact unsafely with prescription and over-the-counter drugs or be toxic in their own right — rather than using the “unnatural chemicals” prescribed by medical professionals, despite the fact that the latter have undergone many years of pre-marketing research, followed by decades of post-marketing surveillance. We’re more willing to expose our children to the 1/330 risk of death due to the measles than the 1/3000 risk of a moderate side effect of measles vaccination (e.g. seizure with no permanent effects, mild rash), and immeasurably small risk of serious side effect. We further eschew the vaccination because, in a complete failure to understand the mechanics of human immunity, we have come to believe that “natural” immunity from disease is superior to “artificial” immunity from vaccination. When it comes to the “natural” versus the “toxic” and/or “chemical,” we’re chasing flies out of the chicken coop while the foxes sneak in.

So what do we do about it? This is difficult. We know that all substances are toxic in the right (wrong?) dose, but when it comes to many substances, we still don’t know what that dose is. Some exposures are unavoidable (by virtue of living in a city, for instance, one is going to be exposed to a certain amount of benzene from exhaust, industrial processes, etc). Some exposures are avoidable, but avoiding them reduces quality of life (no one HAS to eat foods containing coloring agents, for instance, many of which are of questionable safety, but the complete avoidance of these would make for a stoic existence, particularly for children). In most cases, when it comes to toxic chemicals (and once more, all substances are chemicals, and all chemicals are toxic when one is exposed to them…all together now…in the right dose), one must do a risk-to-benefit analysis. Some cases are relatively clear. Is codeine toxic? Yes, in the right dose. Is it worth the risk to take codeine for recreational purposes? Probably not. Is it worth the risk to take codeine after a painful surgery? Probably. Is water toxic? Yes, in the right dose. Is it worth the risk to drink water when one is thirsty? Absolutely. Is it worth the risk to drink water to win a contest? Probably not. Some cases are less so, as with the previous example of BPA. With the evidence still equivocal, financial means and convenience likely become a large part of the decision. Those of greater means or with greater willingness to be inconvenienced might buy the BPA-free rubbery ducky, the BPA-free cabinet safety locks. Others might decide to buy the BPA-free food storage, but be content with the plain old, BPA-containing bath caddy. Regardless of these personal decisions when it comes to substances of yet-unknown safety, it’s worth remembering that the media, the product manufacturers, and the fad-authors capitalize upon the lucrative combination of public confusion and fear, and that the words “chemical,” “toxic,” “artificial,” and “natural” are as powerful as they are misused and misunderstood.

References:

Marquet et al. In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption? Arch Toxicol. 2011 Sep;85(9):1035-43. Epub 2011 Feb 2.

Are Bubble Baths Safe For Girls, Or Do They Cause UTIs?

Got another great question recently (keep them coming, readers; I love answering these!):

I’ve heard that girls shouldn’t take bubble baths because they can get urinary tract infections. I have some around the house, though, and in a moment of weakness, I let my toddler use it. Now she wants a bubble bath all the time! The package says it’s “safe for girls” but I am not sure what chemical it is that gives them UTIs so I find the whole thing confusing. Is it safe to use bubble bath for a girl?

This is an interesting case of some old and erroneous research that’s been propagated in the medical field (and among women) for several decades. Back in the 1960s and 70s, a few studies suggested that bubble baths caused urinary tract infections (UTIs) in girls (see, for example, Neumann et al). This belief has continued to show up in more recent journal articles for medical professionals. The truth is that while it’s certainly possible for soaps, fragrances, and other chemicals in bubble bath to irritate the vulva (Modgil et al) and urethra (see, for example, Johnson et al, Santen et al), there isn’t any scientific support for them causing UTI.

A study of college-age women examined a number of potential risk factors for UTI (including bubble baths, diaphragm use, tampon use, sexual activity, and various hygiene practices), and concluded that only diaphragm use was reasonably correlated with increased urinary infection risk (Strom et al). A 2006 meta-analysis (study of studies) revealed that while many pediatricians advise parents to avoid bubble baths for female children, there is no reasonable scientific support for the notion of a connection between the two (Modgil et al). Indeed, despite the lack of scientific evidence, a survey of health care professionals and women noted that both groups believed there was a link between bubble baths and UTIs (Rink).

It’s possible that the mistaken belief about bubble baths and urinary infections comes from the tendency of some healthcare practitioners and researchers to view children as “little adults” (Todd). In fact, however, signs and symptoms of UTIs are not the same in little girls as they are in adult women; one of the most notable differences is that while adult women often experience dysuria (painful urination) with UTI, most girls do not (Santen et al). The ability of frequent bubble baths to cause urethral or vulvar irritation in some girls and women, which can in turn lead to painful urination, combines with the mistaken belief that painful urination typically indicates a UTI in a young girl to produce the erroneous notion of a bubble bath/UTI link. In the end, however, with no reasonable scientific support for a link, Modgil et al sum up the risk-to-benefit analysis nicely, in saying:

We believe that the enjoyment of bubble baths outweighs the limited evidence of their proposed harm.

There is, of course, the question of whether some bubble bath products might produce less skin, vulvar, and urethral irritation than others. Very sensitive children and those with allergies to specific chemicals may be more likely to react to any given product. Still, some bubble baths are milder than others, with fragrance-free varieties almost always ranking milder than those containing fragrance. The Environmental Working Group (EWG) is a somewhat reactionary organization that likely overestimates the toxicity of and risk associated with chemicals, as I discuss in this post. Still, they provide a nice guide to various personal care products — bubble bath included — that at the very least can be used to determine which of the bubble baths on the market are most mild.

Science Bottom Line:* There is simply no scientific evidence to support the notion that bubble baths increase a girl’s risk of urinary tract infection. Children with sensitivities may do better with a milder product, however, as well as less frequent use. Because bubble baths can cause irritation to the skin and female genitals, it may be reasonable to consider rinsing with plain water after a bubble bath.

 

Do you let your little girl take bubble baths? What’s your favorite type?

 

References:

Johnson et al. New advances in childhood urinary tract infections. Pediatr Rev. 1999 Oct;20(10):335-42; quiz 343.

Modgil et al. Should bubble baths be avoided in children with urinary tract infections? Arch Dis Child. 2006 Oct;91(10):863-5.

Neumann et al. Constipation and urinary tract infection. Pediatrics. 1973 Aug;52(2):241-5.

Rink, E. Risk factors for urinary tract symptoms in women: beliefs among general practitioners and women and the effect on patient management. Br J Gen Pract. 1998 Apr;48(429):1155-8.

Santen et al. Pediatric urinary tract infection. Emerg Med Clin North Am. 2001 Aug;19(3):675-90.

Strom et al. Sexual activity, contraceptive use, and other risk factors for symptomatic and asymptomatic bacteriuria. A case-control study. Ann Intern Med. 1987 Dec;107(6):816-23.

Todd, J. Management of urinary tract infections: children are different. Pediatr Rev. 1995 May;16(5):190-6.

Sunscreen Safety and Oxybenzone

Is oxybenzone in sunscreen safe? From Squintmom/Beautiful EntropyI love getting questions about science-related issues from readers. I particularly love it when a question intersects with an issue I myself am curious about, as happened when a reader got in touch with me last week:

I need some advice about sunscreen. I just read some articles on CNN about new FDA guidelines and the Environmental Working Group’s 2012 sunscreen review. Of particular concern is oxybenzone. The FDA claims it’s safe and very effective at protecting against UVA and UVB rays. However, the EWG says that oxybenzone is carcinogenic. Hmm… use sunscreen to prevent skin cancer, but sunscreen causes… skin cancer? That seems like a big time conundrum to me. The other thing I wonder about is who is the EWG? All I really know is they came up with the “Dirty Dozen” foods you should always buy organic. So what’s the deal? Should I toss all of last year’s sunscreen with oxybenzone and buy new? Is the EWG generally a trustworthy, “non-woo” authority?

The oxybenzone molecule

Let’s start with my professional opinions of the Food and Drug Administration (FDA) and of the Environmental Working Group (EWG). The FDA is routinely accused by consumer groups and conspiracy theorists of being “in bed with Big Pharma,” engaging in cover-up operations, putting profit ahead of consumer health, and so forth. I really don’t agree with this take on the organization, as I discuss in this post. The FDA’s history in the US is one of a largely appropriate trajectory. They’re a behemoth organization, and as such, they move slowly. They’re slow to approve new drugs because they insist on rigorous testing; this is one of the things that pisses off consumers who want to see new drugs come to market quickly. They’re relatively quick to warn consumers if there’s evidence that a pharmaceutical or substance is harmful, though they’re not alarmist and rarely respond to the results of an isolated study. The FDA is, to put it simply, stuck performing an impossible balancing act: they’re under public pressure to approve substances quickly, while they’re simultaneously under public pressure to keep anything that could potentially be harmful off the market. These missions are mutually exclusive, and I have to say that for the most part, the FDA handles their task as elegantly as a behemoth government organization can do. Have they made mistakes? Absolutely. But what I appreciate about the FDA is that they correct over time, such that their trajectory is generally appropriate and stable.

The EWG, on the other hand, is far more alarmist than the FDA. They’re not a government organization, but are rather a research and lobbying group made up of citizens and scientists. A survey of toxicologists (unaffiliated with the organizations about which they were questioned) revealed that most felt the EWG overstates risks associated with products. Specifically, toxicologists gave the EWG an accuracy score of 4.2 (1 = significantly understates risks, 3 = accurately states risks, 5 = significantly overstates risks). By comparison, the FDA got a 3 from the toxicologists, indicating that they felt the organization was accurate in assessing and reporting risks. For those who are curious, the U.S. Centers for Disease Control and Prevention (CDC) and the American Medical Association (AMA) also scored near 3, reflecting accurate portrayal of risks, while Greenpeace got a 4.5 — the highest score given — for significant overstating of risks. The Pharmaceutical Research and Manufacturers of America (PhRMA), on the other hand, scored a 2.3 for being the most significant understater of risks. Note that PhRMA is not a government organization, and is not tied to the FDA, the CDC, or other government health regulators.

As far as the EWG goes, I think they have their place. They report on research, but often issue warnings on the basis of single studies or studies with limited applicability. Case in point, they warn consumers against sunscreen containing retinyl palmitate (vitamin A) on the basis of a 2009 study that looked at mice rubbed with the chemical and exposed to light. The vitamin A mice developed more tumors, leading the EWG to report a link between retinyl palmitate in sunscreen and cancer. However, there are significant issues that limit the study’s applicability. Most notably, sunscreen only ever contains a small amount of retinyl palmitate. Dose is very important in toxicology; any substance — even water — is toxic in sufficient quantity. As such, a pure retinyl palmitate rub applied to mice doesn’t provide information about the toxicity of small amounts of the compound in sunscreen. In the end, groups like the EWG help to promote research on issues pertaining to toxicology and public safety, but speaking for myself, I look for corroborating research or concern from more moderate institutions before acting on an EWG warning. In response to the question from the start of this post, I think we can safely say that the EWG is “non-woo,” but they are a little jumpy.

On to sunscreen safety. First and foremost, there’s a major risk-to-benefit analysis that one must conduct when determining whether to use sunscreen and what type to use. This is because the sun emits ultraviolet radiation (UV) that damages cells, leading to development of wrinkles, aging of tissues, and skin cancer. Sunburns are an indication of particularly severe cellular damage — just one or two sunburns before the age of 18 significantly increases risk of skin cancer later in life — but even a so-called “healthy” tan is a sign that damage has occurred. Sunscreen is a part of protecting the skin from sun damage, but it’s not the entire equation. In fact, staying out of the sun during intense radiation hours (midday) and using physical protection such as clothing, sunglasses, and hats provides the best protection from harmful UV radiation. No sunscreen provides complete protection. To this end, one of the new FDA regulations regarding sunscreen labeling is that sunscreens will no longer be allowed to refer to themselves as “sunblock,” on the grounds that this inappropriately overstates protection. While there’s been some muttering by the EWG and other groups about whether sunscreen truly helps to prevent skin cancer, these concerns are largely based upon use of sunscreens that protect from only one type of UV radiation (broad-spectrum sunscreens are best, but not all sunscreens are broad-spectrum) and inappropriate use of or reliance on sunscreen. The general consensus among medical and government organizations, including the CDC and the AMA, is that sunscreen is an important component of safe-sun behavior.

The active ingredients of a barrier sunscreen.

There are two major classes of sunscreens: barrier sunscreens containing minerals (like zinc oxide and titanium dioxide) that reflect light, and chemical sunscreens that absorb the light and prevent it from penetrating cells. There is essentially no risk of absorbing the barrier compounds through the skin, leading even the EWG to note that these sunscreens are likely the safest and most effective. In times past, barrier sunscreens were unpopular because they had a greasy white appearance on the skin (remember Zinka from the 80s?). Newer technology allows for smaller particles (nanoparticles) of barrier compounds, which are less visible on the skin, though some formulations may still be greasy. There’s also some question as to whether these nanoparticle formulations appropriately protect from UVA, one of the types of UV (UVB is the other type). Unfortunately, while the sunlight reaching Earth is made up of mostly UVA, the SPF rating on sunscreen applies to UVB protection only. The new FDA regulations propose a set of standards for reporting UVA protection, as UVA exposure also leads to skin cancer. With regard to barrier sunscreens, then, the most effective UV protection comes from the old-school stuff: greasy, white, and slathered on thick. The next most effective UV protection comes from a nanoparticle formulation combined with a chemical sunscreen containing oxybenzone or similar for enhanced UVA protection. Of course, protection from UV is only part of the equation when it comes to assessing sunscreen safety; the other part is the safety of the sunscreen ingredients themselves.

The active ingredients of a chemical sunscreen.

Oxybenzone is currently raising hackles at the EWG, and is one of the reasons that their Sunscreens 2012 report contains so few “approved” choices. The compound occurs in nature — it’s in flower pigments — and is incredibly common in personal care products. It’s not only a sunscreen, it’s also a fragrance enhancer, preservative, flavor enhancer, and so on. The CDC reports that a recent random sample of Americans revealed oxybenzone in 97% of urine samples (Calafat et al). However, the significance of this information has not yet been determined. The EWG calls oxybenzone a “potential hormone disruptor,” citing the European Commission on Endocrine Disruption (pdf) (ECED), which basically means that the EWG is saying they don’t like oxybenzone on the grounds that the ECED doesn’t like oxybenzone. As to why the ECED takes issue with it, they (like the EWG) are exceedingly cautious. The EWG cites two studies (Ma et al,* Ziolkowska et al) that show the potential for weak endocrine disruption. {Note that the Ma et al reference is incomplete on the EWG website, and I was able to find no evidence of it in the scientific literature}. The extent to which the results of these studies, conducted on cells with pure oxybenzone compound, are relevant to use of the compound in sunscreen are unknown. As the American Cancer Society points out:

Virtually all substances known to cause cancer in humans also cause cancer in lab animals. But the reverse is not always true – not every substance that causes cancer in lab animals causes cancer in people. There are different reasons for this.

First, most lab studies of potential carcinogens (cancer-causing substances) expose animals to doses that are much higher than common human exposures. This is so that cancer risk can be detected in relatively small groups of animals. But doses are very important when talking about toxicity. For example, taking a couple of aspirin may help with your headache, but taking a whole bottle could put you in serious trouble. It’s not always clear that the effects seen with very high doses of a substance would also be seen with much lower doses.

Second, there may be other differences between the way substances are tested in the lab and the way they would be used, such as the route of exposure. For example, applying a substance to the skin is likely to result in much less absorption of the substance into the body than would be seen if the same substance is swallowed, inhaled, or injected into the blood. The duration and dose of the exposure also help determine the degree of risk.

While the above refers to cancer risk, the same is true of other toxic effects of compounds that are revealed through laboratory and animal studies. With specific regard to cancer and oxybenzone, even the cautious EWG notes that there’s no evidence that oxybenzone is carcinogenic — or, more accurately, THERE IS evidence that oxybenzone IS NOT carcinogenic (non-mutagenic in 4 of 4 studies: CTFA, 1980; DHEW, 1978; Hill Top Research Labs, 1979; Litton Bioneics, 1979).

Taking all the information together and conducting a risk-to-benefit analysis, I think it’s fair to say that because of the limited data available and the availability of alternatives to oxybenzone, it may be worth avoiding it in sunscreen, but there’s no reason to get particularly excited about previous use or occasional future use. Given that it’s present in almost all chemical (non-barrier) sunscreens, this essentially leaves the barrier sunscreens containing zinc oxide and titanium dioxide. If one chooses to use the nanoparticle formulations with somewhat reduced UVA protection, one must then decide whether to use a chemical sunscreen for additional protection — but this once again leads to oxybenzone exposure.

One last thing: with regard to old sunscreen, if in doubt, throw it out. The CDC recommends that sunscreen be no more than three years old if there’s no expiration date on the bottle. If the bottle has an expiration date, abide by it. The protective chemicals in sunscreen break down over time, meaning that protection wanes.

Science Bottom Line:* Given that there is no sunscreen that provides complete protection, the evidence suggests that the safest choice (particularly for children) is the use of zinc oxide or titanium dioxide sunscreen (I prefer nanoparticle formulations for convenience and aesthetics), without a chemical sunscreen backup. This should be augmented through the judicious use of shade, clothing, sunglasses, and hats, particularly during the most intense periods of sunlight.

 

How do you protect your family’s skin outdoors?

 

References:

Calafat et al. Concentrations of the sunscreen agent benzophenone-3 in residents of the United States: National Health and Nutrition Examination Survey 2003–2004. Environ Health Perspect. 2008 Jul;116(7):893-7.

Ziolkowska et al. Endocrine disruptors and rat adrenocortical function: studies on freshly dispersed and cultured cells. Int J Mol Med. 2006 Dec;18(6):1165-8.

The Zombie Apocalypse, The CDC, and The FDA

The U.S. Centers for Disease Control and Prevention, in their continuing effort to promote public health and health awareness, has outlined the basics of zombie apocalypse preparedness. Yes, for real.

As it turns out, preparing for the zombie apocalypse is similar to preparing for any other disaster: stock up on non-perishable food, water, and medications, have copies of important documents gathered together in a safe and accessible place, have a “family meeting place” picked out, and so forth. The CDC outlines emergency preparedness elsewhere on their website, but apparently no one really wants to read about preparing for a mudslide, a hurricane, or a fire evacuation. What people do want to read about, apparently, is the zombie apocalypse. Thus, figuring that getting the message out was more important than the mechanism by which they got the message out, the CDC went with a partially tongue-in-cheek, partially no-nonsense discussion of the undead and what happens when they attack. Good for them for their fun-loving and light-hearted approach to a serious matter. Particularly as, until the publication of the zombie article, “fun-loving” and “light-hearted” would not have been high on the list of adjectives I’d apply to the CDC, or any government agency, for that matter.

If zombie preparedness made the CDC the government’s equivalent of a cool kid, the Food and Drug Administration (FDA) is the class nerd: both an object of contempt and a scapegoat. I have to admit I feel sorry for the FDA, because they have one heck of a balancing act to perform, and they’re given less credit for their actions and more credit for autonomy than they deserve (the FDA’s actions and powers are determined by congress, so where they “fail” to provide for public safety, it’s often because they literally can’t take action.)

In an article published in the Journal of the American Medical Association, Dr. ­Joshua Sharfstein addresses the dilemma the FDA faces. They are an organization responsible for overseeing the safety and regulating the approval of both pharmaceutical and over-the-counter drugs (as well as a large portion of the food available in the U.S., which increases their workload). On the one hand, they’re under tremendous pressure to approve drugs, both from consumers (who want to see potential treatments for diseases become available) and from pharmaceutical companies (who want to make money — more on this later). On the other hand, we live in a society that is not willing to accept risk, and we find it completely unacceptable when an approved drug causes harm. The FDA thus has to balance quick drug approval with appropriate safety precautions.

Long ago, the FDA didn’t require drug manufacturers to prove that a drug was safe or effective before bringing it to market. The proverbial “snake-oil salesman” could sell anything (even something ineffective, dangerous, or both), and make any claim he wished, and he wouldn’t be crosswise with the FDA. As of 1906, the FDA required that manufacturers label their wares correctly and that the medications be contaminant-free, but there were no further requirements. In 1937, a pharmaceutical company marketed sulfanilamide elixir (a solution of sulfanilamide antibiotic in diethylene glycol solvent). Diethylene glycol is sweet and did a good job of dissolving the antibiotic, which made the elixir popular with parents, since it was easy to give to children. Unfortunately, diethylene glycol is chemically similar to antifreeze, and just as toxic. Of 353 children who took the medication, 100 died of kidney failure. The public outcry was phenomenal; as a result, congress passed the 1938 Food, Drug and Cosmetic Act, which was the first legislation to require proof of safety in marketed drugs. Further acts and amendments followed, shaping the legislation that outlines the responsibilities of the FDA today.

Obviously, this legislation has improved the safety of drugs brought to market. Even “failed” drugs that are pulled off the market for poor safety records do nowhere near the damage sulfanilamide elixir did. Take Baycol, for example (a cholesterol drug), which was pulled off the market in 2001. While Baycol appeared safe during extensive drug trials, post-marketing surveillance revealed that it increased risk of potentially fatal muscle weakness. 52 people died in all. How many total took the drug? Hard to know for sure; those are difficult numbers to come by. Maybe tens of thousands, maybe more. Regardless, compare Baycol’s “unacceptable” safety record to that of sulfanilamide elixir to get an idea of how successful the FDA is in helping to prevent large-scale pharmaceutical disasters. The FDA did everything right. They required Bayer (the pharmaceutical company) to provide evidence of safety and efficacy in animals before the drug was even approved for human trials. They required years and years of human trials before the drug was brought to market. Everything looked good. All this to the background noise of consumers complaining that the FDA takes too long to approve new drugs for marketing to the public, but the agency took its time and released Baycol only when it appeared truly safe and effective. And then the FDA continued to do its job; they monitored the safety of the drug post-marketing, because some side effects are so rare they don’t show up in human safety trials (even large ones), and others take years to show up. When adverse reactions to Baycol started cropping up in the public, it was removed from the market. Let me say it again: the FDA did its job. But Baycol is often cited as an example of an FDA “failure.”

We want our drugs, and we want them NOW; we aren’t willing to wait years and years for testing. We also want our drugs completely safe, so FDA had better ensure that companies test for safety carefully (but quickly!). Oh, and we don’t want our drugs tested on animals (because that’s cruel), but neither do we want them tested on people (because they could be dangerous, and no one should be exposed to that. Or they could be effective, in which case it’s not fair that some people get randomly assigned to the placebo). We’re unhappy with the FDA no matter what they do. And to boot, we’re unhappy that all the safety testing costs pharmaceutical companies millions and millions of dollars per drug, which they have to recoup, which increases drug prices. So we want our drugs SAFE, FAST, and CHEAP, and we resent the FDA for “standing in the way” of our safe, fast, cheap drugs with a checklist that they insist on filling out before they allow all those (undoubtedly perfect, life-saving) drugs that they’re “withholding” to come to market. Yes, I feel sorry for the FDA. As Sharfstein astutely notes, “Some claim the FDA is captive to manufacturers…others assert the agency [moves too slowly]. Sometimes stories outlining conflicting perspectives appear on facing pages of the same newspaper.”

Maybe what the FDA needs is to spiff up their image a bit. They should take a lesson from the CDC, and incorporate zombies into their policy statements. Or…maybe not, since ultimately, the CDC’s cool image proved as tenuous as Patrick Dempsey’s in “Can’t Buy Me Love.” Now that the buzz about zombie apocalypse preparedness has died down, the CDC’s image is right back where it was beforehand: a geeky institution that we’re morosely convinced is in bed with big pharma (why else would they push all those vaccinations!?), and that overstates the danger of “routine” childhood illnesses. Oh well. I guess you can’t win. Unless you write about zombies.

 

Why do you think it’s so hard for us to believe other than the worst of government agencies?

 

References:

FDA Baycol. Accessed 14 Oct 2011.

Furberg et al. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med. 2001;2(5):205-207.

Sharfstein, J. The FDA — A misunderstood agency. JAMA. 2001 Sept 21; 306(11): 1250-51.

Soothing Tender Gums Part 2 — Alternative Remedies

Last week, I addressed pharmaceutical options for relieving teething discomfort. There are a number of reasons a parent might want to consider non-pharmaceutical options, however. For instance, teething pain can cycle up and down for weeks at a time, and neither acetaminophen nor ibuprofen are appropriate for long-term use. Even clove oil, which is likely safer for long-term use than other pharmaceutical options, causes a tongue-numbing effect to which you may not want to subject your child on a routine basis.

Before considering the non-pharmaceutical options for relieving teething pain, there are some important points to address. First, while many parents feel that “natural” cures are safer than “chemicals” or “drugs,” this is simply not true. Not only are there a variety of toxic natural substances (in fact, the most toxic substance known to man — botulin toxin — is natural), the FDA regulates natural substances differently than they do drugs and pharmaceuticals per the Dietary Supplement Health and Education Act of 1994. In fact, the FDA does not require manufacturers of dietary supplements to prove safety or efficacy prior to distribution. Herbal treatments fall into the category of dietary supplements. Homeopathic treatments are regulated somewhat differently, and don’t fall into the category of dietary supplements as defined by the FDA. They’re a bit more tightly controlled than herbal remedies with regard to safety, but aren’t required to submit new drug applications (like over-the-counter and prescription pharmaceuticals), and aren’t required to provide efficacy data. The important thing to bear in mind when considering an alternative remedy for any condition — teething pain or otherwise — is that just because the remedy is natural doesn’t mean it’s safe. It could be inherently toxic, as some herbs are, or it could be contaminated with a toxic substance. Contamination is less likely to be discovered right away in a dietary supplement or homeopathic remedy than it is in a pharmaceutical because of differences in regulation. Finally, since homeopathic and herbal remedies don’t have to provide proof of efficacy, you could end up spending your money on something completely ineffective.

Because herbal compounds are regulated so loosely with regard to safety, and because there’s insufficient efficacy data for any herbal teething remedies, I will not address herbal compounds here; there’s simply no evidence to support their use in the case of teething.

Homeopathy is a type of alternative medicine that relies upon two principles. The first of these is the “Law of Similars,” which claims that symptoms are relieved by taking a substance that causes similar symptoms in healthy individuals. The second principle of homeopathy is that dilution strengthens the preparation. While there is no physical evidence or scientific hypothesis to support or explain this belief, homeopaths believe that the more dilute they make a solution, the more powerful it becomes. Many homeopathic remedies are so dilute that the odds are there is no longer even a single molecule of the remedy substance in the preparation. While most practitioners of traditional Western medicine (i.e. mainstream physicians) dismiss homeopathy and claim that any benefit from it is the result of a placebo effect, some scientific studies have shown that homeopathic remedies can be effective in certain conditions (see, for instance, Linde et al, who present a review of many homeopathic research trials). The Linde review, however, is by no means the only analysis of homeopathic research. Others (see, for instance, Shang et al) have also reviewed the body of published homeopathic research and have reached different conclusions. Notably, though they examined many of the same studies, the Linde analysis came to the conclusion that homeopathy can have a significant (i.e., not placebo) effect on some conditions, while Shang and colleagues reported just the opposite. Part of the confusion here is that there are no hard and fast “rules” for analysis of the research conducted by others; researchers conducting such analyses are free to interpret results as they deem most appropriate.

Unfortunately, while there are placebo-controlled, double-blind, high-power (basically, this all means well-conducted) studies documenting the safety and efficacy of homeopathy in treating some conditions — including allergies (Reilly et al) and diarrhea (Jacobs et al) — there are no such studies demonstrating that it has an effect on teething pain. Nevertheless, major homeopathic drug companies sell single substance remedies (generally chamomile) and compound remedies purported to help alleviate discomfort. Despite the lack of evidence to support efficacy of homeopathic teething remedies, these preparations are so dilute as to generally cause no adverse reactions, and have a good safety record, according to the National Center for Complementary and Alternative Medicine (NCCAM). While NCCAM doesn’t go so far as to recommend homeopathy (on the grounds that there’s no evidence to support its efficacy), and while they warn that liquid homeopathic preparations can be high in alcohol and present a hazard to children for that reason, they do not find any reason to warn against use of homeopathic pill preparations on safety grounds.

One popular compound preparation for teething, Hyland’s Teething Tablets, was recently pulled from the market by the FDA on the grounds that the pills contained inconsistent quantities of the active ingredients (particularly belladonna, which has the potential to cause severe adverse reactions in sufficient quantity). Hyland’s explains that adverse reactions to the tablets, which led the FDA to investigate further, were never conclusively tied to use of Hyland’s tablets. Further, they note that the quantity of belladonna in even the most concentrated tablets was insufficient to cause symptoms of belladonna poisoning. Regardless, the popular tablets are now back on the market, hopefully with greater preparation consistency.

Another option for relieving teething pain, popular with some moms, are Baltic amber teething necklaces. These necklaces are designed to be worn, not chewed, and supposedly help to reduce teething pain due to an analgesic compound in the amber that absorbs into the body via the skin. The compound, succinic acid, is a small carbon-based molecule. There is scientific evidence to suggest that succinic acid has biological activity (Haeseler et al showed that it affects muscle excitability) and it has been shown in some cases to diminish physical affects of stress (Rachkov), but there is no plausible explanation for analgesia produced by topical application of the molecule. Succinic acid has a chemical structure that makes it incapable of penetrating the skin. As such, while there may be some other compound responsible for the suggested analgesic effects of a Baltic amber necklace, no plausible hypothesis has yet been proposed. Neither is there any scientific evidence to suggest that such necklaces are effective.

Science Bottom Line:* There is no scientific evidence to support use of herbs for teething pain. While there is some scientific evidence to support the use of homeopathy for some conditions, there is no such evidence to support the use of homeopathy for teething. However, it’s unlikely that there are major concerns associated with trying homeopathic teething remedies. It’s probably worth using a remedy whose ingredients are non-toxic (like chamomile), rather than a remedy with toxic ingredients (like belladonna), on the off chance that pills have inconsistent quantities of the active substance. There is no scientific evidence to support use of an amber teething necklace.

 

What are your favorite alternative teething remedies?

 

References:

FDA Dietary Supplements. Accessed 26 Sept 2011.

FDA Conditions Under Which Homeopathic Drugs May be Marketed. Accessed 5 Oct 2011.

FDA Consumer Safety Alert, Hylands Teething Tablets. Accessed 5 Oct 2011.

Haeseler et al. Succinylcholine metabolite succinic acid alters steady state activation in muscle sodium channels. Anesthesiology. 2000 May;92(5):1385-91.

Hyland’s Teething Tablets Recall Information. Accessed 5 Oct 2011.

International Academy of Classical Homeopathy, Materia MedicaChamomilla. Accessed 5 Oct 2011.

Jacobs et al. Treatment of acute childhood diarrhea with homeopathic medicine: a randomized clinical trial in Nicaragua. Pediatrics. 1994 May;93(5):719-25.

Linde et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet. 1997 Sep 20;350(9081):834-43.

National Center for Complementary and Alternative Medicine Homeopathy. Accessed 5 Oct 2011.

Rachkov, A. [Metabolic effects of succinic and nicotinic acids in emotional pain stress]. Farmakol Toksikol. 1988 May-Jun;51(3):41-5.

Reilly et al. Is evidence for homoeopathy reproducible? Lancet. 1994 Dec 10;344(8937):1601-6.

Shang et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet. 2005 Aug 27-Sep 2;366(9487):726-32.

High-Fructose Corn Syrup — Big Problem or Just Another Sweetener?

High-­‐fructose corn syrup (HFCS) is ubiquitous in the American diet, and unless you make a concerted effort to avoid the stuff, your child consumes it in everything from soda to fast food to the convenient prepared snacks and juice boxes you tuck into backpacks and leave in the pantry for after school. The debate over the health effects of HFCS is intense, with the corn industry claiming that it’s essentially identical to table sugar, and healthier food companies scrambling to reformulate products so that they no longer contain the sweetener. Who’s right? Is HFCS the dietary disaster some scientists claim, or is the corn industry correct in saying it’s table sugar by another name? Should you particularly avoid feeding your child HFCS, or are all sweeteners equally unhealthy?

Obesity rates among children and adolescents are on the rise in the United States, with a disturbing 17% of America’s youth affected, according to the U.S. Centers for Disease Control and Prevention. As obesity among the young has soared, so have rates of type 2 diabetes — so much so that the disorder, which was once known as “adult-­‐onset diabetes,” had to be renamed. Because the American obesity epidemic picked up steam right around the time American consumption of HFCS increased dramatically, studies including Bray et al. have suggested that the HFCS might be to blame.

The corn industry vigorously opposes such accusations, however, on the grounds that HFCS isn’t much different from table sugar. Table sugar, formally known as sucrose, consists of two smaller sugar molecules — glucose and fructose — chemically bonded together. When you eat sucrose, your body digests it into its glucose and fructose components, and you absorb these and use them for energy. Too much sugar — or any other energy-­‐providing nutrient — in your blood, and your cells begin to convert the excess into fat. It’s therefore completely true to say that too much of any sugar can lead to obesity. With regard to chemical makeup, sucrose is 50% glucose and 50% fructose. HFCS-­‐55, the most common of the HFCS formulations, is 55% fructose, 42% glucose, and 3% larger sugar molecules (White 2008). In the end, based purely upon composition, there are significant chemical differences between table sugar and HFCS.

Two new studies particularly underscore the differences between HFCS and other calorie-­‐containing sweeteners, including table sugar. In the first of these, researchers determined that rats drinking sweetened water (sweeteners included fructose, glucose, sucrose, and HFCS) didn’t adjust the calories of rat chow they ate to account for the additional calories they were taking in (Light et al 2009). While not necessarily an indictment of HFCS in particular, it’s certainly a good argument against sweetened beverages in general. Additionally, however, the rats drinking HFCS-­‐sweetened water gained more weight than any of the other rats, despite the fact that they didn’t take in more total calories than the other rats drinking sweetened water. This demonstrates that HFCS can promote weight gain to a greater extent than other sweeteners per calorie consumed.

In the second study, rats fed HFCS and rat chow gained more weight —especially in the abdominal region, which is particularly unhealthy — than those fed table sugar and rat chow (Bocarsly et al 2010). These findings particularly impressed researchers because the HFCS-­consuming rats actually managed to gain more weight on fewer total sugar calories than the table sugar-­consuming rats. This suggests that HFCS doesn’t just promote weight gain more than table sugar does, it actually promotes the most dangerous kind.

Science Bottom Line:* Evidence suggests that too many foods with added sweeteners increase the risk of obesity, and that this is particularly true of sweetened beverages (like sodas and juice drinks). HFCS appears to be especially problematic, because it encourages the body to put on weight to a greater extent than other sweeteners on a calorie-­‐for-­‐calorie basis.
Do you worry about HFCS and other additives in your food? What do you do to encourage your children to eat a healthy diet?

 

References:

Bocarsly et al. High-­‐fructose corn syrup causes characteristics of obesity in rats: Increased body weight, body fat and triglyceride levels. Pharmacol Biochem Behav. 2010 Nov;97(1):101-­‐6.

Bray et al. Consumption of high-­‐fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr. 2004 Apr;79(4):537-­‐43.

Light et al. The type of caloric sweetener added to water influences weight gain, fat mass, and reproduction in growing Sprague-­‐Dawley female rats. Exp Biol Med (Maywood). 2009 Jun;234(6):651-­‐61.

U.S. Centers for Disease Control and Prevention Overweight and Obesity Data and Statistics. Accessed 11 Sept 2011.

White, JL. Straight talk about high-­‐fructose corn syrup: what it is and what it ain’t. Am J Clin Nutr 2008;88:1716S–21S.

*The “Science Bottom Line” at the end of each article is not intended as medical advice. It is merely my analysis of one or more papers referenced in a given post.

**”SquintMom’s Decision,” likewise, is not intended as medical advice. It’s merely what I do in my own home, based upon the results of my analysis of the information available.