A Minty-fresh Stalemate on Menthol Cigarettes

The story I’m about to tell you is figuratively yesterday’s news. Literally it comes from March of 2011, from 2009 and from 2 very different Perspective pieces published online in the New England Journal of Medicine (NEJM) a few days ago. These editorials address the debate surrounding a report presented to the FDA by the Tobacco Products Scientific Advisory Committee (TPSAC), which was created two years ago and tasked with determining whether menthol cigarette pose a greater risk to public health than your standard non-minty smokes. This is a large and complex issue, which will be addressed here with a certain brevity (and perhaps even bullet points) as I am leaving for vacation in less than 24 hours.

A Committee is Born

The TPSAC was created as part of the 2009 Family Smoking Prevention and Tobacco Control Act. This legislation also banned flavored tobacco products, with the notable exception of menthol cigarettes. Instead of being part of the original ban, menthols were given temporary exemption until their hazards could be assessed by the newly-formed committee.

The Controversial Report

After a lengthy examination of peer-reviewed literature on menthol cigarettes (as well as tobacco industry submissions), the TPSAC delivered an equally lengthy report.* It stated that, because there was not consistent evidence of greater toxicity in cigarettes treated with menthol, the risk to any individual smoker was no different whether they chose a minty or unflavored product. However, considerable evidence showed that menthol smokers had a harder time quitting than non-menthol smokers. Even more problematic, menthol cigarettes were determined to make it easier for people to start smoking in the first place. By softening the taste and feel of tobacco, menthol cigarettes facilitate smoking for novices who might otherwise be deterred by these harsh sensory realities. They are the wine coolers and peppermint Schnapps-spiked hot chocolates of the cigarette world.

The Report Card

The most frequently quoted sentence from the TPSAC report is its overall recommendation, “Removal of menthol cigarettes from the marketplace would benefit public health in the United States.” Critics – such as Dr. Michael Siegel, who wrote one of the aforementioned NEJM editorials – criticized the language for being weak and for deliberately avoiding making any recommendation for a ban. The second NEJM article, written by two doctors who served on the TPSAC, defended the report stating that critics failed to understand the purpose of a scientific advisory committee. They likened the maligned quote to the 1964 Surgeon General’s report on smoking, which stated, “Cigarette Smoking is a health hazard of sufficient importance in the United States to warrant appropriate remedial action.”. Okay, also a bit ambiguous, but one gets a better sense of what is being suggested. The “if, then” structure of the TPSAC recommendation fails to convey any urgency.

Mint-flavored Market

Perhaps the most interesting part of the menthol controversy is the history of the cigarette itself and how it became – in the U.S. –  a product marketed specifically to black consumers. Menthols were unleashed onto the public in the 1920’s, so the story goes, by Lloyd “Spud” Hughes, who accidentally discovered the idea after storing his own tobacco overnight in tin that also contained menthol. Spud cigarettes, with their purported breath-freshening properties, were originally marketed to the fashionable smoking elite. As the century progressed, they began to be viewed more as cough drops. One switched to soothing menthol cigarettes when stricken with a cold and then returned to their usual pack once they were on the mend.

But in the mid 20^th century, the cigarettes began being targeted at the growing African American market. Cigarette manufactures not only created ads designed to appeal specifically to these consumers, they also ingratiated themselves by donating money to black community organizations and civil rights groups. By the 2000’s, menthols were the cigarette of choice among 70% of African American smokers (versus only 30% of white smokers). Given that African Americans have higher mortality rates from lung cancer than American whites, the role of menthol becomes not just a health issue, but potentially one of racial equality. In fact, Siegel suggests, the TPSAC was assigned the duty of investigating menthol cigarettes only because the exemption of menthol from the original legislation met with such strong opposition from the Black Congressional Caucus. But that’s a larger issue than can’t be tackled today, so on to…

The Bullet Points

• Personally, I’m more for warnings than bans. Yet it does seem a bit odd that the Family Smoking Prevention and Tobacco Control Act would go through the trouble of banning something as obscure as cherry and strawberry flavored tobacco products and then exclude the one flavor that actually sells in meaningful numbers.

• One of the weaker arguments against banning menthol cigarettes is that such a ban could create a black market for this sought after product. Seriously? (rhetorical question alert) Does anyone actually believe that menthol smokers would find drug dealers to sell them contraband cigarettes rather than just buying a non-mentholated brand they can get at their grocery store? And if black market business is such a concern, why are various recreational drugs illegal?

• Is the FDA doing anything about Camel Crush cigarettes? Do those things still exist? They were being rather aggressively marketed when I first moved to Austin, with company representatives handing them out in downtown bars. It’s a regular cigarette that can be transformed into a menthol by simply squeezing the filter. This breaks a small menthol capsule that leaks minty fluid into the cigarette. The crushing of the capsule sounds similar to glass breaking. It just seems like a bad idea.

And now, I’m off to Europe where I’m told everyone smokes unfiltered, unflavored cigarettes and drinks hot coffee even in the middle of Summer.

* It’s over 200 pages and I don’t have time to read it right now. If you want to give it a shot, be my guest. It can be downloaded as a PDF from the FDA’s website.

Warning Colors

Image Credit: Benjamin Golub

Late last month the FDA shot down a petition to ban the use of artificial coloring in foods, despite acknowledging evidence that these additives may aggravate hyperactivity in children with behavioral disorders. In fact, the agency decided that even mandating warning labels about the correlation was unnecessary. Parents throughout the U.S. have been ranting about this ever since. How mad should you be over the FDA’s ruling? If Yellow No. 5 and its ilk are so safe, why don’t Europeans have to eat them? And who needs colorful food anyway?

Seeing Red

Controversy over food coloring is nothing new, and what makes or breaks a proposed ban is a mixture of science, public perception and industry lobbying. Early laws prohibiting the use of artificial yellow in margarine had more to do with bullying from the dairy industry (who stood to lose money to a cheaper new product) than with public health. Similarly, the 1976 FDA de-listing of Red No. 2 occurred despite inconclusive scientific data. Studies aimed at demonstrating the hazards of the additive were flawed and inconsistent, but a public relations storm was brewing and, in this instance, the FDA found it more favorable to appease consumers than the industry. By the time the decision was made, public opinion of Red No. 2 was so low that the makers of M&M’s candies discontinued red M&Ms, even though they got their color from chemicals still considered safe at that time.*

Scary cherry.
Image Credit: Jay Keaton

Following a new set of disputed data, in 1990 the FDA promised to phase out another crimson hue, Red No. 3 (used to make the cherries in canned fruit cocktail a shade other than boiled and processed brown), but without actually specifying when. † This time industry pressure was stronger than public outrage. Whining from the fruit cocktail lobby, who wisely assessed that their canned product would become completely undesirable without the pretty cherries, has managed to delay a full ban indefinitely.

Field research for this article – which involved a survey of my own refrigerator, a trip to the grocery store and a whim-driven purchase of a bag of Sour Patch Kids – revealed that maraschino cherries ‡ are as red as ever, but currently get their color from Red No. 40, which is also responsible for the pigmentation of my newly acquired gummy candy, and a long-forgotten jar of HEB brand plum-flavored fruit spread. However, Red No. 3 lives on in the standard set of assorted food coloring I purchased two years ago to make fake blood for a photo shoot (and eventually holiday cookies).

Weighing the Evidence

While not the only data supporting a connection between artificial food coloring and hyperactivity in children, the 2007 “Southampton study” was particularly important as it led to the phasing out of 6 artificial colors in the European Union (EU). It is worth noting that, of the 6 hues involved in the study, only 3 are on the list of colors currently approved by the FDA (Yellow No. 6, Yellow No. 5, and Red No. 40) and that the colors were examined in 4-color mixes (with a preservative added) rather than individually. § Still, the study found adverse effects among 8 to 9-year-old children with both mixes, including the second concoction, which was specifically designed to emulate the dose and variety of additives that would be encountered by the average lolly-eating British kid. As with the Red No. 3, the scandal factor surrounding this issue in Europe was high. In 2008 the Food Standards Agency recommended phasing out all 6 of the dyes used in the Southampton study in the EU. For this reason, people eating processed food (made by the same manufacturers, mind you) on the European side of the Atlantic have their snacks tinted with food-derived colors while those of us on the American side are still consuming the artificially-colored versions.

Color Cues

Unwilling to cope with beige snacks, Europe dealt with the bad news about artificial coloring by decorating foods with things like beet extract and paprika. There is much evidence that both our enjoyment of food and our comprehension of its flavor rely heavily on color. Studies have shown that subjects can better identify flavors in appropriately colored foodstuffs (lime drink colored green) than in those with mismatched colors (lime drink colored red). And let’s not forget the colossal flop of the deliberately de-colored Crystal Pepsi back in the early 1990s. Despite initially attracting consumers with its novelty value, the beverage did not look like a cola and therefore it failed to taste like one.

Without color vision, delicious jellybeans
would just look like insect larva.
Image Credit: Ross Websdale

In his clinical essay, The Case of the Colorblind Painter, Oliver Sacks tells the story of an artist who becomes completely colorblind following a head injury. Forced to view the world in only shades of grey, one of the many losses was that of a tasty meal. Sacks writes, “He found foods disgusting due to their greyish, dead appearance and had to close his eyes to eat.” Gradually, the patient gravitated toward foods that were in reality black and white (olives and rice, for example) as only these appeared “normal”.

From an evolutionary perspective, there is some value to judging a book by its color. Food hues not only warn against items that are likely to be spoiled or poisonous (blue and black) but also draw us toward essential nutrients (red peppers, orange carrots, green broccoli). One of the problems with colored snack food, whether its appearance is achieved through beet extract or through Red No. 40, is that it satisfies the urge to eat colorful foods without providing any of the nutrition benefits of real fruits and vegetables.

"The dose makes the poison"

So said sixteenth-century scientist Paracelsus, whose name was coincidentally brought to my attention this past week. In large enough quantities, drinking water can kill you. While I’m all for better food labeling, I’m not convinced of a need to ban artificial coloring altogether. As a child, I enthusiastically ate Kraft Macaroni and Cheese for lunch daily over the duration of an entire summer, but I wouldn’t call this a healthy meal, even without its synthetically derived yellow. Processed foods with or without artificial colors are often still high in preservatives, saturated fats and sugar – the latter ingredient was discussed at length in a recent New York Times article – and low in vitamins and fiber. The real issue is not the high volume of artificial food coloring consumed by U.S. children (and adults), but rather the high volume of artificial food. Occasional junk food treats are acceptable in low doses, but for everyday eating, the goal should be not to choose foods colored with naturally-derived dyes, but foods that don’t need additional color in the first place.

* Like a disgraced television executive, the red candies returned (a decade later) after the bad press died down.

† The studies in question involved feeding doses of Red No. 3 to mice that were much higher than what a human could ingest through food alone. People disagree on whether an additive should be proven safe in any dose or just safe in normal doses.

‡ I mention maraschino cherries because, shockingly, I did not encounter canned fruit cocktail during my investigations, and Dole’s website would not show me ingredient listings for their canned fruit. For now we’ll have to assume the same cherries are featured in fruit cocktail.

§ It’s entirely possible that a single ingredient is making other more well-behaved colors look bad. The sinister Yellow No. 6, for instance, or even the villainously un-colored preservative sodium benzoate, which appeared in both mixtures tested. This is the kind of experimental design that allows government agencies to stall and request “more research” before taking action.

Who told you this?

Harris, G. “Artificial Dye Safe to Eat, Panel Says.” The New York Times, 31 March 2011.

Burrows, A., 2009. “Palette of Our Palates: A Brief History of Food Coloring and Its Regulation.” Comprehensive Reviews in Food Science and Food Safety 8: 394-408.

Zampini, M., et al. 2008. “Multisensory flavor perception: Assessing the influence of fruit acids and color cues on the perception of fruit-flavored beverages.” Food Quality and Preference 19: 335–343.

“UK Food Standards Agency Cites Southampton Study In New Recommendation On Food Additives.” MedicalNewsToday.com, 13 Apr 2008.

McCann, D., et al. 2007. “Food additives and hyperactive behaviour in 3-year-old and

8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial.” The Lancet 370: 1560-1567.

Diets, Drugs, and How to Live Forever Without Resorting to Vampirism

For a long time the only reliable way to extend lifespan was to eat less. Much less. In experiment after experiment, caloric restriction (CR) increased longevity in everything from yeast to primates. I would call this a fine tradeoff were it not for my deeply held conviction that a life without candy corn is not worth living. Not that I’m advocating industrialized civilization’s current level of run-amok gluttony, but really, a person needs a few empty calories to cope with the tedium of an average workday. Fascinating though the idea sounded, for me, and for most others of my species, caloric restriction was off the table. Then somewhere around 2006 I began reading about a molecule called resveratrol that was found in red wine and had demonstrated health benefits in laboratory animals similar to those provided by CR. But five years have passed and I’m still impatiently awaiting my life-extending miracle drug. What’s taking so long?

Less is More

The study of caloric restriction dates back to the Great Depression, when animal experiments were designed to examine whether prolonged food scarcity might damage longevity in mammals (humans, of course, being the real interest). But lab rats subjected to Depression-esque chronic hunger surprised scientists by living longer than control groups. Further experiments would show the same trend in other animals. Not only did CR extend lifespan, but it also extended health by delaying many diseases associated with aging.

Initially, such benefits were believed to result from a reduction in metabolic strain that causes cellular damage over time (free radical and all that business). But more recent experiments suggest that CR affects regulating pathways that govern gene expression. When the body’s sensors perceive food as being plentiful, resources are allotted to growth and reproduction.* When food is scarce, such expansions are put on hold in favor of damage control. The organism now focuses on cell protection and preservation (life-extended processes) while awaiting the next period of abundance. It’s no great stretch to wonder if one couldn’t somehow trick the body into believing feast was famine, and thus reap the rewards of CR without all the dreary dieting. Enter resveratrol.

Wining and Dining

In 2003 David Sinclair and Konrad Howitz published a paper in Nature asserting that lifespan (in yeast) could be extended by 70% through the activation of a class of proteins called sirtuins by the molecule resveratrol. Resveratrol, a naturally occurring polyphenol, is found in red grape skins and therefore eventually makes its way into red wine. It was an excellent candidate for life/health extension, since Americans had been scratching their heads for decades over how the French could eat meat and dairy-rich foods and still be reasonably slim and healthy (um, smaller portions perhaps?) The answer was clearly red wine. Never mind that the dosage of resveratrol fed to various model organisms was far higher than a human could obtain from wine, even if they had the most formidable of drinking problems.

Sinclair started the biotech company Sirtris to further research sirtuins and resveratrol, and went on to show that resveratrol improved health and reduced mortality in mice fed a high fat, high calorie diet. Videos of the fat-but-fit resveratrol-enhanced rodents outpacing ordinary obese mice on treadmills assured lazy humans everywhere that society was on the verge of having its cake and eating it too. Despite two separate papers that found flaws in the original research demonstrating resveratrol’s sirtuin-activating abilities†, in 2008 Sinclair and his partners sold Sirtris to the pharmaceutical behemoth GlaxoSmithKline (GSK) for a whopping US$720 Million.

And the Rest is History

Commercially, resveratrol is a pretty worthless molecule. As a natural substance it can’t even be patented. Additionally, it was often uncooperative in the lab, with difficulty maintaining consistent levels in blood sited as one significant issue. As a result, Sirtris’ research has focused more on creating and testing new drugs that mimic resveratrol’s (somewhat disputed) activation of sirtuins.‡ Additionally, the goal shifted away from increasing lifespan overall and instead toward treating the diseases of aging, such as type 2 diabetes and certain cancers. Partly this is because Sirtris is an FDA approval company, and the FDA does not consider aging to be a disease per se. But it’s worth noting that, while resveratrol did well for mice subjected to the unhealthy diet, it demonstrated no increase in longevity for normal mice, casting doubt on whether it actually functions by the same mechanism as CR.§

SRT501 was among the first of Sirtris’ drugs to be unleashed in human clinical trials, and in early 2008 it was holding its own in a phase 1 trial for use as a diabetes medication. It continued to climb the ranks of trial phases and to branch out into other disease trials. But in Spring of 2010 a trial testing SRT501 on multiple myeloma patients was called off early after several people developed kidney failure.** Sirtris halted the last of its remaining resveratrol mimic trials later that year. Results from the debacle won’t be released until next year, and nobody seems anxious to divulge much until then. I’m curious to get a look at their findings, but for the moment things aren’t looking good for resveratrol and friends.

In the meantime, you might want to give caloric restriction another thought. While scientists struggle to figure out how caloric restriction works and how to replicate its effects using drugs, in CR we already have a well-demonstrated method of extending lifespan in a wide range of organisms. The technology is ready, and yet not many people want in on the opportunity of a lifetime. It’s hardly shocking. CR requires a 25-30% reduction in daily caloric intake. And since you’d be living off substantially fewer calories and still trying to meet crucial nutritional requirements, every calorie counts. The idea is to craft meals from calorie-sparse, nutrient dense foods, like vegetables. Say goodbye to cookies, ice cream, ice cream made out of cookies, etc. And don’t even think about sugary beverages. Ironically, you probably won't be able to spare enough calories to consume red wine. But on the bright side you’ll have a chance at living long enough to witness the discovery of age-thwarting remedies that will finally allow you to eat a well-deserved cupcake in the year 2100 or so. I think I’ll just go ahead and have mine now.

* Does this mean that CR affects fertility? Yes, it’s certainly a possibility. Think of it as another tradeoff. Who wants kids anyway.

† A fluorescent tag was used in the initial study to gauge the activity of a particular sirtuin – SIRT 1. When similar experiments were conducted using a different measuring tool (and no fluorescent tag), nothing happened. So either resveratrol bypassed its intended target (SIRT 1) and acted directly on the fluorescent tag, or (as the original authors prefer to conclude) the tag mimics some sort of natural cofactor – in other words, that it’s no big deal and we’ll sort out the details later.

‡ Some of these are remodeled forms of resveratrol, whereas others are completely new compounds designed to activate sirtuins.

§ This isn’t the only flaw in the model, and addition concerns have been voiced over whether sirtuins are even that important in controlling aging.

** This problem may have been caused by the disease itself, rather than the drug. Stay tuned for trial results in 2011? 2012?

Who told you this?

Wade, N. “Doubt on Anti-Aging Molecule as Drug Trial Stops.” The New York Times, 10 January 2011.

Fontana, L., et al. 2010. “Extending Healthy Life Span – From Yeast to Humans.” Science 328: 321-326.

Kenyon, C. 2010. “The genetics of ageing.” Nature 464: 504-511.

Lebford, H. 2010. “Much ado about ageing.” Nature 464: 480-481.

Callaway, E. “GlaxoSmithKline strikes back over anti-ageing pills.” Nature, published online 16 August 2010.

Garber, K. 2008. “A mid-life crisis for aging theory.” Nature Biotechnology 26: 371-374.

In Good Hands

It is estimated that approximately 10% of the world’s population is left-handed. And yet roughly half of my boyfriends, half of U.S. presidents over the last century, and half of the Beatles (Paul and Ringo) were/are left-handed.* Clearly, there’s something impressive about the ability to write with one’s left hand. I’ve been fascinated with left-handedness for as long as I can remember and not just because it’s a novelty to ordinary right-handers like myself. Here’s a fun fact – while most right-handed individuals process language in the left hemisphere of their brain, a sizable proportion of lefties process language equally in both hemispheres. What would cause such a difference? And why can’t I do that? Someday I hope to address such curiosities in greater detail, but today I want to discuss a recent study not about handedness prevalence or neurological organization, but rather about the causes of positive and negative association with right and left amongst individuals with different handedness.

In many cultures, right is associated with good qualities and left with evil (or at least uncouth) traits. The English word for left is derived from a Latin word also meaning “sinister”. The French word for left is the similarly unflattering “gauche”. In some theatrical traditions, good characters enter from the right while villains slink in from the left.† But these patterns may just result from the broader influence of a right-handed majority. Various studies have shown preferences in both right and left-handers for the direction that matches their own dominant hand. All other things being equal, when offered a choice between two things (two paths in a forking road, two unfamiliar products, etc) right-handers generally pick the option on the right while left-handers go for the one on the left.

The current study, to be published in a forthcoming issue of Psychological Science, hypothesized that these varied preferences stemmed not from genetic differences that accounted for handedness itself, but instead resulted the actual experience of being able to move more easily with the dominant side. To test this they examined the effects of “induced handedness” (in this case, right-handed subjects being somehow made more clumsy in their genetically dominant hand) on right/left preference.

The study was divided into two parts covering two kinds of induced handedness. The first involved subjects with long-term changes in dominant hand fluency. These were individuals who had suffered strokes that weakened or paralyzed their right sides (or left sides, for the control group). During the second part, examining short-term changes, healthy subjects were rendered temporarily disabled in their right hands for a 12-minute activity that preceded their being asked to choose between right or left options. In a shining example of the creative sadism that typifies good psychological experiments, the disabling was accomplished by having the participants maneuver dominoes while wearing an unwieldy ski glove, (adding real insult to pseudo injury, a second glove was attached to dangle awkwardly from the wrist of the same hand wearing the glove).

As predicted, in those subjects with impaired right hands, both the stroke group and the glove group generally favored left side options when presented with right/left choices, a reversal of the trend seen in those with disabled left hands.‡ 88% of right-side-impaired stroke patients now expressed preferences akin to those of natural left-handers, and the victims of right-hand gloving were five times more likely to favor left-side options than those who had the indignity foisted on their left hands.

The study was only a small one, but it’s a fun foray into the world of handedness and its peculiar effects on your brain. It’s also an handy (pun intened) reminder of how malleable one’s decisions can be, and that going with your “instincts” may just be following a pattern dictated by your environment. I’m not arguing against the existence of free will or anything that drastic. I am merely suggesting that next time you’re lost and trying to figure out if you should turn right or left, you might consider making the decision via coin flip.   

* Just to be clear, these are entirely separate statistics. I have never dated a U.S. president or a Beatle. And it goes without saying that no member of the Beatles could hold the office of U.S. president due to the requirement that this job go to a person born in the United States.

† I seem to recall hearing that this technique is also employed in some films, but I couldn’t find any research confirming it. It sounds cool though, right? I mean, correct?

‡ Please be reminded that this study examined only subjects who were naturally right-handed. And you should be grateful, as keeping track of what’s what with all this left/right business would have been doubly confusing had they also included left-handed individuals.

Where’s Species of the Month?

I’m glad you asked. Your favorite monthly dose of biodiversity has relocated to Earthsky.org, where it now goes under the name “Lifeform of the Week”. That means you get more articles, more often (and with more pictures) and I get less sleep. Everyone wins! Here are the first two posts (one is a reprint from this blog):

Tasmanian Devil

Banded Sea Krait

Tell your friends. Tell your enemies. Tell your shrink. Make me famous and I’ll buy you a drink someday. Just not one of those $15 "specialty cocktails". And not an appletini, those are just gross.

Indifferential Diagnosis #1: Visual Hallucinations

Welcome to a new feature in which we explore the various fascinating conditions that can cause various fascinating symptoms, kicking off today with visual hallucinations. Since the goal is curiosity, rather the actual medical utility, these won’t be exhaustive lists of causes. I will include only those conditions that I deem worthy of my time and yours. Additionally, I can’t promise that this feature will be delivered with monthly regularity. I was imagining a timeframe more along the lines of “whenever I feel like it”. That said, I would like to offer the last and most important disclaimer: I am not a doctor and indifferential is not a word. The rest of the information contained here is true to the best of my knowledge. Feel free to use it at dinner parties and when competing against computers on game shows.

A visual hallucination can be summarized as the perception of  an external image in the absence of any existing object. This is different from an illusion, in which one perceives a distorted view of one’s surroundings. Visual hallucinations can be simple (shapes and colors) or complex (vivid landscape or figures). Both categories vary not only in their causes, but also in their appearance, a variation that can at times provide insight into the source of the problem.

Schizophrenia

While many associate visual hallucinations with mental illness, this symptom is not particularly common in schizophrenia or other psychotic disorders. The bulk of hallucinations occurring in schizophrenia are auditory. When visual hallucinations do occur, they are generally complex and may involve humans, animals, and religious figures. The specific content of these visuals may have symbolic value to the person seeing them and are often threatening, or even hostile toward the viewer.

Tell-tale signs: Schizophrenia usually manifests with a host of other psychological symptoms – auditory hallucinations (often disparaging in content), delusions, and disorganized thought – that easily separate it from most of the other conditions we will be looking at.

Migraines

As you probably know, a migraine is a really, really, really bad headache. They can last hours to days and may be accompanied by light sensitivity, nausea and vomiting. If this weren’t bad enough, about a third of migraines commence with a phenomenon known as an “aura” that includes a hallmark visual hallucination. This starts with a simple, usually colorless, flickering and then proceeds to a zig-zag line that spreads from the center of the visual field outward, often leaving a vision-obscuring blotch (called a scotoma) in its wake. The good news is that this phase will be over in an hour or less. The bad news is that if will be followed by an excruciating headache.

Tell-tale signs: The horrible pain associated with a migraine is a pretty good give away as to the cause of this hallucination. Unless, of course, you suffer from…

…Occipital Lobe Seizures

The occipital lobe is the part of the brain where visual processing occurs, so it’s not surprising the electrical abnormalities in this region can cause visual hallucinations. Unlike the classic tonic-clonic (“grand mal”) seizure, which affects the entire brain and features loss of consciousness and convulsions, occipital lobe seizures are pretty subtle.* An observer of such an event may see nothing more than rapid fluttering of the eyelids. But to the person having the seizure, things look quite different. As with migraines, visual hallucinations attributed to this condition are simple and have a consistent design. They are brightly colored and dominated by many circular or spherical shapes. However, the lightshow is much shorter than that of the migraine aura, lasting no more than a few minutes. Despite striking differences in visual content and duration, occipital seizures are frequently mistaken for migraine auras. This is because up to half of such seizures are followed by headaches.

Tell-tale signs: If you’re lucky enough to have health insurance, epilepsy can often be confirmed with an expensive EEG. Just be sure to bring a hat, because they stick those recording electrodes right in your hair with some nasty gel that won’t come out until it’s shampooed.

Charles Bonnet Syndrome

And now we return to the realm of complex visual hallucinations. Charles Bonnet syndrome (CBS) is a condition in which subjects with impaired vision start seeing things. The hallucinations are vivid and elaborate and can involve figures and animals.† They tend to begin in the evening and can last for hours. CBS is most common in older people (possibly because their rate of failing eyesight is higher than the general population) and is unfortunately sometimes mistaken for age-related mental deterioration. However, unlike the complex hallucinations experienced by psychotic patients, these are strikingly lacking in symbolism and contain no special meaning to the people experiencing them.

Tell-tale signs: Oldness and/or near-blindness. Additionally, patients with this condition are perfectly aware that what they are seeing is not real and, aside from nagging doubts about the state of their sanity, generally do not find the hallucinations especially bothersome.

Sleep Disturbances

Didn’t I already cover this back in October? It’s true though, visual hallucinations can occur during transitions between waking and sleeping states of consciousness.

Tell-tale signs: It’s dark and/or you’re in bed.

Alcohol Withdrawal

With all due respect to the alleged horrors of opiate withdrawal, I must say that delirium tremens (aka the DTs) sounds utterly miserable. It occurs following the abrupt cessation of ethanol consumption after a long period of heavy drinking. Symptoms begin with the characteristic tremor and progress to include fever, confusion, agitation and, of course, visual hallucinations. In addition to being unpleasant, this particularly ugly variation of chemical withdrawal can be fatal. The hallucinations vary in duration (brief to almost continuous) and often involve animals. And these aren’t always cute cuddly animals, visions of snakes and insects have been reported by some patients. The severity of delirium tremens can be reduced with benzodiazepines (Klonopin and company), which ironically can also be habit-forming and feature similar withdrawal symptoms if discontinued too suddenly.

Tell-tale signs: Um, history of heavy drinking, shaking, etc. Really, this one sounds kind of hard to miss.

* Seizures that begin localized in one portion of the brain can spread to the rest of the organ, so those prone to occipital lobe seizures may also suffer from grand mal seizures.

† One patient reported seeing Highland cattle grazing in his living room.

Who told you this?

Teeple, R.C. et al. 2009. “Visual Hallucination: Differential Diagnosis and Treatment.” Prim Care Companion J Clin Psychiatry 11: 26-32.

Manford, M. and Andermann, F. 1998. “Complex visual hallucinations, Clinical and neurobiological insights.” Brain 121: 1819-1840.

Panayiotopoulos, C. P. 1994. “Elementary visual hallucinations in migraine and epilepsy.” J Neurol Neurosurg Psychiatry 57: 1371-1374.

Jacob, A. et al. 2004. “Charles Bonnet syndrome – elderly people and visual hallucinations.” British Journal of Medicine 328: 1552-1554.

Doctor’s Orders

Last month marked the 38^th anniversary of the United States Supreme Court decision in the case of Roe v. Wade, which established abortion as a woman’s fundamental right under the U.S. constitution. President Obama spoke on his support of the decision, asking Americans to, “recommit ourselves more broadly to ensuring that our daughters have the same rights, the same freedoms, and the same opportunities as our sons to fulfill their dreams.” Normally, I couldn’t have cared less about relaying such information here. As its name asserts, this blog deals with science. I try to avoid politics. It’s messy and uncouth. But sometimes politics worms its way into science and I am thus coaxed into acknowledging it.

Due to recent shifts in the political balance of power in this country, the abortion debate has been more front and center than usual. It has figured prominently in challenges to the health care act and is a popular topic in conservative rhetoric preparing for the next presidential election. But, as I said, I try to stick to science here. So I’m not going to write about how, in a country where 35% of women live in counties without a single abortion provider, state laws requiring in-person counseling followed by a 24-hour waiting period create an undue burden for lower-income women. Nor will I explain how excluding abortion coverage from federally funded health programs similarly punishes the poorest women, for whom the average $450 cost of a non-hospital abortion can be prohibitively high. These are matters of politics.

Instead, I will focus exclusively on the science behind certain states’ abortion policies. While federal law overrides any state laws banning abortion, states have the power to create some restrictions to abortion access. Often these take the form of waiting periods and parental consent for minors, but several states also have laws mandating that health care providers “inform” women seeking abortions of one or both of the following; A) that abortion increases their risk of developing breast cancer and B) that abortion can cause depression and other mental health problems. These are frightening things to be told and one would hope that lawmakers would not create these policies without good reason. But is there any evidence behind such claims? Well, it sort of depends on what you’re willing to accept as evidence.

DATA GATHERING*

The trouble with many of the studies on both of these alleged links is that they are correlation studies. Randomized controlled trials are the approach used in much of medical testing (efficacy of new drugs for instance), but it is considered unethical to randomly assign abortion/non-abortion outcomes to pregnancies in human subjects. The only way to examine something in which subjects rather than researchers makes such choices is by looking for correlations between two variables. For instance, are individuals diagnosed with lung cancer more likely to be life-long, heavy smokers than those without the disease? † Easy enough. However, you can’t actually infer causality from correlation. Such inferences can miss a third variable that is responsible for the other two. A favorite teaching example of this error is the conclusion that ice cream consumption causes drowning, because rates of both rise and fall in the same pattern. Of course, it is a third variable – hot weather – that increases both swimming (and therefore chance of drowning) and the interest in frozen desserts. Interpretation of correlation data can also mistake a symptom for a cause - for instance, the assumption that marriage counseling causes divorce. What is useful about correlation studies is that they can uncover relationships (or lack thereof) that suggest causality. But the only way to verify cause and effect is with actual experimentation.

Case-control vs. Cohort

In addition to the pitfalls of interpretation mentioned above, correlation studies also vary in format. In case-control studies, a group of people with a particular diagnosis (case subjects, such as women with breast cancer) are matched with another group without the diagnosis (control subjects, such as women without breast cancer) and both groups are reviewed for a variable that is a suspected link (such as reproductive history). A cohort study instead looks at a large population and records a variety of life-history information, and then examines the correlation between variables of interest. A cohort can be a group of individuals living in a particular country, or working in a particular profession, and so on. Often, multiple studies can be created from data gathered on one cohort. Cohort studies are considered to be more reliable than case-control studies.

Retrospective vs. Prospective

One of the reasons case-control studies can be inferior to cohort studies is that the former is generally retrospective, while the latter can be either retrospective or prospective. A retrospective study begins with the outcome (cancer) and looks backward in time to find the potentially correlating variable (reproductive history). Often this is done through interviews or questionnaires, which can be biased. Conversely, prospective studies start with the variable of interest and then follow a cohort to see if a particular outcome occurs. While they can be lengthy and expensive to conduct, prospective cohort studies are about as reliable as it gets in the world of correlation.

ABORTION AND BREAST CANCER

While sporadic research into a possible connection between breast cancer risk and reproductive factors goes back to the early 20^th century, interest in the effect of abortion really picked up during the 1980’s. Doing a literature search on the subject, one encounters a sea of contradictory conclusions, with some finding increased risk, others finding no correlation and some actually reporting decreased risk. As you may have guessed, much of this frenzied, first wave of research took the form of retrospective case-control studies. More recent prospective cohort studies have greater consistency in their results - usually finding no correlation between abortion and breast cancer.

Research interest in this subject was probably fueled in part by controversy over abortion, but it is not unreasonable to consider whether there might be a connection. There has been some indication that full-term pregnancies early in life confer protection against breast cancer. Conversely, pregnancy later in life (and, it turns out, post-menopausal hormone replacement therapy) can increase cancer risk. Since the hormones associated with pregnancy can have positive and negative repercussions, it is worth examining what effect an incomplete dose of these hormones would have on women’s health. But recall that not all incomplete pregnancies are the result of induced abortions. Spontaneous abortions (aka miscarriages) are another possible outcome of pregnancy. Interestingly, studies looking at spontaneous abortions generally find no correlation with breast cancer.

Why should induced abortion have greater correlation with breast cancer than does miscarriage? Well, now we come back to the problematic biases of the dreaded retrospective study. As you may have noticed, induced abortion carries with it more social stigma than miscarriage. Women who obtained abortions are thus more likely to omit this information than women who suffered miscarriages. Additionally, it has been suggested that the tendency to inaccurately report induced abortion history may differ in women who have and have not been diagnosed with breast cancer. Like many people with life-threatening diseases, women with breast cancer, hoping to provide accurate information that might contribute to disease cure or treatment, are more inclined to admit to having had an abortion. Healthy women lack this motivation for honesty. Thus, in retrospective studies, women with breast cancer may report a greater number of abortions not because their rate is actually higher than healthy women, but due to their greater willingness to disclose the information.

One way of getting around the problem of biased self-reported data is to rely exclusively on medical records. Several interesting cohort studies have been conducted using the handy national registries of Denmark. Unlike the U.S., Denmark provides its citizens with universal health care, and all such medical transactions (cancer diagnosis, mental health care, births, abortions, etc.) are logged into various registries. Information from the registries can be anonymously matched using numbers assigned by the Civil Registration System. A 1997 study published in The New England Journal of Medicine used the Danish registries to follow one and half million women. They found no correlation between induced abortion and breast cancer.

While the volume of correlations studies of this subject continues to increase, there is still a conspicuous absence of a demonstrated mechanism for how induced abortion might impact cancer development. Several pregnancy hormones have been associated with the cancer-protective benefits of pregnancy. One of these is human chorionic gonadotrophin (hCG), ‡ which actually peaks during the first trimester of pregnancy rather than lingering throughout like estrogen and progesterone. Since pregnancy hormones have been implicated in both increase and decrease of cancer risk, establishing a mechanism would be essential to demonstrating a link between abortion and breast cancer, particularly given the absence of any good correlation evidence pointing in that direction.

ABORTION AND DEPRESSION

Psychology can be a more nebulous field than cancer research, and so data gathering for depression presents additional challenges. However, there is one advantage. Unlike cancer, whose risk rises with age, many mental illnesses emerge during youth and persist throughout the course of patients’ lives. When examining a proposed causative link between abortion and depression, researchers at least have the luxury of looking at what their subjects’ state of mental health was like prior to an abortion or pregnancy. Stunningly, numerous studies opt not to gather such data. A 2008 study published in The Journal of Psychiatric Research reported a connection between abortion and incidence of various mood, anxiety and substance abuse disorders.§ However, the authors only looked at mental health status after abortion. Despite having no data on subjects’ psychiatric condition prior to abortion, and thus no reason to even suspect (much less proclaim) causality, they felt comfortable writing that, “…abortion is responsible for more than 10% of the population incidence of alcohol dependence, alcohol abuse, drug dependence, panic disorder, agoraphobia, and bipolar disorder…”.

The New England Journal of Medicine recently published a more thorough study on the alleged link between mental disorders and abortion. Once again, Demark’s national registries supplied data that was free from the possible biases of self-reported information. The cohort study looked at “psychiatric contact” – a visit to mental health professionals – in 2 groups of women; those undergoing abortions and those giving birth. Data were taken both before and after these reproductive events. The population of women who had abortions showed no significant change in rate of psychiatric contact afterward, while group of women who gave birth showed an increase in psychiatric visits. The latter should come as no surprise, since postpartum depression and its rarer cousin postpartum psychosis are well documented phenomena. While the study found no link between psychiatric contact increase and abortion, it did show a greater overall incidence of psychiatric contact (ie. both before and after) in the women who had abortions than in women who gave birth. Had the authors only gathered data only from after abortions and births, they too could have reported a link between abortion and psychiatric disorders. But seen in full context, the data suggest entirely different possibilities; such as that depressed women may be more likely to seek abortions. This study should cast doubt on correlation studies claiming to find a link between abortion and mental disorders but failing to include before and after data on mental health.

The New England Journal of Medicine study has its problems too. It does not, for instance, include data on women who neither gave birth nor had abortions. Additionally, taking data from the national registry rather than through interviews, it has no way of even attempting to separate wanted pregnancies from unwanted ones. It has been suggested that what is potentially stressful to emotional health is not abortion but the experience of an unwanted pregnancy. Some studies focusing on three categories of women – abortion, birth and no pregnancy – have reported that while women who obtained abortions had a higher incidence of mental health problems, it was those who never got pregnant in the first place that were the most psychologically healthy. The fact that women who gave birth fell somewhere in between the troubled abortion group and the emotionally stable non-pregnant group, might suggest that some of these births were the result of stressful unwanted pregnancies. Or alternately, it could indicate that more emotionally stable women are less likely to become pregnant unintentionally. Ah, the vagueness of correlation studies.

WHEN WORLDS COLLIDE

Science journalists often report on interesting new findings that are far from established facts, but it’s hard to think of any other subject for which isolated and contested data is converted into policy. Doctors advise us not to smoke and to reduce our consumption of saturated fat, but they shy away from recommending a daily dark chocolate supplement or herbal remedies with no demonstrated efficacy in clinical trials, and the government has yet to instruct them to do otherwise. There is no demonstrated link between abortion and either breast cancer or depression, and no reputable medical organization claims that such a links exist. And yet multiples states have opted to jeopardize the doctor-patient relationship by forcing health care providers to be deliverers of political ideology disguised as the protection of informed consent.

At no point in my reading did I encounter any single perfect study that addressed all variables and decisively established or refuted either of the anti-choice movement’s purported health risks of abortion. But one wouldn’t expect to find such a thing. That’s not how medical research works. However, one might expect to find numerous, well-designed and reasonably consistent correlation studies pointing the way to further lab-based research on possible mechanisms. And one might expect that, during this period, the research would not be presented to patients as proven and indisputable truths. And one would certainly expect that doctors would not be required by law to lie to their patients about these un-established risks, and that patients would not be required to lie to their doctors that they accepted and understood the confusing misinformation given to them. In short, one would expect less politics and more science.

* If you already know everything there is to know about research methodology, I encourage you to skip this section. And if you know even less than I’m giving you credit for, check out this useful glossary compliments of The British Medical Journal.

† In case you’re wondering, the answer is yes.

‡ hCG is what pregnancy tests are checking for and is also the prime suspect in the cause of “morning sickness” during pregnancy.

§ The data were taken from National Comorbidity Survey (NCS) interviews conducted in the early 1990s.

Who told you this?

Guttmacher Institute website: www.guttmacher.org (U.S. abortion statistics)

National Cancer Institute website: www.cancer.gov/cancertopics/factsheet/Risk/pregnancy

Henderson, K. et al. 2008. “Incomplete pregnancy is not associated with breast cancer risk: the California Teachers Study.” Contraception 77: 391-396.

Michels, K. B. et al. 2007. “Induced and Spontaneous Abortion and Incidence of Breast Cancer Among Young Women. A Prospective Cohort Study.” Arch Intern Med 167: 814-820.

Reeves, G. K. et al. 2006. “Breast cancer risk in relation to abortion: Results from the EPIC study.” Int. J. Cancer 119: 1741-1745.

Melby, M. et al. 1997. “Induced Abortion and the Risk of Breast Cancer.” The New England Journal of Medicine 336: 81-85.

Jacobson, H.I. et al. 2010. “A Proposed Unified Mechanism for the Reduction of Human Breast Cancer Risk by the Hormones of Pregnancy.” Cancer Prevention Research 3: 212-220.

Munk-Olsen, T. et al. 2011. “Induced First-Trimester Abortion and Risk of Mental Disorder.” The New England Journal of Medicine 364: 332-339.

Coleman, P. K. et al. 2009. “Induced abortion and anxiety, mood, and substance abuse disorders: Isolating the effects of abortion in the national comorbidity survey.” Journal of Psychiatric Research 43: 770-776.

Dwyer, J. M. and Jackson, T. 2008. “Unwanted pregnancy, mental health and abortion: untangling the evidence.” Australia and New Zealand Health Policy 5: 1-6.

Lazzarini,, Z. 2008. “South Dakota’s Abortion Script – Threatening the Physician-Patient Relationship.” The New England Journal of Medicine 359: 2189-2191.

Jasen, P.2005. “Breast Cancer and the Politics of Abortion in the United States.” Medical History 49: 423-444.