With little notice until recently, a shortage of medicine is starting to impair treatment at America’s hospitals. Common, cheap and necessary drugs needed to fight bacteria or cancer, to ease pain or to nourish premature infants are running out.

Many of these meds are injectables, which must be made under sterile conditions. All are generics, which sell for pennies compared to the buck-buster drugs that feed the bottom lines at the big-name drug companies.

Most shortages are unnanounced until a wholesaler’s shipment arrives lacking an ordered drug. “It’s unbelievable,” says Sara Shull, manager of the drug policy program at the University of Wisconsin Hospitals and Clinics in Madison. “Today I was trying figure out alternatives to papaverin,” an old drug used to prevent spasm in the many surgeries that involve grafting a blood vessel. “We have identified some alternatives, and I am now I working with the surgeon to figure out how to dose them, how to apply them. Is it bathed on? Sprayed on? He’s busy, we’re all busy, and sorting this all out takes a lot of time. The continual need to find replacements gives me a headache.”

Shortage-induced substitution played a role in Alabama, where nine hospital patients were killed by intravenous nutrients this summer, says Allen Vaida, executive vice president of the Institute for Safe Medication Practices, a non-profit that targets medicine hazards. “Because of a shortage, this compounding pharmacy was making a product from raw material, and it got a bacterial contamination.” (The maker of the nutrient solution, Meds IV pharmacy in Birmingham, Ala., is apparently out of business.)

Medications on this rack will restock a robot that fills individual patient envelopes that will be sent tomorrow to nurses’ stations in the hospital. Actually, the robot restocks itself in its 24/7 delivery of thousands of prescription drugs.

Photo: The Why Files

ENLARGE

Source: U.S. House of Representatives

Shortages are growing, especially for injectable medicines.

Running long on shortages

Pharmacists have always had to find substitute medicines, as patients keep coming through the door, but Vaida cites Food and Drug Administration numbers to argue that shortages are now at “crisis” proportions. “The FDA shows 70 shortages in 2006, 129 in 2007 and last year, there were 211. So far this year, we are already above 200 shortages, and the year isn’t done. Shortages have been around forever, but they have never reached this number.”

Some drugs can be substituted, says Vaida, but “especially with chemotherapy and nutritional products, it’s not like are three alternatives for some medications, as there are with blood-pressure drugs. Some chemotherapies are specific for certain cancers, and if they are not available, you may have no alternative or [you] may have to use a third-line alternative.”

The pharmaceutical situation has never been more complicated, with more than 45,000 prescription drug products on the market, from about 1,400 manufacturers. Although we could not easily find numbers, drug shortages are also rising in the United Kingdom, where the supply situation is complicated by the restriction on exports within the European Union.

Shortages have many possible causes, but because manufacturers tend to be closed-mouthed, it’s not clear which problems are most momentous or easiest to solve:

How short is short?

A drug is considered “short” if a specific dosage and formulation is unavailable, and in some cases, a similar item can be substituted. But Shull says that’s still a problem in a big hospital. If a product that is normally purchased in a pre-loaded syringe is only available in a vial, University of Wisconsin Hospitals and Clinics can no longer send a “unit of dose” to the nurse, and “that’s what the nurses are expecting,” Shull says.

Changing procedures complicate care and raise costs, Shull adds. “All our people are working in a complex system, with lives on the line. These shortages can be a recipe for increased errors.” Her hospital must dedicate one staffer to securing supplies of the common blood-thinner heparin, she says. Searching for alternate sources is less rewarding than studying the efficacy of various medication treatments, she adds. “It’s not what I was taught in pharmacy school, but when your back is up against the wall, you have no other options.”

Beyond impairing patient care, shortages have also become a major burden in medical research. Tests of new medicines, often set up to run at several hospitals nationwide, must give standardized meds to the treatment and control groups, and chaos can result when the drugs become unavailable. “These shortages are now affecting clinical trial options for patients with cancer,” Robert DiPaola, director of the Cancer Institute of New Jersey, told the House Energy and Commerce Subcommittee on Health on Sept. 23. “Due to the uncertainty of being able to obtain many of these drugs, enrollment of patients on clinical trials has been delayed or stopped in several of our trials.”

Howard Koh, assistant secretary of health and human services, reinforced that message to the committee: “Many of the cancer drugs in short supply … are mainstays of the anti-cancer arsenal, and were largely developed through federally funded research begun 20, 30, even 40 years ago. They are still essential to treatment and research,” he said. The National Cancer Institute is currently sponsoring 349 clinical trials that require these drugs, Koh added. “Taken together, these studies represent thousands of patients, as well as a significant federal investment in clinical trials research.”

At the same hearing, Mike Alkire, chief operating officer of Premier healthcare alliance, told Congress how widespread the shortages have become. In a recent Premier survey, 53 percent of hospital pharmacists said they had faced at least six shortages “that had the potential to cause a medication safety issue or an error in patient care.” And 34 percent of respondents said at least six shortages had “resulted in a delay or cancellation of a patient-care intervention.”

Premier estimates that the 2,500-plus non-profit U.S. hospitals in its membership pay an extra $66 million per year due to these shortages — which translates to $415 million at all U.S. hospitals.

Market going gray?

When the usual sources run dry, hospital pharmacists often get emails, faxes and phone calls from the “gray market,” sources outside the usual supply chain. In the summer of 2011, the Institute for Safe Medication Practices surveyed 549 hospitals and found that:

Alkire, of the Premier alliance, told Congress that the gray market is “appalling,” with an average markup of 650 percent. Forty-five percent of the offers were marked up at least 1,000 percent above normal price, and drugs for leukemia and non-Hodgkin’s lymphoma were marked up 4,000 percent. “We saw similar markups for medicines for sedation during surgeries; to dilate veins and prevent brain or heart spasms; and to prevent damage during a heart attack,” Alkire said.

For these reasons, University Hospital at UW-Madison does not buy gray, says Shull, although it does buy from a wholesaler that seems to have supplies of drugs when nobody else does.

The gray market arouses suspicion: How do some firms know about shortages before anybody else? How do they obtain drugs when normal sources are short?

“There is speculation going on,” says Vaida. “Some secondary wholesalers may try to buy up some available drugs and sell them for higher prices. Often times, they are looking for people who need the product, and try to obtain it from whatever sources. Some are playing it almost like Wall Street, anticipating what may go on shortage — if two manufacturers have just consolidated, and there’s a generic product that is only going to be made by one of them.”

Cures for missing meds

Many measures have been proposed to ease the medication shortage:

Photo: Armin Kübelbeck

Generic, injectable drugs comprise the majority of shortages.

The FDA seems to be getting the message. In testimony to the subcommittee on Sept. 23, Koh claimed that the agency had already headed off 99 looming shortages in 2011, compared to 38 for all of 2010. But Koh added that today’s shortages “include standard therapies for the treatment of lung, breast, ovarian, testicular and colorectal cancers, as well as several types of lymphomas and leukemias.”

Sometimes, Koh said, common-sense, proven measures can sidestep shortages. “… the FDA was able to mitigate a shortage by allowing the use of a filter to safely remove foreign particles contained within vials of injectable drugs, averting the obvious risk to patients of having metal shavings or other particulate matter injected into their veins.”

A pessimist, of course, could say the higher number of averted shortages simply reflects the greater number of shortages overall.

At any rate, organizations concerned with shortages say they are in a vise. “From our members’ perspective, it’s become [a] crisis,” says Hill. “We are seeing shortages nationwide. We have been tracking this for about 10 years, but in the last few years, we’ve seen a spike in the numbers.”

Given the problem’s multiple and sometimes obscure, roots, Hill sees “no single solution, and that’s the troublesome part. Unfortunately we will be dealing with this for a while. But there are some things we can do. We’d like to establish a mandatory early-warning system, so a manufacturer that has a problem has to notify the FDA. The FDA says it has avoided 99 shortages in the past year when it had that information. When there are multiple sources, the FDA can reach out to other manufacturers and urge them to ramp up production.”

David J. Tenenbaum

Each year, as influenza season approaches, medical authorities must scramble to predict which strains of flu will be most important, and then to grow enough vaccine to inoculate the population. Why does this take so much time, and what are some alternative strategies that might speed the process?

Find the article:

Flu vaccine shortage

Discussion Questions

1. Discuss: How does the influenza virus benefit from having so many strains?
2. What are the key steps in the process for identifying and making flu vaccine?
3. How have scientists proposed to speed up this process?
4. What is the meaning of the “H” and “N” in the virus designations, and how do they help explain the activity of a virus?
5. How is a virus different from a bacterium?
6. Why is influenza so deadly in some years, and not others?

Lesson Plans/Activities

1. Bird flu, swine flu, ferret flu? The flu can be spread between all sorts of creatures. Explore the NCBI Influenza database to find out what kinds of animals have been the source of flu outbreaks. What factors cause diseases to spread from animals to humans?
2. Facebook status: Outbreak! Follow this lesson plan that teaches about epidemiology and contagious diseases using social media.
3. The flu through time. Have students research previous flu pandemics, such as the deadly 1918 outbreak. Have students identify the similarities and differences between these pandemics, including the specific strains of the flu and the symptoms they produced. Aside from vaccines, how can people help prevent the spread of the flu?

You see them, and you sniff. Apples are as boring, as generic as a fruit can get. They lack the cachet of red grapes, oozing life-extending resveratrol. Unlike blueberries or pomegranates, they are not celebrated for supplying palate-pleasing megadoses of antioxidants.

So why did some wit observe, “An apple a day keeps the doctor away”? That question has been on the mind of Bahram Arjmandi, professor and chair of the department of nutrition, food and exercise sciences at Florida State University.

His answer, presented at the Experimental Biology 2011 meeting in Washington this week, admittedly seems too good to be true: Apples have a profound effect on total cholesterol, and also on the “good” and “bad” types of cholesterol. They caused a major reduction in inflammatory proteins that are implicated in a number of serious diseases.

Not only does this “medicine” taste good, but unlike cholesterol-control pills, it does not attack the liver. And last we heard, you can buy them without a prescription.

“An apple a day” or a “fateful fruit”?

In the Bible, “the apple was an evil food in the story of Adam and Eve,” Arjmandi says, “then someone said, ‘An apple a day…’ and that gave them a positive image. I thought, if there is that saying, there might be a reason for it, but you’d be amazed at how little has been done in clinical studies.”

Animals were apparently eating apples long before Adam and Eve. Photo: LASZLO ILYES

To get answers, Arjmandi rounded up 100 women who had just passed menopause — a time when dropping levels of estrogen lead to unhealthy changes in cholesterol levels that allow women to catch up with the male rate of cardiovascular disease.

Randomly dividing his volunteers, Arjmandi asked one group to supplement their normal diet with dried prunes. The treatment group got one-a-day packages containing 75 grams — about 2.5 ounces — of dried apple.

Arjmandi used dry apples rather than the equivalent one or two fresh apples as a way to standardize the “dose,” but he says fresh fruit is likely to be even more healthy.

If the object of these tests was a pill, the results after one year would certainly boost the stock of the drugmaker: among the apple-eaters, total cholesterol fell by 14 percent and low-density lipoprotein (LDL, the harmful fraction of cholesterol) fell 23 percent. High levels of both total cholesterol and LDL are linked to damage to blood vessels, heart attacks and strokes.

Meanwhile, the level of a protective type of cholesterol called high-density lipoprotein (HDL) rose 3 to 4 percent.

(Anti-) inflammatory results

Moving beyond cholesterol, the level of C-reactive protein fell 32 percent. “This is significant, and not just in a statistical sense but in clinical relevance,” says Arjmandi. “CRP is associated with inflammation, and is considered a marker for cardiovascular disease, cancer and Alzheimer’s disease.”

Does 'an apple a day...' translate into Japanese? Photo: Luca Moglia

Seeing such a major reduction from such a simple “treatment” is “amazing,” Arjmandi said.

And although the women in the test group were eating about 240 calories of dry apple each day, they lost an average of about three pounds over the year — perhaps because apple makes people feel full.

The study was partly funded by the United States Department of Agriculture, and got no funding from the apple industry. Although the report, as far as we know, has not been peer reviewed, talks at scientific meetings are routinely used to introduce new studies and new concepts.

And the active ingredient is…

What makes apples so healthy? Although both pectin, a soluble fiber, and chemicals called polyphenols are thought to confer health benefits, Arjmandi says, “an apple is more than these compounds. I’ve been working on functional foods [which give health benefits] for 20 years, and I find it’s not good to approach whole fruit or whole vegetables like drugs. If you isolate the component chemicals and take them, you get some benefits, but you will deprive yourself of greater benefits.”

Are some apples better than others? “For pectin, the firmer the better,” says Arjmandi. “Otherwise, most varieties, from jonathan to red delicious, give more or less the same benefit.”

Polyphenols are concentrated in the peel; pectin is found throughout the apple, he adds.

Last question: Did the study participants get sick of snacking on dry apple day after day? Some did, and quit the study, but “those who like them became addicted,” says Arjmandi. “The longer they were on it, the more they liked apple. Afterwards, some contacted us to ask if we can provide them with apple.”

Supermarkets, actually, carry apples side-by-side with other non-prescription produce.

Based on these results, Arjmandi would like to test the apple-a-day prescription more broadly. “I’d like to do a multi-state trial. Eating 75 grams of apple is not that difficult, and finding people with moderately high cholesterol is not that difficult.”

– David J. Tenenbaum

Step on a jetliner. Sit in a doctor’s waiting room. Take your kid to day care. If it’s flu season, we’re wagering you’re wondering: Am I inhaling enough influenza virus to get sick?

“Yes, if you stick around for an hour.” That’s our bare-bones summary of a new measurement of airborne influenza A virus in these three locations. The study calculated how long virus particles would remain aloft and therefore be subject to inhalation.

Influenza A is the most common and dangerous genus of influenza virus.

Bigger particles can carry more virus, but they also settle far faster than tiny ones.

Among the half of the samples that contained influenza A, the average cubic meter of air contained 16,000 influenza A particles. Since we breathe roughly one liter per inspiration, this means that when influenza is present, one would inhale 16 pieces of flu virus with each breath.

Breathing that air for an hour would be enough to make half of us sick, says Linsey Marr, an associate professor of civil and environmental engineering at Virginia Tech, the study’s corresponding author.

The study sorted the flu-carrying aerosol particles by size, Marr says, which “allows us to say how long the virus particles will stay suspended in the air. We found virus in aerosols small enough to remain suspended for hours.”

About 64 percent of the virus particles were held in aerosols no more than 2.5 millionths of a meter across.

Because few previous studies of influenza A measured the size of the aerosols that carried them, Marr says, “We did not know if they were held in very large droplets that would fall out in a few seconds or minutes,” and thus be less likely to transmit disease.

Understanding the movement of influenza became critical in the late 1990s, when deadly avian influenza arose in Southeast Asia, and again after the 2009 “swine flu” epidemic.

Photo: June 2009, Roger Schultz

Passengers flying from Washington to Buenos Aires during the swine flu epidemic hoped masks could intercept the virus.

Virus: Just another pollutant?

Marr, an air-pollution engineer who says she became interested in viral transmission after her three-year-old came home sick from day care “about every two weeks,” says hunks of influenza A virus are about one-tenth of a micron across, and thus difficult to identify.

Using a version of polymerase chain reaction that detects viral RNA, Marr and her collaborators, including Elankumaran Subbiah, an assistant professor of virology at the Virginia-Maryland Regional College of Veterinary Medicine, examined air samples during flu season.

Half of the samples were influenza free, a strong indication that nobody in the area had the flu. But when influenza A was present, the researchers calculated that the air would contain enough to infect 50 percent of the people after one hour, Marr says.

Such an estimate is necessarily rough, as many factors can affect the health consequences of any exposure to the virus:

“We detected total virus RNA, but that does not tell us whether the particles are infectious,” says Marr, since they could have been inactivated due to ultraviolet light or another cause. Previous studies, many of them decades old, suggest that influenza A can remain infective for two to three hours, but those estimates vary widely, Marr says.

Furthermore, although in general smaller particles can go deeper, and cause more disease, the body is also “pretty good at removing virus in the nasal tract,” she points out.

Making sense

“The research is an important step in better understanding the nature of influenza transmission,” says Jonathan Temte, a professor of family medicine at University of Wisconsin-Madison, and a specialist on immunization. “Influenza continues to be a very significant respiratory pathogen which can spread significantly and almost without abatement, especially when there is little immunity such as we saw during the pandemic of influenza A(H1N1) last year.”

However, Temte says, “This study is limited” because it relied on only 16 air samples, and was performed “when there was almost no transmission of influenza in North America. Hence, the researchers were able to detect influenza at a time when very few individuals were getting sick. From a clinician’s viewpoint, it is necessary to show that viable influenza viruses can be carried in an airborne form and that transmission can occur in this mode and this occurs at a high enough rate to be of significance.” Although the study is an interesting application of technology, “Making the translation from technology to real patient care in the next and necessary step,” Temte says.

Now that the study has confirmed with measurement what we’ve long known — that flu virus can float in the air — we wondered whether we are more likely to catch flu by breathing or by touching our schnozz after shaking hands with an infected person. The answer is not yet clear, says Marr, “but we have showed that the airborne aerosol route is possible.”

Will this intensify fear of flying? Perhaps. “This fear has always been there — if someone is sick, it’s possible that virus is floating around,” says Marr. Face masks could help contain influenza, “But without a proper fit, you short-circuit the mask, and it doesn’t do much good. What would be even better is if infected people wore masks….”

– David J. Tenenbaum

Hangover: Getting to the root of pain

You survived Christmas. Next up: the annual guzzl-a-thon — New Year’s Eve. Will you start the new year with a massive hangover?

Hangovers are an aftershock of acute alcohol intoxication, meaning you get them while recovering from a serious bout of drinking. The symptoms, including headache, nausea, sensitivity to light and noise, lethargy, diarrhea and thirst, often strike people who are already wallowing in self-pity.

Physiology offers explanations: Alcohol causes dehydration. Liver enzymes convert ethanol to the more toxic acetaldehyde. Less glucose reaches the brain, adding to lethargy.

A preventable condition

Short of abstinence, there are ways to reduce hangover. Food, especially fats, slow alcohol absorption, if the food enters the stomach first. James Garbutt, a professor of psychiatry and alcoholism specialist at the University of North Carolina at Chapel Hill, suggests eating a meal before your first drink, and then nibbling through the evening.

Drinking a glass of water between each drink can also cut consumption.

The next morning, Garbutt advises treating the headache with ibuprofen (not aspirin or acetaminophen), and drinking water or a sports drink to restore fluids and electrolytes.
Beyond that, you are on your own: According to a 2005 review¹: “No compelling evidence exists to suggest that any conventional or complementary intervention is effective for preventing or treating alcohol hangover.”

Photo: As Heard From Mars

Think this bloke’s head will be on fire when he wakes from his stupor?

The science of the hangover

Still, The Why Files did track down some cool hangover science:

A good teaching tool? Because that morning of misery is a built-in disincentive to drink, hangovers seldom attract research funding. But a recent survey² of 303 college students chilled the notion that hangover is a good preventative like ice in a shot glass: “The students significantly overestimated the number of drinks it would take to vomit, have unwanted sexual experiences, experience hangovers, and black out in comparison with the actual self-reported number of drinks consumed the last time identical consequences were experienced.” If you tossed your cookies after five drinks, but thought you could absorb 10 next time, what have you learned?

Image from: Innocorp

Cops and health educators use these goggles to dissuade teens from drinking and driving.

Hangover scale: Filling a scientific gap, in 2007, researchers from Brown University³ crafted the “acute hangover scale” to measure the next-morning blues in American college students, recent graduates, and Swedish marine officers (all folks who know which way the bottle tilts). The researchers found that “Do you have a hangover?” was the best single question for identifying hangover, even better than questions about thirst and headache. Why bother? The new scale could help distinguish hangover from other addictive effects of alcohol, the authors explained.

Take the asparagus cure: In 2009, Korean scientists reported that components of asparagus can protect the liver against oxidative stress of alcohol. According to B.Y. Kim of Jeju National University, “These results provide evidence of how the biological functions of asparagus can help alleviate alcohol hangover and protect liver cells.” No word on whether asparagus has a drinking problem … and unfortunately, the leaves, not the shoots that we eat, offered the best protection.

You can’t detect a drunken fruitfly with a breathalyzer, but an inebriometer works just dandy.

Hangover is stupid! A large study⁴ from Scotland found that dumb kids — okay, 11-year-olds with a lower IQ — were more likely to have hangovers in middle age. So, you wonder? Because hangover is a good measure of binge drinking, “This finding may at least partially explain the link between early life IQ and adult risk of mortality ascribed to all causes, cardiovascular disease and, particularly, alcohol related morbidity,” the authors say.

Drunken fruitflies:

A recently discovered⁵ “hangover” gene in fruitflies increases their tolerance to alcohol (when measured, you can’t make this up, in the “inebriometer.”) Because alcohol tolerance is a risk factor for alcoholism, the gene may do something more than just cause headache. Do fruitflies feel queasy the morning after the night before?

The final word

If you drink, drink safe and drink smart. And never, ever overindulge and drive.

And happy New Year from The Why Files!

Urp.

– David J. Tenenbaum

Semi-starve a rat, monkey or yeast, and it’s likely to outlive its free-feeding friends. It’s weird but true: caloric restriction produces longer, healthier lives, although people who restrict their calories do report feeling cold, listless and a certain obsession with food.

But here’s the billion-dollar question: Why does cutting calories by roughly 30 percent produce such benefits if the rest of the diet is sufficient? The best answer is that the lo-cal regime reduces free radicals — molecules and fragments that damage genes, fats and proteins.

A better understanding of this radical-reduction mechanism could support drug discovery. Not to over-dramatize, but the Holy Grail of this research is to find a shortcut to the many benefits of caloric restriction while avoiding that void in the pit of the stomach.

In a study published today in the journal Cell, scientists firmly identified the gene Sirt-3 as essential to some of the benefits of caloric restriction. Sirt-3 is among a group of genes that were already associated with anti-oxidant mechanisms.

Proof in the pudding

“This study is the first direct proof for a mechanism underlying the anti-aging effects we observe under caloric restriction,” says Tomas A. Prolla, a professor of genetics at the University of Wisconsin-Madison, and a senior author of the new study. “We’re getting closer and closer to a good understanding of how caloric restriction works.”

Aging is as hard on mice as it is on people. Both these mice are the same age, but the one in front was genetically engineered to age rapidly for a study led by Tomas Prolla. Photo: Jeff Miller/University of Wisconsin-Madison

The study focuses on mechanisms that control free radicals produced by mitochondria, units in cells that process chemicals so cells can move and perform chemical reactions. Because mitochondria also produce free radicals, the very mechanism that keeps us going in the short run also spells doom in the long run.

But cells have also evolved anti-oxidant mechanisms to defang free radicals, and caloric restriction may be the best way to trigger those defenses.

Bring on the mice

The Cell study focused on age-related hearing loss, a common problem caused by cellular suicide among sensory cells in the inner ear. The scientists compared a control group, which reliably has this loss, to another that lacked the Sirt-3 gene.

Starting at age two months, the mice either stayed on the normal lab diet, or got a 25 percent reduction in calories. At two and 12 months, the mice got hearing tests. As expected, at 12 months, the normal-diet mice, but not the caloric restriction mice, had lost some hearing.

But check this out: the hungry mice without the Sirt-3 gene got absolutely no benefit from the low-cal diet.

The finding was clear, says John Denu, of UW-Madison’s Wisconsin Institute for Discovery. “Caloric restriction no longer prevents age-dependent hearing loss in mice that do not have Sirt-3, and there is thus a clear link between this protein and prevention of age-dependent hearing loss.”

And because hearing loss is considered a legit indicator of the anti-oxidant power of caloric restriction, the study shows that Sirt-3 plays an essential role in the only proven way to retard aging.

Links in the chain

Looking further, the researchers, who included Wei Yu in Denu’s lab and Shinichi Someya in Prolla’s research group, found that Sirt-3 activates an enzyme inside the mitochondria that also participates in a chain reaction that makes the crucial anti-oxidant glutathione, which destroys free radicals.

Even the yeast that fermented this beer live longer if raised under caloric restriction. Photo: cyclonebill

Caloric restriction has many effects, and many genes and proteins are likely to be involved, but Sirt-3 is the first gene proven essential to preserving age-related hearing loss, says Denu, a professor of biomolecular chemistry. “In the mouse, Sirt-3 is one part of the solution.”

Now that Sirt-3 is known to play an essential role, the search is on for a drug that can stimulate it. Finding a key link in caloric restriction is inherently interesting, but the new results may help capture the benefits of caloric restriction, such as better hearing and a longer lifespan, without the pit-of-the-stomach price.

A second approach would be to artificially induce the Sirt-3 stimulating mechanism that caloric restriction uses.

These questions become more pressing now that Sirt-3 is known to be crucial to some of the metabolic benefits of caloric restriction, Denu adds.

Which is just as well, considering that few people can successfully cut calories by 25 percent. “In American culture, it’s more palatable to take a pill than chronically starve yourself,” Denu observes.

We concur. And as the feasts of Thanksgiving approach, we can only say, “Amen. And pass the stuffing!”