Archive for December, 2013

Supplements Tied to Liver Failure

Sunday, December 29, 2013 // Uncategorized

Just because something is “Natural” and available over the counter doesn’t mean that it is safe as this recent article from the New York Times shows.

The New York Times


December 21, 2013

Spike in Harm to Liver Is Tied to Dietary Aids



<When Christopher Herrera, 17, walked into the emergency room at Texas Children’s Hospital one morning last year, his chest, face and eyes were bright yellow — “almost highlighter yellow,” recalled Dr. Shreena S. Patel, the pediatric resident who treated him.

Christopher, a high school student from Katy, Tex., suffered severe liver damage after using a concentrated green tea extract he bought at a nutrition store as a “fat burning” supplement. The damage was so extensive that he was put on the waiting list for a liver transplant.

“It was terrifying,” he said in an interview. “They kept telling me they had the best surgeons, and they were trying to comfort me. But they were saying that I needed a new liver and that my body could reject it.”

New data suggests that his is not an isolated case. Dietary supplements account for nearly 20 percent of drug-related liver injuries that turn up in hospitals, up from 7 percent a decade ago, according to an analysis by a national network of liver specialists. The research included only the most severe cases of liver damage referred to a representative group of hospitals around the country, and the investigators said they were undercounting the actual number of cases.

While many patients recover once they stop taking the supplements and receive treatment, a few require liver transplants or die because of liver failure. Naïve teenagers are not the only consumers at risk, the researchers said. Many are middle-aged women who turn to dietary supplements that promise to burn fat or speed up weight loss.

“It’s really the Wild West,” said Dr. Herbert L. Bonkovsky, the director of the liver, digestive and metabolic disorders laboratory at Carolinas HealthCare System in Charlotte, N.C. “When people buy these dietary supplements, it’s anybody’s guess as to what they’re getting.”

Though doctors were able to save his liver, Christopher can no longer play sports, spend much time outdoors or exert himself, lest he strain the organ. He must make monthly visits to a doctor to assess his liver function.

Americans spend an estimated $32 billion on dietary supplements every year, attracted by unproven claims that various pills and powders will help them lose weight, build muscle and fight off everything from colds to chronic illnesses. About half of Americans use dietary supplements, and most of them take more than one product at a time.

Dr. Victor Navarro, the chairman of the hepatology division at Einstein Healthcare Network in Philadelphia, said that while liver injuries linked to supplements were alarming, he believed that a majority of supplements were generally safe. Most of the liver injuries tracked by a network of medical officials are caused by prescription drugs used to treat things like cancer, diabetes and heart disease, he said.

But the supplement business is largely unregulated. In recent years, critics of the industry have called for measures that would force companies to prove that their products are safe, genuine and made in accordance with strict manufacturing standards before they reach the market.

But a federal law enacted in 1994, the Dietary Supplement Health and Education Act, prevents the Food and Drug Administration from approving or evaluating most supplements before they are sold. Usually the agency must wait until consumers are harmed before officials can remove products from stores. Because the supplement industry operates on the honor system, studies show, the market has been flooded with products that are adulterated, mislabeled or packaged in dosages that have not been studied for safety.

The new research found that many of the products implicated in liver injuries were bodybuilding supplements spiked with unlisted steroids, and herbal pills and powders promising to increase energy and help consumers lose weight.

“There unfortunately are criminals that feel it’s a business opportunity to spike some products and sell them as dietary supplements,” said Duffy MacKay, a spokesman for the Council for Responsible Nutrition, a supplement industry trade group. “It’s the fringe of the industry, but as you can see, it is affecting some consumers.” More popular supplements like vitamins, minerals, probiotics and fish oil had not been linked to “patterns of adverse effects,” he said.

The F.D.A. estimates that 70 percent of dietary supplement companies are not following basic quality control standards that would help prevent adulteration of their products. Of about 55,000 supplements that are sold in the United States, only 170 — about 0.3 percent — have been studied closely enough to determine their common side effects, said Dr. Paul A. Offit, the chief of infectious diseases at the Children’s Hospital of Philadelphia and an expert on dietary supplements.

“When a product is regulated, you know the benefits and the risks and you can make an informed decision about whether or not to take it,” he said. “With supplements, you don’t have efficacy data and you don’t have safety data, so it’s just a black box.”

Since 2008, the F.D.A. has been taking action against companies whose supplements are found to contain prescription drugs and controlled substances, said Daniel Fabricant, the director of the division of dietary supplement programs in the agency’s Center for Food Safety and Applied Nutrition. For example, the agency recently took steps to remove one “fat burning” product from shelves, OxyElite Pro, that was linked to one death and dozens of cases of hepatitis and liver injury in Hawaii and other states.

The new research, presented last month at a conference in Washington, was produced by the Drug-Induced Liver Injury Network, which was established by the National Institutes of Health to track patients who suffer liver damage from certain drugs and alternative medicines. It includes doctors at eight major hospitals throughout the country.

The investigators looked at 845 patients with severe, drug-induced liver damage who were treated at hospitals in the network from 2004 to 2012. It focused only on cases where the investigators ruled out other causes and blamed a drug or a supplement with a high degree of certainty.

When the network began tracking liver injuries in 2004, supplements accounted for 7 percent of the 115 severe cases. But the percentage has steadily risen, reaching 20 percent of the 313 cases recorded from 2010 to 2012.

Those patients included dozens of young men who were sickened by bodybuilding supplements. The patients all fit a similar profile, said Dr. Navarro, an investigator with the network.

“They become very jaundiced for long periods of time,” he said. “They itch really badly, to the point where they can’t sleep. They lose weight. They lose work. I had one patient who was jaundiced for six months.”

Tests showed that a third of the implicated products contained steroids not listed on their labels.

A second trend emerged when Dr. Navarro and his colleagues studied 85 patients with liver injuries linked to herbal pills and powders. Two-thirds were middle-aged women, on average 48 years old, who often used the supplements to lose weight or increase energy. Nearly a dozen of those patients required liver transplants, and three died.

It was not always clear what the underlying causes of injury were in those cases, in part because patients frequently combined multiple supplements and used products with up to 30 ingredients, said Dr. Bonkovsky, an investigator with the network.

But one product that patients used frequently was green tea extract, which contains catechins, a group of potent antioxidants that reputedly increase metabolism. The extracts are often marketed as fat burners, and catechins are often added to weight-loss products and energy boosters. Most green tea pills are highly concentrated, containing many times the amount of catechins found in a single cup of green tea, Dr. Bonkovsky said. In high doses, catechins can be toxic to the liver, he said, and a small percentage of people appear to be particularly susceptible.

But liver injuries attributed to herbal supplements are more likely to be severe and to result in liver transplants, Dr. Navarro said. And unlike prescription drugs, which are tightly regulated, dietary supplements typically carry no information about side effects. Consumers assume they have been studied and tested, Dr. Bonkovsky said. But that is rarely the case. “There is this belief that if something is natural, then it must be safe and it must be good,” he said.

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Sex as Exercise?

Tuesday, December 17, 2013 // Uncategorized

Yes.  It is the equivalent of walking up a hill.  The question is, how long can you do it?

New York TimesDecember 6, 2013

Sex as Exercise: What are the Benefits?


View Original Article

This article appeared in the Dec. 8, 2013 issue of The New York Times Magazine

As far back as the 1950s, couples have been asked to strap on monitors, blood-pressure cuffs, oxygen masks and other paraphernalia and copulate, to scientifically quantify the impacts of sex. The focus is often on whether sex can kill you by precipitating a heart attack. Happily, these studies generally show that heart rates rise during intercourse, but tolerably. In a 2008 study, middle-aged subjects’ heart rates jumped at the point of orgasm by only 21 beats per minute in men and 19 in women, about the same response as if they’d just done a few jumping jacks. The risk for sex-related cardiac arrest is, in fact, vanishingly small, statistics show, though it may be greater when the act is extramarital.

The issue of sex as exercise, however, has remained largely unexplored. “There are these myths,” including that sex burns at least 100 calories per session, said Antony D. Karelis, a professor of exercise science at the University of Quebec at Montreal who undertook a study, published in PLOS One in October, to look at how much energy is actually exerted during sex. “But nobody had tested” those assumptions.

To do so, Karelis and his colleagues recruited 21 young heterosexual committed couples from the local area and had them jog on treadmills for 30 minutes, while researchers monitored their energy expenditure and other metrics, in order to provide a comparison for the physical demands of sex. The scientists next gave their volunteers unobtrusive armband activity monitors that gauge exertion in terms of calories and METs, or metabolic equivalent of task, a physiological measure comparing an activity to sitting perfectly still, which is a 1-MET task. Then the scientists sent the couples home, instructing them to complete at least one sex act a week for a month while wearing the armbands, and to fill out questionnaires about how each session made them feel, physically and psychologically, especially compared with running on the treadmill.

When the researchers analyzed all of the resulting data, it was clear, Karelis said, that sex qualified as “moderate exercise,” a 6-MET activity for men and 5.6-MET activity for women. That’s the equivalent, according to various estimates, of playing doubles tennis or walking uphill. The jogging, by comparison, was more strenuous, an 8.5-MET activity for the men in the study and 8.4 for women. (Though some men, according to their activity monitors, used more energy for brief periods during sex than they did jogging.) The sex also burned four calories per minute for men and three per minute for women, during sessions that ranged from 10 to 57 minutes, including foreplay. (The average was 25 minutes.) Men burned about 9 calories per minute jogging and women about 7.

Over all, the data reveal that “sex can be considered, at times, a significant exercise,” Karelis said, worth encouraging in people who otherwise balk at working out. Ninety-eight percent of Karelis’s volunteers reported that sex felt more fun than jogging. The other 2 percent, I suspect, will be back in the dating market soon.

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Is There an Optimal Time to Drink Coffee?

Monday, December 16, 2013 // Uncategorized

One of my patients asked me about this post.  It amounts to some interesting musings on chronopharmacology.  Most of the time when one reads about chronopharmacology it involves timing of medication for optimal effect.  This is the first that I’ve read about timing of drinking coffee.

Wednesday, October 23, 2013

The best time for your coffee

Ever wonder what the best time is to drink your coffee? You probably know it is not a good idea to drink part of your daily dose of caffeine in the afternoon. Especially for those who have problems sleeping. But, do you ever drink your coffee and feel like it just didn’t work? I know I have that feeling sometimes. The explanation for this has to with a concept that I think is extremely interesting but rarely discussed: chronopharmacology.

Chronopharmacology can be defined as the study of the interaction of biological rhythms and drug action. One of the most important biological rhythms is your circadian clock. This endogenous 24 hour clock alters your physiology and behavior in variety of ways but it can also alter many properties of drugs including drug safety (pharmacovigilance), pharmacokinetics, drug efficacy, and perhaps even drug tolerance. But, what part of the brain produces this 24 hour cycle and what signals does it receive in order for it to do so properly? It has been known for a long time that light is a strong zeitgeber. A zeitgeber is a term used in chronobiology for describing an environmental stimulus that influences biological rhythms. In the case of mammals, light is by far the most powerful. Following the discovery of connections between the retina and hypothalamus (the retinohypothalamic tract), investigations were aimed at the hypothalamus as the putative master clock. Indeed, in some of the most elegant brain lesion experiments, Inouye and Kawamura (1979) provided some of the first evidence demonstrating that the hypothalamus acts as the master clock in controlling the circadian rhythm. By creating an “island” in the brain by methodically cutting the hypothalamus away from any surrounding tissue, the circadian clock was completely lost (Inouye and Kawamura, 1979).
What does that mean? Well, the output of the hypothalamus nucleus (the suprachiasmatic nucleus or SCN) that controls the circadian clock has a variety of functions. The SCN controls your sleep-wake cycle, feeding and energy consumption, sugar homeostasis, and in addition to a few other things it controls your hormones. And, with respect to your alertness, the SCN’s control of cortisol (often referred to as the “stress” hormone) production is extremely important.
Most readers here, especially the ones in science enjoy–and desperately need–their morning coffee. I’ve seen some striking posts (here and here – note the caffeine consumption map with the number of researchers map) on the internet lately showing the correlation between science and caffeine. Not surprisingly to me, wherever there are scientists, there is a lot of caffeine consumed. And, a scientist also happens to be #1 the profession with the greatest caffeine consumption. But, if you are drinking your morning coffee at 8 AM is that really the best time? The circadian rhythm of cortisol production would suggest not.
Drug tolerance is an important subject, especially in the case of caffeine since most of us overuse this drug. Therefore, if we are drinking caffeine at a time when your cortisol concentration in the blood is at its peak, you probably should not be drinking it. This is because cortisol production is strongly related to your level of alertness and it just so happens that cortisol peaks for your 24 hour rhythm between 8 and 9 AM on average (Debono et al., 2009). Therefore, you are drinking caffeine at a time when you are already approaching your maximal level of alertness naturally. One of the key principles of pharmacology is use a drug when it is needed (although I’m sure some scientists might argue that caffeine is always needed). Otherwise, we can develop tolerance to a drug administered at the same dose. In other words, the same cup of morning coffee will become less effective and this is probably why I need a shot of espresso in mine now. Although your cortisol levels peak between 8 and 9 AM, there are a few other times where–on average–blood levels peak again and are between noon to 1 PM, and between 5:30 to 6:30 PM. In the morning then, your coffee will probably be the most effective if you enjoy it between 9:30 AM and 11:30 AM, when your cortisol levels are dropping before the next spike. Originally, when I heard a lecture on this topic, the professor said that since light is the strongest zeitgeber he suggested driving into work without sunglasses on. This would allow for stronger signals to be sent along the retinohypothalamic tract to stimulate the SCN and increase your morning cortisol production at a faster rate. I still tend to drive with them on since I feel blinded by the sun in the morning. However, on mornings when it is partially cloudy out and I did not get a lot of sleep, I drive with them off because this will help me feel more alert than if I was shielding what little sunlight was available. I thought this an important post for anyone but especially with the upcoming Society for Neuroscience annual conference in San Diego. Now us conference attendees should know just when to enjoy their coffee to stay alert for all of the new neuroscience!

References: Debono M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, Newell-Price J, Darzy K, Merke DP, Arlt W, & Ross RJ (2009). Modified-release hydrocortisone to provide circadian cortisol profiles. The Journal of clinical endocrinology and metabolism, 94 (5), 1548-54 PMID: 19223520
Inouye, S.T., and Kawamura, H. (1979). Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus Proceedings of the National Academy of Sciences of the United States of America DOI: 10.1073/pnas.76.11.5962claimtoken-5268404e1ecbb

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A Medical Education Bubble?

Sunday, December 1, 2013 // Uncategorized

Medical students have an increasing amount of debt.  The average student who rotates through my practice is $160,000 plus in debt. Studies as to whether that influences the choice of medical students is conflicting.  There is a concern, however, that finances deter students from choosing lower paid specialties like pediatrics, family practice and general internal medicine.  The following is an editorial from the New England Journal of Medicine which suggests that we may be pricing ourselves out of medical care.


Are We in a Medical Education Bubble Market?

David A. Asch, M.D., M.B.A., Sean Nicholson, Ph.D., and Marko Vujicic, Ph.D.

N Engl J Med 2013;  369:1973-1975November 21, 2013DOI:  10.1056/NEJMp1310778


In November 1636, the prices of tulip bulbs in the Dutch market rose rapidly from their normal level to the point where a single bulb might sell for 10 times the annual earnings of a typical worker. Just as quickly, in May 1637, tulip-bulb prices returned to their previous values. The causes of this dramatic rise and fall remain in dispute. The event occurred during the Dutch Golden Age, when stock exchanges, central banking, and many of the fundamental structures that govern contemporary capital markets and the approaches deployed by MBAs today were developed.

One modern economic analysis suggests that the precipitous decline in tulip-bulb prices resulted from a February 1637 change in the way that futures contracts were enforced, which immediately reduced the value of those contracts by 97%,1 but this analysis doesn’t explain why the prices had shot up in the first place. Clearly, tulipmania was a bubble market fueled by speculation rather than intrinsic valuation. After all, why would people be willing to pay 10 times the average annual wage for a single tulip bulb unless they were confident that they could sell it to an even greater fool willing to pay even more?

Bubble markets are created when an asset trades for increasingly higher prices as it is bought by people who are hopeful about its future value and then sold to others with even more optimistic views of that value. Recent examples include the U.S. housing bubble, in which home prices rapidly rose until 2007 and then just as rapidly fell, and the dot-com bubble, in which prices of Internet stocks rose until 2000 and then plummeted. Bubbles burst when some new sense of lower intrinsic value appears. The last buyers are stuck with something they paid too much for and can no longer unload. It’s like being caught without a chair when the music stops, but whereas even the losers at musical chairs knew that at some point someone would be left standing, bubble markets are usually recognized only in retrospect — the losers never saw it coming.

Are we in a bubble market in medical education? In medicine, students buy their education from medical schools and residency programs (which pay wages that are lower than the value of the work that residents provide in return). This education is transformed into skills and credentials that are then sold to patients in the form of services. So long as it is believed that patients, or whoever purchases health care on their behalf, will keep paying more and more for physicians’ services, students and trainees should be willing to pay more and more for the education that enables them to sell those services.

A simple measure of this market economy is the ratio of the average debt of a graduating student to the average annual income in the profession on entry into the workforce. There are more precise ways to measure the return on investment in medical education — for example, the net present value of the stream of cash flows out (for education) and in (for services). But that value isn’t very intuitive for most prospective students. In contrast, debt-to-income ratios reflect what students must borrow rather than what they must pay and, given whatever other assets they may have, how much in the hole they have to go. Thus, these ratios may better reflect how students actually feel about buying education.

Figure 1Figure 1Ratio of Debt to Income, According to Medical Specialty. shows these ratios for selected medical specialties over the past 15 years and reveals that the ratio has become less favorable for students overall but particularly unfavorable for students entering family medicine or psychiatry. Although the cost of becoming a doctor is roughly the same whether you go into pediatrics or orthopedics, you earn much more in orthopedics.

The graph is instructive in another way: the debt-to-income ratio reveals the connection between what physicians can charge patients and what schools can charge students. Just as tulip bulbs can be sold at high prices only to people who think they can resell them at still higher prices, schools can sustain their high tuitions only if students can be convinced of higher returns in the form of payments from future patients. So, the amount that schools are able to charge students is inextricably linked to how much we pay doctors now and how much we plan to pay them in the future. Medical students can take on enormous debt only because the costs of that debt can be easily passed along to others down the road.

So are we in a medical education bubble? We would realize we have been in one if a sudden collapse in what patients are willing to pay doctors made it impossible to sell medical education at current prices, causing applications to fall and some medical schools to cut tuition to continue to attract qualified applicants. Figure 1 might be seen as suggesting that we are approaching such a collapse in primary care fields and psychiatry. But that is not likely to be the case. First, at least at the level of undergraduate medical education, schools charge a single price to students whether they go into family medicine or orthopedics. Although it isn’t necessarily clear to students or schools which students will choose what fields, the income of the average doctor can sustain the debt of the average doctor even as the differences among specialties create pressures for primary care and psychiatry.

Second, as high as the debt-to-income ratios may be for primary care and psychiatry, they are even higher for some other fields — notably, veterinary medicine, optometry, pharmacy, and dentistry, as shown in Figure 2Figure 2Ratio of Debt to Income, According to Occupation.. For veterinarians, incomes have risen slowly even as student debt has exploded.2 Yet although such company may ease the misery of primary care physicians, it does nothing to solve the underlying problem.

The problem is this: if we aim to reduce the costs of health care, we need to reduce the costs of medical education. We don’t have to believe that the high cost of medical education is what causes increases in health care costs in order to develop this sense of urgency. We just have to recognize that the high costs of medical education are sustainable only if we keep paying doctors a lot of money, and there are strong signs that we can’t or won’t. Only about 20% of health care costs are attributable to physician payments, and many of the current efforts to reduce costs are aimed elsewhere, such as hospital payments, and have only indirect effects on physicians’ earnings. But physicians’ and dentists’ earnings have been sluggish since the early 2000s.3,4 Even if prospects for physicians’ income fall fast, a burst bubble can be averted if schools see it coming before their students do and lower their prices.

The general lesson is that if we want to keep health care costs down and still have access to well-qualified physicians, we also need to keep the cost of creating those physicians down by changing the way that physicians are trained. From college through licensure and credentialing, our annual physician-production costs are high, and they are made higher by the long time we devote to training.5

Although it seems unlikely that we’re in a bubble market for medical education, we may already be in one for veterinary medicine. That bubble will burst when potential students recognize that the costs of training aren’t matched by later returns. Then the optometry bubble may burst, followed by the pharmacy and dentistry bubbles. At the extreme, we will march down the debt-to-income-ratio ladder, through psychiatrists to cardiologists to orthopedists . . . until no one is left but the MBAs.

Disclosure forms provided by the authors are available with the full text of this article at

This article was published on October 30, 2013, at

Source Information

From the Center for Health Equity Research and Promotion, Philadelphia Veterans Affairs Medical Center; and the Perelman School of Medicine and the Wharton School, University of Pennsylvania — all in Philadelphia (D.A.A.); Cornell University, Ithaca, NY (S.N.); the National Bureau of Economic Research, Cambridge, MA (S.N.); and the American Dental Association, Chicago (M.V.).

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