Follow the Label – The Rise of “Gluten-Free”

What if your health could be improved instantly, in every possible way, by eliminating gluten from your diet? It sounds like the exact inverse of a pitch for a 19th-century patent medicine: instead of consuming an exotic mix of ingredients as a panacea for your ills, omit a common component of bread and other grain products, the “base” of the old USDA food pyramid. But this unlikely recommendation has garnered surprising cultural weight, driven largely by Dr. David Perlmutter, author of the bestselling “Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugars—Your Brain’s Silent Killers.

Is the gluten in this basket of bread delicious or deadly? Courtesy of TripAdvisor.

Dr. Perlmutter argues that up to 30 percent of people may be sensitive to gluten, with consequences ranging from Alzheimer’s to ADHD, from skin disorders to depression. To counteract this danger, he proposes an inversion of the food pyramid known as the “paleolithic diet,” a distribution of food supposedly closer to that consumed by humanity’s prehistoric ancestors: high in saturated fats and proteins from animal sources, low in carbohydrates from agricultural sources.

Similar diets have proven effective for the treatment of celiac disease, a life-threatening autoimmune disorder in which the body’s own natural defense systems turn against the gluten protein. But celiac disease only threatens 1 to 2 percent of the population; is a gluten-free diet necessary, or even desirable, for the vast majority of eaters? While a limited number of studies have recorded improvements in mental issues such as epilepsy and dementia due to a gluten-free diet, integrative medicine practitioner Chris Kresser emphasizes that “just because a low-carb diet can help treat neurological disorders, doesn’t mean the carbs caused the disorder in the first place.”

Dr. Perlmutter claims that a high-carbohydrate, high-gluten diet represents a deviation from the norm that humans are equipped to handle, but both evolutionary and anthropological evidence contradict that assertion. Humans possess more copies of the AMY1 gene, which codes for the alpha-amylase protein that breaks down starches, than do closely related primates such as chimpanzees. What’s more, human populations that have traditionally consumed more grains, such as the rice-eating Japanese, contain more copies of the gene than do hunting and gathering populations such as the Mbuti pygmies of the Congo. The human genetic code is not static but evolves over time to handle changing conditions like the rise of agriculture. Many traditional cultures also seem to function well on high-carb diets. Kresser points out that the Tukisenta people of New Guinea consume over 90% of their calories as carbohydrates while possessing some of the lowest recorded rates of neurological disorders.

Regardless of the evidence, food manufacturers are rushing to benefit from the skepticism surrounding gluten and carbs in general. Gluten-free products represented a $4.2 billion dollar industry in 2012, and new FDA guidelines allow products whose original formulations never contained gluten, such as vodka and bottled water, to be marketed as gluten-free. Consumers should beware the hype and instead focus on eating a balanced, scientifically supported diet.


Follow-Up: Genetic Disease Testing and the FDA

In June, I published a post on genetic disease testing after the highly publicized double mastectomy of actress Angelina Jolie, who had the procedure after a genetic screen showed she possessed a version of the BRCA1 gene associated with breast cancer. Consumer genomics has since garnered attention from the US Food and Drug Administration, which claims that manufacturers of home genetics kits are effectively selling unlicensed medical devices. The FDA’s scrutiny of genetic testing recently escalated in a strongly worded letter sent to Anne Wojcicki, the CEO of 23andMe, the largest American manufacturer of these tests.

Anne Wojcicki, CEO of 23andMe, courtesy of 23andMe.

In this warning letter, FDA director of in vitro diagnostics and radiological health Alberto Gutierrez ordered 23andMe to “immediately discontinue marketing the PGS [Personal Genome Service, the company’s genetic testing kit] until such time as it receives FDA marketing authorization for the device.” Although the company has previously attempted to register some of the tests included in the PGS under 510(k) applications, which bypass costly clinical trials by proving that a test is substantially the same as one already on the market, the FDA claims that these efforts are insufficient for the long list of conditions assayed by the kit

The letter focuses on the risks of false positives and negatives, using the same BRCA test that Jolie took as an example. “[I]f the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist.”

Wojcicki has apologized for her company’s failures to comply with the FDA’s past information requests, saying that “We stand behind the data that we return to customers—but we recognize that the FDA needs to be convinced of the quality of our data as well.” However, the company has issued no comment on whether it will discontinue sales of its kits while it prepares regulatory submissions to the government.

UPDATE: 23andMe has announced that while it will continue to sell its kits, it will restrict the results of the tests it releases to its customers to ancestry and raw data. None of the company’s previous health-related claims will be included.

Restless Nights – The Evolution of Sleep

Last month, Marvin Anthony Alexander of Phenix City, Ala., drove his SUV over a guardrail, falling 40 feet to the highway below and killing three teenaged passengers. Police determined that he was not under the influence at the time, but instead had fallen asleep at the wheel after an extended drive back from a vacation. Alexander, although he experienced the worst of what sleeplessness has to offer, is far from alone in his condition: according to a recent poll by the Centers for Disease Control and Prevention, 32 percent of Americans admit to “drowsy driving” on at least a monthly basis, and the National Sleep Foundation reports that 20 percent of US adults get less than six hours of sleep nightly. The basic sleep need of adults is generally agreed to be in the range of seven to nine hours nightly, and most experts recommend that this sleep come in a single, unbroken block.

Yet according to Roger Ekirch, a historian at Virginia Tech University, this recommendation may actually be counterproductive to achieving proper rest.  In his book “At Day’s Close: Night in Times Past,” Ekirch argues that the ideal of eight hours of uninterrupted sleep is a modern invention, promoted by the availability of artificial lighting that disrupted natural sleep cycles. Light suppresses the production of melatonin, a hormone that regulates sleepiness and is of great importance to the body’s circadian rhythm, or “biological clock.” Before streetlamps and lightbulbs, the night was significantly darker, and historical records suggest that people divided the night with two periods of sleep, scientifically known as biphasic sleep. Between the “first” and “second” sleeps came an hour or two of wakefulness, during which people would do everything from pipe smoking to visiting neighbors to praying. As sleep scientist Thomas Wehr writes, “Waking up after a couple of hours may not be insomnia. It may be normal sleep.”

Sample sleeping schedules, courtesy of Chase Hamilton.

Some adventurous sleepers are trying to break their rest into even further divisions in patterns of polyphasic sleep, often with the goal of reducing the total time spent in bed. These patterns aim to maximize the proportion of rapid eye movement (REM) sleep, the stage associated with dreaming, which is considered most important in helping the brain cement what it has learned over the course of the day. One of the most extreme sleep designs is called the “Uberman” schedule, which calls for less than three hours of sleep a day, broken into 20-30 minute chunks distributed every four hours. Scientific evidence on the success of these patterns is limited, but the Internet abounds with polyphasic success stories (as well as a considerable number of failures).

The temptation to reduce the time spent asleep and channel it into more productive activity is understandable, but fails to recognize the basic needs of the body. Whether it be in an unbroken stretch or the two halves perhaps favored throughout history, adequate sleep is absolutely necessary for human health and well-being.

Circus of Value – The End of Chimpanzee Testing

American animal rights activists rejoiced late last month over a decision by the National Institutes of Health to eliminate a majority of the chimpanzees the agency now employs for scientific research. The primates, which share an estimated 96 to 99.4 percent of DNA with humans, have been employed as a model organism for medicine in the United States since psychobiologist Robert Yerkes bought “Chim” and “Panzee” in 1923. The NIH currently houses 360 chimps, of which 310 will be retired to the federal sanctuary system and 50 will be retained, but not bred, as possible subjects for future work. Said NIH director Francis Collins, “Chimpanzees are very special animals. They are our closest relatives. We believe they deserve special consideration.”

A young chimpanzee in its natural habitat, courtesy of National Geographic.

The bioethics of conducting science on animals is based on the framework of “the three Rs” model: replacement, reduction, and refinement. Whenever possible, living systems should be replaced by in vitro (cell culture) models or computer simulations; if animals are absolutely necessary, less “advanced” organisms such as worms or other invertebrates are preferable. An animal study should then strive to reduce the number of individuals it involves while maintaining scientific validity. Good statistical analysis and experimental setups like the repeated measures design can help get the best results from the fewest animals. Finally, the procedures that are conducted should minimize the pain and distress experienced by the subjects. Measures like sedating research subjects before surgery may seem obvious, but stories like those of the unanesthetized baboons in the Experimental Head Injury Laboratory of the University of Pennsylvania should serve as constant reminders to those engaged in animal studies.

In the past, the closeness of chimpanzees to humans has made them a valuable resource for scientists. As the only animal model that can be infected by all strains of hepatitis, chimps were involved in the development of the hepatitis A and B vaccines, and the similarities in their immune systems made chimps a model for the study of HIV/AIDS. The most well-known chimpanzee experiment may be that of “Ham,” whose spaceflight paved the way for the first American astronauts. Yet these uses have been superseded by advances in technology: hepatitis vaccines can be produced in yeast, new HIV/AIDS work has progressed straight from in vitro experiments to human clinical trials, and humans are signing up at $250,000 a head to be shot into space. While future diseases may require chimps as the only viable research model, the present state of science has made them largely unnecessary, and their use therefore less morally defensible.

Recent neurobiology research has also suggested that non-human animals may experience significantly more consciousness than previously thought. The Cambridge Declaration on Consciousness, signed by luminaries such as Stephen Hawking and Francis Crick, states that “the weight of evidence indicates that humans are not unique in possessing the neurological substrates that generate consciousness.” In other words, the similarities of chimpanzees to humans may extend to their feelings of pain, and scientists should ensure that any benefits they gain from chimp research are worth this moral burden.

Ounces of Prevention – Genetic Disease Testing

Actress Angelina Jolie, it could safely be said, has one of the most admired figures in the world. It is then understandable that her recent decision to undergo a double mastectomy also received a great deal of attention. Jolie chose to have the procedure after a genetic screen revealed that she carries a rare variant of the BRCA1 gene associated with a greatly increased risk of breast cancer. The spotlight attached to such a high-profile celebrity has been turned on genetic testing, much like attention was given to colonoscopies after Katie Couric of the Today Show broadcast her own, and many women are now considering tests for BRCA and other potentially harmful mutations.

A 23andme testing kit, courtesy of Paul Stamatiou.

The market is certainly willing to provide these sorts of tests, many of them without the consultation of a medical professional. 23andMe, for example, provides a self-administered kit for $99 that screens for over 240 health conditions,  while GenePlanet offers a comprehensive analysis of disease risk and drug interactions for €499. These tests operate using relative inexpensive SNP (single nucleotide polymorphism) techniques; in essence, they search for a difference in one “letter” of the genetic code that has previously been associated with a given health condition. Many of the tests used in a hospital setting, however, involve the sequencing of at-risk genes, reading the full “sentence” of the DNA that codes for a protein or regulates other parts of the code. These tests can be quite pricey: Myriad Genetics, the company behind Jolie’s BRCA testing, charges up to $4,000 for its most comprehensive examination of breast cancer risk. Myriad currently holds patents on the BRCA genes, granting it a monopoly on tests for harmful mutations (a monopoly currently being challenged in the Supreme Court).

These kinds of price tags, which in many cases may not be covered by insurance, have caused some doctors to question whether the enthusiasm for genetic testing may be premature. A pressing issue for many is that, while testing may provide information on disease risks, in most cases there are few preventative actions that can be taken. Mastectomy and breast cancer is an obvious exception, but as Stanford University’s Andrew Fire has been quoted, “if someone off the street is looking for pointers on how to live a healthier life, there’s nothing these tests will tell you besides basic physician advice like ‘eat right, don’t smoke and get plenty of exercise.’” For genetic tests of conditions like Lou Gehrig’s disease or Parkinson’s disease, a positive result can at present yield little but stress and referral to genetic counseling. In the future, it may become possible to replace faulty regions of the genome in a process called gene therapy, but the science of this technique, while promising, is still very much in the exploratory phase.

However, a powerful reason for more widespread genetic testing is that these tests become more powerful the more they are administered. SNP tests work by correlating differences in DNA with diseases; these correlations are not perfect, as many other factors are usually involved in the development of a disease. Yet after a person is tested for a given SNP, whether they develop a given disease becomes a data point for the interpretation of that genetic variant. The statistical strength of the test increases with the sample size, making predictions for other patients more accurate. Those who undergo testing today are laying the groundwork for the future, where it may be possible to do more about the results than wait and worry. Each individual must weigh whether that contribution to science is worth the potential pain of learning about a disease for which little can currently be done.