Paradigm Shift?

The most powerful explanatory model in medicine is the germ theory of disease. It’s simple and it’s elegant: find the offending microbe, kill it, and cure the disease. This approach has led to some of the most dramatic and effective advances in medical history: identifying the leading cause of pneumonia (the pneumococcus bacillus), finding a chemical that kills the bacteria without harming people (penicillin), diagnosing disease (by some combination of physical examination, a chest x-ray, and examination of sputum under the microscope), and treating the patient with antibiotics. The result?  Pneumonia cedes its place as the leading cause of death in older people to heart disease. 

Life has turned out to be a bit more complicated than the germ theory suggests. Expose a group of people to exactly the same dose of a microbe and not all of them will get sick. Of those who do become ill, not everyone is equally sick. Other factors proved to matter, ranging from the vigor of the patient’s immune system to socioeconomic status. And pneumococci were not the only causes of pneumonia: all kinds of other bacteria can cause much the same clinical and radiographic picture, as can a whole host of viruses. Even with our enhanced understanding of the causes of disease and of how and why illness develops in different individuals, we haven’t been able to eradicate pneumonia. Together with influenza, it’s still the seventh leading cause of death in older people.

These caveats mean we’ve had to refine the model, to elaborate on it. But the germ theory of disease still stands as the gold standard for all of medicine. Doctors in areas under than infectious disease seek to find a similar master key that unlocks the diseases of their particular organ system. Cardiologists have focused on atherosclerosis as the unifying feature underlying coronary heart disease; neurologists have seized on amyloid as the basis for Alzheimer’s disease. But the reductionist view of the world seems to break down when it comes to geriatric syndromes, problems such as falls and incontinence that are responsible for so much misery in older people. What seems to explain reality more effectively is a multifactorial understanding. Maybe that’s why even though last week’s JAMA includes two reports of failed efforts to stave off Alzheimer’s disease, one with anti-oxidants taken as nutritional supplements, and one with exercise, the editorial accompanying the articles optimistically maintains that we can make a difference. We just have to eat well and exercise and play mind games.

Now there are a number of possible reasons that the JAMA studies may have been unable to find any benefit of their interventions. The anti-oxidant study was carried out in older patients with macular deterioration, a chronic eye disease. Its main hypothesis was that supplements would stave off progressive visual loss—preventing cognitive impairment was a secondary aim. Conceivably, people with macular degeneration are sufficiently different from the general population that what works, or doesn’t work, for them may not be the same as for everyone else. The trial used pills, not diet rich in anti-oxidants, and there are at least some nutritionists who maintain that the purified version of a chemical won’t work the same way as that chemical in combination with food. The exercise study used moderate intensity physical activity such as walking, it used resistance training, and it used flexibility exercises, which it compared to an educational program. It’s at least possible that other kinds of exercise, or exercise of different intensity or duration, would have been more effective. 

The commentary in JAMA, written by a psychiatrist and an internist from Ontario, Canada, mentions these possibilities. But it also seizes on a different study, one of the few encouraging ones in a field littered with negative results. And that is the FINGER trial, a multifaceted intervention involving diet, exercise, and cognitive training in Finland in people aged 60-77. After two years, there were measurable benefits to the study population as determined by psychological testing. So despite the negative findings of the two studies they are charged with reviewing, the editorialists put on their rose-colored glasses and assert that “it is still likely that lifestyle factors such as diet and physical activity have important roles in the prevention of cognitive decline, dementia, and performance of the activities of daily living.”

There is precedent for a multifactorial intervention working when no single approach succeeded. In her path-breaking work on falls, Mary Tinetti of Yale found that fall rates in community dwelling older people could be significantly decreased if they had an evaluation that focused on physical hazards (throw rugs or poor lighting), on a medication review (getting rid of drugs that cause orthostatic hypotension or confusion), and on strength training. Similarly, Sharon Inouye, now at Harvard, recognized that delirium in the hospital is difficult to prevent, but found the most effective strategy involved a multi-component intervention targeting sleep, mobility, vision, hearing, cognition, and fluid intake. 

So maybe we can make a difference in preventing dementia or delaying its onset or slowing its progression. Maybe the recent meta-analysis that was widely quoted in the media (published in the somewhat obscure Journal of Neurology, Neurosurgery, and Psychiatry) as claiming that “modifiable risk factors” are responsible for 2/3 of the risk of Alzheimer’s disease is onto something. Or maybe it’s all wishful thinking and we should redouble our efforts to look for the magic bullet, the switch that we can turn off amyloid deposition in the brain, stopping dementia before it starts. Or maybe we just have to do something. Eating vegetables, going for walks, and doing crossword puzzles won't hurt. They don't cost a lot of money. They won't jack up the cost of American health care. And in combination, they just might help.

Food for Thought

The global anti-aging industry is valued at over $195 billion and will grow to $275 billion by 2020. But the assessment of the effectiveness of its products made by three leading scientists in 2002 has not changed. And what they said is that “no currently marketed intervention—none—has yet been proved to slow, stop, or reverse human aging, and some can be downright dangerous.” They then go on to say that "the public is bombarded by hype and lies." Or, as one of the triumvirate put it in a recent NY Times article, "as soon as the scientists publish any glimmer of hope, the hucksters jump in and start selling."  

In light of this reality, my internal alarms started going off when I saw the headline in last week’s NY Times, “My Dinner with Longevity Expert Dan Buettner (No Kale Required).” Granted, the article was in the “Fashion and Style” section of the Times, not the health section and not the science section. Now don't get me wrong: diet and exercise do matter: eating well and remaining active decrease the chance of developing disease and disability. Not only that, but modifying what you eat in the hope that it will promote longevity is far more benign than purchasing expensive supplements or herbal remedies that have no proven efficacy and are quite possibly harmful. But still—is Dan Buettner really a “guru of the golden years” who has spent “the last 10 year unlocking the mysteries of longevity?” He traveled to five of the places on the globe with the longest lived people: Icaria, Sardinia, Okinawa, the Nicoya Seaside of Costa Rica, and Loma Linda, California and wrote up his interviews. He was not funded by the NIH as the report would have us believe: he was funded by National Geographic to report on peoples who were being studied by teams of scientists funded by NIH. He did write a cover story for National Geographic in 2005 about the people he met on his travels and how they lived, particularly how they ate. And he converted his article into a book, The Blue Zone Solution, published by National Geographic Press this past spring.

            National Geographic ran a cover story about diet and longevity once before. The magazine reported in 1973 on Dr. Alexander Leaf’s travels to the Caucasus where he studied people who ostensibly were 120 years old. It would turn out that these human marvels were actually only in their nineties, at best. In fact, according to Dr. Tom Perls, head of the New England Centenarian Study, 98% of claims of age over 115 are false, as are 65% of claims to be 110. 

            I’m not sure why the NY Times ran this story. But I was sufficiently intrigued to look into what we do know about diet and longevity.

         For starters, it’s important to distinguish between people who live a long time and people who live a very long time. What is pretty clear is that the variability in life span for people in the first category can be explained by a mixture of environmental and genetic factors. We can’t control who our parents were, but we can control, to some extent, our environment. So what we eat is one of the things that does matter, at least as far as increasing our chances of making it into our eighties is concerned. Exceptional longevity—centenarians and “super-centenarians” (people over age 110) are a different story. For this group, it’s all about genetics. 

            But can we say much more than what was concluded from the Whitehall study, a longitudinal study of aging in Canada that found the 4 behaviors that increased the chances of being in good health after age 60 are regular physical activity, eating fruits and vegetables daily, drinking alcohol in moderation, and not smoking? What do we learn by looking at  the dietary habits of people in Buettner’s “blue zones” of above average longevity?  

          For several decades, geriatrician Bradley Willcox and his twin brother, anthropologist Craig Willcox, have been leaders of the Okinawan Centenarian Study. They have identified a variety of factors which, together, seem to account for the long lives of Okinawans. It’s not just about diet. It’s also about living in a culture that values group activities and fosters a strong sense of community. It’s about living in a slower paced, low pressure world where people get around by bicycle. But yes, it’s also about diet. And while each of the longevity hot spots of the world has its own culinary specialties, they all have much in common. They all feature a high intake of unrefined carbohydrates and a moderate intake of protein, mainly from fish and legumes. Their foods have a low glycemic load, include a goodly number of anti-oxidants, and are low in saturated fats.

         How much of a role diet plays in the 30-50% of longevity that is due to environmental factors is unclear. Also unclear is whether diet interacts with social factors to make a difference. It’s conceivable that what you eat matters, but it matters a good deal more if you also live in an all-embracing community. At least as interesting as the Sardinians and the Costa Ricans are the Seventh Day Adventists of Loma Linda (whom, to be fair, Buettner visited as well). The people of Loma Linda are physically active and tend to be vegetarians. They are also very involved in their community and deeply committed to their religious faith. So maybe, just maybe, it’s not only what we eat that determines how long we live. Just some food for thought.