Flavor

by Bob Holmes

  But they didn’t. Over the three weeks of the experiment, the smorgasbord rats ate no more food, and gained no more weight, than the boring-food rats. What really mattered, it turned out, was how much sugar and fat was in the rats’ diet. A third group of rats that got a much higher-fat, higher-sugar diet (let’s call it the fast-food diet) did indeed balloon up, regardless of whether they got a diet with monotonous or varied flavor. In other words, it’s not about the variety. It’s about the reward-pathway pull of concentrated calories.

  Even so, many people manage to navigate past the siren calls of fast-food calories without gaining weight. That’s because we have a separate system for regulating the total amount of food we take in. A complex network of hormones with names like leptin, ghrelin, and neuropeptide Y regulates our levels of hunger and satiety to keep calorie input roughly equal to output in the long run. When I eat a varied holiday dinner, I’m likely to eat a little bit more than usual. Most people do—not just because of the variety, but also because the social context says we’re supposed to. But we compensate for that later, by eating a little less the next day, or by skipping a snack or two. And you can forget the old saying, “Never trust a skinny chef”—as a general rule, people don’t gain weight just because their diet is especially tasty. “There’s nothing out there—and I’ve asked around—that really shouts that if you make food as palatable as you can, people overeat,” says Mark Friedman, a researcher who’s been studying flavor and appetite for decades. “For something that everybody believes, there’s not much there.”

  Nor does bad-tasting food make you eat less. (Just ask any college student on a meal plan.) If you make rats’ chow less palatable, such as by adding a bitterant to it, they’ll avoid it for a little while, but if they have no other options, hunger kicks in eventually and they scarf the stuff down anyway. Likewise, people who suddenly lose their sense of smell—a malady we discuss later in this chapter—usually don’t end up losing weight. For that matter, most of us can think of someone we know who cooks boringly, or even badly, and they’re generally not emaciated.

  Further evidence that we probably can’t fix obesity by tinkering with flavor comes from the field of genetics. You’ll recall that each of us carries a unique set of genetic variants in our taste and odor receptors, and as a result no two of us perceives the flavor world in exactly the same way. If our flavor perception was an important cause of obesity, then you’d expect that people with some flavor-gene variants would be more likely to be obese than others. For example, people with my sweet-receptor variant tend to prefer sweeter flavors, which might put us at greater risk of eating too many sugary treats and gaining weight. Or people who are especially sensitive to bitter tastes might eat high-calorie french fries in preference to lower-calorie broccoli.

  One way geneticists look for patterns like this is through something called a genome-wide association study (GWAS), which is often used to identify genetic diseases. Researchers compare the genomes of people with and without the disease—Alzheimer’s disease, say, or a strong family history of cancer—and look for parts of the genome that differ in the two groups. The disease-related genes they’re looking for must lurk somewhere within those regions of difference. In the case of obesity, a GWAS would compare the genomes of overweight people against their normal-weight peers. Sure enough, those studies do turn up regions of difference, suggesting that there must be genes that affect obesity. However, not a single one of those regions of difference includes any taste receptor or odor receptor genes. How we perceive the flavor world doesn’t seem to matter at all in determining our risk of obesity.

  And there’s yet another reason for suspecting that flavor, by and large, doesn’t have a lot to do with how much we eat. If our overeating was driven by delicious flavors, then people who lose their sense of flavor—especially smell—should lose interest in food, and they should have a hard time eating enough. This was the question that led me to Monell’s boardroom to eat tasteless hamburgers with Gary Beauchamp. And to see what happens after long-term loss of flavor senses, I headed just a few blocks down the street to the University of Pennsylvania Medical Center and Richard Doty’s clinic on smell and taste disorders to meet some of his patients.

  Patricia Yager had never had a serious health problem. “I go to Antarctica for a living. They don’t let you go there if you aren’t healthy,” says Yager, an oceanographer who studies climate change and the oceans. In January of 2014, though, Yager—a slender woman with a broad face, heavy-lidded eyes, and long hair streaked lightly with gray—noticed a persistent metallic taste in her mouth. As scientists do, she worked through the possibilities: acid reflux, menopause, diabetes. Nothing fit. Her doctor found a little fluid in her middle ear and suggested decongestants, but the metallic taste persisted.

  Then one day she was cooking in her kitchen when her preteen son came rushing in saying there was a terrible smell in the house. It turned out that some cheese had bubbled over in the oven and was burning. “I didn’t smell the smoke,” Yager recalls. “I thought, oh my gosh, something serious is going on here!” An ear, nose, and throat specialist guessed that her sense of smell was damaged, and the likeliest causes were permanent nerve damage or a brain tumor—not what she wanted to hear. “So I ended up in a puddle on the floor.” Fortunately, an MRI ruled out the latter, scarier option, which is how Yager ended up in Richard Doty’s clinic in Philadelphia.

  Doty, a neuropsychologist, directs the Smell and Taste Center at the University of Pennsylvania, which is widely regarded as the best place in North America for diagnosing and treating smell and taste disorders. “We’re a unique center in the world, really,” says Doty. By the time patients make it to his center, many have already seen several doctors without understanding their condition, and they’re desperate for Doty’s specialized knowledge—even though he often can’t fix the problem. “Much of what we do is correct misinformation and put people at ease,” says Doty. “One of the things I like about this job is that most people are thankful that they came to see us, since we understand their problem.”

  A few days each month, he sees patients in his small, crowded office at the center. It’s a classic academic office: books, papers, and binders cover his desk and side tables in teetering stacks a foot and a half high. The desk alone has six of these piles, and he and Yager have to peer between the towers to see each other. At first, Yager tells him, things either had no smell at all, or else they all had the same, unpleasant smell. Lately, though, she’s noticed that she can sometimes distinguish among different smells. “None of them smell good yet, and none of them smell like they used to smell. Watermelon doesn’t smell like watermelon, but it has a very distinctive, unpleasant smell.” Vanilla now has an odd, turpentiney smell.

  Most likely, Doty tells her, a viral infection has killed some of the nerve cells that carry odor receptors. We start out with a few million of these cells, each one carrying just one of our four hundred or so odor receptor molecules. A severe viral infection of the nasal passages can sometimes kill enough cells that some—or, in extreme cases, all—of the odor receptors effectively go extinct in the nose. The effect is like progressively cutting some strings on a piano: the chord begins to sound dissonant, then unrecognizable. Cut enough strings and the piano falls silent. It’s also possible that Yager’s smell loss is the result of a head injury, since she did hit her head in a fall while roller-skating a few weeks before she noticed the loss. That fall—mild though it seemed at the time—could have severed the connection between the olfactory epithelium and the brain.

  Doty sends Yager off for a battery of tests to measure her senses of smell and taste. His associates measure the shape of her nasal cavity and the airflow through it; they test her sense of taste by dripping sweet, salty, sour, or bitter test solutions on each quadrant of her tongue, and by stimulating the tongue with an electric probe; they give her the University of Pennsylvania Smell Identification Test—the same scratch-and-sniff test that Doty had given me
a few months earlier in Florida. The test is multiple choice, which avoids the complication of recognizing a smell but being unable to name it. That also makes it easier for Doty to spot malingerers who are faking smell loss in the hope of profiting from a juicy lawsuit.

  While Yager is off doing the tests, Doty explains that viral infections are one of the three most common causes of smell and taste problems, along with head trauma and chronic nasal and sinus inflammation. Many of the patients he sees arrive in his office complaining of a loss of taste, but most of the time his tests reveal that the problem is actually with their sense of smell—further proof that most people can’t really distinguish between their two main flavor senses. Olfactory defects are surprisingly common, affecting one in five people by most estimates, and about one person in twenty has no sense of smell at all. Often, people are completely unaware that they have a problem—in fact, one study found that asking people if they have a defective sense of smell tells you nothing useful about whether they actually do. (Oddly, older people tend to have lost olfactory ability without knowing it, whereas younger people tend to underestimate their sense of smell.) “Every time you get a bad cold, or are exposed to pollution, it takes a toll on the olfactory epithelium,” he says.

  Sometimes—as, apparently, with Yager—a single infection is enough to push a person “over the waterfall,” as Doty puts it. Other times, the damage accumulates gradually, and our ability to smell slips away bit by bit, without our noticing, as we age. (Taste may fade a little bit with age, as well, but not enough for most people to notice.) Most of us, if we live long enough, will eventually have trouble with smell: Almost 30 percent of seventy-year-olds and about 60 percent of people over the age of eighty have significant impairments of their sense of smell, with men more likely to lose function than women. Surprisingly, scientists haven’t tracked enough people through their lifetimes to be sure whether age-related loss creeps up slowly, or whether we reach a threshold where problems suddenly become much more common. Often, studies simply compare a group of older people with younger ones and report that the older ones have a worse sense of smell.

  One sparkling exception to that rather dismal track record came in 1986, when every one of National Geographic magazine’s 10.5 million subscribers received a scratch-and-sniff smell survey with their September issue. For each of the six odors, the subscribers were asked to rate the odor’s intensity and pleasantness, and pick the best description of the odor from a list of twelve possibilities. They also answered some questions about themselves, so that the masterminds behind the survey—Monell researchers Charles Wysocki and Avery Gilbert—could make sense of their responses.

  The survey was a huge success, with more than 1.2 million readers returning their questionnaire. When Wysocki and Gilbert tabulated the results, they found—as expected—that more older people than younger ones had trouble detecting some or all of the odors. Surprisingly, though, people’s sense of smell didn’t fade uniformly—they lost some odors faster than others. Virtually everyone could smell the banana, clove, and rose odors right up into their sixties, and even after that age, the ability to smell those odors trailed off slowly. Even among ninety-year-olds, 90 percent of men and almost 95 percent of women could still smell the clove and rose odors, and the success rate for banana was only a few percent lower. In contrast, the ability to smell mercaptans—the stinky chemicals added to natural gas to make people aware of leaks—began to drop off when people were in their forties.

  Scientists aren’t sure exactly why our sense of smell often fades as we age, but most of them think it’s just part and parcel of our body’s diminished ability to repair itself. The cells of the olfactory epithelium are among the few nerve cells that the body regularly replaces during adult life. As with other regularly replaced cells—skin and hair follicles are obvious examples—problems accumulate over time. The olfactory epithelium of a newborn infant is a nice smooth, solid sheet of cells, but it gets more ragged and patchy as we age.

  But something else may be going on, too. Even as the olfactory epithelium breaks down, the responses of its remaining cells may start to blur. To show this, a team led by Beverly Cowart, yet another Monell researcher, collected biopsy samples from the olfactory epithelium of elderly and middle-age volunteers. This is as creepy a procedure as it sounds. Under local anesthetic, doctors thread a fiber-optic scope into one nostril and insert something called a “Kuhn-Bolger giraffe forceps”—a scissorslike clamp with a long, offset neck—up the other nostril to grab a little pinch of olfactory epithelium. The resulting cells can be grown in petri dishes to see which odors—or, in Cowart’s case, odor mixtures—they respond to. Each cell from middle-aged noses responded to just one of the two odor mixtures Cowart used. By contrast, about a quarter of the cells from elderly noses responded to both. That suggests that older people’s noses blur together details they once could have resolved—an olfactory analogue of cataracts, perhaps.

  The healthier we stay, though, the more likely we are to keep our sense of smell intact: The “successfully aged elderly” often continue just fine. Smell loss, in fact, can be an early warning sign of more serious medical problems such as Alzheimer’s disease and Parkinson’s disease. That’s not surprising: the olfactory system is basically part of the brain, so many degenerative brain diseases should affect the sense of smell, as well. Oddly, some oncologists also report that one of the first warnings of a developing cancer is that food doesn’t taste right—even when the tumor is in the breast or prostate or some other organ unrelated to flavor perception. Indeed, seniors who have lost their sense of smell are four times as likely to die within the next five years, compared with people of the same age with good olfaction. (It’s important to note that olfactory loss is not a death sentence—most people who lose their sense of smell still survive just fine.)

  Whatever the cause, loss of smell can bring major problems. In one study, nearly half of the patients with smell disorders reported experiencing depression and anxiety, and more than half felt isolated and had difficulties relating to other people. The effect on flavor is even worse, with 92 percent of people reporting less pleasure in eating—and that brings social difficulties of its own. “Most of our social interactions involve food,” says Cowart. “It becomes very difficult to justify going out to eat and paying a lot of money for food they can’t taste, or going to a friend’s house and not being able to tell the host that the meal tasted great.”

  You could hear that loss in the voices of the patients in Doty’s office—though, being nonspecialists, they tended to talk about failures of taste, not smell. “I don’t taste my food at all,” said one elegantly dressed older woman. “It tastes like eating sawdust when I eat a cracker.” Or, as another put it, “The only reason I know what I ate is that I’m looking at it, and I remember what it tasted like.”

  Despite complaints like this, most people find ways to cope, and about two-thirds manage to maintain their usual weight. Only a small minority—one expert puts it around 10 percent—of people with a damaged sense of smell actually lose weight as a result. And those tend to be people who suffer not total loss, but distortion of smell, like Yager’s turpentiney vanilla and stinky watermelon. Often, patients report that everything has the same “burnt-chemical” smell—probably the best they can do at describing something unfamiliar and unpleasant. Olfactory bugaboos like this can actively turn people off their food. Among the elderly, people who have lost their ability to smell are far more likely to be undernourished—but that may be because loss of smell is linked to other health problems, rather than because they find their food less appealing.

  On the other hand, a few people who suffer a sudden loss of smell actually gain weight as a result. These tend to be people who were already susceptible to food cravings, which are often more about habit than about deliciousness. (One researcher who tried to create cravings for other foods by putting people on a boring diet of vanilla-flavored meal-replacement drinks found that the subjects act
ually began to crave the boring drinks. “They tried to scam cans of this stuff off the technicians in the lab,” she recalls.) The craving gives them a sensory template, a hole waiting to be filled—and with no sense of smell, they keep eating in the futile hope of finding satisfaction.

  When Yager returns to Doty’s office that afternoon, he gives her the results of the tests: no problems at all in her sense of taste, but on her smell tests she scored no better than if she’d been guessing randomly. Clearly, what little smell she has left is so badly degraded that she can’t tell the difference between familiar odors like grape and peanut butter.

  And unfortunately, says Doty, medical science can’t do much to fix the problem. About half of the people who suffer smell impairment get some function back within a few years, but less than a quarter recover fully. Among people with complete loss of smell, like Yager, the odds of full recovery drop to just 8 percent.

  There might be ways to improve that discouraging prognosis, he notes. There are a few reports that a supplement, alpha-lipoic acid, might help. And some studies suggest that even a failing sense of smell might improve with practice, because nerve cells are more likely to be replaced or regrow if they’re being used. Grab bottles of spices—“Anything that says McCormick”—and keep them beside your bed, he tells Yager. Sniff through them three or four times first thing in the morning and before you go to bed for the next three or four months, and see if it helps. She brightens at the thought that she might be able to do something about the problem.

  A year later, I checked in with Yager to see whether the exercises helped. No luck, she reported—she still can’t smell anything. “I’ve grown accustomed to it, I suppose,” she says. She’s learning to cope by making sure her food is well seasoned with salt, pepper, and lemon, which don’t depend on smell for their flavor impact, and admits that “Sriracha has become a close friend.” (The chili burn uses a different nerve to reach the brain, so she still gets full value for that flavor component.) She rarely drinks wine any more, except to be sociable, since it doesn’t offer much to interest her. These days, her preferred tipple is gin and tonic, which is still exciting in her mouth, thanks to its pronounced hit of bitterness.