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ARTICLE RE-PRINT FROM TODAY'S WSJ -
Ghrelin Hormone Foils Dieters
By Stimulating More Hunger
By LAURA JOHANNES
Staff Reporter of THE WALL STREET JOURNAL
Ever notice that the more you diet, the hungrier you get?
Now, scientists believe they may have found the biochemical culprit. It's ghrelin, a hormone produced in the stomach that is one of the most potent hunger stimulants ever discovered.
Scientists at Eli Lilly & Co. first found that ghrelin made rats ravenous two years ago. Then last year, British researchers discovered that human study subjects who were injected with ghrelin pigged out at an all-you-can-eat buffet.
Thursday, in a study published in the New England Journal of Medicine, a team of Seattle scientists chronicle the sad story of a dozen diligent dieters who lost weight only to be rewarded with a dramatic rise in their blood levels of ghrelin. The study subjects, who weighed an average of 220 pounds when the study began, lost an average of 38 pounds in three months through abstemious eating and exercise. Then they kept it off for three more months.
But, unbeknownst to the dieters, the level of hunger-causing ghrelin in their blood was rising. Before starting the diet, each of the obese volunteers -- just like the normal-weight people enrolled to provide a comparison -- experienced a big spike in ghrelin levels three times a day, before each meal.
After the six-month diet period, ghrelin levels rose about 25% in 12 of the 13 research subjects. Indeed, after the subjects finished the diet, their lowest ghrelin levels were nearly as high as their premeal peaks had been before the program began, suggesting that if the dieters felt their biology was working against them, they weren't imagining it.
The researchers didn't keep in touch with all the patients after the experiment ended, but they suspect most have regained the weight they lost. One participant, Lynn Still, a 49-year-old insurance salesman from Lynnwood, Wash., says he felt "hungry all the time" during and after the experiment. Mr. Still lost 20 pounds, but as soon as he was no longer monitored by doctors, he succumbed to a powerful craving for sweets. Mr. Still regained everything he lost, plus 15 more pounds, and now tips the scales at 345 pounds.
"Unbelievable," said Philadelphia obesity advocate Lynn McAfee when told of the findings. "It's nice to have a name for the feeling you thought was insanity."
Ms. McAfee, 53, has tried dozens of diets in her lifetime but still weighs 415 pounds. She believes the reasons are biological. "When I look at a frosted butter cookie, the bells in my head that go off are like standing on top of a cathedral," she says, adding, "For most people, a cookie doesn't do that."
The study's lead author, David Cummings, a researcher at the University of Washington and the Veterans Affairs Puget Sound Health Care System in Seattle, says the study results suggest ghrelin may be the reason that most people can't lose more than 10% to 15% of their body weight through behavior modification.
While it is made in the stomach, ghrelin works on the brain. Research shows that injections of it raised people's perceptions of how hungry they were. The injections also caused them to eat a lot more.
But ghrelin isn't the reason people get fat in the first place. In fact, Dr. Cummings says, ghrelin levels drop slightly in obese people as the hormone "tries to help" when it senses that the body has too much fat. But when people start dieting in earnest, the body senses deprivation, and ghrelin kicks into high gear again.
In ambushing diets, it's possible that ghrelin is working in conjunction with leptin, a hormone known to create a feeling of satiety. Leptin levels drop after a diet, so the ghrelin findings suggest that the two hormones may be creating a double-whammy to foil the best of intentions.
Leptin, discovered in 1995, has so far proved a disappointment as a diet nostrum because overweight people tend to have a resistance to it. Today, ghrelin is the hot new kid on the block. "Every pharmaceutical company I know" is hunting for drugs that stymie its action, Dr. Cummings says.
The ghrelin programs are shrouded in secrecy, for competitive reasons. Merck & Co., Whitehouse Station, N.J., is working on the hormone but is mum on the details. Lilly will say only that it has "an active program" in ghrelin research. "Our scientists are extraordinarily interested in this topic, but we really can't comment," says spokeswoman Kindra Strupp.
The New England Journal findings may also explain the remarkable success of a surgical weight-loss method called gastric bypass. That approach, which has gained popularity in recent years for the treatment of morbidly obese people, involves bypassing most of the stomach by sewing off all but a tiny pocket at the top. That pocket is linked directly to the intestine. The surgery effectively creates a very small stomach, limiting food intake.
The surgery can be dangerous, and even fatal. But researchers have found in recent years that it can also be extraordinarily effective, allowing patients to lose 50% to 80% of their body weight and keep it off for a decade or more. Certainly, a smaller stomach would be expected to cut hunger somewhat, but scientists would have expected bypass patients to retain some of their former cravings and adapt to the surgery by eating many smaller meals throughout the day.
Mysteriously, most don't. The reason, again, may be ghrelin. In a separate group of patients who had undergone bypass surgery, ghrelin levels dropped like a stone and remained at extraordinarily low levels, according to the New England Journal article. After surgery, ghrelin didn't even rise before meals as it does in most people.
Scientists don't yet know why gastric bypass surgery turns off ghrelin production, but they suspect that when the stomach is empty for very long periods, as in a fast, the body just stops bothering to make it.
That explanation makes sense to James Rudolph, 55. Mr. Rudolph, of Ocean Shores, Wash., saw his weight fall to 265 pounds, from 460, after bypass surgery three years ago.
Like the others in the study, his ghrelin fell sharply. Prior to the surgery, Mr. Rudolph says, "I'd finish breakfast and want to know what we were having for dinner." Now, he often doesn't notice he's hungry until his blood sugar is so low he feels faint. After he gets the shakes, he says, "I go 'Oops, I guess I should eat something.' "
Ghrelin Hormone Foils Dieters
By Stimulating More Hunger
By LAURA JOHANNES
Staff Reporter of THE WALL STREET JOURNAL
Ever notice that the more you diet, the hungrier you get?
Now, scientists believe they may have found the biochemical culprit. It's ghrelin, a hormone produced in the stomach that is one of the most potent hunger stimulants ever discovered.
Scientists at Eli Lilly & Co. first found that ghrelin made rats ravenous two years ago. Then last year, British researchers discovered that human study subjects who were injected with ghrelin pigged out at an all-you-can-eat buffet.
Thursday, in a study published in the New England Journal of Medicine, a team of Seattle scientists chronicle the sad story of a dozen diligent dieters who lost weight only to be rewarded with a dramatic rise in their blood levels of ghrelin. The study subjects, who weighed an average of 220 pounds when the study began, lost an average of 38 pounds in three months through abstemious eating and exercise. Then they kept it off for three more months.
But, unbeknownst to the dieters, the level of hunger-causing ghrelin in their blood was rising. Before starting the diet, each of the obese volunteers -- just like the normal-weight people enrolled to provide a comparison -- experienced a big spike in ghrelin levels three times a day, before each meal.
After the six-month diet period, ghrelin levels rose about 25% in 12 of the 13 research subjects. Indeed, after the subjects finished the diet, their lowest ghrelin levels were nearly as high as their premeal peaks had been before the program began, suggesting that if the dieters felt their biology was working against them, they weren't imagining it.
The researchers didn't keep in touch with all the patients after the experiment ended, but they suspect most have regained the weight they lost. One participant, Lynn Still, a 49-year-old insurance salesman from Lynnwood, Wash., says he felt "hungry all the time" during and after the experiment. Mr. Still lost 20 pounds, but as soon as he was no longer monitored by doctors, he succumbed to a powerful craving for sweets. Mr. Still regained everything he lost, plus 15 more pounds, and now tips the scales at 345 pounds.
"Unbelievable," said Philadelphia obesity advocate Lynn McAfee when told of the findings. "It's nice to have a name for the feeling you thought was insanity."
Ms. McAfee, 53, has tried dozens of diets in her lifetime but still weighs 415 pounds. She believes the reasons are biological. "When I look at a frosted butter cookie, the bells in my head that go off are like standing on top of a cathedral," she says, adding, "For most people, a cookie doesn't do that."
The study's lead author, David Cummings, a researcher at the University of Washington and the Veterans Affairs Puget Sound Health Care System in Seattle, says the study results suggest ghrelin may be the reason that most people can't lose more than 10% to 15% of their body weight through behavior modification.
While it is made in the stomach, ghrelin works on the brain. Research shows that injections of it raised people's perceptions of how hungry they were. The injections also caused them to eat a lot more.
But ghrelin isn't the reason people get fat in the first place. In fact, Dr. Cummings says, ghrelin levels drop slightly in obese people as the hormone "tries to help" when it senses that the body has too much fat. But when people start dieting in earnest, the body senses deprivation, and ghrelin kicks into high gear again.
In ambushing diets, it's possible that ghrelin is working in conjunction with leptin, a hormone known to create a feeling of satiety. Leptin levels drop after a diet, so the ghrelin findings suggest that the two hormones may be creating a double-whammy to foil the best of intentions.
Leptin, discovered in 1995, has so far proved a disappointment as a diet nostrum because overweight people tend to have a resistance to it. Today, ghrelin is the hot new kid on the block. "Every pharmaceutical company I know" is hunting for drugs that stymie its action, Dr. Cummings says.
The ghrelin programs are shrouded in secrecy, for competitive reasons. Merck & Co., Whitehouse Station, N.J., is working on the hormone but is mum on the details. Lilly will say only that it has "an active program" in ghrelin research. "Our scientists are extraordinarily interested in this topic, but we really can't comment," says spokeswoman Kindra Strupp.
The New England Journal findings may also explain the remarkable success of a surgical weight-loss method called gastric bypass. That approach, which has gained popularity in recent years for the treatment of morbidly obese people, involves bypassing most of the stomach by sewing off all but a tiny pocket at the top. That pocket is linked directly to the intestine. The surgery effectively creates a very small stomach, limiting food intake.
The surgery can be dangerous, and even fatal. But researchers have found in recent years that it can also be extraordinarily effective, allowing patients to lose 50% to 80% of their body weight and keep it off for a decade or more. Certainly, a smaller stomach would be expected to cut hunger somewhat, but scientists would have expected bypass patients to retain some of their former cravings and adapt to the surgery by eating many smaller meals throughout the day.
Mysteriously, most don't. The reason, again, may be ghrelin. In a separate group of patients who had undergone bypass surgery, ghrelin levels dropped like a stone and remained at extraordinarily low levels, according to the New England Journal article. After surgery, ghrelin didn't even rise before meals as it does in most people.
Scientists don't yet know why gastric bypass surgery turns off ghrelin production, but they suspect that when the stomach is empty for very long periods, as in a fast, the body just stops bothering to make it.
That explanation makes sense to James Rudolph, 55. Mr. Rudolph, of Ocean Shores, Wash., saw his weight fall to 265 pounds, from 460, after bypass surgery three years ago.
Like the others in the study, his ghrelin fell sharply. Prior to the surgery, Mr. Rudolph says, "I'd finish breakfast and want to know what we were having for dinner." Now, he often doesn't notice he's hungry until his blood sugar is so low he feels faint. After he gets the shakes, he says, "I go 'Oops, I guess I should eat something.' "
