Article by Samantha Murphy

Change your stomach, change your brain - 16 May 2012 - New Scientist

Weight-loss surgery cures food cravings. But it also makes some minds sharper, others duller. Find out why – from someone who's been through it

IT HAD been so long since I had had anything to drink but water. Finally, the day I had been waiting for arrived and I mixed a glass of my favourite peach iced tea. Anticipating its tart sweetness, I took a big swig of the drink, holding it in my mouth to savour the flavour. My euphoria turned to horror. It tasted like fish.

I spat the foul brew into the sink and tried the raspberry flavour. Fish, again. I slumped dejectedly onto the sofa. Why had no one warned me about this?

Two weeks earlier, I had had surgery to help me lose weight. Eating and drinking had been a struggle ever since: my new hypersensitivity to sweetness was surpassed only by the nausea that hit me when I smelled cooking meat. What was going on?

I hunted for answers in online forums. While my turncoat taste buds seemed to be a common phenomenon after weight-loss or bariatric surgery, no one offered a convincing explanation. But I soon realised that I had got off lucky: the forums were filled with horror stories detailing side effects, from memory loss and anxiety to auditory hallucinations. Even more puzzling were the unexplained mental boosts. About three months after surgery, a significant number of people experienced a sudden burst of "mental clarity".

No obvious thread linked these effects - but it seemed that when surgeons operated on our stomachs, something had happened in our brains, too. Even more intriguing, the surgery seems to work precisely because it creates fundamental changes in the brain. How can this be happening?

For me, surgery was a last resort. I had struggled with my weight since early childhood, and last year I finally opted to have a surgical procedure called a duodenal switch.

Surgery offers many ways to reduce the size of the stomach (see diagram). Least invasive is a band that constricts it, but if you want to surgically restrict the stomach, the most popular option is Roux-en-Y or "gastric bypass". All such bariatric surgeries work on the same principle: they reduce the amount of food the body can absorb. In the US, where 36 per cent of the population is classified as obese, at least 200,000 people sign up to have the surgery every year, and that number keeps climbing.

Keeping the weight off

That's because surgery works. Whatever procedure people have, most find that their excess weight melts away within 18 months (Obesity Surgery, vol 6, p 651). For at least 50 per cent of those who choose the more invasive methods like Roux-en-Y, the weight stays off, demolishing the abysmal long-term success rates of diets and pills (Annals of Surgery, vol 254, p 272).

Initially, this success was thought to be down to the mechanics - constricting the stomach simply meant a person ate less. There was just one problem with that logic. If it were so simple, 50 per cent of people wouldn't regain their weight, for example by eating high-calorie, liquid foods like heavy cream-based soups and ice cream milkshakes. Those who kept the weight off did so in spite of the availability of such workarounds. There had to be another reason for their success.

The first clue lay in my taste buds' bizarre behaviour and how that affected my food preferences. Most doctors will tell you that long-term weight loss is only possible with sweeping lifestyle changes: eating foods with less fat and fewer calories. Unfortunately, by definition, most weight-loss methods foster a temporary "dieting" mentality, which is quickly discarded when the goal is reached or when disappointment overtakes motivation.

One reason it is so hard to keep weight off is that we are fighting our very nature. We are all hard-wired to crave unhealthy foods, and these cravings only intensify after we have lost weight by dieting.

But a strange thing was happening after bariatric surgery - food cravings were immediately, massively dampened. "People who have lost weight after surgery don't report a compensatory increase in food cravings or hunger the way dieting people do," says Stephen Benoit, a behavioural neuroscientist at the University of Cincinnati, Ohio, who studies obesity. Quite the opposite: they tend to report reduced levels of hunger, fewer food cravings and an overall altered relationship with food.

Food cravings aren't simply reduced, they are transformed. Within hours of any weight-loss surgery, many people can't stand the taste of sugar or fat and sometimes find the very smell offensive, says Carel le Roux, a bariatric endocrinologist at the Imperial Weight Centre in London. For Roux-en-Y, the effects linger. "In the long-term, we find people shifting their food preferences and going for the salad bar instead of a burger and fries," he says.

Might the switch be psychological? Perhaps, after expensive and physically demanding surgery, people convince themselves they crave only healthy foods. So le Roux and his team devised a test to tease out what lay behind these behavioural changes. They performed Roux-en-Y surgery on rats and then tested their subsequent food preferences. Like so many of their human counterparts, the rats almost instantly shifted their tastes to favour lower-fat, lower-sugar items. "These rats had never met a dietician," says le Roux, "so it wasn't as though they were suddenly more motivated to make healthier choices because they had surgery."

Le Roux had confirmed that these changes were physiological. But what could be causing them? An obvious starting point would be the hormones generated by the digestive system. The upper stomach, for example, produces a powerful hunger-promoter called ghrelin. The small intestine releases a number of appetite-suppressing hormones that promote satiety, including glucagon-like peptide-1 (GLP-1) and peptide YY, or PYY. Even fat cells play a part in regulating appetite, releasing leptin, a hormone that inhibits the desire to eat and regulates metabolism.

Weight-loss surgery cuts into these major hormone manufacturing areas, radically altering their production. "Gastrointestinal hormones and leptin levels change after Roux-en-Y, and do so in a favourable direction," says Lauren Beckman, a researcher at the University of Minnesota in Minneapolis who is studying hormonal changes in people who have had bariatric surgery.

Rearranging the stomach also lowers the production of appetite-stimulating ghrelin, which might explain why many surgery recipients have to force themselves to eat (Journal of Parenteral & Enteral Nutrition, vol 35, p 169). Leptin, too, is affected, spiking immediately to damp down hunger (Journal of Clinical Investigation, vol 118, p 2380).

Could it be that these hormone changes were triggering the weight loss? Beckman thinks so. If it were the other way around, she explains, "elevated hormone levels would not be expected to occur until at least one month later". Instead, she and other researchers are finding that concentrations of appetite-suppressing GLP-1 and PYY increase within about two days. Not only do these changes happen immediately, but they stay that way, Beckman found, for at least one to two years after surgery.

Intriguingly, the effects of GLP-1 and ghrelin seem to reach beyond the metabolism. Recent animal studies have shown that both hormones can disrupt the nervous system and synaptic plasticity - the very mechanisms that create structural and functional changes in the brain. For example, ghrelin alters the wiring of mouse neurons (The Journal of Clinical Investigation, vol 116, p 3229).

Researchers are not completely sure what these fluctuating hormones do to the human brain, but they have a ready-made experimental pool: people who have had weight-loss surgery.

"Super normal"

The post-surgical flood of GLP-1, for example, immediately creates changes in the brain's reward centres in the orbitofrontal cortex, says le Roux. Could this explain the permanent shift in food preferences? To test the connection, last year, he and his colleagues at Imperial College London used MRI scanners to look at the brains of people before and after they had Roux-en-Y surgery. The results were staggering. Before surgery, pictures of cakes or burgers caused large areas of their reward centres to light up. But when the experiment was repeated just four days after surgery, their reward centres were impervious to the sight of the tempting foods. "Their exaggerated satiation makes the patient in effect 'super normal'," le Roux says, which accounts for the permanent weight loss. Their brains' circuits were being rewired to make them think like thin people.

That's not all. There is also evidence that changing the gut hormones' balance explains the improved brain function people reported on the weight-loss surgery forums.

GLP-1 is a particularly strong candidate for this effect. Because it suppresses the appetite by lowering blood sugar, it appears to have a strong effect on insulin, whose production drops dramatically within hours of surgery. Lower insulin levels, in turn, reduce the insulin resistance caused by excess weight, which has itself been tied to neurological problems (Neuroepidemiology, vol 34, p 222).

Although we don't understand exactly why, most researchers agree that obese volunteers tend to perform less well than leaner people on some learning and memory tasks, specifically ones that measure what is called inhibitory control. This is a subtle measure: your ability to remember where you parked your car this morning depends on your short-term memory. But distinguishing where you parked your car this morning from where you parked it yesterday morning requires inhibitory control, which involves suppressing yesterday's information. So while it is certainly not true that obese people are less smart, it seems they aren't able to distinguish this information as well.

Some researchers think the simple act of balancing insulin levels lifts this cognitive burden. In 2010, Gladys Strain, an obesity researcher at Cornell University's medical college in Ithaca, New York, found that just three months after weight-loss surgery, people scored better on cognitive tests than they did prior to surgery. One year later their test scores were even better (Surgery for Obesity and Related Diseases, vol 4, p 465). Benoit says his group is also finding evidence of cognitive improvements after weight-loss surgery.

But there is a stinging caveat to evidence that the brain is permanently altered by surgery: not all of the changes are positive.

Keith Josephs made the connection by accident. Several years ago, Josephs, a neurologist at the Mayo Clinic in Rochester, Minnesota, began seeing a steady increase in patients with a variety of cognitive problems. Frustrated when batteries of tests revealed nothing amiss, they had turned to him. "They were coming to me with issues like having trouble finding the right word, difficulty concentrating at work, being slow to respond to people talking to them and short-term memory issues," he says. Initially, he was nonplussed. Then he began to see a pattern. All of them had had Roux-en-Y surgery.

Josephs set to work pulling participant records from the hospital database and comparing them against two control groups: obese people who had not had surgery, and people of a normal weight. His results, published late last year, were alarming.

MRI scans revealed that those reporting cognitive problems had 24 per cent less volume in the thalamus, a small area of the brain associated with memory, attention, concentration and sensory information about taste (Journal of Clinical Neuroscience, vol 18, p 1671). In particular, the thalamus contains binding sites for ghrelin and GLP-1 (Brain Research Reviews, vol 58, p 160).

Large changes in these hormones could affect this brain area in the same way they alter the reward centres. And just as the positive changes in food preference appear not to be temporary, so do these negative changes. "Once the thalami have shrunk, there is nothing we can do to regrow these nerve cells," Josephs says.

Josephs is cautious about the results of his small study, and acknowledges that it needs to be replicated. Nonetheless, he can't ignore or dismiss the results. The group was thorough about checking for confounding factors. For example, because the average age of the participants was 54, they screened for signs of Alzheimer's disease. They also tested rigorously for surgery-related vitamin deficiencies, and found none. Only hormonal changes could explain the shrinkage, he says: "The probability that this occurred just by chance is at best 1 in 1000."

These cognitive problems indicate that the effects of bariatric surgery are far more complicated than most surgeons currently imagine. Even my comparatively harmless fish tea defies explanation. "Taste changes after bariatric surgery in strange ways," le Roux says. "Something is scrambling the signal from the taste buds to the brain."

Are certain populations more susceptible to the positive effects of bariatric surgery? Is one kind of surgery more likely to lead to cognitive decline than the others? Questions like these are only now being asked. The US National Institutes of Health, for example, has just funded a series of longitudinal studies to track the long-term health of people who have had different kinds of bariatric surgery. Some researchers are beginning to wonder whether these changes point to a "knifeless solution" that makes use of these hormonal fluctuations to combat obesity at the neurological level (International Journal of Obesity, vol 35, p 40).

Seven months and 45 kilograms later, I find myself benefiting from some of these effects. I still encounter the occasional unexpected cup of fish tea, so I find myself drinking a lot more water. Chocolate remains a joy, but only less sweet dark chocolate, and only in small doses.

There's no question that the possibility of neurological problems is scary. But for me, at least, they are easy to put into perspective. Weight-loss surgery is a life-saving procedure: with a few well-placed cuts, it knocks out diabetes, high blood pressure and sleep apnea, among others. In the context of my new mental clarity, healthier future, and all the small ways my everyday life has been improved, the threat of permanent cognitive effects seems to me a fair trade. Even with the occasional cup of fish tea.

Samantha Murphy is a freelance writer based in Pennsylvania