Richard G. Petty, MD

The Neurology of Eating

Any attempt at weight management that fails to address the whole person is doomed to failure.

It is not enough to diet and exercise, and whatever the truth of manifesting, you cannot think yourself thin. Success demands an approach that integrates every system of your body, mind, social and subtle systems. For many people there is even an important role for integrating their spirituality into a plan for healthy living.

So we need to learn as much as we can about each component. Some fascinating new research has added some important pieces to the puzzle.

Writing in the journal Nature a group of scientists from University College London and King’s College London used peptide YY (PYY), a naturally occurring hormone that regulates appetite, to investigate which areas of the brain are involved in controlling food intake.

PYY is released into the bloodstream from the intestine after we eat something. In animals PYY signals the appetite control centers in the hypothalamus and brainstem that food has been eaten. Injections of this hormone have been shown to decrease food intake both in healthy volunteers and in people with obesity.

The hypothalamus and brainstem are ancient regions of the brain involved I te most basic functions. But humans have complex, highly developed brains, and the question was to discover how PYY regulates eating in humans.

The study involved eight normal weight men in a double blind placebo-controlled study. After 14 hours without food the subjects were given an intravenous infusion of either PYY or placebo for 100 minutes. During all this their brains were scanned continuously using functional Magnetic Resonance Imaging (fMRI). Thirty minutes later they were offered an unlimited meal. Each subject was tested twice one week apart, once with PYY and once with the placebo. PYY infusion reduced food consumption in all 8 subjects and on average caused a 25% reduction in the calories eaten.

Now it gets interesting. The fMRI scans showed that PYY not only targets the primitive parts of our brain that control feeding but it also acts in the corticolimbic brain regions that are involved in the rewarding and pleasurable aspects of eating.

The greatest change in brain activity in response to PYY was within the orbitofrontal cortex (OFC), a region that acts as an integrative center in the brain and is also implicated in reward processing. The change in OFC activity predicted how much food the volunteers subsequently ate. The greater the activation, the less people.

When we are hungry, brain activity within the hypothalamus predicts how much food we should eat. However an infusion of PYY tricks the brain into thinking that it has eaten, and switches on the circuits that control eating. The activity in the orbitofrontal cortex now predicts how much people will eat in the future.

If you have not eaten for a long time, you get full very quickly. It is not that your stomach has shrunk; it is that the production of hormones like PYY has been turned down. When you eat, they are over-produced and switch off more eating. When someone has gastric bypass surgery, their levels of PYY go up and stay up.

An important aspect of weight management is to retrain and reprogram the mind and body.

This research helps to show us how the approach works.

A Pill for Every Ill?

Many of us have been becoming more and more worried by the idea that if we don’t like something, then we should take a pill, rather than trying to get to grips with the causes.

Can’t sleep? Take this pill. {Ahem, but why not try sleep hygiene first?)

Shy? No, you’re not allowed to be shy, you have social phobia, take this medicine.

Don’t like the size of your tummy? Don’t exercise; we have just the pill for you!

Not only does this approach undermine our responsibility and autonomy, it also minimizes the suffering of people with real clinical problems. When every headache gets labeled a “migraine” and every cold gets turned into “’flu,” it is easy to lose patience, empathy and understanding for people who are really suffering with the genuine article.

Here is a fine example of an announcement that has doubtless caught the attention of headline writers around the world. Researchers from the Medical Research Council’s Human Reproduction Unit in Edinburgh in Scotland are reported to be working on a pill that would simultaneously boost a woman’s libido while at the same time reducing her appetite for food.

So what is this all about? Professor Robert Millar leads the Edinburgh team that has been looking at the properties type 2 gonadotropin-releasing hormone (GnRH), one of the hormones responsible for the release of sex hormones.

When it was given to monkeys, they displayed mating behavior such as tongue-flicking and eyebrow-raising to the males. When it was given female musk shrews, they displayed their feelings via “rump presentation and tail wagging.” These are two interesting visual images.

The thing is this. The tongue-flicking, eyebrow-raising tail wagers also ate around a third less food than they normally would. So now the search is on to find a pharmaceutical company that would like to make some kind of GnRH pill that would, presumably, produce libidinous skinny women.

Not only is this a frightful type of reductionism, but it raises all kinds of ethical issues.

The researchers in Edinburgh have been turning out a substantial body of very respectable data over the years, and this story looks very much like something that has been embellished.

Few people believe that eating or human sexuality are reducible to single chemicals in the brain. Low libido is a common problem, but it is usually a sign of stress, fatigue or relationship problems, rather than a chemical imbalance in the brain. And what, when and how we eat is an extraordinarily complex issue that is as much psychological and social as it is chemical. Stimulating the libido of someone in a lousy relationship is unlikely to lead to peace and harmony.

The whole concept also returns to the question of “what is normal?” when it comes to food, size or sex.

Do Healthy Foods Taste Bad?

There is a valuable study in the Journal of Marketing, which I must confess is not normally on my overloaded reading list. At least it wasn’t until I discovered an astonishing number of articles that are highly relevant to our basic themes of Health, Integrated Medicine, Meaning and Purpose.

We are all constantly puzzled by the way in which so many people seem to enjoy unhealthy foods. This is a matter of enormous importance: countries like China and India are now getting fattest the fastest, partly because of their peoples’ craving for Western junk food, coupled, in many cases, with a metabolic inability to process the food in the same way that most Europeans do.

Well, according to this study, foods that we think are healthy taste worse. This is the “unhealthy = tasty intuition.” In one of the experiments, test subjects were offered a mango lassi, an Indian yogurt drink that has the consistency of a thick milkshake. Those who were told that the lassi was “unhealthy” liked the drink significantly more than those who were told the drink was “healthy.”

When I was a young student one of my teachers told me that patients always believe that if something tastes foul then it must be doing them some good. A lesson that I had learned from my grandmother when still a small child. By the age of five I already knew that any rash or snivel would mean having to take some pungent and disgusting potion: some secret recipe that had been in the family for generations. Even then I wondered how it was that so many family members had lived to great ages. It didn’t seem possible.

This research fits in with the teachings of my grandmother and my professor. People assume an inverse relationship between tastiness and healthiness. In the study people believed that what they were consuming was unhealthy, they guessed that it would taste better, be more enjoyable to eat and that they would be more likely to choose it in a test.

This is important research and has a number of practical implications for helping people to adopt more healthy eating patterns.

This reminded me of a salutary lesson. Some years ago I spent a very happy year doing a part time course in wine tasting. Fascinating topic taught by Masters of Wine who said that they could tell incredible things about a wine after the smallest taste. A couple of years ago such claims were put to the test in Bordeaux in France, which is, of course, famous for its wines. In the first experiment 54 acknowledged wine experts were asked to give their impressions of two glasses of wine: one white and one red. The wines were actually the same white wine, one of which had been tinted red with an odorless food coloring. But here it gets interesting: the experts described the “red” wine in language typically used to describe red wines. For instance one said tat the colored wine had a “flavor of crushed red fruit.” Not a single one noticed it was actually a white wine.

In a second experiment an inexpensive wine was presented to the experts in two different bottles, one fancy and one plain. The experts gave the two bottles completely different evaluations. The experimenters described their results in terms of the interaction between vision of colors and odor determination. But we can also interpret the data in terms of expectation and perspective. If we expect something to taste good it tends to do so. Yes of course you can get a nasty surprise, but there is a powerful subjective component in how we interpret sensations.

I strongly suggest that you analyze your own reactions to food. Do you believe that healthy foods have to taste awful?

This may be an important key to changing your own eating patterns.

“Life expectancy would grow by leaps and bounds if green vegetables smelled as good as bacon.”
–“Doug Larson”

“As for food, half of my friends have dug their graves with their teeth.”
–Chauncey M. Depew (American Politician and, from 1899-1911, Senator from New York, 1834-1928)

“To lengthen thy life, lessen thy meals.”
–Benjamin Franklin (American Author, Inventor and Diplomat, 1706-1790)

“If you have formed the habit of checking on every new diet that comes along, you will find that, mercifully, they all blur together, leaving you with only one definite piece of information: french-fried potatoes are out.”
— Jean Collins Kerr

(American Author and Playwright, 1923-2003_

Insulin Resistance, Diabetes and the Timing of Meals

At a meeting of the American Diabetes Association in June 2006, Professor Markus Stoffel from the Eidgenossische Technishe Hochschule in Zurich and Rockefeller University in New York, received the Outstanding Scientific Achievement Award for his extremely interesting and important research on the molecular mechanisms involved in the developmental insulin resistance.

This may sound as interesting as watching paint dry, but in actual fact the research is supremely practical, and may lead to a complete re-working of some commonly used dietary strategies.

Many physicians have not yet been taught that the liver is the key organ involved in the genesis of insulin resistance and of type 2 diabetes mellitus. Up to 90% of the glucose circulating in your blood has come from your liver. As the liver becomes less sensitive to the actions of insulin, it starts producing more glucose, particularly after meals. This in turn causes blood glucose to rise and with it insulin levels. One of the other consequences of insulin resistance is that the liver stops storing triglycerides, which then start circulating, while at the same time storing other types of fat, leading to what we call, not surprisingly, fatty liver. Or in the dog Latin that doctors use to confuse the general public, hepatic steatosis.

When we are fasting, the liver switches on banks of genes that produce the enzymes responsible for oxidizing fatty acids to produce fuel.

The main objective of a balanced diet is to maintain balance: we want to avoid sudden swings in glucose, fatty acids or insulin: it is these sudden changes that can cause inflammatory changes in blood vessels and in the liver and may lead to some of the circulatory problems that are such distressing complications of diabetes. We want to try and keep our insulin levels smooth and low. The best way not to do that is to have frequent high calorie snacks and to eat late at night. The best way is to follow the plans that I’ve talked about before. Eat little and often, keep the balance of nutrients just right, and be aware of the exact times at which you eat. Nothing except a little protein in the 2-3 hours before you retire for the night, and go very easy on alcohol, which can wreck your metabolism.

“The secret of life is balance, and the absence of balance is life’s destruction.”
–Hazrat Inayat Khan (Founder of the Sufi Order of the West, 1882-1927)

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Acupuncture for Obesity

I was recently astonished to realize that it is now 25 years since I began my training in acupuncture.

It is an extraordinary system of prevention and treatment, yet one of my biggest disappointments has been the lack of effect in smoking and obesity. I have plenty of friends and collegues who have had great results, but I just have not. In fact I find that the "tapping therapies" seem to be a lot more helpful.

So I was interested to see a note about a report from Germany, that claimed modest success in treating the weight gain that can accompany treatment with some prescription medications. It will be interesting to see if anyone else is able to replicate the study. If they do, I shall report it immediately.

In the meantime, we have enjoyed considerable success with an integrated weight management strategy that addresses the physical, psychological, social, subtle and spiritual aspects of the issue. If you try only to diet and/or exercise, the long term results are usually disappointing.

Address everything at once in a very carefully coordinated manner, and the results can be spectacular. Remember the adage: Combinations are Key.

I outline our strategy in the last chapter and CD of Healing, Meaning and Purpose. Later this year we shall be publishing the entire program, and inviting researchers to examine our approach objectively.

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Another Controller of Appetite and Weight

We recently discussed the role of cytokines in modulating appetite and energy balance. Now a study in mice has shown that animals deficient in interleukin-18 (IL-18) develop a voracious appetite, very marked obesity and insulin resistance. The insulin resistance is secondary to the obesity that was induced by increased food intake and occurred in the liver as well as muscle and fat.

When the little creatures were given recombinant IL-18 their food intake returned toward normal.

Only recently discovered, IL-18 is an important regulator of innate and acquired immune responses. The fact that a modulator or immunity and inflammation has a key role in feeding and in energy metabolism shows us once again just how closely all these systems are tied together. You lose weight when you are sick or depressed because the body is battling the illness. As you recover, the body needs to replace everything that was lost and re-establish your resilience. These systems don’t just exist in humans, they are found in all mammals and even some birds and fish. So they have evolved over millions of years and we need to be very careful about tinkering with these complex systems. Or of allowing stress or environmental toxins to compromise these protective mechanisms.

This finding may well pave the way not just for new pharmacological approaches to weight management, but also to some non-pharmacological approaches.

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Cytokines and Weight

Anyone who has ever had a sick child knows that one of the surest signs that he or she is recovering is a return of appetite. From a biological perspective, this is an attempt by the body to make up for any losses that took place during the illness. The major mediator of this effect is one set of a group of chemicals known as cytokines.

Cytokines are glycoproteins that behave like hormones and neurotransmitters, serving as chemical messengers between cells. There are many families of cytokines, including leptin, that we have met before. In recent years most of the attention of researchers has been directed not at the cytokines themselves, but at their receptors, whose activity is far more subtle.

Cytokine receptors are involved in the regulation of cell growth and repair and have important roles in immune responses. Apart from their role in feeding behavior, cytokines have roles in fatigue, fever, sleep, pain and stress. Some key cytokines: interleukin (IL)-1,  IL-6 and IL-8 are dysregulated in fibromyalgia.

At a meeting of the 6th International Congress of Neuroendocrinology in Pittsburgh last month, researchers from the Centre National de la Recherche Scientifique (CNRS) at the Pasteur Institute and the University of Lille, France, presented evidence that The cytokine interleukin-7 (IL-7) is not only involved in immune function, but also prevents obesity-prone mice from getting fat. This is the converse of those cytokines that cause weight gain. IL-7 interacts with the regions of the hypothalamus involved in appetite control. This is yet another piece of evidence indicating that the immune and neuroendocrine systems are closely inter-linked.

This is not really a surprise. One of the big problems I people with many chronic illness, particularly cancer, is that they tend to lose appetite and weight. Sometimes they lose a great deal of weight even while maintaining a decent diet. The anorexia of cancer is caused by many factors working on the signaling pathways in the hypothalamus that modulate energy homeostasis. Research has shown that cytokines are major mediators of weight and appetite loss in cancer patients, by working on two systems known as melanocortin and neuropeptide-Y. It also seems likely that the weight loss that happens with stress, depression and chronic inflammation are all mediated by specific cytokines. These same cytokines increase the risk of developing heart disease. A recent study from Ireland has shown that treatment with an SSRI antidepressant reduces measures of systemic inflammation.

It may be that this new insight into the relationship between inflammation and weight will offer up some more solutions for the problems of obesity, but we are going to need to be alert to the possibility that anything that modulates cytokines may increase the risk of vascular disease.

The more that we learn, the more that we understand about the miraculous checks and balances that keep us healthy.

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Satiety: Another Kind of Gut Feeling

According the World Health Organization, there are currently over one billion overweight people in the world today. The ever-increasing prevalence of obesity in young people promises that this pandemic is likely to worsen in the coming years, putting an intolerable strain on healthcare systems. I have frequently commented on the problems of using a reductionist approach to weight management. You probably know from personal experience that any diet works for a while and then, unless something drastic happens, the weight usually returns. Similarly some of the drugs available for treating obesity may indeed work, but usually only in the short term and their usefulness is limited by side effects.

I want to say more about why the problems of weight can be difficult to manage and why the solution is not another fad diet aimed at modulating one hormone, such as leptin, or one neurotransmitter like serotonin or dopamine. I have mentioned before that there are multiple systems involving at least 260 tightly interconnected hormones and chemical transmitters coordinating the control of body weight. There are so many because weight is critical to survival and, with the possible exception of the brain, the more critical a system, the larger the number of fail safes and backups: the greater the degree of redundancy. Imagine a tent being secured by 260 ropes. But not just any ropes, these are intelligent cooperative ropes. Cut one, and the tent will stay in place because there are still hundreds left in place. Give it a little time, and the remaining 259 ropes will take up the slack, and the tent remains unmoved. Professor Steve Bloom from the Hammersmith Hospital and Imperial College Faculty of Medicine in London, has been a world leader in research into intestinal hormones and weight management for over thirty years, and he has just published a brief overview that focuses on just a few of the hormones known to be involved in the maintenance of body weight, and highlights the reason why some of them are attracting the interest of pharmaceutical companies. As well as holistically-oriented physicians.

It is now known that the regulation of appetite and food intake involves a complex series of interactions between higher cognitive centers in the brain, more primitive brain regions that we share with birds and reptiles, and the rest of the body. Amongst the key players in this whole vast orchestra are the endocrine systems of the gut, that play an important role in inducing and maintaining feelings of satiety.

The list of gut hormones involved in the maintenance of weight is a long one, that can be confusing to people who are not expert in the field. Here are just a few of them:

  • Cholecystokinin
  • Glucagon-like peptide 1
  • Peptide YY
  • Oxyntomodulin
  • Ghrelin
  • Pancreatic polypeptide

This is by no means the whole list, but you get the idea. At least one model for obesity suggests a breakdown or deficiency of some of the gut hormones that normally signal satiety. In effect, people do not know when they are full. In addition, disturbances of some of these hormones may lead to fat being deposited in some of the danger areas of the body, particularly inside the abdomen.

If I were to give you a breakdown of all the recognized weight control systems in the brain, I think that both of us would probably fall asleep

Yes, these understandings will enable drug manufacturers to produce new drugs to help with obesity. But that is only part of the story. We have found time and again, that the most effective way to normalize weight and eating habits is to deal with it from five different directions:

    1. Physical
    2. Psychological
    3. Social
    4. Subtle
    5. Spiritual

In previous articles I have already given some broad brush strokes about what constitutes healthy eating. Strategies that work WITH rather than against systems that have been evolving for millions of years. In future articles I shall also share some of the weight management techniques that I detail in my book Healing, Meaning and Purpose.

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Fat Facts

I was very pleased to see that Dean Ornish is now writing a column for Newsweek magazine, and that Andrew Weil will be contributing to Time. This is good news: both of them have made original contributions to holistic health care, and have always been very reasonable in their pronouncements.

Dean’s debut column has just come out. As you might expect, given his long history of making valuables contributions to the diet debate, he has called his article The Facts About Fat, and he reports on an important article published earlier this month in The Journal of the American Medical Association. The study presents some of the results of the Women’s Health Initiative dietary modification study, which followed nearly 49,000 middle-aged women for more than eight years. The study compared those on a regular diet to those on a low-fat diet, to see if dietary modification could help prevent heart disease and cancer. The women in the “dietary change” group were asked to eat less fat and more fruits, vegetables, and whole grains each day to see if it. The women in the comparison group were asked to continue on their usual diets.

The results of the study have caused some consternation, because low-fat diets did not appear to protect against heart disease, or stroke, or breast cancer, or colon cancer. But here we come back to a point that I have made in other articles. We must not take studies at face value, but instead analyze the data in detail. It is hard work to extract the real message from published data, but it is incredibly important to do so.

So what were the limitations of this study?

1. The reduction in dietary fat was very small.

2. People are not good at keeping diet diaries, and often think that they are eating more healthily than they are. (Some years ago we did an experiment in which we estimated our daily calorie intake and also kept diet diaries. We were all experts in human nutrition, but each of us under-estimated out intake by about 300-500 calories per day)

3. The increase in consumption of fruit and vegetables was small.

4. The control group that was supposed to stay on their regular diet actually did not. Most of us know something about healthy eating, and most people are making some changes toward better diets.

5. Eight years is actually quite a short duration for a cancer prevention study.

Dean then returns to a favorite and important theme: the study didn’t distinguish between beneficial and harmful fats. Several previous studies have shown that the omega-3 fatty acids found in salmon, halibut, mackerel, walnuts, and flax seed oil may reduce your risk of a heart attack by 50 percent or more, as well as perhaps reducing the risk of inflammation and some forms of cancer.

I am certainly persuaded by the data on omega-3 fatty acids, as well as recent evidence indicating that reducing overall dietary fat to around 33 grams of fat per day, reduces the risk of breast cancer recurrence by 42%.

Dean also endorses another comment that I have made in previous posts: what you include in your diet is as important as what you leave out.

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