More on the Neurology of Obesity
The last year has seen a mass of new obesity research linking intestinal hormones and the brain.
Over the last 25 years, there has been increasing evidence that many people with significant weight problems have problems in a region of the brain called the hypothalamus that is involved in the control of appetite, feeding, temperature and a range of other bodily functions. On April 18th, I mentioned the intriguing possibility that viruses could be one previously unrecognized explanation for the obesity pandemic. It is hypothesized that these viruses might alter the normal functioning of the hypothalamus, causing an increase in feeding, and perhaps also of appetite and inactivity.
A study from Albert Einstein Medical College in New York, published in this month’s Journal of Clinical Investigation provides further evidence that there may be something wrong with the normal functioning of the hypothalamus.
We normally have a sensitive mechanism in the hypothalamus for sensing fats, which provide a strong signal to stop eating and also to start normalizing blood glucose. There are strains of obese rats, and in these little creatures the fat sensing mechanisms do not work properly. Not only do they keep eating, but also they cannot control their blood glucose properly. Those two things together conspire to produce yet more obesity. What was so interesting in this study, was that the researchers found that if they inhibited a single enzyme involved in fat metabolism, the levels of fatty acids rose in the hypothalamus, the animals were once again able to sense fat levels, and both their feeding and glucose levels normalized.
This is one of the first times that it has been possible to find a single enzyme that would normalize metabolism. The next question is to see whether this might constitute a viable treatment for obesity, or if the body would quickly work around the treatment and return to its old ways.
Technorati tags: weight control hypothalamus obesity
More Advances in Understanding Weight Control
I have on many occasions discussed the problem of over-simplifying the mechanisms controlling our weight and appetite. They are complex and have multiple fail-safes and multiple levels of redundancy, which is why most weight loss programs only last for short periods of time. The body gets used to the diet, believes that it is starving, and immediately gets to work to conserve energy: our metabolism slows and our physical activity levels begin to fall.
We can tinker with leptin, cortisol or insulin to our hearts’ content, and each will probably help for a while. But if we ignore the body’s starvation-protection mechanisms, to say nothing of the psychological, social and subtle aspects of weight, our efforts will usually be fairly short-lived. Most of us now understand that food intake is only part of the equation; we also need to maximize our metabolic rate and increase our level of physical activity. One of the problems has been how to help someone exercise whose body wants to go into starvation mode.
Steve Bloom’s group at Imperial College and the Hammersmith Hospital in London has published another valuable report helping to elucidate some of the complex mechanisms involved in appetite, weight and metabolism. Steve has been working in this area since the early 1970s, and is one of the most highly cited scientists in the world. In a field that constantly sees new discoveries replacing the old, he is unusual in that that virtually all of his work has stood the test of time.
This report concerns the intestinal hormone oxyntomodulin, which has a dual action, increasing energy expenditure as well as reducing food intake. It appears that oxyntomodulin may let the brain know it has an adequate energy supply and that it can afford to do productive things rather than just concentrating on food seeking behaviors or energy conservation. The hormone signals the brain that it can increase exercise by letting it know that the energy is available to do so.
At the moment oxyntomodulin has to be given by injection, and, given the complexity of the weight maintenance systems it is unlikely to be the whole answer.
Technorati tags: weight control obesity oxyntomodulin energy expenditure weight management
Viruses and Weight Gain
Another discussion in Healing, Meaning and Purpose revolved around the evidence that in addition to toxins, viruses have been attracting a great deal of attention as causative agents of obesity in humans. There are currently seven viruses known to cause obesity in animals and three in humans. This work began almost twenty years ago when a Dr. Nikhil Dhurandhar was working in India and discovered that viruses could cause obesity. It started with a chance observation: thousands of chickens were dying, and when they did, they were found to be abnormally heavy. He then discovered that people who had been exposed to a chicken adenovirus called SMAM-1 were consistently fatter than those who had had no exposure. He later moved to the U.S., and has collaborated with other researchers to study whether human adenoviruses, which are common throughout the human population, could be having a similar effect. This led to the discovery that the human adenovirus Ad-36 caused significant fat increases in animals, and furthermore was associated with obesity in humans. Now we have a new report from Leah Whigham and her team at the University of Wisconsin in Madison who tested several human adenoviruses for their ability to increase fat in both live chickens and in cell culture.
It is not at all far-fetched to suggest that there may in the future be vaccines to prevent one of the many causes of obesity. But for now, follow simple rules of hygiene and do everything that you can to improve your own resistance to infection. Which gets us straight back to Healing, Meaning and Purpose!
Technorati tags: weight gain, Nikhil Dhurandhar, virus,
Hunger and Memory
It’s always a good idea to see how new findings fit in with previous knowledge, and also to see if they make sense. We have previously met the hormone leptin, which is involved in decreasing appetite. Its twin is the hormone ghrelin. Discovered in 1999, ghrelin comes from some of the cells lining the stomach and acts in the hypothalamus to increase appetite. When the stomach is empty it is released into the circulation and travels to the brain where it activates receptors in many different regions. Some research has indicated that one of the reasons why gastric bypass surgery may be effective is because it reduces levels of ghrelin and therefore reduces appetite.
Research published in December 2004 showed that in healthy young men, sleep deprivation caused a decrease in leptin levels and an increase in ghrelin levels, which, as expected, was associated with an increase in hunger and appetite. This is one reason why getting less sleep than you need may cause you to gain weight.
A new study published in the journal Nature Neuroscience, has found an intriguing link between ghrelin and memory. I noticed that the BBC also picked up on this interesting story. Researchers at Yale have discovered that ghrelin acts in an ancient part of the brain known as the hippocampus: so named because it is shaped like a sea-horse. (As an amusing aside, the old German pathologists thought it looked like a silk worm, so that’s what they called it!) The hippocampus has a number of functions, but is most of all essential for learning new material.
The researchers showed that mice who lack the ghrelin gene had 25% fewer synaptic connections between their hippocampal neurons. They then did the next step, and injected normal mice with ghrelin. They promptly increased the number and density of their synaptic connections, which correlated with significant improvements in the animals’ performance on several tests of learning and memory.
So that means that a hormone produced by the stomach can control some brain functions, and this may represent a link between metabolism and the ability to learn. The more that we discover, the more we see the intimate interactions between the brain, intestines and heart.
This link makes good sense: we know that memory can be switched on and off by a range of factors. In order to help us come up with options for handling the environment and for remembering things to avoid, memory is often switched on at times of stress. Hunger is a form of stress, and it makes good biological sense that we might be more alert and better able to remember and to recall information when hungry. It stands to reason that this has enormous survival advantage. If our early ancestors had not had this hunger/memory link, they might well have died out in the competition for food.
This gives some credence to the old advice that it is best not to try to study or to take an exam on a full stomach. Just have enough food to make sure that you have ample fuel, and that you are not distracted by hunger pains.
Technorati tags: hunger, memory, stress, study habits
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:
- Physical
- Psychological
- Social
- Subtle
- 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.
Technorati tags: satiety, weight loss, weight control, diet, holistic diet, healthy eating
Green Cheese Claims and Needless Dietary Chaos
The front cover item of today’s Newsweek Magazine concerns the confused and confusing state of dietary advice in America, and indeed around the world. So much of the advice on offer is based on political considerations and a fundamental misunderstanding about the way in which knowledge grows.
People outside the academic world are often astonished to discover that it is not a world of quiet painstaking investigation and careful intellectual deliberation, but is instead a hot bed of neo-Darwinian competitive frenzy. Every academic is under constant pressure to publish or perish. There are constant and intense demands to bring in grant money. This pressure can lead to huge problems. Data is often published before it is ready.
As regular readers of my columns know already, I have been vigorous in exposing scientific misconduct, but I am also concerned about raising false hopes or giving false guidance on the basis of single studies. Any study, however well designed and executed and however many subjects it contained, still needs to be confirmed and confirmed again. If somebody at NASA produced evidence that the moon was made of green cheese, I doubt that they would be believed. Not unless the observation could be confirmed by hundreds of independent investigators around the world.
Yet every day I see people who have fallen victim to green cheese claims. People who have been persuaded to part with millions of dollars to buy supplements to help them lose weight, on the basis of very limited data and sometimes wild extrapolations. Often they are just not needed. As an example, people are usually not told that ten minutes in the sun and a glass of low fat milk will give them all the calcium and vitamin D that they need for a day.
The Newsweek article does a great job of teasing apart many of the competing claims.
A year ago Mike Johanns, the Secretary of Agriculture, launched the new MyPyramid initiative to highlight the 2005 Government Guidelines for healthy eating, which for the first time emphasized the importance of individualizing any approach to diet and exercise. Although there were all the usual allegations that the guidelines were simply a confection designed for the health of American farmers rather than the health of the American population, I really cannot agree with those comments. The guidelines represent a considerable advance on the old food pyramid, but as I have pointed out in previous postings, the problem with weight management is not just what you leave out, but also what to include in any healthy eating plan. I really do suggest that if you haven’t already, you look back at some of the suggestions that I’ve made previously on this blog.
Let me also direct you to another resource: The Psychiatric Resource Forum’s article “Nutrition for Americans” will point you toward other good sources of information that we have carefully vetted for accuracy. Although this blog was created for healthcare professionals, it also contains a lot of information of value to readers of this blog.
Later this year, we plan to publish a short book on the precise approach to healthy eating that I have been using with great success for many years now.
Technorati tags: green cheese, diet advice, MyPyramid, Newsweek
Integrated Health and Aging
An important principle of the emerging laws of health and healing is that anything helpful should help more than one system of the body at a time. So a diet that might help mitigate the effects of aging in the skin should also have beneficial effects on the major organs of the body.
So I was encouraged to see a new report indicating that cardiovascular health and a healthy lifestyle are associated with maintaining the health of our brains as we age. This is, of course, intuitively obvious, but it is always nice to see such things confirmed by empirical research.
The new report is from a multi-Institute collaboration of the National Institutes of Health (NIH) published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The chair of the committee was Hugh Hendrie, the Scottish-born professor of psychiatry from the University of Indiana, and the committee members were many of the most eminent people in the fields of aging and Alzheimer’s disease.
What is encouraging about this new report is that many of the factors associated with cognitive decline as we get older are eminently remediable: we have within our reach a set of potential interventions that could significantly reduce our personal risk of developing cognitive problems later in life. These are the things that we need to work on if we want to reduce our risk of developing cognitive decline later in life:
- Hypertension: There is excellent evidence that inadequately treated hypertension correlates strongly with cognitive decline.
- Physical activity: There is good evidence that elders who exercise regularly are less likely to experience cognitive decline. This is over and above the general improvement in quality of life that accompanies regular exercise. The earlier in life that we start, the easier it is to continue.
- Increased mental activity throughout life, including learning new things and going through higher education may benefit the health of the brain.
- Moderate alcohol use and the use of vitamin supplements also seem to be brain protectors, though the report does not specify which supplements.
- Social disengagement and depressed mood are both associated with poorer cognitive functioning, so it is important to be alert to signs of depression, and to maintain a social network. I discuss this in more detail in my book Healing Meaning and Purpose.
There are doubtless some genetic and environmental factors about which we can do little. But the idea that we now have a list of things that we can do to protect our brains is very exciting.
This report also signals another important change. In recent years we have seen the growth of Positive Psychology, the study of how to improve ourselves rather than the constant focus on psychopathology. This report calls for the research community to study health maintenance of the brain with the same energy that it has brought to bear on the study of diseases of the brain. To which I would add, that we must not just focus on how to maintain the health of the brain, but how we can enhance it’s function so that we can all reach and exceed our full potential.
Technorati tags: aging, Integrated health, Positive Psychology, healthy lifestyle,
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.
Technorati tags: Dean Ornish, Newsweek, Nutrition, low-fat diet
Lectins, Leptin and the China Study
I have just reviewed a most interesting book called The China Study at Amazon.
This book, touted as the most comprehensive study of nutrition ever conducted, is indeed a treasure trove of useful information. The first point that I particularly liked is that the author is not a reductionist. He understands that the idea of trying to reduce the value of foods to one food type or one nutrient is deeply flawed. Let me give you an example: there is some good evidence that tomato-derived lycopene has a great many health benefits, but that does not mean that the solution to all that ails us is a diet consisting solely of tomatoes. I was once asked to see a person who had a genuine problem with a series of food sensitivities: a well-meaning but poorly educated practitioner had put her on a diet of lettuce leaves, rice and spring water. Several months later I saw her because of profound weight loss and malnutrition. The problem was a lack of balance in the dietary approach, and failing to see the big picture.
T. Colin Campbell is definitely one who sees the big picture, both in terms of his own research, and the broader context. He rightly points out that trying to divorce nutrition from the whole diet and lifestyle is a fundamental mistake.
I noticed something rather interesting, which I have just seen picked up by another reviewer: there seems to be a strongly positive correlation between wheat consumption and the risk of sustaining a myocardial infarction.
The reason that I perked up on seeing this is that I have just been analyzing a paper from Lund in Sweden. The investigators’ fundamental premise is that the rise of agriculture and the consumption of cereals might be the underlying explanation for many of the diseases of affluence. The researchers did a study of pigs, and showed that by putting them on a cereal-free diet, the pigs’ insulin resistance, blood pressure and C-reactive protein all fell, which are excellent markers of cardiovascular health. They went even further and provided a biochemical explanation, pointing out that for all its many benefits, agriculture is exposing our bodies to novel lectins: plant proteins that bind to specific carbohydrate groups on cell membranes. (We met lectins in my previous posting on blood types). These lectins seem to have the worst type of biochemical properties that enable them to block the action of a key metabolic hormone called leptin. First discovered in 1994, leptin produces a satiety signal, telling your brain to stop eating. In some animals it may also cause insulin resistance. Leptin was very hot news a few years ago, because if an animal or a person is resistant to leptin, they become morbidly obese. So a number of pharmaceutical companies tried to develop obesity treatments based on leptin. Sadly, to date all of them have failed. It is not surprising that nutritional interventions based on modulating leptin have also been disappointing. At last count there were over 260 hormones and neurotransmitters involved in the maintenance of body-weight. So trying to manipulate just one of them is hardly likely to be crowned with success.
As I have said in other posts, there will always be someone, somewhere, who will respond to any kind of eating or life plan. The trick is in predicting who will respond to what, and in that we are still scratching our heads. So if you want an approach that has the highest overall chance of success at maintaining and improving your health, rather than just focusing on pounds, I’m going to repeat my advice from an earlier posting:
1. It is important for you to maintain your energy balance, between input and output
2. Calories do count
3. What you include in your diet is as important as what you exclude: we are designed to consume not just rice and lettuce, but an array of other nutrients.
4. Make only moderate dietary changes at any time: making big dietary changes can be a pretty violent attack on your body and your mind
5. Avoid the “trans-fatty acids”
6. Try to consume some omega-3 fatty acids every single day
7. Eat fewer simple carbohydrates
8. Use weight management and exercise strategies that enhance your overall health and well-being
9. Take more exercise: even small amounts can have a big effect.
And now I am going to add a tentative number 10:
10. If your weight and metabolic parameters are still not as they should be, discuss a gradual reduction of cereal intake with your health care provider, and how to ensure that you still get the amount of fiber that you need. Depending upon your own genetic make-up that may be the missing piece.
Technorati tags: The China Study, T. Colin Campbell, diet, lifestyle change, nutrition
Diet and Blood Types
One of my earlier posts entitled “What in Your Blood?” elicited a most interesting and important question from a reader:
“Does any of this have to do with the research that Dr. Peter D’Adamo has in his "Blood Type Diet" book? I have had clients tell me diseases and pains vanished when they followed his diet, while others had no effect. I would be interested in hearing your take on it all.”
This is a great question that gives me the opportunity to comment about this whole issue. I think that many of us have made similar observations to the reader who asked the question.
For people not familiar with this theory, D’Adamo’s notion is that our ancestors originally all had type O blood group, and that the appearance of agriculture was associated with the appearance of type A blood group, and then as recently as 10,000 B.C.E. – A.D. 1000, types B and AB started to evolve.
In this scheme, people with Type O blood group are the descendents of Hunters, the dominant, hunter-caveman types that require meat in their diet and should avoid wheat and beans. They are supposed to be most likely to suffer from asthma, hay fever, and other allergies. People with Type A blood are originally the Cultivators, and they should eat a vegetarian diet since they are predisposed to heart disease, cancer and diabetes; Type B blood group people were allegedly Nomads, and are dairy-eating omnivores who are susceptible to chronic fatigue and autoimmune disorders, such as systemic lupus erythematosus and multiple sclerosis. The rare individuals who have the AB blood group require a mixed diet, but should avoid chicken. They are supposed to be at risk of heart disease, cancer, and anemia, but tend to have the fewest problems with allergies. So D’Adamo decided that we should eat according to our blood types.
Like a lot of simple models, it is attractive and can be seductive. Yet the underlying concepts are deeply flawed. There are some weak associations between some blood groups and some physical ailments: to name just two, blood type A and coronary artery disease, and type O and gastric ulcers. That second one we now understand: people with blood group O are not able to mount a strong immune response to the usual causative organism: Helicobacter pylori. I did a literature review and dug up over 700 research papers on the subject of blood groups, disease and lectins (the adhesion molecules found, amongst other places, on red blood cells). There was nothing whatsoever to confirm D’Adamo’s claims. Indeed I think that some of his claims are potentially risky. Few people would agree with the idea of feeding some people high fat diets, and the theory takes no account of ethnic differences in food tolerability. For instance the high rates of insulin resistance amongst most people of Indian heritage, or the dairy intolerance common in much of the Asia-Pacific rim.
D’Adamo’s theory of blood group evolution is not correct. Far from having developed new blood groups with the arrival of agriculture, there is solid molecular evidence that the different blood groups were already present at least 5 million years ago. Gorillas and chimpanzees possess similar blood groups. One of the scientists quoted on the D’Adamo website is Winifred Watkins, who was one of the team that first described the structure of the molecules determining blood group types. She was only 29 at the time, and later she became a Fellow of the Royal Society and a mentor of mine. She passed away about three years ago. She was the person who first told me about the evolution of blood groups, and there’s now a fair bit written about it. The last great African Diaspora occurred long before the development of agriculture, and the migrants took their diverse blood groups with them. That is one of the ways in which migration patterns have been tracked. So there is no link between blood groups and “professions.” It is still possible that there is some other arcane link between optimum nutrition and blood groups, but it is now ten years since D’Adamo’s book came out, and we have to ask why there is no published research to support the claims. His website contains a lot of references to research papers on blood groups. Many are quite old, and there is no critical evaluation of the papers.
Yes, some people will benefit from any kind of diet or intervention, which is why some of your clients have benefited, but the predictive value of the four major blood group types is clearly very low.
Technorati tags: blood type diet,
