Richard G. Petty, MD

Nutrigenetics: A Peak Into the Future

At any given time only about ten percent of you genes are thought to be active. They are switched on and off in response to all kinds of internal and environmental changes. This is particularly true in the metabolic pathways, where gene activation is an essential part of the normal response to dietary changes. We also know that many of us have genetic reasons for varying in our nutritional requirements.

Anybody who has looked into diet and nutrition knows that there is no one approach that works for everyone, and the Holy Grail of weight management is to be able to identify which diet will work for whom.

This goal has just come a little closer with the publication of a report from researchers in Greece, London and Colorado that has been published in the Nutrition Journal.

The paper, “Improved weight management using genetic information to personalize a calorie controlled diet” is available for free download.” The study population consisted of 50 patients who had failed to lose weight. They were offered a nutrigenetic test screening 24 variants in 19 genes involved in metabolism. 43 patients attending the same clinic were selected for comparison using algorithms to match age, sex, frequency of clinical visits and BMI at initial clinic visit. The second group of 43 patients did not receive a nutrigenetic test. BMI reduction at 100 and over 300 days and blood fasting glucose were measured.

The results are very promising. After 300 days of follow-up individuals in the nutrigenetic group were more likely to have maintained some weight loss (73%) than those in the comparison group (32%). Average BMI reduction in the nutrigenetic group was 1.93 kg/m2 (5.6% loss) vs. an average BMI gain of 0.51 kg/m2 (2.2% gain). Among patients with a starting blood fasting glucose of >100 mg/dL, 57% (17/30) of the nutrigenetic group but only 25% (4/16) of the non-tested group had levels reduced to <100 mg/dL after >90 days of weight management therapy.

The paper concludes by saying that the addition of nutrigenetically tailored diets resulted in better compliance, longer-term BMI reduction and improvements in blood glucose levels.

This is a small “proof of concept” study, and the effects are not enormous, but there is easily enough here already to vigorously pursue this genetic approach.

Genes, Breastfeeding and IQ

Studies on intelligence and breastfeeding have come up with conflicting results. The major question has been whether the results have been skewed because more educated or more affluent mothers were more likely to breastfeed.

A new study by colleagues in London, New Zealand and here in the United States has just been published in the Proceedings of the National Academies of Sciences and indicates that a single gene influences whether breastfeeding improves a child's intelligence.

The gene in which the researchers were interested is a fatty acid delta desaturase – FADS2 – that is involved in the genetic control of fatty acid pathways. Children with one version of the FADS2 gene scored seven points higher in IQ tests if they were breastfed, but breastfeeding had no effect on the IQ of children with a different version of the gene.

Researchers at the Institute of Psychiatry, Kings College London, used data from two previous studies of breast-fed infants in Britain and New Zealand that had involved more than 3,000 children. IQ was measured at various points between the ages of five and 13 years in the studies. The only thing that we do not know is exactly how long the children were breastfed.

This is yet another study to show us why the nature/nurture debate needs a radical re-think. Nutrition and genetics act together. People have been arguing about the roots of intelligence for at least a hundred years, and this research shows nature working via nurture to create better outcomes.

Around 90% of people carry the version of the gene that was associated with better IQ scores in breastfed children. We do not know if there are any ethnic differences in those numbers, but there may be.

And that seven point difference in IQ? It s not going to determine how well someone is going to do in life, but in school it might be enough to put the child in the top third of the class.

Burning Fat And Carbs

I was just flipping through a few magazine articles about diet and exercise and it amazed me how each writer was telling the reader that THIS was THE TRUTH about how to exercise and burn calories, and yet many contradicted each other.

This confusion and attempt to insert some order and certainty should not be too much of a surprise: there is still an enormous amount about metabolism that is simply not known. All of the articles were well written and well intentioned. Yet I am sure that many of the writers probably do not realize how much of what they are saying is guesswork!

The whole field of exercise and metabolism remains in a state of flux, though good progress is being made.

In a some new research from the Copenhagen Muscle Research Center at the University of Copenhagen in Denmark has been published in the Journal of Physiology, that helps us to understand a little more about the way in which muscles metabolize during exercise.

During exercise and physical activity, the primary fuels used by muscles are carbohydrate and fat. When you do mild exercise you tend to burn relatively more fat and less glucose. But as the exercise becomes more intense, a higher percentage of the energy demands of the muscles are supplied by glucose, until at the highest intensities almost only carbohydrates are used. One key question for any aspiring exerciser is how and why this happens? Is the shift in fuel source a property of the muscle itself, or does it represent the interplay between what is happening in the muscle and the exercise-related responses in the rest of the body.

The research looked at muscle fuel utilization in the quadriceps muscle during graded exercise done with only one leg. Nine healthy males did the one-leg exercise at 25, 45, and 85% of maximal workload. Their results showed that when only a small mass of muscle is contracting, the shift in fuel source from fat to glucose with increasing intensity does not happen. The explanation is that blood flow and oxygen supply are easily able to keep up with the demand.

The key to understanding the shifts in fuel source do not lie in the muscles at all, but in adaptations in the whole body during exercise. The oxidation of fat during exercise requires a fine interplay between the cardiovascular, neurological, endocrine and muscle metabolic systems.

The research also helps explain why athletes "hit the wall" during events like a marathon: the body can no longer switch fuels efficiently.

There are also some implications for the adaptations made in middle-aged adults who are using exercise to prevent or treat conditions like diabetes or obesity.

What we need to do is use slower training methods with good quality loose breathing to maximize oxygenation of the blood. This in turn allows fat oxidation to be maintained even during intense exercise with a large muscle mass.

And it looks as if we are heading back to the idea that cardiovascular work should be done before we start lifting.

The Integrated Approach to Maintaining a Healthy Weight

Regular readers will have noticed that I have been posting much less than usual over the last couple of months. It is not that I have run out of things to say (!), but I have been working on some new projects that I shall be telling you about fairly soon.

There has also been something else that I had not planned to talk about until a conversation that I had a couple of days ago. I mentioned in passing that I had noticed that my weight had crept up a bit over the last couple of years, but that I had identified the reasons, corrected it, and lost twenty pounds over the last eight weeks. I was immediately surrounded by people wanting to know the secret. Well it’s no secret. It is a series of techniques that I, and people that I have trained, have used with thousands of people over the last thirty years. Then I realized that this secret had somehow not got as much coverage or publicity as it should have.

The other day I was talking to someone who has had some legitimate concerns about her weight for over ten years. She has tried every fad diet going, and has spent a fortune on books, tapes and courses. All to no avail.

I asked her, “Why do you keep falling for these fad diets? They are the nutritional equivalent of get-rich-quick schemes!”

“But there must be an answer somewhere,” she replied.

Well, she was half right: there is an Answer that is based on impeccable scientific research, and has been validated with tens of thousands of people. But it is not a fancy diet, supplement or exercise plan.

The first point is that we never recommend, “dieting” to get healthy. You get healthy so that your body can keep you do the work that it was designed to do. And that includes keeping you at your ideal weight.

Humans participate in multiple relationships, from our cells to our soul, and from the smallest atoms to the largest galaxies: we are connected to all of them. Weight problems invariably imply an imbalance in one or more of these relationships. We are more than physical bodies. We are also psychological, social and spiritual beings who are engaged in these multiple relationships. And the quality of these relationships is essential to our well bring.

The approach that we have used for three decades is very precise and consists of two parts.

First is the Plan: a series of steps that involve the re-integrations of your body with your mind, your relationships, the subtle systems of your body and your spirituality. Part Two consists of a series of “Rescues and Re-starts.” Anybody who has ever tried a weight management program knows that it is easy to fall off the wagon. There are times when things happen. You are tempted to miss an exercise session or to eat something that your body does not need. The beginner’s mistake is to respond by feeling bad, becoming disheartened or having someone reprimand you. Those are all a waste of energy. The smart thing is to have a series of sixty-second strategies that rescue you and start you on the Plan.

The first step is to treat you body so that you are ready to achieve and maintain a healthy weight. Remember the “hidden” causes of weight gain:

• Stress
• Salt
• Pesticides
• Viruses
• Intestinal bacteria

It can he hard to rid ourselves of all of these, but we can certainly reduce the effect that they have on us.

There may be other physical factors that contribute to weight problems. One that has recently attracted some publicity has been the idea that some people have a “leaky gut” – and increase in intestinal permeability - that allows them to absorb toxins that should stay out of the circulation. I have a friend and colleague who, starting in the early 1980s, did a ton of research on intestinal permeability in illnesses like alcoholism, celiac disease, inflammatory bowel disease, arthritis and schizophrenia. I also did a study of intestinal permeability in migraine, which was negative. There certainly are ways in which intestinal permeability can be increased: alcohol, allergies and some drugs will do it. But so far the evidence that increased intestinal permeability is a common cause of weight problems or other symptoms is not good. That could always change: that is what science is all about: testing falsifiable hypotheses and changing models, practice and recommendations if the evidence changes.

After attending to the physical side of weight maintenance, we go on to recommend some simple psychological work. As I said at the beginning, if your brain thinks that you are trying to kill yourself by starving to death, it will sabotage you: millions of years of evolution have designed you to stay alive and to put on weight whenever possible. So we it is essential to understand and work with those psychological mechanisms from the very beginning.

But it is not enough to simply change your thinking: much of your behavior is driven by unconscious, preconscious and subconscious “thoughts.” We also have several sets of emotional systems that drive our behavior. What’s more, there are separate sets of habits and automatic behaviors that we need to identify and deal with. We also have to deal with the effects of certain foods on your moods and perceptions: countless eating plans have failed because nobody considered that a person might be sensitive or allergic to some foods, or that changes in diet can have a big impact on the way in which our brains function. When we work with all of them the results start to come in very quickly.

We also have to deal with the social aspects of weight: have you been stigmatized because of weight? Have you been sabotaged by people around you, or family members? Do you or your family use meal times to socialize? Do you constantly eat out? There are a huge number of social issues that can mess with healthy eating. Ignore them, and it will be nearly impossible to achieve your aims.

We then also work on any disorganization or blockages in the subtle systems of the body, as well as the spiritual aspects of health and wellness.

It may sound odd to talk about spirituality when considering weight management and health, but they are inseparable.

It is only after we have done all of those things that we look at the precise composition of your diet, tailored to your age and gender. Just as important as what you eat, is when you eat. The way in which you exercise, stretch, breath and sleep can be as important as what and when you eat, and each has to be carefully tailored to the individual.

On a future occasion I shall explain exactly how your can work with each of the five systems of you body – Physical, Psychological, Social, Subtle and Spiritual – to create and maintain vibrant health and a radiance that at the moment you can only dream about.

That’s a promise!

“I don't eat junk foods, and I don't think junk thoughts.”
--Peace Pilgrim (a.k.a. Mildred Norman, American Peace Activist, 1908-1981)

“He that takes medicine and neglects diet, wastes the skill of the physician.”
--Chinese Proverb

“Give the body the attention it deserves, but not more. When you cultivate the attitude that you are the body, the body will demand from you more food, more variety in food, more attention to appearance and physical comfort.”
--Sathya Sai Baba (Indian Spiritual Teacher, c.1926-)

Insulin, Intestinal Metabolism and Arteriosclerosis

Here is some research that provides further evidence of the links between systems of the body.

Diets high in sugar and fats can cause chronic elevations of insulin. High levels of insulin are a key feature of insulin resistance, a metabolic problem that affects at least a third of people living in the Western world and is also growing extremely rapidly in much of the developing world. Insulin resistance may be caused by a diet or genetics, or most commonly a combination of the two. It is known that insulin resistance can lead to the development of diabetes and arterial disease. The question has been how?

Almost forty years ago it was first suggested that insulin itself might be the problem. Not only is insulin involved in metabolism, it is also a potent growth factor for some of the smooth muscle cells found in the wall of major blood vessels. There has also been a suspicion that some of the metabolic effects of insulin increase the risk of arteriosclerosis by actions in the liver and intestines.

In research published in the journal Atherosclerosis, nutritional scientists at the University of Alberta have found a connection between high insulin levels and dysfunction of intestinal lipid metabolism. The finding provides critical support for the notion that impaired intestinal metabolic function plays a critical role in the development of cardiovascular disease.

Using a type of obese rat, the researchers found that excessive insulin slows the removal of chylomicrons from the blood stream following a fatty meal. Chylomicrons transport dietary fat from the intestine to the rest of the body.

Excessive amounts of insulin appear to alter the dynamics of the walls of blood vessels, allowing chylomicrons and cholesterol to build up in them. Over time this build up may creates blockages in the flow of blood.

It is good to see research that is re-examining the role of chylomicrons in vascular disease. Interest in them began to wane about twenty years ago, and since then most of the research and most of the screening recommendations have been based on cholesterol. Most doctors have been taught that cardiovascular disease is connected to increased levels of low-density lipoprotein (LDL) cholesterol, which is derived from the liver. However, fifty per cent of cardiovascular disease events occur in the presence of normal LDL-cholesterol levels. That is one of the reasons why many experts in metabolism have been saying for years that we must not forget the contribution of triglyceride and chylomicrons. This research confirms that we were right.

Although there are no accepted guidelines on this, people at risk of developing cardiovascular disease should not only have their LDL-cholesterol and HDL-cholesterol levels checked, but should also have the level of chylomicrons measured.

Technically it is not a difficult thing to do, although not all laboratories are able to do it. If chylomicron levels are high, it is an extra incentive to reduce fat consumption, and there are new medicine being tested that may help reduce chylomicron levels.

This research provides yet more evidence about the importance of the intestine in general health and disease. I constantly have people telling me that certain diets, colonic irrigation or probiotics may improve intestinal health and therefore general health and well-being. They may be correct. But what we really need is research to discover if there are viable ways of improving intestinal health that can prevent disease onset and progression.

Medication-induced Weight Gain

It is not really a surprise that medicines that are designed to have effects on emotion might also have other effects. After all, emotion originally evolved as an outgrowth of the sympathetic nervous system, which, as every student of biology knows, is involved in the "Four F's:"

• Fear
• Fight
• Flight
• Sexual activity

So if powerful medicines influence emotion, they will likely also influence one or more of these.

Cocaine and amphetamine lead to a loss of appetite for food, though I am told that marijuana makes people hungry. I do not, of course, know that from personal experience.

Many antipsychotics, mood stabilizers and antidepressants cause weight gain by an array of different mechanisms.

New research published by colleagues from Johns Hopkins has done a lot to clarify the role of histamine in the appetite problems that often occur with antipsychotics.

You may be interested in reading more here.

The conclusion? Histamine has a major role to play in antipsychotic-induced appetite increase.

But it is not the only factor in the weight gain, insulin resistance and diabetes problems that seem to bedevil some of these medicines.

Before the book comes out, I shall write some more about the ways in which the Atlanta Approach successfully - and uniquely - deals with all of those problems.

Chiropractic Treatment and Diabetes?

There is an interesting, thought still preliminary, article in the Journal of Vertebral Subluxation Research about the possibility that chiropractic manipulation may be able to make a valuable contribution to an overall program of wellness to help people with diabetes.

There is a case report of an insulin-requiring person with type 2 diabetes, whose diabetes stabilized as he had a short course of chiropractic manipulation. I've seen many such cases with acupuncture and homeopathy as well as osteopathic and chiropractic manipulation. But it has always been very difficult to tell if there was a causal relationship.  Diabetes is such a variable group of illnesses that something as simple as stress reduction or a person sleeping better can both help normalize glucose levels, as least for a while.

What I really liked about the article was the measured tone: the editor makes it clear that it's an interesting observation but that it's still early days. Nothing so irritates people in conventional medicine than wild grandiose claims that some treatment or other can cure everything.

The editor also calls for more research, and I totally agree. I've spent the last 25 years trying to get research moving in the fields of complementary, alternative and Integrated Medicine, and we have already had a decent level of success in getting many projects funded and completed.


“The simple exercise of stretching helps to counter the congestions, compressions, and adhesions which obstruct the flow of the vital force through the spinal column with its sixty-two branching nerves and thus to regain energy. This truth of the need of spine-loosening movement is instinctively known by every dog and cat, every lion and tiger, for they apply it immediately after awakening from sleep. The back, the legs, and even paws are bent and stretched and even rolled by them in this natural exercise.”
--Paul Brunton (English Spiritual Teacher and Author, 1898-1981)

Aging and Exercise

It is a common observation that it becomes more difficult to do a lot of exercise as we get older, and the biceps no longer bulge quite as much after an hour in the gym. We have to exercise harder to get the same results.

Metabolism slows down as well, and for years it has been assumed that those events are linked: we slow our metabolism and find exercise harder because we gradually lose muscle mass.

But new research shows that it isn’t quite so simple, and the results should encourage any of us over forty to stay in the gym.

A new study published in the journal Cell Metabolism will likely help our understanding of that difficulty, as well as unlocking another of the secrets of type 2 diabetes.

As we become older, we hide more fat in our muscles and livers, and this fat has been linked to the age-related rise in insulin resistance that may go on to cause type 2 diabetes and hypertension.

A research team from the Howard Hughes Medical Institute based at Yale University School of Medicine compared the skeletal muscle of rats aged three-month-old and two-year-olds.

They found that an enzyme called AMP-activated protein kinase (AMPK) slowed down its activity in the older animals. AMPK's role in skeletal muscle is to stimulate the body to burn off fat and to provide fuel for the cells. It does this by producing mitochondria – the power packs of the cell. So AMPK activity in our skeletal muscle does at least three things: it stimulates glucose uptake, increases fat oxidation and promotes the production of new mitochondria.

It has been known for some time that the skeletal muscles of marathon runners have a much greater mitochondrial content and a greater capacity to burn fat. This is probably linked to high levels of AMPK activity.

The animals were exposed to a chemicals that produce that produce acute or chronic stimulation of AMPK. They were also exercised and some were fed more food, each of which should stimulate the production of new mitochondria.

The researchers found that the older rats had lower AMPK activity than the younger animals. In addition, the muscle of young rats who did more exercise had double the normal AMPK activity while in older rats this effect was severely blunted.

The message is this: as we age it is not muscle mass but enzyme activity that falls first. We have to work harder when trying to maintain the same benefits from exercise as we did when we were young.

We know that loss of skeletal muscle mass and function as we age is a major problem that has a significant effect on quality of life of older people. If this study is confirmed in humans it would have enormous implications. In the older rats, the AMPK activity was almost gone, implying that no amount of exercise would bring those muscles back. But it would be good to know if we can work out some other methods for bringing those enzymes back to life.

Although the paper doesn’t mention it, there is also some evidence that AMPK activity may be important in controlling feeding behavior in the hypothalamus at the base of the brain and the “stress hormone” norepinephrine plays a critical role in the way in which exercise stimulates AMPK. As we get older we usually find that our tempers are less fiery and part of the reason for that is that we produce less norepinephrine.

Start exercising early in life, and never get out of the habit. For if you do, you might lose that AMPK activity forever.

“Wholesome physical exercise reconstitutes energy, stemming the aging process, making the body light and firm, while safeguarding against fatigue and inducing cheerfulness.”
--Sushruta Samhita (Indian Surgeon who wrote the book the Sushruta Samhita, c. 6th Century B.C.E.)

“Exercise is the chief source of improvement in our faculties.”
--Hugh Blair (Scottish Presbyterian Minister and Writer, 1718-1800)

“It is exercise alone that supports the spirits, and keeps the mind in vigor.”
Marcus Tullius Cicero (Roman Political Figure and Orator, c.106-43 B.C.E.)

Juices, Cardiovascular Disease and Cancer

There was an important study that came out a few months ago in the International Journal of Food Science and Nutrition.

Investigators from Dundee in Scotland decided to look at the health benefits of fresh fruit juice. While it is widely accepted that fruit and vegetables lower the risk of some cancers and of most cardiovascular diseases, the role of pure fruit and vegetable juices has never been clear. In fact many textbooks have said that 100 percent juices play a less significant role in reducing risk for both cancer and cardiovascular disease than whole fruits and vegetables since they contain less fiber, and it had been assumed that it was the fiber that was the key to their value.

The researchers analyzed a variety of studies that looked at risk reduction attributed to the effects of both fiber and antioxidants. They found that the positive impact offered by fruits and vegetables is derived not from just the fiber but also from antioxidants which are present in both juice and the whole fruit and vegetables. Juices are comparable in their ability to reduce cancer and cardiovascular risk compared to their whole fruit/vegetable counterparts.

This research  goes a long way in demonstrating that fruit and vegetable juices may play an important role in reducing the risk of various diseases.

A study published in the American Journal of Medicine in September found that consuming a variety of 100 percent fruit and vegetable juices was associated with a reduced risk for Alzheimer's disease. Japanese American individuals who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer's disease than those who drank juice less than once per week. That finding seemed robust, even taking into account other potential variables. So I think that we may be able to add juices to our strategies for reducing the risk of developing Alzheimer's disease as we get older.

There is another point of importance. Some of the fad diets claim that fruit juices should be avoided at all costs, since they can cause the release of insulin, and insulin is bad. Those proclamations have usually come from people with a limited background in biochemistry or metabolism. The research shows that they were not correct. The key is balance, and as part of a comprehensive nutritional approach, juicing can be very helpful.

And a final point: careful use of juices has long been one of the "secret" components of our system of weight management.

“Drinking freshly made juices and eating enough whole foods to provide adequate fiber is a sensible approach to a healthful diet.”
--Jay Kordich (American Health Expert, Author and Lecturer, 1921-)

“If people would only stop putting into their bodies the things that are creating their physical problems, and eat a predominantly raw vegetarian diet, along with raw vegetable juices, almost all physical problems would soon disappear from the face of the earth!”
--Reverend George M. Malkmus
 (American Minister and Originator of the Hallelujah Diet, 1934-)

Chromium

When talking about chromium we’re not talking about that stuff that gets applied to metals to make them shiny.

For more than 20 years I've been interested and intrigued by its role in metabolism. This month's issue of Harvard Men's Health Watch highlights some of the research indicating possible links between chromium deficiency and diabetes, high cholesterol, heart disease and weight management.

The journal is only available for subscribers, but let me summarize some of the data for you.

Chromium exists in many forms and not all are either absorbed or biologically active. Antacids, phytates found in grains and tannins found in tea may all lower the absorption of chromium.

A point that always comes up when we discuss supplements is that some people will feel that recommended daily allowances are too low and that using larger - sometimes vast - amounts will achieve additional biological effects. There is some evidence that very large amounts of chromium may damage cells in tissue culture but very little evidence for chromium toxicity in humans. People probably vary greatly in their tolerance to chromium.

1. Diabetes: Chromium has attracted most interest because of its action on the binding of insulin to at least one of the insulin receptors. Insulin is more effective if chromium is present. Chromium also has a positive influence on one of the glucose transporters in cultured fat cells. The effects of chromium on glucose and insulin seems to vary in different species. So it is difficult to extrapolate from an animal study to humans. In people with both the major types of diabetes, the consensus seems to be that chromium supplements containing 200-1,000 mcg chromium as chromium picolinate a day have been found to improve blood glucose control. Chromium picolinate is the most efficacious form of chromium supplementation. There is a small pilot study that found that in women with polycystic ovarian syndrome, a low dosage of chromium picolinate improved glucose tolerance, but did not help with the hormonal or ovulatory disturbances. This has just been confirmed in a study using a higher dosage (1,000 mcg/day). Based on a detailed review of the literature, the United States Food and Drug Administration (FDA) has determined that chromium - at least chromium picolinate - does not reduce the risk that you might develop insulin resistance or diabetes and the American Diabetes Association agrees that the benefit of chromium supplements has not been conclusively demonstrated.
2. Cholesterol: Chromium deficient rats develop high cholesterol levels. But the evidence that chromium supplementation helps cholesterol levels in humans is thin. Chromium may also help people with diabetes to lower their cholesterol levels. The published evidence indicates that any beneficial effects of chromium on cholesterol is much smaller than the effects of diet and exercise.
3. Coronary artery disease: There is a study suggesting a correlation between chromium levels and the risk of having a heart attack, with lower levels being associated with higher heart attack risk. That does not, of course, necessarily mean that taking chromium supplements will reduce the risk of a heart attack.
4. Weight management: Despite all the advertisements, chromium supplements have not been shown to be effective in producing sustained weight loss.

There remains a possibility that some other form of chromium may be more effective on some of these parameters. There has recently been some interest in a product called Diachrome, that contains chromium and biotin. There have been several very interesting presentations about it at international meetings, but we need to see if the results pass peer review and replication.

A diet containing plenty of whole grains, nuts, broccoli, and green beans, should provide you with enough chromium. Chances are that taking a supplement will not cause harm and may perhaps help if you are at high risk of diabetes. But the evidence is still controversial.

I know of several other studies that are underway, and I shall report them to you as they appear.

But for now, when it comes to buying supplements, this is another one of those times that I say, "Caveat emptor!"

The Ape Diet

The BBC is carrying an article today about an experiment done for a television program in the United Kingdom.

Nine volunteers aged 36 to 49 set up home in a tented enclosure at Paignton Zoo, Devon, right next door to the ape house.

They were then put on what was essentially a vegan diet for a week followed by a vegan and fish diet for five days. They didn't call it a vegan diet, choosing the more catchy name of an Evo Diet. The nutritionist who designed the eating plan was inspired by the diet consumed by apes in the wild.

She devised a three-day rotating menu of fruit, vegetables, nuts and honey. The prescribed menu was designed to be safe to eat raw; to meet adult human daily nutritional requirements; and it provided 2,300 calories - between the 2,000 recommended for women and 2,500 for men.

They typically ate 5kgs {Yes, ELEVEN POUNDS (!)} or 2,300 calories of fruit, vegetables, nuts and honey.

On a 3-day rota, they typically ate broccoli, carrots, radishes, cabbage, tomatoes, watercress, strawberries, apricots, bananas, mangoes, melons, figs, plums, oranges and hazelnuts.

Volunteers could also drink water. In the second week, standard portions of cooked oily fish were introduced. The idea was that this was to simulate the diet of a hunter gatherer.

Although this is really a mock experiment, it was a shame that they added the fish in the second week: it would have been nice to have seen the impact of just twelve days on a vegan diet.

Even so, the results were remarkable. The average cholesterol of the group fell by 23%, they lost an average of just under ten pounds and average blood pressures fell from 140/83 to 122/76.

I don't find any of this at all surprising: I've done countless experimental diets on healthy volunteers, on patients and I've also tested them all on myself.

Eating the kind of diet to which we adapted over hundreds of millenia obviously makes good sense. And is far more likely to be successful than the latest fad diet based on some highly unnatural approach. The trouble with this experiment was that it actually did not simulate our ancestral diet: some - but not all - people do much better if they "eat with the seasons:" eating summer fruits in the summer, winter vegetables in the winter and so on. From what we know from the fossil record, it appears that our ancestors became omnivorous a very long time ago, and fish may have been a relatively recent addition to our diet.

Apart from those nit picky theoretical objections, the main problem with this diet is practical: it can be hard to carry around eleven pounds of fruit and vegetables. I've done it as part of an experiment, so I know that it is doable: it depends on how much you want to take control of your body.

There are, of course, loads of supplements for sale that claim to give you all the goodies packed into those eleven pounds of food, but in one convenient little pill. The trouble is that natural foods contain many other nutrients, not all of which have yet been identified. The bulk and the fiber are also important components of your diet.

The second problem is psychological: in Healing, Meaning and Purpose we spend a whole chapter/CD on methods for maintaining motivation and overcoming the psychological, social, subtle and even spiritual problems that often prevent us from looking after our bodies.

“As houses well stored with provisions are likely to be full of mice, so the bodies of those who eat much are full of diseases.”
--Diogenes (a.k.a. Diogenes Laertius, a.k.a. Diogenes the Cynic, Greek Philosopher and Founder of the Cynic School, c.412-323 B.C.E.)

“To become vegetarian is to step into the stream which leads to nirvana.”
--Buddha (a.k.a. “The Awakened”, a.k.a. Siddhartha Gautama, Indian Religious Figure and Founder of Buddhism, c.563 B.C.E. – c.483 B.C.E.)

“It's bizarre that the produce manager is more important to my children's health than the pediatrician.”
--Meryl Streep (American Emmy and Oscar-winning Actress, 1949-)

Genetic Testing in the Treatment of Depression

By a remarkable “coincidence,” less than a week after the appearance of two items (1. 2.) questioning the value of using genetic testing to help predict response to treatment in people suffering from depression, an important report has been released today.

The report is supported by a collaboration of the Agency for Healthcare Research and Quality and the Centers for Disease Control (CDC) and Prevention’s National Office of Public Health Genomics, and it was the CDC that funded it.

It is gratifying to see that the findings of the report are identical to those published in the two articles last week. The main conclusion of the report is that there is insufficient evidence to determine if current gene-based tests intended to personalize the dose of medications in a class of drugs called selective serotonin reuptake inhibitors (SSRIs) improve patient outcomes or aid in treatment decisions in the clinical setting.

The investigators reviewed 1,200 abstracts that led to the final inclusion of 37 articles. As we learned last week, the evidence indicates the existence of tests with high sensitivity and specificity for detecting only a few of the more common known polymorphisms of the cytochromes 2D6, 2C19, 2C8, 2C9, and 1A1.

They found mixed evidence regarding the association between CYP450 genotypes and SSRI metabolism, efficacy, and tolerability in the treatment of depression, mainly from a series of heterogeneous studies in small samples.
There were no data regarding:

1. If testing for CYP450 polymorphisms in adults starting SSRI treatment for non-psychotic depression leads to improvement in outcomes versus not testing, or if testing results are useful in medical, personal, or public health decision making.
2. If CYP450 testing influences depression management decisions by patients and providers in ways that could improve or worsen outcomes.
3. If there are direct or indirect harms associated with testing for CYP450 polymorphisms or with subsequent management options.

This report confirms that there is little point in doing these genetic tests.

It also raises another point. It is now some years since some of these tests became available commercially. If they were really of value then we have to ask why there hasn’t been an avalanche of research on the topic – especially by the people marketing the tests – and why none of major psychopharmacology groups in the United States, Europe, Japan or Australia picked up on the tests. I probably know most of the people in these hospitals, universities and research centers and none has been much interested in this work.

So when someone suggests that you undergo some new test or investigation, remember to use your common sense. If there is only one person doing it - whether it’s a genetic test, a brain scan, some non-standard type of thyroid or adrenal test, or a Vega test - ask why nobody else is using it and why nobody has published any decent research on the method.

When it comes to your health use your common sense, your intuition and impartial information to be your guide and your support.

Parkinson's Disease and Cholesterol

Within the last week we have talked about the association between Helicobacter pylori and Parkinson's disease and the way in which Parkinson's disease may often get better if people are treated with a cocktail of antibiotics. We have also discussed the association between Parkinson's disease, allergies and inflammation.

Now new research from the University of North Carolina at Chapel Hill has  found that people with low levels of LDL cholesterol are more likely to have Parkinson's disease than people with high LDL levels. This is the form of cholesterol sometimes referred to as "bad cholesterol." This study followed the strange observation that people with Parkinson's disease have a lower rates of heart attack and stroke than people who do not have the disease. It is also known that known that cigarette smoking, which increases a person's risk for cardiovascular disease, is also associated with a decreased risk of Parkinson's disease. 

Few scientific stories are clear cut: it usually takes a while to get things right. Just to prove it, a study from the Netherlands found that high total cholesterol levels were associated with lower rates of Parkinson's disease, but only in women.

So what to make of all this: infections, allergies and now cholesterol?

To try and understand this, I think that we need to introduce another actor to the stage. Since the early 1950s the medical community has been concerned about a striking concentration of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia among the Chamorro people on the island of Guam. A number of lines of evidence have suggested that this group of illnesses has been caused by some neurotoxic agent in the environment, though nobody has been able to work out exactly what it is. One of the most attractive recent theories is that it might have something to do with toxins from Cycas plants. So the idea is that similar cholesterol-containing neurotoxins can come either from Helicobacter or from eating Cycas plants, or animals that have fed on the plants.

There is a complex inter-relationship between LDL- and HDL-cholesterol, and HDL-cholesterol appears to be anti-inflammatory: high levels of HDL-cholesterol are associated with low levels of inflammation. And it has recently been shown that simvastatin may cut the risk of developing Parkinson's and Alzheimer's diseases. Not just by lowering cholesterol but from its inflammatory activity.

It may also be that low levels of cholesterol may impair the activity of another factor: one that interests me is coenzyme Q10.

From a practical perspective, this new evidence reinforces a point that I made in Healing, Meaning and Purpose and on this blog: "boosting" one component of the blood or lowering another is not sensible. Whether dealing with cholecterol or immunity, we need to moduate and harmonize all the systems of our bodies and our minds.

Follow our systems for modulating the inflammatory mediators in your body and that alone should - theoretically - reduce your risk of many illnesses.

I shall keep you posted as this story continues to develop.

Multiple Sclerosis and Vitamin D

I have commented before that the increasing rates of multiple sclerosis as we move away from the equator has lead to speculation that it might have something to do with lack of sunlight and therefore reduced production of vitamin D in the skin.

A lack of vitamin D may also explain the increased rates of both type 1 and type 2 diabetes, as well as cluster headache at higher latitudes.

Vitamin D is not a single vitamin, but is instead a group of fat-soluble prohormones as well as the metabolites and analogues of these substances. There are two major forms of vitamin D: D₂ (or ergocalciferol) and D₃ or cholecalciferol. Vitamin D₃ is produced in skin exposed to sunlight, specifically ultraviolet B radiation. Very few foods are naturally rich in vitamin D, and most vitamin D intake is in the form of fortified products including milk and cereal grains.

It used to be that we all made plenty of Vitamin D simply by being outside in the sun, but our time outside has been steadily falling since the beginning of the Industrial Revolution, and there are the increasing concerns about exposure to sunlight and some skin cancers.

Vitamin D is involved in many critically important chemcial reactions in the body, and Vitamin D receptors are found in cells in most organs in the body, including the brain, heart, skin, gonads, prostate, and breast. Apart from its effects on regulating calcium and phosphorus, Vitamin D is involved in maintaining the integrity of cell membranes and in modulating the immune system. There is some evidence that a modest increase in Vitamin D intake may reduce the risk of colon, breast and ovarian cancers.

There is a risk of overdosing with Vitamin D. The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) of vitamin D for childern and adults is 50 micrograms/day (2000 IU/day). In adults, a daily intake of 2500 μg/day (100,000 IU) can, over a period of weeks and months, produce toxicity  and, if taken for years, as little as 50 to 75 μg/day (2000 to 3000 IU) can produce toxicity.

In this week's issue of the Journal of the American Medical Association, there is an important report that endorses everything that we have been saying. Researchers from several prominent institutions in the United States have examined the hypothesis that higher levels of 25-hydroxyvitamin D are associated with a lower risk of multiple sclerosis.

The study confirmed the hypothesis: the risk of multiple sclerosis (MS) fell as blood levels of the vitamin rose.

The researchers uncovered 257 cases of MS among more than seven million military personnel who had given blood samples to the US Department of Defense.

Amongst white personnel, there was a 41% decrease in MS risk for every 50 nanomoles per litre increase in 25-hydroxyvitamin D, the key form of the vitamin found in the blood.

Those whose vitamin level was in the top 20% had a 62% lower risk of MS than those whose level was in the bottom 20%.

The researchers found no such association among black and hispanic personnel, but this could be a reflection of the smaller size of these sample groups.

This new research ties in with other work that has shown that Vitamin D supplements can prevent or favourably affect the course of a disease similar to MS in mice, as well as evidence that if you live in the Northern Hemisphere, being born in May is associated with a lower risk of MS than if you were born in the winter. If you are born in May, your mother will probably have been exposed to more sunlight - and therefore have produced more Vitamin D - during the later part of pregnancy when the final development of the nervous system takes place. Or alternatively you may have had a heathy dose of sunlight in the weeks immediately after your birth.

It is most likely that the Vitamin D helps by modulating the immune system and suppressing autoimmune reactions caused by specialised T helper 1 cells attacking myelin, the insulating material that sheathes most nerves. It is these attacks that are thought by most experts to play a key role in the development of MS.

If confirmed, the finding suggests that many cases of MS could be prevented or its severity reduced by increasing our levels of Vitamin D.

The data also confirm a point that we have made before: we should not be aiming to "boost" our immune systems, but to "modulate" them.

If you see an advertisement for some potion that is supposed to boost your immune system to help you ward off colds, the flu or something more serious, be suspicious: if the seller does not know the  difference between boosting and modulating, it would be best to move on.

Chloroquine, Insulin and Inflammation

Your humble reporter was fascinated to read about some new research using the anti-malarial agent chloroquine as a potential treatment for the insulin resistance syndrome.

I have a personal reason for being interested. Hypoglycemia (low blood glucose) is an occasional feature of treatment with chloroquine and in 1980 a study first indicated that chloroquine might slow the break down of insulin by the liver. In the early 1980s there were a flurry of papers indicating that chloroquine did some subtle things to insulin and insulin receptors in many tissues. So we came up with the idea of measuring its effects in humans. There was a memorable occasion on which I was doing an outpatient clinic with an intravenous line in my arm. (English doctors are well known for doing experiments on themselves: I had a professor in medical school who said that you should never do to a patient what you haven’t had done to yourself. I shall leave it to you, gentle reader, to wonder if I've tried everything....).

So there I am doing my clinic when, around 11AM I begin to feel really strange: my glucose level was almost unrecordable and my insulin level was off the chart. Nothing that couldn’t be solved with a large dollop of sugar, but it made me very sympathetic to people who get hypoglycemic from their regular treatments.

Sometimes Nature does our experiments for us: we did a lot of work on diabetes because it is associated with high rates of vascular disease. So understanding the mechanisms by which diabetes does that may help illuminate some of the cellular disturbances underlying arteriosclerosis in general. We are also interested in the few illnesses in which a single disturbed gene may lead to a definable set of signs and symptoms. There is a rare illness known as ataxia telangiectasia in which sufferers have a high risk of developing some cancers particularly lymphomas and leukemia. People with the illness are very sensitive to ionizing radiation, have a specific type of immune deficiency, degeneration of parts of the brain related to muscle function and coordination and they age prematurely. More than ten years ago it was discovered that a single gene - ataxia-telangiectasia mutated (ATM) gene – was responsible for the illness. The gene is responsible for producing a protein that recognizes damage to DNA. It now seems that ATM may also be linked to metabolic and cardiovascular diseases. It does this by inhibiting a protein called JNK, a stress kinase involved in inflammation with related effects in insulin resistance and atherosclerosis. So to everyone’s surprise a gene that can cause a rare disease can also cause insulin resistance.

In the November issue of Cell Metabolism, researchers at Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital in Memphis, Tennessee report that a small dose of chloroquine eased many symptoms of metabolic syndrome in mice, reducing blood pressure, decreasing hardening and narrowing of the arteries and improving blood sugar tolerance. The results suggest we may only need very low and perhaps infrequent doses of chloroquine to achieve similar effects in humans. Both insulin and chloroquine activate the ATM gene.

This adds to the data that some of the metabolic dysfunctions triggered by obesity may be linked to the inflammatory responses that go wrong in autoimmune disorders like arthritis and systemic lupus erythematosus.

And an older treatment for rheumatoid and lupus just happens to be chloroquine.

Chloroquine itself has some side effects, but this is important information that will help us design more effective and carefully targeted holistic treatments for both metabolic disturbances and inflammatory conditions. All in all, very good news indeed.

Hidden Harbingers of Weight: Salt Intake and Obesity

In Healing, Meaning and Purpose, I discuss some of the evidence for four previously little recognized causes of obesity:

1. Stress
2. Salt intake
3. Pesticides
4. Viruses

Each of these has been widely discussed in the professional literature, but little has percolated out into the general population except in advertisements for agents like Cortislim. I remain skeptical about these products. Tinkering with just one of the 260 hormones and neurotransmitters implicated in the control of weight is unlikely to be crowned with success. And their ingredients may also have the potential for causing problems. Recent advertisements have also mentioned that one of these products may elevate mood. Sad to say, in the last year we have seen two people who developed manic symptoms after taking one of the supplements. We are urging colleagues to see if there are any other cases, or whether these two were just coincidental.

I recently mentioned some of the evidence for viruses as a cause of weight gain.

Now a new publication from the Universities of Helsinki and Kuopio is out in this month's journal Progress in Cardiovascular Diseases, that provides powerful support for the salt hypothesis.

The researchers report that an average 30-35 % reduction in salt intake during 30 years in Finland was associated with an extraordinary 75 % to 80 % decrease in both stroke and coronary heart disease mortality in the population under 65 years. During the same period the life expectancy of both male and female Finns increased by 6 to 7 years.

As expected, reducing salt intake has a beneficial effect on blood pressure.

But in my view the most interesting finding of the study is the close link between salt intake and obesity.

As bartenders, pub landlords and tavern owners have known since the beginning of time, increasing a person's intake of sodium produces a progressive increase in thirst. (You didn't think that those peanuts on the bar were put there out of the goodness of the establishment's heart did you??!)

The progressive increase in the average intake of salt explains the observed increase in the intake of sugar-containing beverages which, in turn, has caused a marked net increase in the intake of calories during the same period in the United States.

Here is an extraordinary statistic: Between 1977 and 2001, energy intake from sweetened beverages increased on the average by 135 % in the United States. During the same period, the energy intake from milk was reduced by 38 %. The net effect on energy intake was a 278 kcal increase per person a day. The American Heart Association has estimated that, to burn the average increase of 278 kcal a day and avoid the development or worsening of obesity, each American should now walk or vacuum 1 hour 10 minutes more every day than in 1977. As we all know, that has not happened.

In the decade from 1976-1980 to 1988-1994 the overall prevalence of obesity increased 61 % among men and 52 % among women. During 1999 to 2002, the prevalence of obesity was 120 % higher among men and 99 % higher among women as compared with the 1976 to 1980 figures. The increased intake of salt, through induction of thirst with increased intake of high-energy beverages has clearly made a significant contribution to the increase of obesity in the United States.

It is also of note that until 1983 the use of salt did not change or even showed a continuous decreasing trend in the United States. The prevalence of obesity was relatively low and remained essentially unchanged from early 1960s to early 1980s.

This new study suggests that a comprehensive reduction in salt intake, which would reduce the intake of high-energy beverages, would be a potentially powerful means in the so far failed attempts to combat obesity in industrialized societies.

There is now conclusive population-wide evidence that indicates that we could achieve powerful beneficial health effects simply by reducing our overall salt intake. These benefits include a decrease in obesity.

As an aside, the population-wide long-term experience from Finland indicated that a remarkable decrease in the salt intake has not caused any adverse effects.

A number of years ago we were engaged in some experiments in which we replaced regular table salt - sodium chloride - with potassium chloride. For the first three weeks food seemed rather tasteless. But then we all suddenly discovered a new universe of flavors that had previously been hidden under a thick coating of salt. So a dietary change does have a temporary effect on your taste buds.

Although the paper doesn't say so, there is also some data that salt may itself increase cortisol release.

The bottom line?

We now have clear, empirical data to support three out of the four points that I made in Healing, Meaning and Purpose, and there is some less robust data for the fourth.

I urge you to try gradually to reduce your personal intake or salt, and to encourage your family and friends to do the same. I mentioned that food may initially seem a little less flavorful, but then things change rapidly and for the better.

And your body will love you for the change!

Renal Cell Carcinoma and Bread

Renal cell carcinoma (RCC) is the most common type of kidney cancer, and accounts for 2 percent of all adult cancers. It has been known for some time that diet plays a role in RCC risk, but attempts to identify which foods have harmful or beneficial effects have been inconclusive.

The smart money has been on foods that elevate insulin levels, because RCC is one of the cancers associated with obesity, and some RCC cell lines grow when exposed to insulin or insulin-like growth factors.

A new study by researchers form the Institute of Pharmacological Research "Mario Negri" in Milan, conducted a large case-control study of 2301 Italians. They found a significant association between high bread consumption and renal cell carcinoma. Eating a lot of pasta and rice may also raise the risk, while eating many vegetables may lower the risk. The study published online October 20, 2006 in the International Journal of Cancer, the official journal of the International Union Against Cancer (UICC), and is available via Wiley InterScience.

The researchers enrolled 767 adults diagnosed with RCC and 1534 controls who did not have the disease between 1992 and 2004. Two controls were matched to each case by gender, age range, and location. The researchers collected sociodemographic information, height, weight, lifestyle habits and personal and family medical history from each participant. They also administered a 78-item food frequency questionnaire which asked about the average weekly consumption for each item over the previous two years. They then performed statistical analyses to discover odds ratios (OR) with a 95 percent confidence interval.

They found a significant direct association was observed for bread consumption and a higher RCC risk. A modest non-significant risk increase was also observed for pasta and rice. On the other hand an increasing intake of poultry, processed meat, and all vegetables, both raw and cooked, all reduced the risk of RCC.

These findings confirm our guess about insulin and/or insulin-like growth factors. This association between elevated cereal intake (bread, pasta and rice) is most likely due to the high glycemic index  of these foods, leading to an over-production of insulin and insulin-like growth factors.

The inverse relationship between vegetable consumption is consistent with previous studies and may be related to their content of vitamins, micronutrients or elements such as carotenoids, flavonoids and phytosterols.

This is not a perfect study: it is limited by the fact that the interviewers who gathered each participant's information and administered the food questionnaire were not blind to who was who. But its big strengths include the sample size and the reproducibility and validity of diet information.

This study is important and speaks to the point that we have made before: a balanced diet is key, and your body does not want to be exposed to constant variations in glucose or insulin.

It also confirms all the advice that we have been offering you about what and when to eat. Click on the links to review what I have said before!

Breast is Best, But…

I think that everyone knows that breastfeeding confers considerable advantages on a baby. So much so that the American Academy of Pediatrics recommends exclusive breastfeeding for the first six months of life. Though some mothers cannot manage this for a whole range of reasons, and it’s always a real shame when women are made to feel guilty if they cannot breastfeed.

Amongst some of the likely health benefits for both mother a baby:

1. Mother and child are more likely to bond
2. A reduced risk of the child developing some respiratory problems, ear infections and gastrointestinal problems
3. A reduced risk of developing allergies later in life
4. A reduced risk of obesity in adulthood
5. A reduced rate of attention deficit disorder
6. A reduced risk of developing type I diabetes
7. There may also be a reduced risk of developing osteoporosis in later life
8. The mother has a reduced level of stress and postpartum bleeding
9. Mothers who breastfeed have a slightly reduced risk of some types of cancer

To this list we can add that breastfed children are more intelligent. That is not a new discovery. It was first reported in the 1920s. A new study published in the British Medical Journal has re-examined the question. Most of the earlier studies failed to consider the mother’s intelligence, despite the well-recognized association between maternal education and breastfeeding. That association often breaks down in professional women who have to go straight back to work after giving birth, but it remains a key variable.

The researchers examined data from 3,161 mothers and 5,475 children, who were followed in a twenty-five year prospective study. Premature babies were excluded and the children’s’ intelligence was measured up to age five.

The breastfed babies had slightly higher IQs, but the effect was entirely accounted for by their mothers’ intelligence. Breastfeeding itself had little or no effect on intelligence scores. The mothers of the breast-fed children tended to be older and to be more likely to provide the growing child with a stimulating and supportive home environment.

In a separate study from the Australian Raine Study at the Telethon Institute for Child Health Research, that has tracked the growth and development of more than 2500 West Australian children over the past 16 years, it now emerges that children who were breastfed for longer than six months have significantly better mental health in childhood.

Children that were breastfed had particularly lower rates of delinquent, aggressive and anti-social behavior, and overall were less depressed, anxious or withdrawn. This makes sense: apart from the psychological impact of having a mother who is willing and able to breastfeed, breast milk is a rich source of polyunsaturated fatty acids - examples include docosahexaenoic acid and arachidonic acid - that are important for brain development and the growth of nerve cells.

There is also evidence that breastfeeding may reduce the risk of developing schizophrenia later in life, although it is difficult to be sure if it because of the breast milk itself or the kinds of mothers who breastfeed.

Glycemic Index Revisited

If you are anything like me, you probably find loads of adverts in your mailbox for magical ways to lose weight, either by using some form of the Atkins diet, manipulating cortisol (it doesn’t work), or by paying attention to the glycemic index of the food that you eat.

Last January I summarized some of the recent research that showed that glycemic index and glycemic load were not related to measures of insulin sensitivity or secretion, or to the amount of fat in the body. However, the intake of fiber in the diet was found to have beneficial effects on insulin sensitivity, adiposity and the secretion of insulin by the pancreas. I went on to give some uncontroversial advice on how to eat.

Nobody thought that the glycemic index issue was dead: insulin and the other hormones involved in fat and carbohydrate metabolism are powerful and have multiple roles in the body.

A study published in the Archives of Internal Medicine in July, helps further refine our understanding about glycemic index. High carbohydrate foods with a low glycemic index are the best way to reduce your risk of cardiovascular disease. The problem is that you want to avoid sudden surges in glucose after you eat a meal. What normally happens is that those surges are accompanied by sudden rises in triglycerides and insulin. The three together can cause all kinds of mischief to the insides of your blood vessels. High protein and low glycemic index diets will help with weight, but it’s only the combinations of high carbohydrates with low glycemic index that reduces the risk of vascular disease.

My redoubtable Web Mistress, Carol Kirshner, has found a most useful resource at the University of Sydney, that you can use to help guide your food choices.

This is such a useful resource that we are going to attach it to our blogs and websites.

However, it’s essential that we don’t get seduced by the idea that high carbohydrate/low glycemic index eating is the solution to all of our ills.

We still need to follow the basic principles of a balanced diet:

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 violent attack on your body and your mind
5. Avoid the “trans-fatty acids”
6. Try to consume some Mercury-free 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.
10. Make it a goal to gradually reduction your overall intake of cereals

Retinoic Acid and Suicide

Retinoic acid is an organic compound derived from Vitamin A, that is involved in the development of the brain and in normal visual function. It is because of the involvement in the formation of the brain that medicine containing retinoic acid like compounds must not be given to women who could become pregnant.

In recent years it has become clear that it is also involved in the function of the mature nervous system, and there have been suggestions that it may have a role in illnesses life Alzheimer's disease and schizophrenia.

One of the big breakthroughs in skin care was the introduction, in 1982, of a form of retinoic acid - isoretinoin - for the treatment of severe acne. It is marketed as Accutane in the USA and Roaccutane in the United Kingdom. Since its introduction there have been claims that it has caused depression and suicide in some patients taking it. The package insert specifically mentions this possible association. The trouble has been trying to sort out whether people taking it for acne became depressed because of the acne, whether it was the drug, or whether it was a chance association. 13 million patients have taken it world-wide, so sadly some depression might occur by chance.

That it was the drug causing the problem was supported by reports of people developing depression within days of starting the medicine. But it's always difficult to go from association to causality. After all, it has not been possible to prove that smoking causes lung cancer, though nobody doubts it, becuase the association between the two is so strong.

The Medicines and Healthcare products Regulatory Agency had received 1,588 reports of suspected adverse events experienced by people taking the drug up to this month. This included 25 people who died from suicide.

Now a paper in the journal Neuropsychopharmacology has added substantial support the the notion that the medicine may cause depression. The researchers gave a form of retinoic acid to adolescent mice. They found that while there was no change in the physical abilities of the mice, the rodents spent significantly more time immobile in a range of laboratory assessments designed to test their response to stress.

This was interpreted as a sign that the animals were exhibiting signs of depression.

It's difficult to extrapolate from mice to humans, and this certainly does not nail down the problem. It also does not mean that people should stop their treatment: this medicine works. But it emphasizes the importance of doing what the package insert says: watching young people with acne who are on treatment for any signs of depression.

A Missing Link: Serotonin, Inflammation and Psychiatric Illness

We have previously looked at the extraordinarily high rates of inflammation in psychiatric illnesses, as well as the evidence implicating disturbances in the serotonin transporter and an array of psychiatric and physical illnesses, including fibromyalgia and irritable bowel syndrome. Disturbances in serotonin homeostasis as well inflammation-promoting (pro-inflammatory) cytokines have both been implicated as causative factors in major mental illness. So the hunt has been on to see if there’s some way of uniting these two causative pathways.

There’s an exceptional important paper out this week in the journal Neuropsychopharmacology.

Investigators from the Vanderbilt University School of Medicine in Nashville, Tennessee, have established that the pro-inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Using rat cells, they were able to show the precise mechanism by which these cytokines could regulate the activity of the serotonin transporter.

So why is this so important? Not only does it open up several new options for treating mental illness, but it may also explain some puzzles.

It’s recently been shown that mental illness is more common in overweight people. Large amounts of fat in the abdomen act as a kind of inflammation factory, soaking the circulation in inflammatory mediators. So here we have a link between ever expanding waistlines and the increasing rates of mental illness in the population. It’s not just stress and environmental overload; it is likely also fat causing inflammation.

Acids and Alkalis

Have you seen those books and advertisements about supplements that are supposed to “alkalinize” your body and therefore avoid the effects of nasty acids? Many have frightening titles, like “Alkalinize or Die.” Some time ago I read a whole bunch of these books while I was trying to help two people with interstitial cystitis. This is a nasty problem, and I had failed to help with conventional medicine, naturopathy, acupuncture or homeopathy. One of the many books that I read claimed that altering the acidity of the urine would cure the problem. It did not.

The basis for these claims that we need to alkalinize our bodies comes primarily from three sets of observations:

1. That manipulating the external environment of cells in culture and isolated organs can have dramatic effects on the activity and life expectancy of these cells and organs
2. That some of the products of exercise or metabolism are acidic, and so need to be buffered or expelled from the body
3. A great many anecdotes about people benefiting from following an “alkalinization” protocol of some sort.

That all sounds good, but it is a big jump to go from cells in culture and perfused organs to whole human beings. Or to base medical advice on anecdotes ALONE.

There is also another origin for some of these ideas, and they derive from the work of Edgar Cayce and some oriental healing traditions: I have enormous respect for both.

I'm a card-carrying biochemist and metabolic physician, so some things about acid/base balance I know well.

Our blood is maintained at a pH of 7.42, and even the tiniest shift can cause major health and psychological problems. So there are sophisticated systems for keeping things in balance. Most of the popular books fail to mention much about the easiest way to change pH, and that is by changing your rate of breathing!

We show people how to do that every day in clinical practice. And when doing electrical recordings of the brain – electroencephalograms - hyperventilation is a good way of inducing some types of abnormal electrical activity.

We know a great deal about how changes in the pH of the blood can impact behavior and many physiological approaches. I’ve worked with hundreds if not thousands of people with disturbances in the acid/base balance of their bodies. Usually as a result of diabetes that was out control, but also scores of other illnesses. Many of them rare but educational.

The populist writers then often talk about excess acid being a stressor. So we don’t want to have acid in our systems because it depletes the alkaline buffers that are supposed to keep things in balance. An interesting idea, but one that can quickly be shown to be deeply flawed. It’s easy for a biochemist to calculate the amounts of acid in single cells, organs and the whole body. We’ve done it thousands of times when treating people with medical conditions like diabetic ketoacidosis and lactic acidosis.

Sadly some of the writers of popular books and articles on acids and alkalis have clearly not studied the literature in any detail.

There have also been some examples of what we call the “Trudeau effect:” vague comments about studies that are supposed to have been completed, but which, if they have been read at all, have never been analyzed by the writer. And often odd statements from books and from research are taken out of context and cited as the Gospel truth. There’s a legal loophole that Trudeau and some others get away with saying things about health that are not supported by any data.

Levels of Evidence
An important concept is what we refer to as levels of evidence. In the past it was often thought that the only kind of evidence to be of any value in clinical decision making had to have been obtained by randomized controlled trials. Yet we all know from experience that there are other types of evidence. A teacher or a colleague may have recommended a course of action based on experience or observation, and this can provide valuable guidance. We now recognize four types of clinical evidence:

1. Case reports
2. Case series and uncontrolled observational studies
3. Retrospective database analyses
4. Controlled analytic studies, including randomized clinical trials

You will see from this is that even single case reports go into the mix. Numbers one and two and used not as proof, but as ways to generate testable hypotheses.

If you tell me that you have slept better since you started an alkalinization regimen, I’ll see if what you are doing can be applied to others (that’s a pragmatic study), and also whether there could be an explanation for your report (that will need an analytic or mechanistic study).

When we review evidence or perform meta-analyses we give each type of evidence a rating. Controlled studies are given a higher rating than case reports, because the evidence can be generalized to many individual patients. A further refinement is to factor in the source of the study. So research by a pharmaceutical company or a manufacturer of an herbal supplement tends to get a lower rating than an independent study.

Recently someone did indeed tell me that she had slept better since following a special diet. When we looked carefully at the protocol that she was following, it was probably not the alkalinization, but the hops in the diet.

There are many, many claims of health benefits from various diets. The benefits may be genuine, but we need to be very cautious about attributing the success of a diet or any other form of treatment to just one factor.

There is no question that some illnesses, for instance peptic ulcers or gastro-esophageal reflux disease can be made worse by eating an acid diet, and having acid urine can sometimes be very irritating to the bladder.

But the evidence for the benefits of alkalinizing of the whole body – even if it were possible to do it - just does not exist.

You also need to be aware of a potential consequence of "alkalinizing diets:" they can dramatically alter the absorption of some herbs, medicines and supplements.

So what should you do?

1. The key to any diet is balance: it would be a mistake to be on a diet consisting of just one thing. Experts are always very wary of health claims based on one juice, herb or supplement. Your body is not designed that way: you need a mixture of different fruits and vegetables. When someone tells us that the key to healing is a berry that can only be found in a hidden valley in the Himalayas, we have to ask, “How could that have happened?” How could it be that we evolved or were created with a key ingredient missing?
2. Avoid drinking carbonated drinks. The old story about a can of Pepsi Cola being a good way to remove oil from your driveway is true. In high school we did the experiment of taking a small nail and leaving it in a sealed container with some carbonated soda. The nail had largely dissolved inside a week.
3. Keep up your intake of pure water. The current recommendations vary depending upon the time of year and where you live. In the Southern United States, during the summer time, it is currently recommended that you should drink 120 fluid ounces of pure water each day. I personally prefer pure spring water or distilled water. But also bear in mind that if you choose not to drink fluoridated water, that your chance of dental cavities increases. You can get around that problem by applying fluoride directly to your teeth and then rinsing it out. Ask you health care provider about that.
4. Listen to you body: you should avoid anything that feels irritant, causes indigestion, diarrhea or urinary symptoms
5. Use you intuition: the answers are within you. One of the most valuable uses of your intuition is not to help you pick lottery numbers, but to help you make wise decisions about your body, your relationships and your subtle systems. I have already written a little about some techniques for listening to and amplifying your intuition, and I shall soon be writing and recording a lot more about those essential topics.

Training Doctors to Use New Medicines

I was saddened to see a press briefing by four senior members of the British Pharmacological Society  at the Society’s 75th Anniversary meeting in London. They called for an immediate improvement in the training of medical students and doctors in pharmacology and clinical pharmacology. They lamented the reduction in the teaching of the basic and clinical principles underpinning the use of medicines, that was leading doctors to be less confident in prescribing. This at a time when medicines are becoming increasingly powerful and complex to use, and when patients are more likely to be taking a number of different drugs.

I have known all four of the people who made these statements, and none is given to hyperbole. Professor David Webb from the University of Edinburgh had this to say: “Patients are becoming ill and some are dying as a result of poor prescribing. There is no doubt about that. A substantial proportion of that is undoubtedly avoidable.”

I was in San Francisco earlier today, and I was shocked by one of the questions, “What is the P450 system?” This is one of the most important metabolic pathways for medicines in the liver and the intestines, and it was worrying that a prescriber did not know that. In my view if a student doesn't know something, it's the teacher's fault, so it means that we trainers are not doing as good a job as we should, and that the problems are not confined to the United Kingdom.

The discussion soon turned to the increasing evidence that some medicines may be associated with metabolic disturbances in some people who take them. We soon started talking about the broader issues of drug side effects. My view is that we don’t need to blame doctors or pharmaceutical companies, that have no interest in bringing unsafe medicines to market: the financial and legal consequences can be devastating. And in any case, I’ve met hundreds of people working in senior position in over thirty pharmaceutical companies and the vast majority of them are deeply committed to trying to improve the lot of humanity.

I think that the problem is not with medicine itself or with doctors or companies. The problem is inadequately trained and/or bad doctors and bad companies.

And fortunately all of those are uncommon. But if these pharmacological luminaries are flagging up a problem, we all need to re-double our efforts to ensure that everyone working in medicine is trained in the basics.

Technorati tags: Pharmacology Medical training Cytochrome P450

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.

Technorati tags: Cytokines Weight management Insulin resistance Interleukin-18 Inflammation

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.

Technorati tags: Cytokines Leptin Cancer cachexia Weight control Inflammation

Fibromyalgia

Fibromyalgia can be one of the most difficult of clinical problems. Sadly this illness or group of illnesses is often dismissed as no more than a series of symptoms caused by depression, and people then do not get the treatment that they need. Fortunately we are now seeing the emergence of consensus guidelines on how to diagnose the problem.

Fibromyalgia is a common syndrome of chronic pain and fatigue, but it is a great deal more than just pain. It may affect many systems of the body, and depression and cognitive symptoms are common.

One of the key difficulties in people with fibromyalgia is a disturbance in pain thresholds. There has also been a lot of interest in the idea that people with fibromyalgia are “hypervigilant,” as a result of disturbance in the serotonin pathways in the brain. Something similar happens in many people with other types of chronic pain, particularly low back pain. The problem with all of this research has always been the chicken and egg problem: how many of these abnormalities are due to having chronic pain, and how many might be the cause of the problem?

As an example, I was treating someone with fibromyalgia, and as part of the package of treatments, she was to have acupuncture. If practiced by a professional, acupuncture is usually painless. I had not seen anyone experience pain from the treatment in many years; however, this person was so sensitive that even gentle tapping was excruciatingly painful for her. I have colleagues who take this to be evidence that the whole thing is psychological. But I am sure that they are not correct. To a neurologist this is wrong on three counts:
1.    There is a lot of data indicating metabolic disturbances in people with fibromyalgia that is quite different from anything seen in anxiety or depression. These include reductions in the activity of the cellular powerhouses - the mitochondria - as well as subtle effects in blood flow.

2.    A number of other illnesses, like migraine, are associated with changes in pain threshold, indicating a disturbance in the mechanisms that control pain sensation, either in the brain stem on the thalamus.

3.    This notion that “it’s psychological rather than physical,” harks back to the kind of dualism that is not very helpful.

Recent research  indicates that although fibromyalgia is a little more common in women, the old view that it is predominantly a female illness is not correct. There are also some strong associations with other illnesses, including depression, anxiety, headache, irritable bowel syndrome, chronic fatigue syndrome, systemic lupus erythematosus, and rheumatoid arthritis.

In the days that I treated a great many individuals myself, I always found that fibromyalgia and chronic fatigue syndrome were amongst the most difficult.

I’ve long been interested in the links between sleep disturbances and fibromyalgia as well as the modest improvement in people with a meditation program.  There is also another factor that is often not much talked about: people with chronic pain, from whatever cause can develop pain cycles: pain begins in some part of the body, but is then maintained by neurological circuits in the spinal cord and brain. Interfering with these pain cycles for even a day or two can sometimes be very helpful.

Fibromyalgia is one of the groups of conditions in which combinations are key. Trying just to use a medicine or just a diet is rarely likely to be crowned with success. The most helpful strategies that we have found have been combinations of:

1. Physical care:
   
   1. Appropriate medications to help with pain transmission and symptoms of depression
   2. Sleep hygiene, and some of the other approaches that I’ve suggested for dealing with disrupted sleep.
   3. Low intensity exercise
   4. Nutrition: this one of the clinical conditions that first persuaded  me that there are some people who have genuine food and environmental sensitivities, and, in some rare cases Candida overgrowth. There are quite a number of foods that may be very helpful, depending upon the individual’s likes and dislikes.   
   5. I’ve had colleagues who’ve had some great results with herbal remedies and supplements, but there is little published  evidence that these work.      
   6. Some people seem to have biochemical disturbances that can be  helped with some of the Schussler tissue salts.
2. Psychological support: there is some good evidence that some personality types and temperaments may be at increase risk of developing fibromyalgia, so any thing that helps build resilience and cope with negative cognitions can be very helpful. Some of the  tapping therapies can be very helpful adjunctive treatments, as can music therapy.
3. People with fibromyalgia are often very sensitive to the people around them, and their nearest and dearest often need help in understanding how best to support the person with the illness.
4. The subtle systems of the body are invariably compromised in people with fibromyalgia, and acupuncture – if people can tolerate it – as well as homeopathy can be very helpful. We have often used both together, though this is anathema to many classical homeopaths or acupuncturists. Perhaps they could not have been used in combination 50 years ago, but people have changed physically, psychologically, socially and energetically, and the rules have changed.
5. As with most people struggling with chronic illness, many people with fibromyalgia lose contact with their Source. And this is why - in my books and recordings – I spend so much time helping people  re-establish meaning and purpose in their lives, and help them use the illness not simply  as a barrier to be overcome, but as a stimulus for internal growth. I have also seen a number of indivudals in whom fibromyalgia was symptommatic of a spiritual awakening.       

One of my biggest worries with fibromyalgia, as with so many chronic illnesses, is that many desperate sufferers and their families can become victims of the unscrupulous. I have seen countless people selling advice and treatments that have no basis in fact.

Not everything that I have discussed here is evidence based: there is so little research on things like acupuncture and homeopathy. But those are treatments to be used in combination with more conventional approaches. Using all together is usually the best way forward. And everything that I’ve discussed here has been used in working with hundreds of people around the world.

Technorati tags: Fibromyalgia Chronic pain Integrated medicine Irritable bowel syndrome Sleep disturbance Candida

Systemic Psychiatry

“Once a disease has entered the body, all parts which are healthy must fight it: not one alone, but all. Because a disease might mean their common death. Nature knows this; and Nature attacks the disease with whatever help she can muster.”
--Paracelsus (a.k.a. Theophrastus Phillippus Aureolus Bombastus von Hohenheim, Swiss Physician and Alchemist, 1493-1541)

It is usually a mistake to try and look at an illness in isolation.

We are all human beings, and physical challenges affect the whole organism, as well as our mind, our relationships and our spiritual connections.

There is currently a very hot area of research that is still unknown to most people: even to most people working in psychology and psychiatry. This hot new area proposes that schizophrenia, bipolar disorder, major depressive disorder and autistic spectrum disorders, are disturbances affecting the whole body, but with prominent effects in the brain and on emotion and behavior. This may help provide one part of the explanation for why people struggling with chronic mental illness - and their relatives - suffer from an array of physical illnesses that cannot be explained by stress or poor lifestyle choices alone.

You can find a brief review with a stack of references here.

This idea of psychiatric problems being generalized systemic disturbances that have their primary effects on the brain and on behavior is important to the general themes of this blog. We are always interested in looking beyond the obvious causes, to a dynamic integrated vision of a person that includes every part and every dimension of his or her being. If we want to help people recover from illness, to triumph over adversity, and to use challenges as springboards to transcend themselves and the limits placed upon them, it is only possible if we take account of the whole person.

Perhaps we can reduce mental illnesses to disturbances in cell membranes or a few chemicals in the brain. But I do not think so. It is more accurate for us to be thinking about a perturbation or disturbance in the Informational Matrix that underlies the subtle systems of the body, that in turn support the biochemical reactions that provide the structure for the external expression of life itself.

We live in very interesting times.

“Good timber does not grow with ease. The stronger the wind the stronger the trees.”
--Willard J. Marriott (American Businessman and Founder of Marriott Hotels, 1900-1985)

Technorati tags: Schizophrenia Bipolar disorder Diabetes mellitus Phospholipid Cell membrane Systemic illness Informational matrix 

Predicting Responses to Supplements

The other day I was being asked about the use of S-adenosyl methionine (S-AME) for depression and the same day somebody was asking me about some of the supplements – mainly creatine - being taken by body builders.

The research data for each of these is patchy. When S-AME is injected, it seems to help with mild to moderate depression. But oral S-AME is a different issue, because the compound is about a soluble as sand. Not that much is absorbed, which is why we give fairly large amounts so that some gets into the body. Some research has been positive and some not. Similarly, when we look at creatine, there is a limit to how much can be taken up into the intestines or into muscles.

These are not nit-picky observations: When we take a supplement, it is good to know the chances that it will help. You don’t want to waste money on something that has little chance of getting into your body. It is always possible that a supplement works by some unknown mechanism, and we don’t want to dismiss that possibility: if you take a large dose of Vitamin C, most of it will be out of your body and into the plumbing within two hours. But that does not exclude the possibility that during those two hours it is doing something useful inside your body.

This is why we look at five things:
1.The research data, and also who did the research? With pharmacological agents as well as herbs and supplements, there have been countless examples of research funded by the manufacturer, generating glowing testimonials that don’t hold up to independent scrutiny
2. Individual accounts of benefit. Though they don’t carry the same weight as controlled studies, they can’t be minimized
3.The origin, purity, dose, concentration and expiration of the supplement. With many herbs and supplements there is a great deal of variability in quality control from one company to another and sometimes even from one batch to another
4.The plausibility that a treatment could be helpful. If a medicine cannot get into the body, it is not that likely to be helpful.
5.The possibility that a herb or supplement may be acting by some entirely novel mechanism

Rest assured that when we write our articles, we always check out all of these five things, as well as analyzing all the data in the reports of the research. I have mentioned before that when I read a paper, I sit down with a notepad and calculator so that I can check everything in the study. Many journals now post all the raw data online, and we check through that as well.

There are countless magazines and websites that try to bring you all the latest and greatest information. When you read their material it is a great idea to see if they have checked all of these five points as well as analyzing the data in the studies. Many of them do, but not always.

Some of us have been pulling our hair out every time that we see a well-known marketer present more of his infomercials. He is one of that band of people who quote research without really understanding it, perhaps in the hope that nobody will check up on them!

If you are interested in some herb or supplement, let me know and I shall see if I can help you. And if I do not know, I promise that I shall tell you!

Technorati tags: dietary supplement S-adenosyl methionine creatine intestinal absorption