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.
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.
- 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.
- 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.
- 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.
- 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!“
