Intestinal Microbes: A Hidden Cause of Obesity
It is no secret that many famous people swear by colonic irrigation. The late Princess Diana used to say that it helped her stay fit and keep her weight steady, though personally I always thought that good genes and regular exercise were the real explanations.
In previous posts I have talked about some of the emerging lines of evidence suggesting that there are at least four previously little recognized causes of obesity:
- Stress
- Salt intake
- Pesticides
- Viruses
Following a paper in today’s issue of the journal Nature, it looks as if we shall have to add a fifth: the intestinal microbes that are collectively known as “gut flora.”
We have within us vast communities of microbes that outnumber our own body’s cells by 10 to 1, and may contain 100 times more genes than our own human genome.
We have known for many years that we each contain pounds of these microbes and that they are doing a great deal more than simply sitting there. We have known since the 1950s that many of the microbes are involved in digestion, absorption and immune function. That is one of the reasons why most doctors worry about the unnecessary use of antibiotics: some can knock out the gut flora, sometimes with serious consequences.
It is the first of these – digestion and absorption – that has been attracting attention. Under normal circumstances our bacteria break down many complex molecules like polysaccharides into simple sugars that we absorb and use for energy.
Colleagues from the Washington University School of Medicine in St. Louis have made a remarkable discovery. It seems that the balance of two major families of intestinal bacteria: Firmicutes and Bacteroidetes have a major impact on digestion and obesity. Together these two families constitute 90 per cent of the bacteria in the intestines of humans, and, coincidentally, white mice.
The researchers conducted two parallel studies. In the first they found that as obese people lose weight, the balance between the Firmicutes and the Bacteroidetes changes – the latter increasing in abundance as an overweight person gets slimmer.
The second study used white mice. Here, researchers discovered that the bacteria in the lower intestines of obese white mice were more efficient at extracting calories from complex carbohydrates than the bacteria in the intestines of slimmer mice.
In an earlier study the researchers had shown that the intestines of obese mice had the same depletion of Bacteroidetes as found in the innards of obese humans.
The practical consequence of this finding is immense: it means that if two people are on the same diets and doing the same amount of exercise, one may gain weight and the other stay the same weight. Simply because the person who stayed the same had more Bacteroidetes in his large intestine, extracting fewer calories from the same amount of food. The main reason why his friend gains weight is because he has more Firmicutes and fewer Bacteroidetes.
The researchers suggest that intestinal bacteria could become “biomarkers, mediators and potential therapeutic targets” in the fight against obesity.
I find it impressive that some advocates of natural healing had predicted something along these lines in the early days of the 20th century. I am not too keen on colonic irrigation, though I have many colleagues who use it routinely. But there are many other ways of changing your intestinal flora, including probiotics and prebiotics. You may be interested to look back at a few words that I wrote about them in late August.
I would be happy to detail some other evidence-based strategies that we have used for normalizing intestinal flora.
“A man is not rightly conditioned until he is a happy, healthy, and prosperous being; and happiness, health, and prosperity are the result of a harmonious adjustment of the inner with the outer of the man with his surroundings.”
–James Allen (English Author and Mystic, 1864-1912)
“You cannot poison your body into health with drugs, chemo or radiation. “ Health” can only be achieved with healthful living.”
–T.C. Fry (American Writer on Natural Healing and Originator of the Life Science/Natural Hygiene Course, 1926-1996)
Another Nail in the Coffin of BMI
In August I outlined some of our reasons for believing that the most common measure of overweight and obesity – the body mass index (BMI) – can be very misleading and should probably be abandoned, or at least consigned to the back burner.
A team at the Hammersmith Hospital in London led by Professor Jimmy Bell has been using a novel type of MRI scan to locate the distribution of fat in the body. The problem is that 40% of the population has “bad” fat around some of their internal organs including the heart, liver or pancreas, even though many appear thin. So even though they may look slim, they may still be at risk of conditions like insulin resistance, diabetes and hypertension because of this hidden fat.
As we have said before, from a health perspective, it is the distribution of fat that is all important, rather than just the amount of it. This study confirms what metabolic physicians have been saying for years: BMI gives you the wrong idea about how much fat you have.
Once you know about the distribution of your fat, we can design precise lifestyle changes to work on it. As an example, the strategies that we use for overall weight management are not the same as the strategies that we use for reducing intra-abdominal fat. There are very good physiological reasons why diet does little to reduce the fat around organs. It is there to provide fuel during exercise, so specific exercises are the way to rid yourself of this internal fat.
At the moment there are very few centers that can do this kind of scanning, but with the growing evidence of its importance, that is likely to change. In the meantime, be aware that aerobic exercise and strength training, particularly if it involves the large muscles of the back trunk and lower limbs is the quickest way to rid yourself of these dangerous fat deposits.
Fat in itself is essential for normal health, but fat in the wrong places can be a killer. And BMI tells you nothing about the fat lurking in the hidden parts of your anatomy.
Aerobic Exercise, Diet and Abdominal Fat
Most of us are probably aware of the difference between fat inside the abdomen – “intra-abdominal,” also called visceral fat – and fat on the hips or the outside of the abdomen. The fat inside the abdomen is associated with insulin resistance, diabetes and at least a dozen other medical problems. This fat is also covered in cortisol receptors and breaks down and reforms extremely rapidly. By contrast the fat on the outside of the body has relatively few metabolic consequences until the amount of it becomes extreme.
Excess fat in general is not a good idea, but it is the intra-abdominal fat that is the best target for treatment.
New research has shown that the addition of aerobic exercise to a standard dietary weight loss program can preferentially reduce abdominal fat in overweight people.
The investigators did a twenty week prospective study in which looked at 45 obese women with an average age of 58 years. During the study the participants bought their own breakfast in consultation with a dietitian, but had their lunch and dinner prepared by the kitchen staff of the hospital. They were either told to continue with their normal routine of daily activities, or to do low-intensity or high-intensity aerobic exercise. The investigators not only did all the standard measurement on their volunteers, they also did fat biopsies and measured the size of the fat cells.
They all lost weight, but in the people who did the high-intensity aerobic exercise, they also had a reduction in the size of the fat cells in subcutaneous tissue taken from the abdomen.
This is interesting, but it’s necessary to sound a note of caution about the experiment: the investigators were measuring subcutaneous fat cells rather than the all important intra-abdominal fat cells. The trouble with measuring those is simply getting at them. It is not easy trying to get fat out of the abdomen without some invasive procedures.
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:
- Stress
- Salt intake
- Pesticides
- 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!
Food, Reward and Weight Gain
There’s a short review with a link to an online research paper that you might find interesting.
Although the paper has to do with the mechanisms of weight gain in people with schizophrenia, many of the same principles apply to many people with weight problems. The systems of the brain involved in salience – deciding what is important in the environment – appear to be disrupted.
Gene-Jack Wang at the Brookhaven National Laboratory has discovered that the brains of morbidly obese people seem constantly to be turned toward finding food: The regions of the brain connected to the mouth lips and tongue are overly active, and, like the addicts who get the biggest rush from drugs, they seem to have fewer dopamine receptors in the reward systems. Perhaps like the addict, the morbidly obese eat to compensate for an underactive dopamine system.
In Healing, Meaning and Purpose, we coined the term, “Salience Disruption Syndrome,” to describe a group of problems that are normally thought of as separate entities, but which are inextricably linked. They include not just over-eating, but:
- Impulse control disorders
- Substance abuse disorders
- Pathological gambling
- Pathological shopping
- Attention deficit with ot without hyperactivity
- Bipolar disorder
The list is a long one and the reason for highlighting it is that we have been able to devise new treatments based on this new principle of a disruption in salience. If there is interest, I shall post some more about the methods that we have devised.
Thrifty Genes, Thrifty Bodies and the Barker Hypothesis
“They have sown the wind, and they shall reap the whirlwind.”
–The Bible (Hosea, 8:7)
In 1962, a geneticist named James Neel first proposed a “thrifty gene” theory to explain why 60% of adult Pima Indians living in the United States have diabetes, and 95% are overweight. Neel’s theory was that populations like the Pimas, that have for millennia relied on farming, hunting and fishing for food, would experience alternating periods of feast and famine. Neel hypothesized that in order to adapt to these extreme changes in caloric needs, people developed a “thrifty gene” that allowed them to store fat during times of plenty so that they would not starve during times of famine.
A similar theory was advanced to explain the high rates of diabetes in people from the Indian subcontinent, once they are exposed to plentiful supplies of food. These was traced by the great Diaspora from central Asia at the end of the last age, when the ancestors of modern Indians and Pakistanis made the great trek through modern Afghanistan into the Indus valley. A journey that had been impossible at the height of the Ice Age and which was still difficult. The idea was that people who could quickly lay down a lot of intra-abdominal fat would have a huge survival advantage.
This is an attractive hypothesis, but here have always been some problems with it:
- The gene or genes would have to be able to work with the environment: the Pimas of Mexico and people living in rural India do not have the high rates of diabetes and obesity
- Despite looking for over 40 years, no such gene has yet been found
- If the thrifty gene is so advantageous, why doesn’t everyone have it?
- Until recently, famines were rare and usually occurred every 100-150 years. As John Speakman has pointed out that would mean that most human populations have experienced at most 100 famine events in the course of their evolutionary history
- Famines do increase mortality but only in about 10% of the population
- In famines most people die of disease rather than starvation, and the worst affected are the young. Having a “thrifty gene” would not help them survive starvation OR disease
- Simple genetic models would suggest that famines would not provide enough selective advantage and there has not been enough time for a “thrifty gene” to have penetrated the population
There could yet be some complex genetic model involving “reserve” genes that appear when needed, or some epigenetic inheritance, but we have no evidence for that either.
A second concept is gaining a lot of traction. It is what is known as the “Thrifty phenotype,” and is part of a larger theory called the “Barker Hypothesis.” I’m going to stick my neck out, and predict that David Barker may receive the Nobel Prize in medicine for his discoveries. They are that important.
Essentially the Barker Hypothesis suggests that in addition to genetic, epigenetic and environmental factors in disease, there is another, and that is the intrauterine environment. The idea is that if a mother is malnourished, she can modify the development of her unborn child. From an evolutionary perspective, her body is preparing the unborn child to survive in an environment where food is in chronic short supply, resulting in the “Thrifty phenotype:” smaller body size, lower metabolic rate and a propensity to be less active.
The problem is this. If you are born with the thrifty phenotype and actually grow up in an affluent environment, you are more likely to develop obesity, diabetes and vascular disease later in life. If true – and virtually all the evidence suggest that it is – then it has serious implications for countries that are transitioning from sparse to better nutrition, and may have contributed to some of our current health problems. Many of us were born to mothers who had poor nutrition, either because of the Great Depression, the Second World War, poverty, or just plain poor information about good nutrition during pregnancy. And now we are reaping the whirlwind.
The hypothesis has become sophisticated. If you are born small or premature, then your liver and kidneys may not have completed their final growth spurt, which might predispose you to metabolic problems and hypertension.
The story of how this all came to light would be worthy of Sherlock Holmes himself.
English counties used to have people who were responsible for providing midwifery services. In the county of Buckinghamshire a single midwife collected data for almost thirty years. Information about the mother, the length and weight of the baby and the weight of the placenta. Information that would be impossible to collect these days. Some civil libertarian somewhere would probably dream up some way of hiding this enormously important information.
David Barker discovered these extraordinarily good records, and then set about finding the adults that these babies had become. And what he found has changed medicine: babies who had small placentas – a good measure of being small or premature – were more likely to develop obesity, diabetes or hypertension as adults. Then he and others turned their attention to other early physical characteristics and found correlations with health later in life. The highest risk of coronary heart disease was seen amongst people who were born small and became heavier during childhood.
The practical implications?
Find out your own birth weight and anything else that you can about your early development.
If you were a very large baby (bigger than nine and a half pounds), it implies that your mother may perhaps have had a metabolic problem. If you were small (less than five and a half pounds), then you should get the regular health checks that we recommend for anyone in a “high risk” group.
BMI R.I.P.
For experts in metabolism, we have long worried about the over-emphasis on the use of body mass index (BMI) as the arbiter of a "healthy" weight. It is one of those measurements that is in some senses too easy, and the results are deceiving. I regularly see people claim that a certain BMI will "predict" the risk that someone will develop cardiovascular disease or diabetes. The truth is very diferent.
There are two ways to calculate your BMI:
1. Metric system – Kilograms and Metres
[Your weight] divided by [Your height squared]
2. Imperial System – Pounds and Inches
[You weight] divided by [Your height squared] times 703.5
A person is said to be healthy if his or her BMI is between 18.5 and 24.9.
The trouble with this is that the calculation lumps together fat and muscle: a muscular six foot tall football player weighing 300 pounds and with 3% body fat, would have an "unhealthy" BMI of 26.3. That is clearly absurd, and one of the reasons that most experts use BMI only as one part of an evaluation of health.
Our scepticism has been confirmed by an important study from the Mayo Clinic in Rochester, Minnesota, and published in this week’s issue of the medical journal The Lancet.
The researchers looked at 40 studies involving 250,152 patients. Their analysis revealed that people with a BMI of 30-35 were at lower risk of cardiovascular disease than those whose BMI was below 20.
BMI does not correlate well with fat. A better way to distinguish between fat and muscle is to take a cross-sectional view of the abdomen, and to focus on the waist-hip ratio.
A separate study by researchers at the London School of Hygiene and Tropical Medicine of 14,833 people over the age of 75 was published in the American Journal of Clinical Nutrition. They also came to the conclusion that BMI is a poor indicator of health in both men and women in this age group. These researchers also agreed that waste-hip ratio was a better indicator of mortality risk.
This is all music to my ears. For almost three decades we have been teaching about the importance of different stores of fat and the limitations of the BMI calculation. It has been known since the 1940s that gaining weight on the hips, or developing "lover’s handles" are only very weak predictors of diabetes and vascular disease: it is the intra-abdominal fat that is the problem.
There are particular problems with using BMI in the elderly and in some ethnic groups, especially people from the Indian sub-continent and Japan.
The bottom line?
BMI is misleading, and in some age groups and races, grossly misleading.
Much better to use weight and waist-hip ratio.
And BMI only if there is a space on the medical forms where they still need to have it filled in.
Insulin Resistance, Polycystic Ovarian Syndrome and Sleep Apnea
Polycystic ovarian syndrome (PCOS) is a common endocrine disorder that affects between 5-10% of women in the Western World. It is a leading cause of infertility, and although the underlying cause is still speculative, it is very heavily associated with insulin resistance.
There was an International Consensus Workshop sponsored by the European Society of Human Reproduction and Embryology and the American Society of Reproductive Medicine came up with this set of criteria. PCOS is present if a woman has at least two out of three of:
- Oligoovulation and/or anovulation (ovulating only occasionally or not at all)
- Excess androgen (male sex hormone) activity
- Polycystic ovaries (which needs a gynecological ultrasonography) and other causes of PCOS are excluded
There is still a great deal of debate about the precise way to define the syndrome. We are currently preparing a scholarly article on the subject and our literature review has included over three thousand papers.
The combination of an excess of the male (androgenic) hormones and insulin resistance can cause an array of symptoms apart form the menstrual disturbances and infertility, including:
Central obesity
Acne
Hirsutism, while at the same time experiencing alopecia
Skin flaps and dark patches of skin, usually on the neck or in the armpit
Sleep apnea
It is the last of these that I would like to highlight today.
A new study by Dr. Esra Tasali and her colleagues from the University of Chicago has found that in women with PCOS, sleep apnea is, as expected, associated with high fasting insulin levels. Sleep apnea might worsen the metabolic consequences of insulin resistance.
Regular readers may recall that I highlighted the association between insomnia, insulin resistance, weight and diabetes a couple of months ago. Here we have yet more confirmation of this link.
Not getting enough sleep – for any reason – can play havoc with your metabolism. It seems that in women with PCOS, it’s really easy for a vicious circle to become established:
Insulin resistance -> weight gain -> sleep apnea -> insomnia -> more insulin resistance -> more weight gain and so on.
It is important for everyone to know about this association, because chances are that you know someone with PCOS and/or sleep apnea.
Gall Bladder Disease and Insulin Resistance
When I was a young student, everyone learned that gallstones were more common in people who were “Fat, female, fair and forty.” As you can see we lived in different times and nobody would say anything quite like that today. Not least because it’s now only partially correct. Gallstones are occurring at ever-earlier ages, because they are a recognized complication of obesity. And we all know that we are in the midst of a pandemic of overweight and obesity.
We have also been remarking on the number of people with bipolar disorder who have a history of gallstones.
For many years now, the explanation for the link has been to do with an increasing levels of cholesterol, which are a major precipitant of gallstones. There’s also evidence that high carbohydrate diets increase the risk of gallstones. Weight loss reduced the risk of developing them, though suddenly losing a lot of weight with an unbalanced diet may increase the risk of gallstones.
Now a paper from colleagues at three medical schools has just been published this month, and it helps clarify the connection. The conclusion of the scientists is important: insulin resistance itself seems to cause problems with the normal emptying of the gallbladder, and that would predispose people to the development of gallstones.
Insulin resistance is a feature of increasing weight. Several studies that have found increased rates of insulin resistance in people with bipolar disorder implying an increased risk of gallstones. Though gallbladder disease didn’t show up in a recent study from some friends in Toronto, I could not find any systematic studies of gallstones and bipolar disorder. And it is a study that needs to be done.
So there’s a tip for a researcher who can’t think of a project!
