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!“
A New Understanding of Mood Medicines and Cells
We are in the midst of a revolution in our understanding of how many medicines work. Most students are still taught that the key to their actions is simply a matter of binding to a receptor, and then some magic occurs in the cell. But over the last few years there has been a sea change in how we see the actions of many medicines. In many ways the focus on receptor pharmacology is so 1990s.
Several years ago our group and others began to speculate that one of the ways of modulating the interaction of insulin with cells was to modify the characteristics of the cell membrane in which the insulin receptors sit. If we could change the fluidity of the cell membrane, then we could change the sensitivity of the insulin receptor. We also went a bit further and wondered whether high cholesterol levels might be associated with coronary artery disease because it changed the way in which growth factors interacted with cells in the vessel walls.
One of the reasons that fish oils may yet turn out to be helpful in some mood disorders is because they may change the behavior of cell membranes and therefore the behavior of receptors.
I have admired the work that has bee done by Husseini Manji and his group that is now at the National Institute of Mental Health in Bethesda, Maryland. Their interest is in bipolar disorder and there is a very nice update on the group’s work in the journal Biological Psychiatry.
The group is unraveling the ways in which effective medicines work at the cellular level and what actually goes wrong in bipolar disorder. We know that people with severe mood disorders may experience regional impairments of what we call structural plasticity and cellular resilience. This means that the cells find it more difficult to learn and respond to environmental changes. We think that this is why some people with severe mood problems fail to benefit from many medicines and also have so many long-term cognitive problems. So the search is on for strategies that may enhance and maintain the normal connections between neurons. The good news is that there are several new strategies on the horizon.
This notion of impairment in the normal plasticity and resilience of the brain is also why psychosocial approaches are an essential component of successful treatment. When they are coupled to the right medicine as well as the strategies that we employ in Integrated Medicine, the effects can often be very gratifying.
The Heart Master Cells
There are two extremely important papers (1, 2,) in this month’s issue of the journal Cell.
The heart is composed of three major types of cell: Cardiac muscle cells that make up the heart itself and whose contractions pump blood; smooth muscle that cells that are found in the walls of the heart’s own blood vessels and finally endothelial cells that line the heart’s blood vessels. There are many other special types on neural and endocrine cells in the heart, but these three form the basis of the circulatory pump that keeps you alive.
In one of the papers, scientists identified a cell that has the capacity to produce all three major tissues in the heart, the other group found a cell that produces two of the three cell types. One appears to generate structures on the left-hand side of the heart, and the other on the right-hand side. The findings challenge the old idea that the heart’s different cell types are so different that they must have come from separate sources.
What this means is that some unknown mechanism can make a single stem cell “decide” to become one of the three cell types.
Until very recently it was assumed that there was no way that a damaged heart or brain could regenerate itself. We now have proof positive that this dogma is wrong and it raises some extraordinary possibilities for repairing the heart.
These new papers follow others that have worked out the mechanism by which a little creature common in the tropics – the zebrafish – is able to mend his heart if it gets broken, and some research published in the journal Nature that showed that a molecule called thymosin beta-4 can make progenitor cells in the outer layer of the heart migrate deeper into the heart and carry out repairs.
My old friend Professor Jeremy Pearson – with whom I shared a lab and an office for seven years – is now the Associate Medical Director of the British Heart Foundation, and he had this to say about the second of those papers:
“By identifying for the first time a molecule that can cause cells in the adult heart to form new blood vessels, Dr Riley’s group have taken a large step towards practical therapy to encourage damaged hearts to repair themselves, a goal that researchers are urgently aiming for.”
And Professor Colin Blakemore, the chief executive of the British Medical Research Council, said:
”Finding out how this protein helps to heal the heart offers enormous potential in fighting heart disease, which kills more than 105,000 people in the UK every year.”
Jeremy Pearson was very helpful when I first started fleshing out and presemting the ideas about the reversibility of problems like arteriosclerosis, ischaemic heart disease, stroke and Alzheimer’s in the late 1980s. He was initially very skeptical, but did what a good scientist should. He didn’t shut down the discussion but kept it going with challenging questions.
The important point from all this research is not just that it supports many of the basic concepts of Integrated Medicine, but it also reminds us that when someone says that a disease is untreatable or irreversible, they may well be wrong.
In Sickness and In Health
I recently talked about the importance of healthy relationships and some ways to establish and maintain them.
Here is an interesting study that was published in the Journal of Personality and Social Psychology.
The research into 111 coronary artery bypass patients showed that the partner’s personality traits played a major role in how well they had recovered 18 months after their operation.
Pollyannas are probably the best sort of significant other when you’re sick. It is interesting to learn that their cheerful chatter might sound like the last thing an ill person needs but it is such a tonic that patients recover much better and faster.
A homeopath, acupuncturist or Integrated Practitioner would quickly identify who would like the Pollyanna and who would not.
What you definitely don’t want is a “generally neurotic and anxious” partner. These spouses increase the patients’ risk of developing clinical depression. Such depression is increasingly recognised as a significant risk factor in causing slow recovery and deaths from conditions such as coronary disease.
And most specialists recognize that depression and anxiety can be catching.
Another Reason to Eat Your Greens
“Health requires healthy food.”
–Roger Williams (Indian-born American Chemist who did pioneering work on the Vitamin B Complex, 1893-1988)
Earlier this year several news outlets including Time picked up a story that has been causing a great deal of discussion in medical circles.
Most of us have been extolling the virtues of fruits and vegetables for decades, but it’s always nice to have an extra piece of evidence to support what we’ve been saying. The question has been how to go from large-scale epidemiological studies proving the benefits of vegetables to the inner workings of a person’s arteries.
Investigators from Wake Forest University School of Medicine in Winston-Salem, North Carolina published an important study in the Journal of Nutrition. What they did was to study genetically altered mice, who had been bred to have a very high risk of developing rapid arteriosclerosis: the formation of fatty plaques in the arterial wall that can eventually block blood flow and lead to heart attacks and stroke.
Half the mice were fed a vegetable-free diet and half the mice were fed a diet that included broccoli, green beans, corn, peas and carrots.
After 16 weeks, the researchers measured the cholesterol content in the blood vessels and estimated that plaques in the arteries of the mice were 38% smaller. Cholesterol, and particularly the “bad” cholesterols VLDL and ILDL fell markedly in the mice on the healthy diet, but these improvements were not on their own enough to explain the improvement in the blood vessels: the anti-atherogenic effects of the vegetable diet remained largely unexplained by the variation in plasma lipoproteins or body weight.
There was a 37% reduction in serum amyloid – a marker of inflammation in mice – suggesting that consuming vegetables may inhibit inflammatory activity. This is line with data from other studies indicating that fruit and vegetables should be key components of an inflammation-lowering program. This is very important: in the last twenty years it has become very clear that arteriosclerosis is intimately associated with inflammation in the arterial wall.
Many inflammatory conditions including rheumatic fever, rheumatoid arthritis, systemic lupus erythematosus and psoriasis, are all associated with an increased risk of developing arteriosclerosis.
Interestingly some years ago Dean Ornish presented evidence indicating that diet and exercise could reverse arteriosclerosis. I’ve always found Dean’s work interesting, well done and persuasive. It surprises me to see how many people remain unconvinced. This new research provides indirect support for his work.
The average person only eats three portions of fruit and vegetables a day: we should all be eating at least five, and they should be of as many different colors and types as possible: there is excellent evidence that combinations of fruits and vegetables are much better for your health than just eating one or two types.
As an aside, I must admit that I’m no fan of animal experiments: I don’t and won’t do them. And every time that I hear about them, I think that we need to say a sincere thank you to the animal kingdom for their sacrifice in helping us.
“God, in His infinite wisdom, neglected nothing and if we would eat our food without trying to improve, change or refine it, thereby destroying its life-giving elements, it would meet all requirements of the body.”
–Jethro Kloss (American Nutritionist and Writer 1863-1943)
“In fresh fruit and vegetables and nuts are all the vitamins and minerals and high grade proteins the human body needs to bring it to a state of physical perfection and to MAINTAIN it in that state indefinitely.”
–Herbert Shelton (English Evolutionary Philosopher, 1820-1903)
“Nothing will benefit human health and increase the chances for survival of life on earth as much as the evolution to a vegetarian diet.”
–Albert Einstein (German-born American Physicist and, in 1921, Winner of the Nobel Prize in Physics, 1879-1955)
Laughter is The Best Medicine
“Time spent laughing is time spent with the gods.”
–Japanese Proverb
In the book and movie Anatomy of an Illness, Norman Cousins reported how he overcame a sever arthritic condition with a combination of huge doses of vitamin C, together with a positive mental attitude and hours of laughing at Marx Brothers movies. He wrote that, "I made the joyous discovery that ten minutes of genuine belly laughter had an anesthetic effect and would give me at least two hours of pain-free sleep. When the pain-killing effect of the laughter wore off, we would switch on the motion picture projector again and not infrequently, it would lead to another pain-free interval."
I’ve had a longstanding interest in the vascular endothelium, the single layer of cells that line blood vessels. Some very small blood vessels consist only of endothelial cells. These cells form the interface between the blood and the tissues, and they are involved in many disease processes. They are involved in diabetic vascular disease, arteriosclerosis, inflammation, many infections, and they play a role in the spread of tumors. There is some new evidence that laughter is good for you in more ways than one.
Investigators from University of Maryland School of Medicine found that watching a funny movie had a healthy effect on blood vessel function, allowing them to expand and contract more effectively in response to changes in blood flow. But watching a mentally stressful movie, like a war drama, may have the opposite effect, causing the vascular endothelial cells to narrow and restrict blood flow. On average, artery diameter increased by 22% during laughter and decreased by 35% during mental stress.
This work follows on from earlier research that showed an inverse association between sense of humor and coronary heart disease: people who laughed a lot seemed less likely to suffer form heart disease.
There is a very nice review article available online that confirms what is intuitively obvious humor and laughter may have a positive influence on health and on the outcome of many diseases.
There may be something to the old saying, "You don’t stop laughing because you grow old; You grow old because you stop laughing.”
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.
Cranberries and the Inflammation Associated With Severe Gum Disease
There is an interesting study from a team of researchers from Quebec, Canada. The findings, published in the Journal of Antimicrobial Chemotherapy, reveal that natural compounds in cranberries may help ward off periodontitis, or severe gum disease, by serving as a powerful anti-inflammatory agent. This anti-inflammatory effect may be attributed to unique compounds in the fruit that prevent the bacterium P. gingivalis from adhering to the teeth below the gum line. Though it is early days, this new research offers promise for the estimated 67 million Americans affected by periodontitis, the primary cause of tooth loss in adults.
The reason for the study was that cranberries have what are known as "anti-adhesion" activity. This helps guard the body from certain harmful bacteria that cause urinary tract infections (UTIs), gastric ulcers and gum disease. This anti-adhesion activity is primarily due to molecules called proanthocyanidins (PACs) found naturally in cranberries and other foods. Cranberry PACs contain a unique A-type structure that is responsible for this anti-adhesion mechanism of action, while most other foods contain only the more-common B-type PACs.
Researchers discovered that cranberry compounds can reduce the growth of P. gingivalis and subsequent plaque development — the initial step in the development of periodontitis. Periodontitis occurs when inflammation or infection of the gums is left untreated or treatment is delayed. Infection and inflammation spreads from the gums to the ligaments and bones that support the teeth and eventually leads to tooth loss.
In a paper in the Journal of Dental Research the same researchers had previously shown that cells treated with cranberry juice showed significantly less inflammation than cells that were not treated.
Not only can cranberry compounds decrease the growth of P. gingivalis, they may also prevent certain oral bacteria from directly destroying gum tissue itself — another major factor contributing to periodontitis. This may have more widespread implications as recent studies have also linked severe gum disease with an increased likelihood for heart disease and stroke.
The study was part funded by the Ocean Spray agricultural cooperative that sells cranberry juice.
Brushing, flossing and regular professional cleaning reduces the risk of developing periodontitis by helping to prevent the onset of gingivitis, or gum infection. Cranberries may provide an interesting ingredient in the development of new therapeutic approaches for treatment of periodontitis.
Technorati tags: Cranberries Dental disease Heart disease Urinary tract infection Inflammation
