Another Reason Why Breast Is Usually Best
Last month we looked at some of the extraordinary benefits of breast feeding.
There is an interesting paper in this month’s issue of the journal Pediatrics.
Approximately 19 percent of children are prone to the chronic and recurrent ear infections collectively known as otitis media. These infections can cause deafness and thereefore interfere with the development of language and lead to learning difficulties. We have known for many years that there can be a genetic predisposition to otitis media, but there has been little research to try and pinpoint the specific genes involved. There is also a complex relationship between genes, specific infectious agents and environmental factors such as exposure to cigarette smoke and breast-feeding.
The new research from the University of Texas Medical Branch at Galveston examined genetic samples taken from 505 children in Texas and Kentucky, about 60 percent of whom were classified as "otitis media susceptible" because they had:
- Suffered an ear infection before the age of 6 months
- Or undergone three or more episodes of acute otitis media within a six-month period
- Or four or more episodes within a 12-month period
- Or had six or more episodes by age 6.
- Or had required drainage tubes to reduce recurrent or persistent ear infections
The researchers looked for small genetic variations called "single-nucleotide polymorphisms," – or SNPs – in three important genes that produce inflammatory signaling molecules for the immune system.
Two genes known known to generate the immune proteins known as tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). SNPs in each individual gene were enough to create an increased risk for childhood ear infections, and simultaneous SNPs in both genes increased the risk even further. These particular genetic variations cause a greater production of inflammatory signaling molecules and reduce the effectiveness of the immune system.
But here is the fascinating thing: the researchers found that the genetic effect could be counteracted by breast-feeding, which is well known to increase immune resistance.
We have here another fine example of how a healthy practice can overcome a genetic predisposition to illness. Remember what I have said many times before: Biology is not destiny.
On the hand another environmental factor – exposure to cigarette smoke – increased vulnerability to otitis media in children with the TNF-alpha gene variation. Cigarette smoke exposure alone was not enough to increase the risk for ear infections.
Stress and the Skin
You have probably noticed how stress can have an impact on some people’s skin. Increasing stress can initiate or worsen skin disorders such as psoriasis and atopic dermatitis. There has also been a lot of discussion about whether stress can also exacerbate acne and cause cold sores to erupt.
A new study published in the December issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology sheds important light on this association.
It is well known that one of the physical effects of stress is to increase levels of a range of steroid hormones called glucocorticoids. The best known glucocorticoid is cortisol or hydrocortisone. So the question was whether the missing link between stress and skin problems might be one or other of the glucocorticoids.
Researchers from the Veterans Affairs Medical Center, San Francisco and the University of California at San Francisco and Yonsei University Wonju College of Medicine, Wonju, Korea decided to study this possible connection.
You may have heard that the skin is the largest organ in the body and provides the critical barrier between the environment and the internal organs. Its most important function is providing a permeability barrier that prevents us from drying out. When we are healthy we are approximately 65-70 percent water. We are able to survive and function in dry environments because the skin forms a permeability barrier that prevents the loss of water.
The physical location of the permeability barrier is in the outermost layer of the epidermis that is known as the stratum corneum. The stratum corneum is composed of dead cells surrounded by lipid membranes. The stratum corneum layer continuously sloughs off, and therefore has to be constantly regenerated. The epidermal cells in the lower epidermis are continuously proliferating to provide new cells, which then differentiate, move toward the surface and ultimately die, to form a new the stratum corneum. This process is going on in your skin right now, though it can be disrupted by damage such as sunburn. If the process becomes overactive, it can lead to the development of thick, hardened skin.
It was already known that psychological stress disturbs this elegantly balanced system by decreasing the proliferation of epidermal cells and inhibiting their differentiation. As a result the function of the permeability barrier is impaired.
To test the hypothesis that glucocorticoids would have adverse effects on skin function, they stressed some hairless mice by putting them in small cages in constant light and forcing them to listen to the radio for 48 hours.
Before being stressed one group of mice was treated with mifepristone, which you may know by its two other names, RU-486, or the “morning after” pill, which blocks the action of glucocorticoids. A second group was given a drug called antalarmin, which blocks glucocorticoid production. A third group was stressed but received neither drug and a fourth group remained unstressed in ordinary cages and without the continuous light and sound to which the other groups were exposed.
The mice that received mifepristone or antalarmin showed significantly better skin function compared to the stressed mice that did not receive either treatment.
The experiment demonstrated the important role that glucocorticoids play in inducing the skin abnormalities brought on by psychological stress. Although we hope that the study will lead to a way to treat people who suffer from these skin conditions, there is still a long way to go. It’s always difficult to extrapolate from mice to people. Second, there may be serious side effects of modulating glucocorticoid activity. Glucocorticoids are essential hormones that play many important roles. Blocking their action could have negative outcomes. This is one of the reasons why we are skeptical about advertisements that claim that some herbal concoction can “cure” cortisol-related obesity. If something could really modify the activity of cortisol or other glucocorticoids in the body, it would likely have many most undesirable effects.
The research team is now looking at the effect of psychological stress on the skin’s production of antimicrobial peptides, which play a role in defense against infection. It has long been thought that psychological stress might also reduce the ability of the skin to protect from infections.
I never like to leave a report involving animal experiments without also saying a heartfelt thank you to the animals that participated in the experiments.
This research is interesting and may have a number of spin offs. But I have another rather obvious question: since we already know that there is a link between stress and some skin problems, why not focus on stress management techniques, rather than trying to find new medicines to help counteract the biochemical effects of stress?
Genes, Environment and the Brain
We recently looked at the worrying suggestion that environmental toxins could, in susceptible individuals, be contributing to the apparent increase in autism over the last three decades.
There is increasing evidence that there are complex genetic and environmental interactions that contribute to abnormal aging and neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s diseases.
A new study from Duke University Medical Center in Durham, North Carolina, has done more to dissect this interaction. They collected information on 1136 consecutive patients who presented to the Joseph and Kathleen Bryan Alzheimer Disease Research Center. They showed possible significant contributions of toxic environmental and occupational exposures to pathological aging in 21% of the patients, and interactions of these exposures with common genetic polymorphisms that affect cell injury and inflammation. They found a series of genes that could partially account for differences in the type of cognitive problems that people experience, the age at which they developed them as well as the rate of progression.
The researchers targeted three genes in particular – apolipoprotein E, alpha-1-antitrypsin and the hemochromatosis gene. All three are expressed in the liver and in macrophages: cells that play a critical role in immune responses, inflammation and the body’s response to stress and infections. The first two genes are particularly involved in the metabolism of lipids and the third in the balance of iron and trace minerals. This ties in with another observation. Many chronic illnesses are associated with anemia. It is now thought that this also is a defensive reaction. Not to chronic illness, but to the problem that was far more common during evolution, and that was infection. The liver pulls iron out of the circulation so that bacteria cannot use it for their own growth. This is one of a number of adaptive responses that I discuss in the book and CD series, Healing, Meaning and Purpose.
But it was also clear form this new study that genes were not the only factor. I have spoken before about the small number of strategies that can dramatically reduce our risk of developing Alzheimer’s disease. The authors of this study agree about the importance of factoring in environmental factors including, alcohol use, nutritional deficiencies and sleep and mood disorders, all of which can have an impact on cognition.
This study is yet another step toward clarifying the role of genes, inflammation and cell injury in the development of degenerative changes in the brain.
While pharmacologists can use this information to help devise new ways to protect your brain, you can use it immediately. There is a range of behavioral and dietary strategies that can reduce the burden of inflammation in the body. I shall write about some of them in articles and an eBook in the near future.
We do not know whether these strategies can reduce the risk of Alzheimer’s and Parkinson’s diseases, but there are some intriguing suggestions that they can.
Multiple Sclerosis and Stem Cells
If you have been reading my recent posts about multiple sclerosis (MS), you may be interested in an useful resource from the New York Academy of Sciences.
I have the privilege of being a member of the Academy and I’ve been impressed by its increasing efforts to educate the general public. There are regular "eBriefings" that are well written and succinct.
This one on stem cells and MS is timely and encouraging. It is also a good jumping off point if you want to follow up on some of the issues.
The existence of stem cells in the central nervous system has already raised some intriguing possibilities for treatments based on activating and directing them in the brain. The second idea, of dismantling the diseases immune system and replacing it with a new clean one, is not science fiction but part of a concerted effort to reprogram the body.
This is precisley the kind of approach that we advocate when we use "Information Medicine," designed to correct faulty information that produces faulty DNA and ultimately faulty proteins and organs.
Multiple Sclerosis
Multiple sclerosis (MS) can be a horrible illness that does not respect age or class. Neil Cavuto, Captain Beefheart and Montel Williams are just three well-known people who have said that they have the illness. Here is a list of many other sufferers.
MS is a chronic, inflammatory disease that affects the central nervous system (CNS). MS can cause a wide variety of symptoms, including changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, and pain. The classic pathology is what is known as demyelination (loss of the myelin that insulates nerve cells). Since myelin is white, the lesions are typically fuond in the white matter of the CNS.
The cause remains unknown, though I shall have more to say about some of the MS theories. Amongst the candidates have been autoimmunity, slow viruses, myelinic enzymes and polio vaccination.
Most people begin to experience symptoms between 20 and 40 years old, and rarely after 50. The onset is usually insidious, though every now and then someone starts with sudden onset of a catastrophic neurological or visual problem. Symptoms are usually vague and the diagnosis is often missed in the early stages. Females are affected slightly more than males. MS seems to be a disease of temperate latitudes in both the Northern or Southern hemispheres and is rarely seen in equatorial regions. This association with latitude has fueled some of the viral theories as well as ideas to do with the impact of decreasing sunlight on vitamin D and cell membrane function.
One of the things that makes the disease such a great masquerader is that it is typically marked by apparently random exacerbations and remissions. As the disease progresses, the remissions become less complete and permanent deficit more apparent.
There is an enormous research literature on MS: over 35,000 papers at last count. But there have been some recent highlights.
There has recently been a major breakthrough in discovering the mechanism by which myelin forms. The finding from the Keck School of Medicine of the University of Southern California and the Institut de Recherches Cliniques de Montreal in Canada, could have a major impact on the treatment of multiple sclerosis and demyelination as a result of spinal cord injuries.
Jonah Chan and his colleagues showed that a protein, Par-3, is at the base of the myelination process. This protein becomes localized to one side of the myelin-forming cells that are known as Schwann cells, upon contact with the axon that is to be myelinated. Par-3 acts like a kind of molecular scaffold to set-up an "organizing centre" that brings together the key proteins essential for myelination, in particular a receptor for a molecule that is secreted by the neurons.
The researchers found that when they disrupted this organizing centre, cells could not form myelin normally. Importantly, their discovery demonstrates that Schwann cells need to become polarized so that they know which side is in contact with the axon to initiate wrapping and to bring essential molecules to this critical interface.
These studies open up some new possibilities that should help to identify other components that are recruited at the organizing center set-up by Par-3. In multiple sclerosis, or after injury, Schwann cells can re-myelinate axons of the central nervous system to some degree. Therefore, these experiments bring about the possibility that manipulating the Par-3 pathway might allow for more efficient re-myelination of damaged or diseased nerves.
In a separate study researchers from the Virginia Commonwealth University researchers have identified a unique mechanism of action of a new drug that shows great promise for the treatment of MS.
The researchers reported the unique action of FTY720, or Fingolimod, an immunosuppressant drug that was already known to affect the functioning of the immune system by preventing the egress of white blood cells from the lymph nodes into the blood. The article was published in Blood: The Journal of the American Society of Hematology, that appeared online on Sept. 28.
In this study, the research team found that FTY720 also inhibited the activity of a key enzyme called cPLA2, which is necessary for the production of inflammatory mediators, known as eicosanoids. Eicosanoids drive inflammatory disorders such as asthma and multiple sclerosis.
The inhibition of cPLA2 would shut down the entire inflammatory pathway, possibly without the side-effects caused by medications such as Vioxx, that have been withdrawn from the pharmaceutical market.
FTY720, is a drug developed by Novartis, has shown considerable therapeutic effects in a recent small, placebo-controlled clinical trial involving patients with relapsing multiple sclerosis. The study was published in the September 2006 issue of the New England Journal of Medicine by an international research team.
I could easily select a dozen more important papers published in the last year, but I am particularly interested in basic research that teaches us something new, and treatments that could fit into a comprehensive Integrated plan of treatment.
I am going to post more about the causes of this illness as well as less orthodox approaches to help the physical, psychological, social, subtle and spiritual aaspects of these illnesses.
Turmeric and Arthritis
I recently reported about some research from SIngapore that indicated that the spice turmeric might help with cognition.
Today there is a study form the University of Arizona in the journal Arthritis and Rheumatism suggesting that the spice may also be helpful in experimental rheumatoid arthritis. In line with most other studies of herbal supplements it is interesting that the maximal effect was obtained by using the natural form of turmeric, that contains three major "curcuminoids," the likely active ingredients. If one of the three is missing, the effect is a lot less.
The extracts appears to work by preventing the activation of a protein that controls when genes are switched on or off in the joint. Once the protein known as NF-KB is activated, it binds to genes and increases the production of inflammatory proteins, which in turn attack the joints.
This is not a surprise: In traditional Indian Ayurvedic medicine turmeric has been used for centuries as a treatment for inflammatory disorders including arthritis. Based on that, dietary supplements containing turmeric rhizome and turmeric extracts have been sold for years. However, there’s been little direct evidence that they are helpful.
We are going to need more research before we can sy whether turmeric supplements can be recommended for medicinal pruposes, and eating more spices is unlikely to work.
These findings are opening up a new approach to treating not just rheumatoid arthritis, but perhaps also other inflammatory diseases such as inflammatory bowel disease, asthma and multiple sclerosis. Interestingly the turmeric extract also has another effect: it deactivates a biochemical pathway that leads to the resorption of bone. So it may help with osteoporosis.
Tourette’s Syndrome
No surprise here, but I was just sitting on a plane.
Again.
When I heard people sniggering.
Why? A young man in his thirties was walking along trying to find his seat. As he did so he was constantly grunting, saying partially intelligible words and jerking. As a clinician it was immediately obvious that he almost certainly had Tourette’s syndrome, a developmental disorder of the brain in which people have involuntary, stereotyped, repetitive motor and phonic tics. Some people with the disorder exclaim obscene words or socially inappropriate and derogatory remarks, which together are known as coprolalia.
The illness was originally named for Georges Albert Édouard Brutus Gilles de la Tourette, (1859–1904), a French physician and neurologist, who published an account of nine patients with the now classic clinical features in 1885.
You may not often see someone with this problem, but it is good to know what it is, and that it is an illness that can cause great distress.
We have recently made some interesting discoveries about Tourette’s syndrome.
- It is an illness involving the dopamine systems in the basal ganglia of the brain together with some regions of the midbrain and some very specific linked regions of the cerebral cortex, cerebellum and limbic system.
- In adults with Tourette’s syndrome, the prefrontal cortex is a little smaller than normal, and the corpus callosum linking the hemispheres is larger than expected. These findings correlate with problems in the way in which people transfer information between the hemispheres and modulate attention.
- Very recent evidence has shown us that there are small hyper-intense lesions in the deep regions of the brain in people with Tourette’s, obsessive-compulsive disorder and attention deficit disorder. These three problems seem to have a number of biological links and two or more may co-exist in the same person. In children and adolescents with Tourette’s, the tics tend to get better over time but obsessive-compulsive disorder symptoms become more severe and persistent as they get older.
- There is important evidence that in some people, Tourette’s is linked to a post-infectious autoimmune disorder, and many have antibodies directed against neurons in the brain.
- There is also a link between Tourette’s and having low iron stores. Low iron stores are common in people with many chronic inflammatory illnesses. Iron is crucially important in the development of key regions of the brain. We do not have any viable evidence that giving people iron supplements will reduce the severity of Tourette’s, but it is something that needs to be examined in a formal study.
People have typically been treated with antipsychotic medicines such as risperidone that block dopamine receptors in the brain, and they can certainly help. A more recent approach is to use medicines like aripiprazole that modulate dopamine activity in the brain. A recent study done by some colleagues in the United Kingdom have confirmed that aripiprazole seems to be very helpful in about half of patients with Tourette’s, though neurological side effects do sometimes occur.
There has recently been a lot of interest in Habit Reversal Therapy: a behavioral treatment for tics. The therapy takes a lot of time and effort, but it is very interesting that behavior therapy can help with a neurological illness.
There is no published data on the use of Integrated Medicine in the treatment of people with Tourette’s, but many experts have reported that some patients have been helped with homeopathy and acupuncture.
That guy in the next seat who is cursing may not just be mean and uncouth. He may be suffering.
But maybe not for much longer.
We are getting very close. Not just to discovering the physical basis of the illness, but perhaps its meaning and purpose as well.
New discoveries are coming thick and fast, and I shall keep posting about those that will help individuals and illuminate the principles of Integrated Medicine.
Handedness and Immunity
In 1982, one of my mentors, the late Norman Geschwind, and two colleagues – Al Galaburda and Peter Behan – proposed an extraordinary hypothesis. It was that the levels of testosterone to which a baby is exposed before birth influence the development of both the cerebral and immune systems. According to this theory, high levels of testosterone result in greater incidences of left-handedness, deviations from the standard distribution of cerebral functions and increased autoimmune dysfunction. If the theory is right, then male brains should mature later than female brains, and the left hemisphere should mature later than the right.
It is certainly true that if a boy gets a head injury or infection involving the brain, he is less likely to recover than would a girl, and boys are far more likely to have some types of neurodevelopmental problems like dyslexia.
For a while it seemed as if there was also a strong association between left-handedness and certain types of allergy, and also with inflammatory bowel disease. This association with immunity also seemed to be present in mice: those who had left paw preference had more reactive immune systems, and they were thought to be more likely to produce auto-antibodies, suggesting that the central nervous system was involved in the genesis of some autoimmune diseases. Over the years the data has become less clear-cut, but the idea of an association between anomalous cerebral asymmetry and autoimmune disease never completely went away.
Recent data has again found an association between inflammatory bowel disease and laterality. And left-handers really do have more autoimmune disease.
The Geschwind-Galaburda hypothesis proposes that there should be a four-way association among neurodevelopmental disorders, special talents, non-right handedness, and immune disorders. In a huge study of 11,578 children, less than 1% had all four.
So where does this leave us?
The original theory was half right:
- There is indeed a link between testosterone and early brain development
- People who are left-handed or have a strong tendency toward left-handedness do seem to be at slightly increased risk of several autoimmune conditions
- People who are left-handed or have a strong tendency toward left-handedness may have a slightly increased risk of high blood pressure, asthma and migraine
- People who are left-handed or have mixed handedness are more likely to excel in certain disciplines: creative arts, music, computer programming and mathematics. What we don’t know is whether people with these special skills are more likely to have autoimmune diseases
- Amongst very successful tennis players, there are far more left-handers than would be predicted by chance. This supports the idea that support the notion that left-handed people have neurological advantages in performing certain tasks, such as visuospatial visuomotor cognitive tasks.
I was reminded of the way in which Nature seems to like to balance things out a bit: with some notable and famous exceptions, many successful athletes have not done so well academically and many academics would be unlikely to survive on the plains of Africa. Only some of these differences can be explained in terms of early direction and encouragement in school or while growing up: it seems that most of us cannot hope to become the kind of superman that Nietzsche used to dream about.
Perhaps it’s a way of stopping us from getting too full of ourselves.
