Richard G. Petty, MD

Even Neurons Need Friends

In many neurological diseases, including multiple sclerosis (MS) and some types of neuropathy, myelin – the insulation that covers and surrounds most of the larger nerves – is damaged or deranged.

Scientists at the Weizmann Institute of Science in Rehovot, Israel, working with colleagues in the United States, recently reported finding an important new line of communication between cells in the nervous system that is crucial to the development of myelinated nerves. This new discovery may eventually help us to restore the normal function of the affected nerve fibers.

Nerve cells (neurons) have long, thin extensions called axons. The longest of these axons is in the verves supplying the feet, and they can be over three feet or more in length. The larger axons are covered by myelin, which is formed by a group of specialized cells called glia.

Glial cells move around the axon, laying down the myelin sheath in segments, while leaving small nodes of exposed nerve in between. Myelin provides protection for the delicate axons, and it also allows nerve signals to jump rapidly between the gaps or nodes, increasing the speed and efficiency of the transfer of electrical signals down the axon. When myelin is missing or damaged, the nerve signals cannot skip down the axons, leading to abnormal function of the affected nerve and eventually the now naked nerve may degenerate and die.

In research published in Nature Neuroscience, Elior Peles, Ivo Spiegel and their colleagues in the Molecular Cell Biology Department at the Weizmann Institute and in the United States, provided a new insight into the mechanism by which glial cells recognize and myelinate axons.

They found a pair of proteins that pass messages from axons to glial cells. These proteins, called Necl1 and Necl4, belong to a larger family of cell adhesion molecules. The whole class of cell adhesion molecules does exactly that: they sit on the outer membranes of cells and provide the glue that helps them to stick together. Even when removed from their cells, Necl1, which is normally found on the surface of the axon, and Necl4, that is found on the glial cell membrane, adhere together very tightly. When these molecules are in their natural homes of the axon and glial cell, they not only create physical contact between axon and glial cell, but also serve to transfer signals to the interior of the glial cells, initiating changes needed to undertake myelination.

The scientists found that production of Necl4 in the glial cells rises when they come into close contact with an unmyelinated axon and as the process of myelination begins. If Necl4 is absent from the glial cells, or if they blocked the attachment of Necl4 to Necl1, the axons that were in contact with the glial cells did not myelinate.

This is an exceptionally important discovery. Most of the approaches that we use for treating MS, peripheral neuropathy and other degenerative diseases, can often help with symptoms and may slow but not cure the diseases. But if we can understand the mechanisms that control the process of wrapping the axons by their protective sheath, we may be able to recreate that process in patients.

Here Comes the Sun: To Screen or Not To Screen?

I have been worried to see some people – all, I think, without scientific training – proclaiming that there is no need to protect ourselves against the sun because there is no evidence that sulight causes any health problems.

Ultraviolet radiation (UVR) from the sun has been part of the environment since the first cells began to form. When we discuss the effects of UVR on human health and the environment, the range of UV wavelengths is often subdivided into:

  • UVA (400–315 nm), also called Long Wave or “blacklight”
  • UVB (315–280 nm), also called Medium Wave
  • UVC (< 280 nm) also called Short Wave or “germicidal”

The key questions are these:
Can sunlight cause health problems?
Do the benefits of sunlight outweigh their risks?”

UVB is required for the conversion of 7-deoxycholesterol to vitamin D, (the sunshine vitamin!) which is critically important in the maintenance of healthy bones, although there may also be another mechanism by which vitamin D is generated in the body. As we have seen research is making clear that vitamin D has other potential roles in the maintenance of human health. Low levels of vitamin D have been linked to:

  • Rickets
  • Osteomalacia
  • Osteoporosis
  • Maintaining the integrity of cell membranes
  • Type 2 diabetes mellitus
  • Schizophrenia
  • Multiple sclerosis
  • Pre-eclampsia (hypertension and accompanying problems during the late stages of pregnancy)
  • Some types of cancer
  • Fibromyalgia-like pains
  • Immune deficiency: Africa Americans do not generate enough of a protein needed to ward off tuberculosis. Why? Because the protein needs vitamin D to be activated, and dark skin is inefficient at absorbing and converting UVR. It may also be that we see epidemics of colds and flu in the winter because that is when we have low levels of vitamin D, which allows the viruses to overwhelm our immune defenses.

This does not necessarily mean that taking extra vitamin D will ward off all of these problems.

In the days before the Industrial Revolution, unless we lived in the frozen North, we had no trouble in getting the amount of vitamin D that we needed. In most of the United States, during the summer months, 10-15 minutes outdoors at midday will generate around 10,000 international units (IU’s) of vitamin D in an average fair-skinned person. This is far in excess of the government’s dietary recommendations of 200 IU’s/day in people up to age 50, 400 IU’s up to age 70 and 600 IU’s in people over 70. Not surprisingly many experts – me included – believe and have provided evidence that these daily requirements are much too low. (Have a look at the comments here.)

Of course many of us do not spend much time outside and don’t take in as much in the way of vitamin D containing foods – such as milk and salmon – as we should. I’ve seen evidence to suggest that we in Atlanta are probably at the Northernmost point in the United States were we could hope to get enough sunshine and therefore vitamin D from modest winter exposure to the sun.

Recent data has suggested that if you spend no time at all in the sun, then you may need as much as 4,000 IU’s of vitamin D/day, though that figure has not yet been widely accepted.

Exposure to UVR, whether of solar or artificial origin, also carries potential risks to human health. UVR is a known carcinogen and excessive exposure, at least to the solar radiation in sunlight, increases the risk of cancer of the lip, basal cell, and squamous cell carcinoma of the skin and melanoma, particularly in fair-skinned populations. There is also evidence that solar UVR increases risk of several diseases of the eye, including cortical cataract, some conjunctival neoplasms, and perhaps also melanoma of the eye.

We have good data for the existence of a threshold amount of UV-B exposure that may lead to the formation of cataracts. The amount needed to cause cataracts depends in part on the amount of pigment in the eye, so albino rats get cataracts with much lower exposures to UV-B.

So what to do?

Sunlight has a definite benefit in preventing or treating many clinical problems and it is no surprise that after 3000 millennia we are adapted to make use of the sun’s largesse. What is less easy to understand is why an excess of sunlight can cause so many problems, unless it is our hairlessness and environmental change that has lead to a loss of the ozone layer.

Some years ago it was suggested that sunscreens may themselves cause skin cancer, but the data has shown that to be false. Indeed modern sunscreens almost certainly reduce melanoma risk.
So how do we balance the positive and negative effects of sunlight? A recent review precisely reflects my own thinking:

  • We need some sunlight
  • Depending on where you live, you need only a few minutes each day
  • Sunscreens confer protection on the skin without blocking all the health benefits
  • If you have a medical reason for avoiding sunlight, then your health care provider should measure your vitamin D status.

Multiple Sclerosis and Vitamin D

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 and Integrated Medicine

Although there are some fairly effective conventional therapies for multiple sclerosis (MS), many people with MS explore complementary and alternative medicine (CAM) therapies for their symptoms. The most effective strategies are to combine conventional and unorthodox treatments that address the physical, psychological, social, subtle and spiritual aspects of the illness. This combined approach also avoids the problem of people taking herbs or supplements that may either interact with each other or with conventional treatments.

It is also essential for us to get over the idea that MS is just something to be conquered. That may seem like an odd comment, but the language and the mindset of fighting, battles and warfare can be problematic. Let me explain something that I discuss at length in Healing, Meaning and Purpose.

There have been two distinct approaches to health in the Western medical tradition. The first is that the role of a physician is to treat diseases. That is the way that all my colleagues and I were trained. The second approach is to consider that health is the natural order of things. So in the first case we constantly hear the use of military metaphors: People speak of  “a war on cancer,” “killer cells,” “magic bullets,” and the need to adopt a “fighting spirit.” Sadly this aggressive attitude by the medical profession may be at odds with the wishes and needs of an individual, the family and the other people in a person’s life. We have to try to strike a balance between the whole instinct to fight and expressions of healing and acceptance.

In the second case, the philosophy is grounded in the idea that we need to work in harmony with nature. The maintenance of health and well being comes from reestablishing balance and harmony not just in ourselves but also in our relationships with each other, with society and with the entire environment around us.

Some of the most commonly CAM therapies include dietary modification, nutritional and herbal supplementation, and mind-body therapies. There has been a revival of interest among MS researchers about the therapeutic potential of low-fat diet and essential fatty acid supplementation in MS. The research on CAM therapies in MS is still exploratory, but considering peoples’ interest and common use of these therapies, further research in this area is clearly warranted. Many sufferers show “spontaneous” recoveries, so reports of cures with unorthodox remedies are often treated with skepticism.

Diet, Vitamins and Supplements: There have been scattered reports of symptoms improving after the removal of dental amalgam, but there is scant evidence that this is really worthwhile. There is some evidence 1. 2. 3. 4. that polyunsaturated fatty acid (PUFA) supplementation may help MS. There used to be a lot of support for something called the “Swank diet,” but over the years the evidence has not been very good. In a small number of people with MS certain foods can make them worse. This is to expected if there is an autoimmune component to the illness. It is always a good idea to see if there is something that makes a person feel worse. The other important qestion is whether food additives may be causing symptoms. Although this must be uncommon, I have written elsewhere about occasional cases of MS symptoms with all the classical neurological, biochemical, radiological and electrical signs that have improved or become completely better after removing aspartame from the diet.

Physical exercise: Exercise is highly recommended for people with MS, though it is best to avoid it during an attack. There is evidence that over-exertion can actually bring on an attack. There is some literature about the use of Feldenkrais bodywork in MS, but a study from the University of North Carolina failed to find any benefit. T’ai Chi Ch’uan, qigong, yoga and graduated exercise have all been helpful to some people with MS, but it is essential to discuss it with a healthcare provider to see how any one of these fits in to an package of care. There is no published data on the use of Pilates in MS. At least not in any of the languages that I can read. But since it has been shown to improve posture and flexibility, it is logical to think that Pilates might be helpful, and it would be very valuable to see some research on it.

Acupuncture: Although widely used, the research on acupuncture in MS is not yet convincing. Like most acupuncturists I’ve had some good results in treating pain, muscle stiffness and fatigue. I’ve also seen people achieve some remarkable recoveries, but there are two issues: MS is a relapsing and remitting illness. And second, many of the people who did well only did so because they shifted their thinking: acupuncture became the vehicle for their personal transformation rather than a device for removing nasty symptoms.

Homeopathic remedies: Even the most enthusiastic homeopaths have fairly limited expectations of what homeopathy can achieve in MS.

From the point of view of homeopathy there is little point in making the diagnosis on multiple sclerosis because the disease has such a variable course with highly variable symptoms. To a homeopath the diagnosis is not useful: it is the symptoms that are all important. The homeopathic treatment of MS is highly individualized: one of the key items is the timing of symptoms and associated features. Some of the most common remedies for people with MS are:

  • Agaricus
  • Alumina
  • Argentum Nitricum
  • Arsenicum
  • Aurum Metallicum
  • Causticum
  • Cocculus
  • Conium Maculatum
  • Ignatia
  • Lachesis
  • Nux Vomica
  • Natrum Muriaticum
  • Phosphorus
  • Plumbum

This is not the whole list of homeopathic remedies that we have sometimes found helpful, but it highlights some of the more commonly used ones in people with the symptoms of MS.

Herbal remedies: Many herbal remedies have been tried in MS, and many experts have told me that they have had some good results. There is an important issue in MS called “apitherapy,” a.k.a. bee venom therapy (BVT). Several reports suggest that bee venom may be an effective treatment for patients with MS. But formal trials suggest that although the treatment appears relatively safe apart from itching and swelling of the skin, it does not seem to be helpful

The best approach is to embrace the best of what conventional medicine has to offer, combine unorthodox approaches and to realize that management of a chronic illness is not about dominating it but learning from it and learning strategies for peacefully co-existing with it.

Multiple Sclerosis and Polio

There have been repeated claims that one of the causes of the rising tide of multiple sclerosis (MS) cases is somehow related to polio vaccinations. This idea has been championed by the brilliant Greek homeopath George Vithoulkas. His hypothesis is that the reduction in paralysis from polio appears to parallel a rise in the incidence of MS, and that it is polio vaccine that is to blame. There are many websites repeating the claim that polio vaccinations are the cause of many illnesses.

Is there actually any evidence for this?

I’ve look at several hundred papers in all the languages that I can read, and this is what I think so far.

It is certainly true that people who already have MS may become worse after some types of vaccination.

There have been very occasional reports of children developing an MS type of illness after vaccination, but probably only in children who were genetically predisposed.

There have been a number of studies on polio vaccination and MS. Most with only small numbers of individuals, but the only link seems to be that people with MS tended to have their vaccinations at an older age.

Many of the best epidemiological studies come from Scandinavia, where there are often superb medical records, and little mobility of the population. One study done in Denmark looked not at vaccination, but instead examined data on every person in Copenhagen diagnosed with polio between 1919 and 1954. They found that there was a slightly increased risk of eventually developing MS. This is very difficult research to do well, since the symptoms of the two conditions so often overlap.

There have only been a handful of well-executed independent studies and they have failed to find a link between vaccination and type 1 diabetes, MS or inflammatory bowel disease.
There do seem to be some unusual cases in which autoimmune phenomena have been clearly related to immunization, such as the neurological illness Guillain-Barre syndrome. But they are clearly uncommon. This also provides evidence against some ingredient in the vaccines being the problem.

Another approach has been to look at the poliovirus receptor gene, and again the findings failed to find a role of the gene in the development of MS.

As an aside, there does not seem to be a link between vaccination against hepatitis B and MS, though there have undoubtedly been occasional case in which the illness started after vaccination, and there remains a nagging concern about a possible association. The question always is the extent to which the vaccination could have caused the problem. The fact is that in complex biological systems there is hardly ever one cause for one effect.

On the evidence currently available the polio vaccine/MS hypothesis is not supported.

And I wonder how many readers remember kids with leg braces and iron lungs? Polio can be a nasty illness and I would hate to see it return to countries that have eradicated it.

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.

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