NOVEMBER 1997 MEETING

TOPIC: "NON-TRADITIONAL THERAPIES FOR MIGRAINE

AND OTHER HEADACHES"

Len Saputo, M.D., is board-certified in Internal Medicine and practices at John Muir Medical Center. He is also self-trained in Process Oriented Medicine, which is based on metabolic function, as opposed to clinical syndrome. This has led him to realize the importance of nutrition in the restoration and maintenance of health and the prevention of disease. Dr. Saputo

was invited to speak to the November 11th meeting of the East Bay Headache Support Group about non-traditional therapies for migraine and other headaches. The meeting was held in the Aspen I Conference Room at John Muir Medical Center with 37 people in attendance.

Following is Dr. Saputo’s presentation, including additional comments(italicized):

When you ask for "alternative approaches" you must recognize what you are really requesting. First of all, the need for another approach only exists when the mainstream either cannot solve the problem itself, or provides a solution that has too many associated complications. You are also asking that we go beyond where our training left off, and create new possibilities. By necessity, these new approaches will initially be unproven by clinical trials, and will be anecdotal. I am always amazed at people who come up with novel methods designed to solve these difficult problems. I am equally amazed at how negative conventional medicine can be towards some of these approaches. Tonight, you are asking me to tackle such an undertaking.

Before we get into how we might approach fixing the migraine problem, let’s take a look at some background material regarding what we know about migraine. There are three important aspects to migraine: Biochemical, mechanical (vascular), and electrical (neurologic) phenomena. The bulk of the medical management of migraine is based on its biochemical aspects. Because there are upwards of 40 different neurotransmitter systems that could be involved, this has become quite challenging, and what has frequently resulted is a kind of "frantic polypharmacy." While this complex approach can be quite effective, it is frequently problematic in that it can be riddled with side effects that can be difficult to live with, and can result in toxicity.

There are really two separate aspects of migraine that are of particular interest: the aura and the headache itself. Understanding the mechanisms that explain these phenomena provides a basis for developing a managing strategy.

The aura is associated with an electromagnetic wave of excited-then-depressed activity in the cerebral cortex. As it advances across the cerebral cortex at a rate of 2-3 mm/minute, there is an associated wave of reduced cerebral cortical blood flow that moves at the same speed towards the visual cortex.

The origin of the pain in migraine develops from abnormal neural activity that is deep in the brainstem, in the raphe nuclei. Magnetoencephalography measurements show this activity to be characterized by bizarre, huge, long-duration, action potentials that originate in the brainstem. It is interesting that when neurosurgeons implant electrodes in the brainstem into the grey matter of the cerebral aqueduct as a procedure that helps in pain control in the body, that many of these patients who never before had migraine develop a kind of acquired migraine headache. Studies on monkeys where the raphe nuclei were stimulated neurologically or chemically resulted in the same vascular patterns that are seen in migraine.

A hypothalamic origin has been suggested based on the fact that many migraineurs have a preaural syndrome lasting up to a few hours, that is charaterized by excitement, anxiety, or elation.

The known and suspected pathophysiology of migraine then can be summarized as follows:

An "intrinsic" defect in the hypothalamus, or a response of the hypothalamus triggered from the sensory cerebral cortex, initiates the migraineous process. The hypothalamus then sends neural stimulation to the periaqueductal grey matter, which then stimulates the raphe nucleus.

The raphe nucleus then initiates constriction of the cortical microcirculation, and the subsequent spreading electrical depression in the cortex, that results in the aura symptoms. At the same time, the raphe nucleus transmits impulses downward to the C1, 2, 3 nerve roots that close the enkephalinergic gate in the spinal cord. This phase, which depends on hyperactivity of both noradrenergic and serotonergic brainstem systems, is succeeded by one of reduced monoamine transmission, and with this the "pain gate" in the cord opens, flooding the head with previously inhibited pain, and simultaneously the afferent gate to the special senses is opened, producing the characteristic, and often intolerable, heightening of sights, sounds, and smells.

All this complicated language is saying is that we have some elaborate theories of how migraine develops, but we don’t really know what is causing the process. We know a lot about what triggers migraine, and through biochemistry we can sometimes interfere with the development of the symptoms, but we still don’t really know its root cause. What we have discovered is that the biochemistry involves interrelationships with up to 40 neurotransmitter systems, though we focus on just 6 primary systems (noradrenalin, acetylcholine, dopamine, histamine, GABA, enkaphalins and serotonin), and that each case of migraine is best managed as a separate case. There is no cookbook approach that works regularly in the treatment of migraine. What works for one patient doesn’t necessarily work for the next.

A great deal of attention has been focused on the effects of serotonin on the vasculature of the brain in the development of migraine because of its potent vasoconstrictor effects and its stimulation of smooth muscle contraction. In addition, many drugs that inhibit the release or effects of serotonin have been effective in managing the pain of migraine. Even Imitrex, a selective 5HT1 blocker, works in this way. But, nothing works all the time. Imitrex is nice when it works, but it doesn’t work for everybody.

Understanding the metabolism of serotonin can help to simplify much of the theoretical pharmacology. We eat the essential amino acid, tryptophan, which is converted to 5-OH tryptophan, and then into serotonin. Serotonin can cause vascular spasm, is a smooth muscle spasm agent, i.e., makes smooth muscles contract. Serotonin is converted to 5-HIAA by MAO or is N-acetylated to form melatonin. It is easy to see why MAO inhibitors might increase the concentration of serotonin. The phase of the migraine process, aura (vasoconstriction) or headache (vasodilatation), has a lot to do with the effects serotonin has on the process.

When we look at the possible nutritional approaches that might be appropriate to the management of migraine, the following factors have been considered:

1. Decreasing serotonin concentration—low tryptophan diet.

2. Low carbohydrate diets may lower the availability of tryptophan and avoid hypoglycemia.

3. Riboflavin (Vitamin B2)—unknown mechanism. A pilot study published in 1994 in Cephalalgia reported on 49 patients with recurrent migraines who were treated with 400 mg/d for 3 months. The average number of attacks fell by 67%, as did the severity of the pain.

4. Stabilizing neuronal cell membranes (Mg, EFA’s, etc.). Serum Magnesium, which stabilizes nerve cell function, was found to be low in 41% of 32 patients with acute migraine. Mg levels on NMR spectroscopy were significantly lower in patients during an acute migraine. There is conflicting data regarding the prophylactic effectiveness of Mg. In menstrual migraine studying 3,000 patients who were given 200 mg/d during the last two weeks of their cycle, there was an 80% reduction in headaches (Headache 1990; 30:168). In another study, 300-600 mg/d showed no effect. IV Mg in the acute setting has been reported to be of value. Dr. Saputo has tried Magnesium intravenously on two of his patients, but found it didn’t work well. He said that 80% of the population is deficient in magnesium. The recommended oral dose is 200-400 ml/day. Magnesium sold by the Tyler Encapsulations Company seems to be the best - it is absorbed better. Magnesium really is important in the management of cell membranes.

5. Copper has a migraine inducing effect through its role in the metabolism of vasoneuroactive amines such as serotonin, tyramine, and catecholamines. Foods high in Cu (chocolate, nuts, wheat germ and shellfish), or which increase intestional absorption of Cu (citrus), or which bind and transport Cu between blood and tissues (MSG), all are potential headache triggering agents.

6. Immunologic factors (especially food allergies).

7. Free radical activity factors. Very reactive chemicals that come in from the outside, or inside--they’re the bad guys. Antioxidants help neutralize these.

8. Analgesic therapy (Boswelia, feverfew, niacinamide, DMSO). Comments by Dr. Saputo: Boswelia comes from the Orient. Feverfew can cause mouth ulcers. DMSO is not recommended by traditional Western medicine practitioners. It is a strong anti-inflammatory agent, an antioxidant, which really works for pain. It is applied directly to the skin. Make certain the skin surface is clean, as this comes out on your breath. For instance, if you had fingernail polish on your nails and applied DMSO over it, your breath would smell like nail polish. DMSO may cause itching.

So then, in summary, a nutritional approach to managing migraine would include a diet that is low in tryptophan, low in glycemic index, high in riboflavin, Mg and EFA’s, and low in copper. It would also avoid food allergies and supplement with antioxidants liberally. Analgesic therapy would include boswelia, feverfew, niacinamide and DMSO. This approach is simple, safe, and may help a significant number of people with migraine headaches, and it makes sense to start treatment here, rather than with pharmaceuticals that are foreign to the body. In theory, however, this approach is no different from conventional therapies that are seeking interventional cures.

Other comments by Dr. Saputo: Nutritional approaches percentage-wise don’t work as well as a pharmacological approach. 13% of migraineurs who followed a low tyramine diet saw an improvement in their migraines. A low carbohydrate diet (which lowers tryptophan) might work prophylactically.

The search for magic bullets to solve the migraine problem is probably like trying to catch that proverbial carrot. We tend to focus on trying to figure out nature and then outfox it in a way that will eliminate the troublesome symptoms. This kind of nutritional approach is no different from conventional approaches with pharmaceuticals. The approach that I’m going to take tonight is different. I’m going to concede that I cannot figure out what is going on with migraine at any deep level, so as to not get hung up on that approach. What I am going to do is show you how to work with nature and support the body’s innate capacity to heal itself, wherein nutritional and natural therapies rather than synthetic, unnatural products, are sought after. We’ve all heard that the primary rule in health care is "physican, do no harm."

I am an expert in Internal Medicine and "Health Medicine." I don’t know much about Chinese Medicine, Ayurveda, Homopathy, Neural Therapy, Aromatherapy, Alphabiotics, breathing exercises, craniosacral, flower essence, etc., though I am quite willing to work with these practitioners, so these "alternatives" will need to be explored another time. Integrative practice is a cornerstone of Health Medicine, so my lack of knowledge is the only reason for not including these potentially very helpful disciplinary approaches.

Tonight, I’d like to introduce you to the concept of process oriented medicine. Its fundamental approach to improving health is based on restoring and maintaining normal metabolic and regulatory processes within the body. Our emphasis, actually, is primarily on the function of single cells. How can you be sick if all your cells are healthy? What makes cells malfunction?

Health Medicine is an integrative practice--be open-minded. Wholism is the inseparability of body, mind and spirit. It is patient-centered--its goal is to empower you. It involves collaboration, shared teaching, shared healing.

In modern medicine we tend to look for ways to intervene with disease processes. We search for solutions to what has already gone wrong…after all, there is so much disease out there. We have not only gone broke trying to operate this way, but everybody is sick from a variety of chronic diseases. The job of trying to keep America from deteriorating even further is now clearly overwhelming.

There is nothing wrong with helping the sick, it would be inhuman to do anything less. There is also nothing wrong with keeping us healthy either, we deserve nothing less. We spend about 3% of the NIH budget on prevention, and far less on wellness. We spend less than 0.1% on alternative approaches to health care…where is the new thinking going to come from?

I like the idea of balance. We should be working together to solve America’s health issues. Prevention is actually the salvation for crisis intervention. Maybe we could afford crisis intervention if fewer people needed it. And, who would mind being healthy anyway?

Let’s go back to the cell now and explore how this system works, and why having healthy cells is so important to people who have headaches, or anything else. From this perspective, there is only one disease: cellular malfunction. There are only two causes of cellular malfunction: Not enough raw materials to allow the cell to do its work, and toxic exposures that can interfere with normal metabolism. 95% of the information listed in the Physician’s Desk Reference (PDR) is about side effects, and only 5% talks about the benefits of the drugs.

Malnutrition in America is a very common disease. 95% of the population has at least one major nutrient deficiency. In a study published in the October 1997 issue of the journal, Pediatrics, the subject of malnutrition in children under the age of 18 was reviewed. The conclusion was that only 1% of this population was getting a healthy diet, and this was based on the minimum RDA’s of healthy people. Further, this 1% was overweight, further revealing that we are consuming food that is not nutrient dense, but certainly is calorie rich. This was shown earlier in the 1970’s, when the government did a study on more than 20,000 people. They looked to see what percentage of people were getting the minimum RDA’s of 15 common essential nutrients. Let’s see what they found.

What is happening that has resulted in this state of affairs? As we migrated from a rural to an urban culture, millions of people began to depend on outside sources of food, and we developed some serious problems. Where can you get enough food, and how can you store it so it will last? This led to the development of methods of handling and processing food that sharply reduce its nutritional content. For example, in refining flour, the husks of the wheat are removed, and in the process 25 nutrients are eliminated. Four are put back in, and then it is labelled "enriched." In the case of sugar, 100% of the nutrients are removed from the sugar cane and all that remains in the package is pure sucrose. Our vegetables and fruits are picked before they are ripe, are stored for weeks or months, are sprayed with a variety of pesticides and preservatives, and then we buy and store them before we cook them. We don’t replenish our soils. How much nutrition can remain in these kinds of products? If this isn’t enough, we often then even "refine" what is left. How about canned, bottled, and frozen foods?

Ironically, the most serious health problem in America today is obesity, and it is getting worse.

Yet, essential fatty acid depletion is the most common deficiency. These fats are critical in the formation of healthy cell membranes, and this is a particularly important issue in migraine.

How many of you have even heard the term omega3 or 6 fatty acid? 95% of Americans tested have essential fatty acid deficiencies. We are loaded with saturated fat, and even worse yet, with trans fats…those fats called partially hydrogenated vegetable oils. Check the labels of almost any food found in a package—it will have a partially hydrogenated vegetable oil in it.

Essential fatty acids are those fats that our bodies must have, but cannot manufacture. We have to eat them. The best and safest forms are found mainly in cold water fish (but then there may be a problem with heavy metals), flax seed oil, and evening primrose oil. While you can get them in many oils, the refining process unfortunately converts them into saturated fats, which are toxic. And flax seed oil is tricky to store and use. How many of us eat fish twice a week or use 1-2 tablespoons a day of flax seed oil? That is why 95% of the population is deficient in EFA’s. To make things worse, many of us, especially those who are sick, cannot metabolize the EFA’s into their important downchain metabolites…a special issue in migraine.

This deficiency leads to the formation of defective cell membranes, abnormal metabolism of substances called prostaglandins, higher cholesterol, thicker blood, higher blood pressure, predisposition to develop cancer, dry skin, and in infants, growth retardation. EFA’s are also very important in conditions like ADHD, dyslexia, dyspraxia, eczema and asthma. In diabetes, the complications related to neuropathy, retinopathy and coronary artery disease can be prevented and partially reversed. Dr. Saputo mentioned, however, that diabetics cannot metabolize omega 3 and 6 fats.

There has been some research done on the role of essential fatty acids in migraine that is interesting. Two abstracts in the AJCN 1983 showed:

1. Feeding people with migraine omega 3 fatty acids (fish oil) resulted in significantly ameliorating severe migraine in a double blinded, placebo controlled, crossed over trial in 8 subjects. They found that there were 50% headache-free days whereas the placeco group had a baseline of 20% headache-free days.

2. In a second study, in 15 severe migraineurs involved in a double blinded, placebo controlled trial, there were similar results. They also measured platelet serotonin release and found it to be decreased by the fish oil group.

There are two possible mechanisms that could explain this kind of benefit: effects of EFA’s on membranes, and their effects on eiconanoid metabolism. It is cost effective and accurate to measure EFA levels in RBC membranes, thereby providing scientific evidence that can guide us in EFA replacements. This type of information is vital to insure normal function of our cell membranes and their internal metabolism.

In the case of migraine, we know that there is a malfunction of cells of the nervous, endocrine, immune, and vascular tissues. If we could normalize the metabolism of these cells, we would expect that they would operate normally. Of course, some of the problems in migraine are related to the regulatory processes of the body…but then, even these processes might be improved if cell metabolism were perfect.

Dr. Saputo suggested taking extra Vitamin C, Vitamin E, Coenzyme Q10 (an antioxidant), and Lipoic Acid, but don’t overdo it. Suggested doses are:

Vitamin C: 1-3 grams per day

Vitamin E: 400 international units per day

Coenzyme Q10: 30-60 ml per day

Lipoic Acid: 50-100 ml per day.

Other important tests that can be of value in assessing any disease process include measurement of:

1. Nutrient levels and their reserves in storage.

2. Free radical production and antioxidant levels. ($300)

3. Liver detoxification profiles.

4. Functionability of the gastrointestinal tract (digestion, absorption, keeping toxins out). ($60)

5. Intracellular magnesium.

6. Hormone levels: estrogens, progesterone, testosterone, cortisol, DHEA.

7. Metabolic function (organic acids and amino acid metabolism).

8. Heavy metal exposures (amalgams?).

9. Pesticide levels.

10. Immune hyperactivity (elisa/act, oligoantigenic diets, conventional IgE mediated tests).

Malnutrition can result even from a diet that is absolutely perfect! What happens if the gastrointestinal tract cannot digest or absorb food stuff normally? This is actually a very common state of affairs. In this era of frantic polypharmacy, we consume far too much in the way of pharmaceuticals that result in the disruption of our gastrointestinal function. Antibiotics, steroids, NSAID’s, BDP’s and chemotherapy are striking examples. Other conditions include infections in the gut (bacteria, viruses, parasites, yeast), inflammatory bowel disease, irritable bowel disease, stress, alcohol consumption, maldigestion (lactose intolerance), and many, many chronic diseases. It is easy to see that it is very easy to be malnourished between the lack of a nutritious diet and the frequency of poor gut function.

Some of these above-mentioned conditions can be related, at least in theory, as a trigger for the development of migraine. When gut function is sufficiently disturbed, as it can be from many of these problems, changes in gut permeability can result. When this happens, the pore size of the gut membrane increases, and larger than normal molecules can then pass across the gut lining. This results in two serious pathophysiological processes that result in increased stress on both the liver and the immune systems. This is known as "leaky gut." The gut is the largest immune organ in the body.

This may possibly afford a reasonable explanation of why so many migraineurs have foods that act as triggers of the headache. There were two excellent articles published in Lancet in 1983 and 1984 that support the role of the immune system in the triggering of migraine.

1. In a study of 88 kids with severe migraine from ages 3-16, 93% recovered on oligoantigenic diets. Most patients responded to several foods. In most patients with other trigger factors as well, such as blows to the head, exercise or flashing lights, migraines no longer were triggered by these factors when on the diet.

2. In a study of patients with severe migraine triggered by specific foods, the trigger could be blocked by pretreatment with sodium chromoglycolate (SCG). This confirms that allergy is the mechanism involved in the triggering process. The SCG is not absorbed across the gut, therefore, the allergic effects must occur in the gut itself. The remainder of the mechanism was thought to be caused by the effects of immune complexes on platelets that resulted in hyperaggregability, and serotonin release.

Another possibility raised is that these immune complexes might also trigger mast cell release of serotonin within the cerebral vasculature.

There are also some interesting studies that were done in the late 1980’s by Claude Andre that show that food allergy can change intestinal permeability—and this can also be blocked by SCG. Nobody has looked at the interrelationship of these two factors together to explain how migraine could be related to the gut and allergic mechanisms.

Dr. Saputo said that it is easy to deal with leaky gut:

1. Give the gut the nutrients it needs.

2. Give it chromalyn (SCG).

3. Reduce the toxic load (amalgam, etc.)

4. Reduce the antigenic load (immune system activity).

Our bodies are under tremendous antigenic stress. The elisa/act test will determine the level of sensitivity of your immune system, and identify how many things you’re sensitive to.

Dr. Saputo said that dentists who put amalgam in your mouth should be sued for malpractice. Amalgam is highly toxic—it is 25% silver and 50% mercury. If a migraineur has amalgam fillings, he should go to an environmental dentist and have them removed.

Leaky gut is caused by:

1. Starvation

2. NSAID’s (except Relafin). He noted that NSAID’s are toxic and cause 20,000 deaths per year and 200,000 to 400,000 hospital admissions per year.

3. Birth control pill

4. Chemotherapy

5. Antibiotics. Antibiotics knock out the flora in the gut, which should be replaced. When taking antibiotics, also take lactobacillus (from the health food store) and extra fiber.

6. Lactose intolerance (70% of people are lactose intolerant)

7. Alcohol

What have we learned?

1. We don’t understand the underlying mechanisms that result in the development of migraine, but through our fragmented knowledge we can often suppress its symptoms, using our silver bullet approaches. Quite often these therapies have troublesome side effects and can be toxic.

2. Alternative silver bullets are also possible, but they too are not any guarantee to work. Generally, however, they are safer and tolerated better. Trying a diet that is low in tryptophan, that has a low glycemic index, that is supplemented with riboflavin, Mg, EFA’s, and antioxidants, is low in copper, and that avoids exposure to allergic foods, is a simple and appropriate start to manage migraine.

3. The process oriented approach to improving health care is oriented towards improving cellular malfunction caused by deficiencies and toxicities, and better enabling the body to heal itself. There are many new tests, covered by Medicare, and readily available, that can be of critical importance in the assessment of metabolic function at the cellular level.

4. Factors relating to gastrointestinal function are frequently important in the development of migraine, and should be studied prior to pharmacologic intervention.

5. The migraine syndrome can be triggered by a wide variety of factors. These factors can often be modified so as to reduce the incidence and severity of the headaches.

The traditional health care system is set up to fix broken things. Two thirds of the population has chronic disease. 90% of those over age 65 have chronic disease and 25% of those under 18 have chronic disease.

Three primary factors for health: Weight control, exercise, having a meaningful purpose in life. We have lost appreciation of why we’re on this planet. Relationships and creativity are important. We have forgotten how to love one another.

After Dr. Saputo’s presentation, he asked the audience for questions. He was asked about MTBE, the gasoline additive. Dr. Saputo said he doesn’t know anything about it, but we should be concerned about cleaning up our environment.

One participant asked him about taking pills purchased from a health food store to obtain the body’s necessary nutrients. Dr. Saputo answered that that was a crummy alternative, but since the majority of humans don’t eat right, it is better than nothing.

He mentioned that in 1900 the incidence of breast cancer was 1 in 33, and now it is found in 1 of every 7 women.

Dr. Saputo quoted Socrates: "Let food be your medicine, let medicine be your food."

When asked about echinacea, he said that it helps the immune system fight off viruses. He stressed again that it is important to use antioxidants for their anti-viral effect, and take Vitamin C to block infections. They work against bacteria, yeast, funguses, and viruses.

Iron is terribly toxic. Measure the serum iron first before taking additional iron. Vitamin C accelerates the absorption of iron.

Taking magnesium can cause diarrhea. Tyler’s magnesium with 3 amino acids is the best.

The 10 tests listed above by Dr. Saputo are covered by Medicare, but may not be covered by your HMO. Check it out.

Finally, Dr. Saputo was asked if he was a vegetarian. He answered that he eats meat, but not feedlot beef, which is too fatty and filled with pesticides. He said that range fed beef is also too fatty. Wild game is the best, and young animals, like lamb.

The intention of the East Bay Headache Support Group is to provide information and resources. It does not provide medical advice, which should be obtained directly from a physician.