All of the different receptors in the body have very specific chemical reactions (locks to activate) they are responsible for. The H1 receptor is mostly responsible for allergic reactions in the body. If the H1 receptor gets turned on by its specific key, then it summons the immune system to seek out, attack, and destroy any foreign invader. All cells have warning flags so to speak inside the cell so that if something sneaks into the cell and destroys the cell or the cell dies for other reasons, these warning flags are released when the cell breaks open and these warning flags hail the H1 receptors in the area or other immune system receptors that in turn send a message to the immune system to come clean up the debris. The first immune cells launched to the site of cell destruction are called macrophages or phagocytes. These are like little eating “Pac Men” that engulf and digest the cellular debris from the destroyed cell. Now these garbage-eating cells also search the garbage for any foreign particles (proteins) to the body and if they find something foreign, they secrete a messenger that runs and tells the immune system commander that more troops are needed. The immune system then sends Natural Killer T-cells as reinforcements and T-Helper cells. These T-cells rush to the site of destruction to kill the foreign invader and they also make a mug shot of the invader and send this picture to the B-cells so that they may make a defense system that will be able to immediately recognize any future invaders that match this description. This future defense system made by the B-cells is called an antibody.

Science doesn’t know a lot about the H3 receptor at this time other than it increases the mucous production in the stomach and intestines as a protectant and it appears to have a regulatory effect on the whole histamine system.

Now the H2 receptors are in charge of regulating numerous chemical reactions (activities) in the body that are much different than the H1 receptor activities. The H2 receptors are involved in regulating the chemical activities in the body that are affected in MS. Thus, these chemical activities will be the focus of the following discussion.
Research shows that MS patients have impaired ability in metabolizing (changing) the histamine molecule into a H2 receptor agonist (H2 Key). This results in a build up of the H1 receptor type and inadequate production of the H2 receptor type. The increased levels of the H1 type may account for the development of food sensitivities and other allergies that many MS sufferers complain about especially earlier on in the disease. Often as the disease progresses, even the production of the H1 type can become decreased because of digestive absorption problems that will be discussed later. These digestive problems result in the inadequate absorption of the amino acid called histidine which is the building block necessary for the production of histamine.

So MS patients are unable to produce enough H2 keys. Inadequate H2 keys results in a cascade of problems. First of all, H2 is a neurotransmitter, meaning it relays a message from one nerve to the next. It is the major neurotransmitter in the hypothalamus, which is like the hard drive of the brain. The hypothalamus is the relay junction center for the brain, messages are carried into the hypothalamus, sorted out and then connected to their proper target destination. Think of it much like the old time operators for the telephone system. The hypothalamus is also our center of well-being. If the hypothalamus is deficient in the H2, a person may feel depressed and lose interest in the goings on of life. The hypothalamus is also involved in our appetite and feeling of satisfaction. If the hypothalamus is lacking enough H2 a person may lose their appetite for food, sex and other activities that are supposed to create a feeling of satisfaction.

The hypothalamus also acts as the thermostat for the body. If the body’s core temperature heats up from exercise or an increase in the ambient temperature such as hot sun, hot room temperature or a hot bath, the H2 production is boosted. The increase in the H2 keys stimulates the pineal gland to make more melatonin which stimulates sweating. The thyroid gland is also stimulated by H2, which stimulates sweating. The increase in the H2 also stimulates the small diameter arteries to the skin, etc. to dilate, which also facilitates sweating. The increase in the H2 keys also increases the water content in the brain that helps to cool the brain and keep it from dehydrating. This is why heat is such a classic stressor to MS patients. MS patients have an impaired ability to produce enough H2 keys so if they encounter an increase in temperature, the body heats up, can’t sweat and the brain can start to dehydrate.

The fact that the thyroid gland is also stimulated by H2 explains why many MS patients have low normal laboratory readings for their thyroid gland activity and this also contributes to MS patients often feeling chilled. The decreased thyroid activity also accounts for the common occurrence for MS patients to have slightly lower body temperatures, i.e. 97.7º F - 98º F.

The decreased H2 also causes the small diameter arteries to constrict (narrow), which contributes to the dry skin, cold feet and hands, and the common symptom of optic neuritis. Tiny blood vessels feed the optic nerve and constriction (narrowing) of these arteries can cause inadequate blood flow to the optic nerve, which can result in swelling and damage.

As mentioned previously, H2 keys activate the pineal gland which makes melatonin and cyclic AMP. Melatonin and cyclic AMP help maintain the blood-brain-barrier. The blood-brain-barrier is a membrane that encases the brain and spinal cord. This membrane protects the brain and spinal cord from damaging toxins, substances, and organisms that may be in the blood from getting across into the brain and spinal cord. It acts as a great protective filter much like our skin is to the body. But just like a tear or crack in the skin can result in things getting past the skin and into the body that normally would not have been allowed had the skin been healthy and intact, so is it the same for the blood-brain-barrier. If the H2 is deficient, the blood-brain-barrier is not healthy and can get cracks in it that allow potentially harmful things to cross the membrane. The blood-brain-barrier has been found to be damaged in MS patients and the pineal gland is atrophied (shriveled up) in MS patients.

Melatonin is also necessary for the productive stage of sleep called Rapid Eye Movement sleep (REM). During REM sleep is when the body does a lot of its repair work. A large swing from high to low in the melatonin levels is required to initiate REM sleep. Again if H2 is deficient, melatonin levels will be inadequate and there won’t be a large enough swing in the melatonin level from high to low to initiate REM sleep. MS patients are deficient in melatonin and thus they don’t enter into REM sleep (the productive (healing) stage of sleep) and so they don’t wake up feeling like they had a good night’s rest. This low level of melatonin also contributes to the paralysis many MS patients develop because low levels of melatonin cause certain nerves to quit firing (sending a message). This is the same as the sleep paralysis that occurs normally during REM sleep when the melatonin has swung from high to its lowest level. Of course a person is unaware of this sleep paralysis called sleep atonia when they are in that deep REM stage of sleep.

Melatonin is also necessary for the metabolism (breakdown and utilization) of fats. H2 through melatonin is necessary for the metabolism of saturated fats (animal fats) and for the safe route of metabolism of unsaturated fats (oils). H2 stimulates the pineal gland, which in turn produces the melatonin. The pineal gland is the only region in the brain that can metabolize these polyunsaturated fats (oils like vegetable oil, flaxseed oil, primrose oil, fish oils, Omega 3 and Omega 6 oils) by what is called lipoxygenation that does not cause the production of toxic molecules called lipid peroxides. All other regions of the brain can only metabolize these polyunsaturated fats by lipid peroxidation that does produce toxic molecules. These toxic molecules (lipid peroxides) are very damaging to the nerve cells and especially the myelin producing cells in the brain and spinal cord called oligodendrocytes. Research shows that MS patients have a large amount of these toxic molecules in their brain, which makes sense because the pineal gland is shriveled in MS patients because of the lack of H2.

The myelin producing cells of the brain and spinal cord are further endangered because of the lack of cyclic AMP. H2 is one of the primary ways the body produces cyclic AMP. Cyclic AMP is necessary to maintain the myelin (the insulation around the nerves) in the brain and spinal cord. Research shows that if the cyclic AMP is lacking, the myelin cells in the brain and spinal cord will self-degenerate (self destruct) and if the cyclic AMP is replenished then these myelin cells will again become healthy myelin producing cells. This same research also shows that the myelin producing cells in the peripheral nervous system (arms, legs, etc.) will not self-destruct if the cyclic AMP is lacking. Thus, deficient H2 keys result in decreased cyclic AMP production, which results in the myelin cells self destructing in the brain and spinal cord but not in the arms, legs, etc. This explains why the lesions showing myelin destruction in MS patients are only in the brain and spinal cord. This self-destruction of the myelin cells also explains why the macrophages (“Pac Man” like eating immune cells) are present at the location of the lesions because when the myelin cells self-destruct, they release the warning flags that summon the immune system to send in the macrophages to clean up the debris and check for invaders. If invaders had been found, the macrophages would have sounded the alarm for the T-cell troops to rev up and come to the scene. Instead of a revving up of the T-cells, the opposite is seen in MS patients during an exacerbation. MS patients have an abnormally low T-cell count during an exacerbation. This phenomenon is explained later on in discussion. Furthermore, if a foreign invader would have been found the B-cells would have been instructed to make antibodies for future defense. Science has never found any antibodies to the myelin in MS patients. The medical community tries to explain the destruction of the myelin, the presence of the macrophages at the lesion sites, and the absence of antibodies to the myelin by saying that something is tricking the T-cells into attacking the myelin. But if this were true the T-cell numbers would be increased in MS patients (instead they are low in number) and if the T-cells perceived something as being foreign to the body’s myelin (whether the T-cell perception is right or wrong) it would still trigger the T-cells to send a message to the B-cells to make antibodies to the myelin. Science has never found any such antibodies.

Cyclic AMP is necessary for every cell to function just like oxygen is necessary for every cell to function. If the body’s ability to make cyclic AMP through the H2 system is impaired, then the body will breakdown its energy molecule called ATP to produce cyclic AMP. This may account for the tremendous fatigue that MS sufferers experience. In fact, fatigue accounts for 65% of the disability in MS patients. The lack in H2 results in the body using up its energy molecule in order to produce the cyclic AMP, which is absolutely necessary for life.

H2 is involved in the sending of messages from one nerve to the next as mentioned previously. Adequate H2 enables these messages to be sent repeatedly and with speed and ease by activating the Na+ - K+ pump (sodium-potassium pump). This is much like the analogy of flipping on the light switch. When the light switch is turned on it makes a connection that allows the electrical charge to flow through the wires. Think of the H2 as turning on the switch (the sodium-potassium pump) which in turn sends the message (electricity) on down the nerve pathway (wire) to the next nerve switch. H2 not only turns on the switch but the more the H2 the greater the voltage, in other words the faster and easier the message runs down the nerve. The less of the H2, the slower the message travels, and the more effort it takes to send the message down the nerve. As the H2 gets depleted, the message gets weaker until finally there just isn’t enough voltage power left at the end of the nerve pathway (wire) to turn on the next switch for the next nerve. At this point the message from nerve to nerve quits running until more H2 is produced or re-circulated and then the nerve message can be sent again. This explains why it is common for MS patients to do a repetitive task like repeatedly touching their thumb to each one of their fingers easier and faster at first, but after a few repetitions these movements get slower and harder to perform until finally they can’t do the task at all. Then after waiting for a brief period of time they can do the task again once the H2 gets replenished.

Stress and MS doesn’t mix, as any MS sufferer will tell you. It is a well-documented fact that stress triggers an exacerbation in MS symptoms. Research shows that stress blocks the chemical that is needed to produce H2. In normal functioning, this blocking is only temporary and actually results in the release of cortisol (human cortisone), which in turn boosts the chemical’s activity in producing H2 as much as 3 times greater dose dependent (meaning the more the cortisol released the greater the activity of the chemical in producing the H2). So ultimately, stress is supposed to increase the H2 production and activity. Early in the MS disease, it is common for the cortisol level to be elevated and this is a result of the decreased (impaired) activity of the chemical that is needed to produce H2. (Remember decreased activity of this chemical results in increased release of cortisol.) The increased cortisol production results in pushing the chemical to work harder at producing H2. This increased H2 production may result in a remission or lessening of symptoms. Unfortunately though, as the chemical becomes more depleted as time goes on and less H2 can be produced, the disability from the disease increases. Furthermore, the continuing decrease in this chemical triggers the adrenal glands to produce more cortisol until finally they burn out. The adrenal gland burn out often becomes apparent when some added stress occurs. This added stress like a viral infection, emotional stress, birth of a child, etc. becomes the “straw that breaks the camel’s back”. The adrenal glands just can not put out any more and the H2 production drops even lower. Many MS patients can recall a particular incident of stress such as an illness or accident that seemed to be the beginning of their downward spiraling progression of the disease and symptoms. Again, it was the “straw that broke the camel’s back”.

The ability of cortisol to increase the production of H2 by priming the chemical to rev up to make more H2 is only temporary though. In normal functioning, the cortisol is only meant to prime the chemical (engine), it is not meant to run it. This is much like the analogy of a starter on an engine. The starter (cortisol) turns the engine (chemical) over until the engine fires and then the engine takes off and runs on its own (producing H2) and the starter disengages (the cortisol release decreases). Now the engine will take off and run if it is in good enough running condition and gets enough gas. If the engine can’t run on its own, the starter can’t keep the engine running. The starter (cortisol) is only meant to start the engine (chemical), not keep it running (making H2). This may explain why an IV steroid treatment can result in almost immediate lessening of symptoms during an exacerbation, but these effects don’t last. The steroids act the same as cortisol (the starter) and they give a boost to the body’s worn out starter (cortisol), which results in a big enough boost to get the engine running (activate the chemical to produce more H2). But remember the cortisol or steroids can’t keep running the engine. Unfortunately, as the engine (chemical) gets in worse shape, not even a big boost from the steroids can get it to produce more H2. Thus, it is seen that steroid treatments lose their effect in lessening symptoms and debilitation as the MS progresses.

H2 regulates the immune system. Increased H2 and the resultant increase in cyclic AMP boost the immune system especially the T-cells and B-cells. Research shows that the H2 levels control the receptor activity on these cells and that the H2 levels are decreased during an exacerbation or chronic progression of MS. Research also shows that MS patients have an abnormally low number of T-cells during an exacerbation. This directly contradicts the autoimmune theory, that the immune system, specifically the T-cells, are hyperactive and attacking the myelin. Instead, the immune system becomes suppressed in MS due to low levels of H2 and cyclic AMP.

H2 increases the production of gastric acid and digestive enzymes. MS patients have inadequate gastric acid and digestive enzyme production. This is why many MS patients complain of having trouble digesting meats because these food items require the digestive enzymes pepsin and gastrin. The decreased gastric acid production due to the decreased H2 causes the closure (sphincter) between the stomach and the esophagus to remain open. This allows food and gastric acid to go back up into the esophagus causing heartburn and is called esophageal reflux that is common in MS patients. The decreased digestive enzyme production resulting from inadequate H2 causes amino acid deficiencies and other nutritional imbalances often seen in MS patients because the food just can’t be broken down adequately to get the necessary nutrition out of it. Amino acids come from the proteins we eat, and one of those amino acids is histidine, which is necessary to make histamine as mentioned previously. The decreased gastric acid and digestive enzyme production due to decreased H2 contributes to the constipation that is common in MS.

Thus, H2 production is impaired in MS. Inadequate H2 production results in difficulty sending messages between the nerves, heat intolerance, myelin self-destruction, fatigue, depression, a poor sense of well-being, digestive problems, immune suppression, and inability to tolerate stress. MS sufferers experience symptoms involving all of these functions of the body which are dependent on the availability of H2.

So now the logical question is, what causes the H2 production to be impaired? Digging through more research, I discovered many factors that can hinder the H2 production. The presence of these factors increases the risk of developing MS. The more risk factors present, the more chance of developing MS. There isn’t one specific risk factor that appears to cause MS, because many of these risk factors are present in other people who don’t develop MS. It is like smoking, you can’t say smoking causes cancer because there are some people who smoke and never develop cancer, but smoking increases the risk of developing cancer and certain individuals because of their genetic make-up may be at more risk than others.

The chemical that is responsible for making the H2 is vulnerable to being inactivated by many factors. First of all, the instructions on how much of this chemical should be produced are encoded on the X chromosome, which may account for any flaws in the production of this chemical to be more common in females than males because females have two X chromosomes and males have one X and one Y chromosome. Next, these production instructions for this chemical are supposed to be put into action during adolescence (this is called the triggering of gene expression). Now the more factors present that can affect this chemical production during this specific time of adolescence can interfere with the amount of chemical produced from that time on. This can result in the production of the chemical being less than optimal for the rest of life. This may also explain why research of MS has shown that where a person resided during their adolescence years acts as a risk factor in their later developing MS. The factors that can play havoc with the production of this chemical are infections, stress, lipid peroxidation, toxins, deficient copper and zinc levels, deficient levels of melatonin production, high estrogen levels, being Caucasian, and being female. Each of these factors will be discussed in the following.

First of all, the female risk factor was previously discussed and being Caucasian increases the risk. Caucasians being lighter skinned already have been instructed by their genes to have less production of this chemical. This chemical that produces H2 is also involved in producing melanin (skin pigmentation). Thus, the darker skinned a person is, the more activity of this chemical. The lighter skinned a person is, the less activity of this chemical because the less melanin (skin pigmentation) is made. This explains why MS is more prevalent in Caucasians than in Blacks or Asians, because lighter skinned people are already working with less production of this chemical so the presence of any more risk factors that can inhibit the chemical’s activity will have a more pronounced effect on Caucasians.

Remember the previous discussion that H2 stimulated the production of melatonin. So if the production of the chemical that produces H2 is already genetically decreased such as in a female or Caucasian, then less melatonin may be produced in these individuals and the presence of any more hindering factors to the chemical’s activity will greatly decrease the melatonin production. Other than through the H2 system, the other way for the body to make melatonin is by direct ultraviolet rays hitting the retina of the eye. Thus melatonin production is enhanced the closer one is to the equator. Melatonin is a powerful antioxidant for the body. It decreases the potential cell damage from toxins and lipid peroxidation. Also remember the previous discussion that melatonin helps maintain the blood-brain-barrier, helps cool the body in heat, helps tell the muscles to move, metabolizes saturated fats, safely metabolizes unsaturated fats, and helps the body to go into the productive stage of REM sleep which is when the body repairs itself. To sum it up, the more melatonin produced, the less stress to the body. As was discussed previously, stress blocks the chemical’s activity that produces H2, so if less melatonin is produced then more stress is encountered by the body. The chemical that produces H2 is hindered which results in inadequate H2 production. Now this explains why MS is more prevalent in the north and south latitudes of the world, which are further from the direct sun which in turn decreases melatonin production which ultimately decreases H2 production.

Deficient melatonin production can also impair the absorption of zinc. Low zinc levels suppress the immune system and that can increase the susceptibility to infection. Furthermore, low zinc levels increase lipid peroxidation that damages cells especially nerve cells and oligodendrocytes (the myelin producing cells of the brain and spinal cord). Lipid peroxidation can inhibit the activity of the chemical that produces H2 up to 60%. MS patients have low blood levels of zinc especially as they age.

Low levels of copper can inhibit the production of the chemical that produces H2 because the chemical is a copper-containing chemical. MS patients have low levels of copper especially when they are younger. The copper to zinc ratio in the body is very important. The low levels of copper when the MS patient is younger causes decreased production of the chemical that makes H2. Then as the chemical decreases the production of H2 decreases, which results in a decreased production of melatonin. Lower levels of melatonin result in less zinc absorption that results in lower levels of zinc in the blood as the MS patient ages or the disease progresses. This results in more lipid peroxidation that in turn inhibits the H2 production, which results in a worsening of the symptoms of MS and a progression of the disease. Do you see how the body gets into a downward spiraling condition that accounts for the steady progression of the MS disease and worsening of symptoms?

So why is the occurrence of MS increasing in males and why is it increasing so rapidly in the U.S. population (the NMSS states that an average of 200 new cases of MS are diagnosed per week in the U.S.)? Perhaps it is in part due to our diet of high carbohydrates and polyunsaturated fats like margarine, vegetable oils, etc and our trend to decrease the consumption of the saturated fats like butter and fats in red meat. High carbohydrate intake results in the body storing these excess carbohydrates in the form of triglycerides, which are just empty fat molecules. These triglycerides cause our body to produce more estrogen. Research has found that the population as a whole is getting too high in estrogen (by the way estrogen increases the risk of cancer and cancer is on the rise). Estrogen inhibits the chemical that produces H2 in the hypothalamus (the hard drive for the brain). So is it any wonder that the high carbohydrate consumption in the U.S. that results in high estrogen production coupled with the high consumption of polyunsaturated fats that cause lipid peroxidation, which will greatly inhibit the production of H2, may be contributing greatly to the increased incidence of MS in the U.S. and the male population?

Thus, many risk factors can lead to the decreased production of H2 keys in the body. These risk factors explain the trends seen in MS occurrence such as: it is more prevalent in Caucasians; affects females more than males but the ratio is changing; it is more prevalent in areas further away from the equator; and where a person was during their adolescent years can put them more at risk of developing the disease. The H2 hypothesis also explains why the immune suppressive therapies have been unsuccessful in treating the symptoms and unsuccessful in ultimately changing the course of the disease.