My theory suggests all tissues of the body depend on the "melatonin-DHEA cycle." I think this cycle is necessary for growth, development, and function during childhood and adolescence and maintenance and function of the adult. I look for disturbances of this cycle to help explain pathology. Migraine headaches and epilepsy may result from malfunctions in melatonin (MLT) and DHEA. Prior to my explanation, increased MLT in epilepsy and reduced MLT in migraines has been discovered. However, according to a medical literature search (medline), no one has addressed any connection of DHEA with migraines or epilepsy.
The main connection of low MLT in migraines is found in the female cycle. MLT "increases significantly from the follicular to the luteal phase" in normal women’s cycles (Cephalalgia 1995; 15: 136); another study found that MLT is significantly reduced throughout the cycle in women with migraines. This second study also found that MLT is decreased during headaches (Caphalalgia 1994; 14: 205). I have read anecdotal remarks on the internet that some women have increased migraines during the second part of their cycles (luteal phase). MLT begins a steep decrease just prior to puberty, and declines rapidly thereafter. Since, "migraine occurs most commonly in men and women aged 25-55 years" (Neurology 1994; 34 Suppl. 2: 6), I suggest that this is a time when MLT reaches critically low levels in susceptible people. Low MLT is somehow connected to migraines, but, I suggest, the levels of DHEA have to be examined to fully explain it.
I suggest migraines result from low MLT and increased DHEA. Women produce more DHEA from birth than men. This extra DHEA should have most effect on migraines prior to the onset of interfering sex hormones, before puberty. It has been found that "when the onset [of migraines] is below the age of puberty there is a striking predominance of women over men in a ratio of 3:1," (Headache 1994; 34: S8). It is part of my theory that the hormone, testosterone, causes DHEA to be used for "testosterone target tissues." This use of DHEA by these tissues should reduce the availability of DHEA, i.e., increased testosterone should decrease migraines. This can be seen in the fact that, following puberty, women still have more migraines and that whites have more migraines than blacks. Blacks produce more testosterone than whites. "In women, migraine prevalence was significantly higher in Caucasians (20.4%) than in African (16.2%)... A similar pattern was observed among men (8.6%, 7.2%, ...)." (Neurology 1996; 47: 52). Interestingly, my theory suggests that people of higher testosterone congregate together, as in cities, and higher DHEA/lower testosterone types tend to live apart from cities.
The prevalence of migraines also follows this pattern. "Females, whites, and individuals residing in rural counties were more likely to suffer migraine headache than their respective comparison groups." (Clinical Therapeutics 1994; 16: 855).
I have read that headaches occur when blood vessels in the brain constrict. Since I have suggested elsewhere that I think DHEA stimulates constriction of blood vessels and increases blood pressure, I suggest increased DHEA causes the constriction of blood vessels in migraine headaches. Constricting blood vessels and reduced blood flow is characteristic in migraines. "The transient neuronal excitatory wave is followed by a longer lasting ‘depressive’ wave, which involves a substantial reduction in cortical blood flow (with an active constriction of resistance vessels) and ionic changes and transmitter release into the extracellular fluid compartment." (Cephalalgia 1992; 12: 75).
I have produced a theory of sleep that explains the connection of MLT and DHEA. At its most basic, I suggest melatonin binds to neurons and shut them down. The connection with DHEA is that MLT shuts down the nerves that release the hormone, prolactin (PRL). It is also known that PRL specifically and powerfully stimulates DHEA. When MLT shuts down PRL, DHEA production is reduced and its stimulating effects on the brain are reduced. This is sleep. Now, to keep this from killing us, PRL is released in rebound to the negative effects of MLT. This cycles slowly until a large release of PRL occurs in the early morning. This large release of PRL then starts a large morning release of DHEA, which awakens us. In the quotation just above, I suggest the "excitatory wave" represents the effects of MLT, i.e., the shutdown of MLT causes nerves to rebound in response. I suggest the "depressive wave" represents the restabilization caused by a subsequent response of secreted DHEA. The increased DHEA causes the blood vessel constriction that causes the migraine headache.
With the foregoing in mind, it should be easier to explain epilepsy with the MLT - DHEA cycle. MLT is high in epileptic people. "Melatonin production in untreated patients with active epilepsy is increased and had a circadian pattern with a phase difference as compared with that of normal subjects." (Epilepsia 1995; 36: 75). In the paragraph, just above, I demonstrated how MLT can induce the production of DHEA. During the day, my sleep mechanism suggests that the larger production of DHEA is involved in inhibiting synthesis of MLT from the pineal gland (where MLT is made). This means that once DHEA is "used up" during the day, there is not enough DHEA to keep the pineal from making MLT. When MLT production occurs, the shut down of PRL occurs and DHEA is reduced to even lower levels. This is how the sleep - wake cycle occurs.
Sleep deprivation keeps MLT from being released. This has been determined. "It was found that the melatonin levels were increased after sleep deprivation..." (Sleep 1988; 11: 362). A much later study found that MLT was not increased by sleep deprivation, but that "Prolactin was higher on the post-sleep deprivation and control nights but did not rise on the deprivation night." (Journal of Pineal Research 1996; 20: 7). Sleep deprivation increases the build up of the thing that stimulates DHEA, i.e., prolactin. Since increased sleep is a consequence of sleep deprivation, I suggest MLT increases. Since it is the PRL that stimulates DHEA production, both of these studies say, essentially, the same.
There is another way of seeing this. I have suggested that DHEA stimulates the nerves that inhibit synthesis of MLT. I suggest that electroconvulsive shock exerts its effects by stimulating DHEA. In the following quotation, I suggest the reduced production of MLT is due to increased DHEA, inhibiting the pineal gland. "In ECS [chronic electroconvulsive shock]-treated rats, both pineal and serum melatonin levels after isoproterenol administration were significantly lower than those in sham-treated animals and in rats receiving subconvulsive shock." (Psychiatry Research 1994: 53: 185).
I suggest that the opposite mechanism explains epilepsy. I suggest the increased melatonin found in untreated epileptics builds up and is released so that nerves are shut down. Individuals susceptible to epilepsy must have entire sections of the brain shut down so much that they "rebound" and call up a large response of DHEA. It is this rebound response that is the large area of stimulated nerves that cause the seizures. Once the brain has stimulated sufficient DHEA, then the seizure stops.
Migraine, Exercise, and DHEA
Sent January 27, 1998, to MGH Neurology Web-Forum, Headace, as a response to "Migraine and Exercise"
My explanation of migraines suggests it is triggered by too little melatonin and too high DHEA. I suggest that melatonin and DHEA act in a cycle, the purpose of which is to stimulate DHEA. It is known that exercise stimulates DHEA. Now, when you exercise, especially when you exercise vigorously, the result is a triggering of this cycle. However, this statement, from the following quotation will explain what may be happening in you, and the others who have responded: 'These results suggest that vigorous exercise training may attenuate rather than augment the secretion of pineal melatonin.' This means that vigorous exercise may actually reduce the melatonin response. You see, according to my explanation, you may be triggering this cycle with your exercise, and you may be altering the ratio of melatonin to DHEA towards DHEA. Now, this may only affect certain people who are prone to migraines, but I suggest this is the cause of your exercise-associated-migraines.
J. Pineal. Res. 1989; 7(2): 185-194 "Melatonin response to exercise training in women"
"Previous human studies have indicated that daytime melatonin levels increase when the organism is subjected to the stress of fasting and exercise. Melatonin, epinephrine, and norepinephrine levels were measured during a mock run and in the course of treadmill exercise performed before (T-1), during (T-2), and following (T-3) a progressive conditioning (running) program. Hormonal responses to the training program were determined by comparing values at T-1 and T-3. Plasma melatonin, epinephrine, and norepinephrine levels rose significantly (P less than .01) from baseline values for each exercise intensity during all three treadmill runs. While a dose-response trend was observed in each of the norepinephrine and epinephrine trials, there appeared to be a progressive diminution of this relationship in melatonin between intensities. Further, as training progressed, the peak melatonin concentration was decreased by 52% from T-1 to T-3, while peak epinephrine and norepinephrine values diminished only 19% and 8%, respectively. These results suggest that vigorous exercise training may attenuate rather than augment the secretion of pineal melatonin. Development of a human model of pineal responsiveness to exercise may contribute to the elucidation of exercise-associated reproductive disorders."
Coma and Near Death Experiences:
It occurred to me a while back when I wrote “Dehydroepiandrosterone and Persistant Vegatative States or Coma,” that my explain of this and of epilepsy contained an explanation of “Near Death Experiences.”
Basically, from my explanation of epilepsy, above, I suggest the “near death experiences” may be explained identically with the inclusion that the DHEA rebound response is delayed almost irreparably. However, the DHEA rebound response is triggered in some individuals before it is too late. I did some research and discovered similarities in epilepsy and NDEs which I am not listing at this time.