Multiple Sclerosis: A Theory

James Howard phis at sprynet.com
Sun Jan 5 14:00:29 EST 1997

Multiple Sclerosis: A Theory
James Howard

This is a new theory of the cause of multiple sclerosis (MS).  
My explanation is based on my theory of the interaction of 
the hormones, melatonin (MLT) and dehydroepiandrosterone 
(DHEA), which I call the "melatonin - DHEA cycle," and 
testosterone, and the effects these have on the nervous and 
immune systems.  I suggest all tissues are dependent on the 
MLT - DHEA cycle, principally the nervous and immune 
systems, and the gonadal (sexual) hormones evolved as a 
means of manipulating this cycle.  MS is a disease 
characterized by demyelination of nerves.  At its most basic, 
my work suggests MS results from an "attack" of the 
immune system on myelin, as a result of over-stimulation of 
the MLT - DHEA cycle in the immune system, triggered by 
lack of normal growth of myelin, as a result of deficient 
effects of testosterone.  (The following treatise explains this 
in detail, it will take some length to do this.  Please bear with 
me.  Since this is written for internet posting, I am not 
including diagrams here; they may be accessed in the articles 
I specify on the internet.)

In 1985, I developed a theory of sleep that explains the 
connection of MLT with DHEA.  (This may be read in detail 
at http://www.naples.net/~nfn03605 on the internet.)  The 
importance of my sleep mechanism to MS is that it explains 
that when MLT levels are high, DHEA is low, and when 
DHEA is high, MLT levels are low.  My work further says 
that DHEA levels will rebound to the suppression of DHEA 
caused by MLT.  It is a "cycle."  A direct connection of 
MLT and MS has been reported by two investigators, 
Sandyk and Awerbuch.  Since no work has been done on 
MS and DHEA, I will show how their work to supports the 
connection of the MLT - DHEA cycle to MS.  MS cannot be 
explained by melatonin alone.

In an abstract of International Journal of Neuroscience 1993; 
68: 209, Sandyk explains the connection of MLT and MS:
"Epidemiological studies demonstrate that the incidence of 
multiple sclerosis (MS) is age-dependent being rare prior to 
age 10, unusual prior to age 15, with a peak in the mid 20s.  
It has been suggested that the manifestation of MS is 
dependent upon having passed through the pubertal period.  
In the present communication, I propose that critical changes 
in pineal melatonin secretion, which occur in temporal 
relationship to the onset of puberty, are intimately related to 
the timing of onset of the clinical manifestations of MS.  
Specifically, it is suggested that the fall in melatonin 
secretion during the prepubertal period, which may disrupt 
pineal-mediated immunomodulation, may stimulate either the 
reactivation of the infective agent or increase the 
susceptibility to infection during the pubertal period.  
Similarly, the rapid fall in melatonin secretion just prior to 
delivery may account for the frequent occurrence of relapse 
in MS patients during the postpartum period.  In contrast, 
pregnancy, which is associated with high melatonin 
concentrations, is often accompanied by remission of 
symptoms.  Thus, the presence of high melatonin levels may 
provide a protective effect, while a decline in melatonin 
secretion may increase the risk for the development and 
exacerbation of the disease.  The melatonin hypothesis of 
MS may explain other epidemiological and clinical 
phenomena associated with the disease such as the low 
incidence of MS in black African and American populations, 

Melatonin is produced in the pineal gland.  It is known that 
calcification of the pineal gland occurs with age and the 
reduction of MLT.  Sandyk and Awerbuch address this in 
"Twenty-one age and sex-matched neurological patients 
served as controls.  PC [pineal calcification] was seen in 
100% of MS patients, while 72.4% patients had CPC 
[choroid plexus calcification].  In the control sample, PC was 
found in 42.8% and CPC in 28.5%.  Thus, the strikingly high 
prevalence between MS and abnormalities of the pineal 
gland.  Moreover, since pineal melatonin is involved in 
neuroimmunomodulation, we propose, for the first time, that 
abnormalities of pineal melatonin functions are implicated in 
the pathophysiology of the disease [MS]."  (International 
Journal of Neuroscience 1991; 61: 61)   Melatonin is 
produced in the highest levels during nighttime, lowest in 
daytime.  In a study of nocturnal melatonin levels, Sandyk 
and Awebuch, reported that: "Abnormal melatonin levels 
were found in 13 patients (52.0%), 11 of whom had 
nocturnal levels which were below the daytime values." 
(International Journal of Neuroscience 1992; 67: 173)  
Calcification of the pineal increases with age.  Now, this fits 
my theory.  If MS represents a state in which the MLT - 
DHEA cycle is increased, then the MLT - DHEA cycle will 
increase.  This will literally increase aging, part of which 
would show as increased calcification of the pineal gland.

I suggest it is the connection of MLT with DHEA that is the 
real connection of MLT with MS.  In Sandyk’s summary 
(1993), he describes the age-dependence of MS.  These ages 
are very important to my explanation of MS, but I want to 
postpone them momentarily and directly consider the times 
and levels of melatonin he lists.  My work at my internet 
page explains why, and shows actual measurements, of MLT 
and DHEA during the human life-span.  When MLT starts its 
steep decline just prior to puberty, DHEA starts a strong 
increase, known as "adrenarche."  My work suggests this 
rise occurs, because the brain is finishing its use of DHEA 
for growth and development in infants and children.  What is 
really happening is that the "measurable" levels of DHEA 
are rapidly increasing as less and less DHEA is absorbed by 
the brain for growth and development.  The importance of 
this rise in DHEA for MS is that this "free" DHEA can then 
be used by the immune system.  (My work suggests all 
tissues compete for DHEA; the brain is simply the best at 
absorbing it.  I will explain how DHEA affects the immune 
system below.)  Sandyk suggests that "the fall in melatonin 
secretion during the prepubertal period, which may disrupt 
pineal-mediated immunomodulation, may stimulate either the 
reactivation of the infective agent or increase the 
susceptibility to infection during the pubertal period."  (A 
number of citations suggest that an infective agent is 
involved in MS; this is why he mentions an infective agent.  
My explanation suggests these potential infections merely 
stimulate increased DHEA; they are not the actual cause of 
MS.  This will be explained.)  Further, Sandyk says: 
"Similarly, the rapid fall in melatonin secretion just prior to 
delivery may account for the frequent occurrence of relapse 
in MS patients during the postpartum period.  In contrast, 
pregnancy, which is associated with high melatonin 
concentrations, is often accompanied by remission of 
symptoms."  The protective effect Sandyk suggests for 
melatonin here is, I suggest, simply due to another use of 
DHEA, similar to that of the brain in infants and children, 
which I described above.  My work suggests that tissues use 
DHEA, therefore, the mother makes DHEA for herself and 
her fetus.  This stimulates the MLT - DHEA cycle in the 
mother; her melatonin increases to stimulate DHEA in large 
amounts for the growing fetus.  This DHEA is absorbed by 
the rapid growth of the fetus, so the DHEA levels actually 
stay low in the pregnant woman.  Her immune system is not 
activated enough to start the MS cycle.  Since DHEA may be 
involved in starting delivery: "labor is associated with a 
significant increase in umbilical artery levels of DHEA" 
(Journal of Clinical Endocrinology and Metabolism 1976; 
42: 744), available DHEA rises at birth.  That is, the fetus 
stops using DHEA, which then becomes available to 
stimulate tissues in the mother.  It is this rise in DHEA at 
birth that starts contractions and also stimulates the immune 
system, and increases MS.  So, I am saying that the 
"protective" effects of high melatonin result from the fact 
that melatonin is high when a very large amount of DHEA is 
needed for growth and development.  These two times of 
high melatonin are times of high DHEA and high DHEA use; 
melatonin does not protect against MS.  The connection of 

My work suggests that DHEA directly stimulates the immune 
system.  This can be seen quite well in a number of studies of 
HIV infection and AIDS.  (Please read my article on 
"AIDS" at my website for citations.)  What is found is that 
DHEA increases dramatically upon infection by the HIV.  I 
think DHEA increases whenever infection, bacterial or viral, 
occurs.  MS appears to be associated with viruses; the 
hypothesis depends on the findings that MS often appears in 
a cluster.

"Geographic and temporal variation and migration studies 
point to an exogenous agent in the etiology of multiple 
sclerosis. If infectious etiology is involved, space-time 
clustering would also be expected. The authors analyzed 381
patients with a clinical onset of multiple sclerosis between 
1953 and 1987 in the county of Hordaland, Norway. Patients 
[MS] within the same birth cohort had lived significantly 
closer to each other than would be expected during ages 13-
20 years, with peak clustering at age 18 years (p = 0.002). 
Clustering was also shown between patients in pairs 
comprised of one individual with initial remittent disease and 
the other with chronic progressive course of disease, 
suggesting a similar etiology for both clinical patterns. 
Clustering between cases with widely divergent dates of 
clinical onset provides evidence of marked variation in 
latency. No similar clustering was observed in age-, sex-, and 
area-matched hospital controls without multiple sclerosis, 
and no clustering was found among the cases when using 
fixed number of years before onset. These results are 
compatible with a common infectious agent, such as the 
Epstein-Barr virus, acquired in adolescence in genetically 
vulnerable persons who are also not protected by an 
infection acquired before this age of susceptibility." 
(American Journal of Epidemiology 1991; 133: 932)

There are other studies that suggest viral infections may be 
part of the mechanism of MS.  However, I suggest that viral 
infections are merely activating the MLT - DHEA cycle.  The 
increased DHEA activates "monitoring" by the immune 
system.  The increased monitoring of the immune system 
picks up a "lesion" that causes an "autoimmune response" 
that causes the MS.  Now, I suggest that this mechanism, 
which will be described below, can manifest itself without 
the influence of an infection.  An infection simply increases 
the probability; infections are not the actual cause of MS.

DHEA and cortisol are the major hormones produced by the 
adrenal glands.  DHEA and cortisol secretions may be 
separated, but often these occur simultaneously.  While no 
one has measured DHEA in MS, and it might actually be 
"low" during active MS because of use by the immune 
system, two studies have found cortisol to be "significantly 
higher" in MS (Experimental and Clinic Endocrinology and 
Diabetes 1996; 104: 31;  Journal of Clinical Endocrinology 
and Metabolism 1994; 79: 848).  While this does not prove 
that DHEA is involved, it does show that the adrenal glands 
are very active in MS.

To summarize to this point, I suggest MS is a state of 
activated DHEA production that stimulates the immune 
system to attack a "lesion."  I suggest the lesion that 
provides the "initial antigenic material to the immune 
system" results from immature myelin in people with MS.
"In a correlative study involving protein chemical, mass 
spectrometric, and electron microscopic techniques we have 
determined that myelin obtained from victims of MS is 
arrested at the level of the first growth spurt (within the first 6 
yr of life) and is therefore developmentally immature.  ...We 
postulate that this developmentally immature myelin is more 
susceptible to degradation by one or a combination of factors 
mentioned above, providing the initial antigenic material to 
the immune system."  (Journal of Clinical Investigation 
1994; 94: 146)   The "factors" suggested by these 
investigators are "genetic, environmental, infective, and 
immunological factors..."

What causes the immature myelin in MS that stimulates the 
immune system?  A number of factors caused me to look at 
the connection of testosterone in MS.  These include:  "A 
review of population studies demonstrates that the 
preponderance of women in MS is almost a constant." 
(Canadian Journal of Neurological Sciences 1992; 19: 466);  
"Mortality rates from MS show a well-known north-south 
gradient, both within the United States and internationally." 
(Neuroendocrinology 1992; 11: 244);  "The data suggest 
that onset of pathogenesis of MS is dependent on passing or 
having passed through the puberty period."  (American 
Journal of Epidemiology 1981; 114: 24); "MS is rare among 
the indigenous black people of Africa." (Journal of 
Neurology, Neurosurgery and Psychiatry 1994; 57: 1064).

Testosterone is lower in women.  My theory, from which this 
work is derived, suggests that the hominids that migrated out 
of Africa, into the north, were hominids of lower 
testosterone.  Therefore, in general, I expect lower 
testosterone in Europeans (Whites) than Africans (Blacks.)  
European and whites represent lower testosterone.  DHEA 
increases, starting at adrenarche, to a high point in the mid-
twenties.  This fits the findings listed by Sandyk, early in the 
paper, that is, that MS peaks in the mid 20s.  DHEA would 
be highest at this time and, therefore, the immune attack 
would be greatest at this time.  Earlier this month, I 
developed an explanation for migraine headaches that 
suggested migraines are caused by increased DHEA.  As part 
of my support of my explanation of migraines, I pointed out 
that blacks produce significantly more testosterone than 
whites (Journal of the National Cancer Institute 1986; 76: 
45).  My work suggested testosterone causes DHEA to be 
reduced in the blood, because testosterone causes DHEA to 
be used more by "testosterone target tissues;"  Blacks have 
fewer migraines than whites.  This fit very nicely with this 
work, too, i.e., MS is rare in blacks.   The increased 
testosterone in blacks would reduce the immune response of 
MS.  However, I found out that women MS patients had 
"significantly higher concentrations of total and free 
testosterone" (Journal of Internal Medicine 1989; 226: 241).

This contradiction caused me to find and propose a reason 
for the "lesion" of MS, the immature myelin.  I suggest the 
immature myelin of MS results from lack of testosterone’s 
effect on growth.  I am saying that myelin growth occurs 
because of two different hormones.  The early large 
production of DHEA following birth causes the early growth 
of myelin of the "first growth spurt."  Subsequent to this, the 
nervous system becomes a "testosterone target tissue."  That 
is, testosterone stimulates growth of the nervous system too.  
Men produce more testosterone than women; the brains of 
men are bigger than the brains of women.  Based on the 
following quotation, I am saying that the "white matter" of 
the brain is a testosterone target tissue.  The "metabolic 
activity" of white matter is mainly due to myelin.  Myelin is 
sensitive to the levels of testosterone.
"Previous results obtained in this laboratory indicate that in 
the rat brain the 5 alpha-reductase, the enzymatic activity 
involved in metabolizing testosterone into 5 alpha-androstan-
17 beta-ol-3-one (dihydrotestosterone), particularly 
concentrated in the white matter.  ...The high metabolic 
activity associated with the white matter structures appears to 
be linked to the presence of myelin, since the specific 
activity of the enzyme is particularly elevated in purified 
preparations of myelin sheaths."  (Journal of Steroid 
Biochemistry 1988; 31: 173). 

I suggest that the low testosterone of women, and people 
whose ancestors developed in the north, is interacting with a 
genetic predisposition toward weak, or malfunctioning, 5 
alpha-reductase in the nervous system.  This could result in 
the "immature myelin" found in MS and the significantly 
increased testosterone in female MS patients.  That is, these 
women are not absorbing and converting their testosterone.  
Therefore, I suggest multiple sclerosis is the result of 
increased DHEA, causing the immune system to attack the 
immature myelin.  This explains the chronic demyelination 
of multiple sclerosis.
James Howard

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