Multiple Sclerosis and Human Evolution

James Howard phis at sprynet.com
Sat Jan 11 07:33:34 EST 1997

Multiple Sclerosis and Human Evolution
James Howard

A few at this newsgroup know that I have developed a new theory 
of human evolution, based on changes in hormones, specifically DHEA,
melatonin, and testosterone.  Basically, my theory suggests that migration
northwards occurred because of increases in DHEA and decreases in 
testosterone.  Now, it is proven that multiple sclerosis is rare in blacks
and occurs more often in people of northern latitudes.  The remainder 
of this post is my explanation of multiple sclerosis (MS).  If you read it, you 
will discover that expression of MS may be directly affected by levels of 
DHEA and testosterone.  This further supports my theory of human 
evolution, and it further demonstrates that levels of DHEA and 
testosterone are directly involved in differences in the races.

Multiple Sclerosis: A New Theory
James Howard (phis at sprynet.com)

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 MS.
"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 MLT is DHEA.

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
1037 Woolsey Avenue
Fayetteville, Arkansas 72701

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