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
U.S.A.
