Multiple Sclerosis And Other Hormone-Related Brain Syndromes


The Law & Order Admin
Jan 4, 2012
:hattip Haagendazendiane for forwarding me this article to post.


Since I am trying to discuss a complex matter in a single article, I have separately outlined the essential technical points of the argument in a section at the beginning, then I explain how my ideas on the subject developed, and finally there is a glossary. If you start with "Short-day brain stress," "Estrogen's effects," and "Symptoms and therapies," you will have the general picture, and can use the other sections to fill in the technical details.

1) The hormones pregnenolone, thyroid, and estrogen are involved in several ways with the changes that occur in multiple sclerosis, but no one talks about them.

2) The process of myelination is known to depend on the thyroid hormone. The myelinating cells are the oligodendroglia (oligodendrocytes) which appear to stop functioning in MS (and sometimes to a milder degree in Alzheimer's disease, and other conditions). The cells' absorption of thyroid hormone is influenced by dietary factors.

3) The oligodendrocytes are steroid-producing cells (1), and steroidogenesis is dependent on thyroid hormone, and on thyroid-dependent respiratory enzymes and on the heme-enzyme P-450scc, which are all sensitive (2) to poisoning by carbon monoxide and cyanide. The steroid produced by the oligodendrocytes is pregnenolone, which is known to have a profound anti-stress action (3), and which appears to be the main brain-protective steroid.

4) Lesions resembling those of MS can be produced experimentally by carbon monoxide or cyanide poisoning.(4) The lesions tend to be associated with individual small blood vessels, which are likely to contain clots. (Since all animals have enzymes to detoxify cyanide, this poison is apparently a universal problem, and can originate in the bowel. "Detoxified" cyanide is still toxic to the thyroid.)

5) Pregnenolone and progesterone protect against nerve damage (5) by the excitotoxic amino acids (glutamic acid, aspartic acid, monosodium glutamate, aspartame, etc.), while estrogen (6) and cortisol (7) are nerve-destroying, acting through the excitotoxic amino acids. Excitotoxins destroy certain types of nerve, especially the dopaminergic and cholinergic types, leaving the noradrenergic types (8), paralleling the changes that occur in aging. The clustering of oligodendrocytes around deteriorating nerve cells could represent an adaptive attempt to provide pregnenolone to injured nerve cells.

6) The involvement of hormones and environmental factors probably accounts for the intermittent progress of multiple sclerosis. To the extent that the environmental factors can be corrected, the disease can probably be controlled.


Shortly after I moved from Mexico to Montana, one of my students, a 32 year old woman, began having the same sensory symptoms her older sister had experienced at the same age, at the onset of multiple sclerosis. Vertigo and visual distortions of some sort made her consider withdrawing from the university. I'm not sure why she tried eating a whole can of tuna for lunch a couple of days after the onset of symptoms, but it seemed to alleviate the symptoms, and she stayed on a high protein diet and never had a recurrence. She told me some of the lore of MS: That it mostly affects young adults between the ages of 20 and 40, that it is common in high latitudes and essentially unknown in the tropics, and that it is sometimes exacerbated by pregnancy and stress. (Later, I learned that systemic lupus erythematosis and other "auto-immune" diseases also tend to occur mainly during the reproductive years. I discussed some of the implications of this in "Bean Syndrome.")

Having enjoyed the mild climate of Mexico, I became very conscious of the harm done to us by northern winters, and began developing the idea of "winter sickness." In 1966-67, allergies, PMS, weight gain, colitis, and arthritis came to my attention as winter-related problems, and I assumed that the high-latitude incidence of MS related to what I was seeing and experiencing. Studies in Leningrad began revealing that mitochondria are injured during darkness, and repaired during daylight. I observed that hamsters' thymus glands shrank in the winter and regenerated in the summer; shrinkage of the thymus gland is a classical feature of stress, and usually reflects the dominance of cortisone, though estrogen and testosterone also cause it to shrink. Winter's darkness is stressful in a very fundamental way, and like any stress it tends to suppress thyroid function. In the hypothyroid state, any estrogen which is produced tends to accumulate in the body, because of liver sluggishness.

I began to see that PMS could be controlled by certain things--extra light, supplements of sodium and magnesium, high quality protein, and correction of deficiencies of thyroid and progesterone. In working on my dissertation, I saw that tissue hypoxia (lower than optimal concentrations of oxygen in the blood) may result from estrogen excess, vitamin E deficiency, or aging. There is a close biological parallel between estrogen-dominance and the other hypoxic states, such as stress/shock, and aging.


As a portrait painter, I had been very conscious of the blue aspect that can often be seen in the skin of young women. In pale areas, the color may actually be blue, and in areas with a rich supply of blood, such as the lips, the color is lavender during times of high estrogen influence--around ovulation and puberty, for example. During these times of estrogen dominance, the blood is not only poorly oxygenated, but it has other special properties, such as an increased tendency to clot. The Shutes' work in the 1930s began with the use of vitamin E to antagonize estrogen's clot-promoting tendency, and led them to the discovery that vitamin E can be very therapeutic in heart disease. More recently, it has been found that men with heart disease have abnormally high estrogen (9), that women using oral contraceptives have higher mortality from heart attacks (10), and that estrogen tends to promote spasm of blood vessels (11). (These reactions are probably related to the physiology of menstruation, in which progesterone withdrawal causes spasms in the spiral arteries of the uterus, producing endometrial anoxia and cell death.)

In toxemia of late pregnancy, or eclampsia, the exaggerated clotting tendency caused by excess estrogen (or by inadequately opposed estrogen, i.e., progesterone deficiency), can cause convulsions and strokes. Vascular spasms could be involved here, too. The stasis caused by the vasospasm would facilitate clotting. (Vascular spasm has been observed in epilepsy, too. Epilepsy can be brought on by the premenstrual excess of estrogen, and in that situation there is no evidence that clotting is involved. Leakage of hemoglobin out of red cells can cause vasospasm, so bleeding, clotting, strokes, and seizures can interact complexly.) The brains of women who have died following eclampsia show massive clotting in the blood vessels, and their livers are characteristically injured, with clots (12).

Tom Brewer and others have shown very clearly that malnutrition, especially protein deficiency, is the cause of toxemia of late pregnancy. (In Nutrition for Women, I discussed the importance of protein in allowing the liver to eliminate estrogen.)

Various researchers have demonstrated that the plaques of MS usually occur in the area served by a single blood vessel (13, 14), and some have suggested that clotting is the cause. MS patients have been found to have an abnormal clotting time, and it has been suggested that an altered diet might be able to correct the clotting tendency.

Studies in animals have shown clearly that a protein deficiency increases the fibrinogen content of blood. (Field and Dam, 1946.) Other factors that increase blood clotting are elevated adrenalin and cortisone. Protein deficiency causes an adaptive decrease in thyroid function, which leads to a compensatory increase in adrenaline and cortisone. The combination of high estrogen with high adrenaline increases the tendency for both clots and spasms of the blood vessels (11).

In experimental poisoning of animals with carbon monoxide or cyanide, the brain lesions resembling MS include blood clots. The patchy distribution of these spots in the brain suggests that the clotting is secondary to metabolic damage in the brain. Presumably, the same would be true in ordinary MS, with clots and spasms being induced in certain areas by metabolic abnormalities in brain cells. The injured cells that are responsible for myelination of nerve fibers are steroid-forming cells. A failure to secrete their protective pregnenolone could cause a local spasm of a blood vessel. The circulatory problem would exacerbate the respiratory problem. Steroid production is dependent on NADH and NADPH, and so requires adequate energy supplies and energy metabolism. The phenomenon of blood-sludging, studied by M. Knisely at the University of Chicago in the l930s and l940s, is apparently a general result of decreased energy metabolism, and is likely to be a factor in energy-and-circulatory vicious circles.


Around 1976 I met a woman in her mid-thirties who heard about my work with progesterone in animals. She had been disabled by a brain disease that resembled MS or Devic's disease, inflammation of the optic nerves. It would sometimes cause blindness and paralysis that persisted for weeks at a time. During remissions, sometimes using a wheelchair, she would go to the medical school library to try to understand her condition. She came across Katherina Dalton's work with progesterone, and convinced a physician to give her a trial injection. Although she had trouble finding people who were willing to give her progesterone, her recovery was so complete that she was able to climb stairs and drive her car, and she came to my endocrinology class and gave a very good (and long) lecture on progesterone therapy. Although her sensory and motor functions became normal, she remained very fat, and chronically suffered from sore areas on her arms and legs that seemed to be abnormal blood vessels, possibly with phlebitis. She appeared to need thyroid hormone as well as larger amounts of progesterone, but never found a physician who would cooperate, as far as I know.

In the late 1970s I was seeing a lot of people who had puzzling health problems. In a period of two or three years, there were five people who had been diagnosed by neurologists as having multiple sclerosis. In talking to them, it seemed clear that they had multiple symptoms of hypothyroidism. They weren't severely disabled. Since they weren't fat or lethargic, their physicians hadn't thought they could be hypothyroid. When they tried taking a thyroid supplement, all of their symptoms disappeared, including those that had led to their MS diagnosis. One of the women went to her doctor to tell him that she felt perfectly healthy since taking thyroid, and he told her to stop taking it, because people who have MS need a lot of rest, and she wouldn't get enough rest if she was living in a normally active way. The assumption seemed to be that the diagnosis was more important than the person. (When I refer to a "thyroid supplement" I mean one that contains some T3. Many people experience "neurological symptoms" when they take thyroxine by itself. Experimentally, it has been found to suppress brain respiration, probably by diluting the T3 that was already present in the brain tissue.)


The rate-regulating step in steroid synthesis involves the entry of cholesterol into the mitochondria, where the heme-enzyme P-450scc then removes the side-chain of cholesterol (by introducing oxygen atoms), to produce pregnenolone. This enzyme can be poisoned by carbon monoxide or cyanide, and light can eliminate the poison (15); this could be one aspect of the winter-sickness problem.

Peripheral nerves are myelinated by essentially the same sort of cell that is called an oligodendrocyte in the brain, but outside the brain it is called a Schwann cell. It is easier to study the myelin sheath in peripheral nerves, and the electrical activity of a nerve is the most easily studied aspect of its physiology. Certain experiments seemed to indicate a "jumping" (saltatory) kind of conduction along the nerve between Schwann cells, and it was argued that the insulating function of the myelin sheath made this kind of conduction possible. This idea has become a standard item in physiology textbooks, and its familiarity leads many people to assume that the presence of myelin sheaths in the brain serves the same "insulating" function.

For a long time it has been known that heat production during nerve conduction reveals a more continuous mode of conduction, that doesn't conform to the idea of an electrical current jumping around an insulator. Even if the myelin functioned primarily to produce "saltatory conduction" in peripheral nerves, it isn't clear how this process could function in the brain. I think of the issue of "saltatory conduction at the nodes of Ranvier" as another of the fetish ideas that have served to obstruct progress in biology in the United States. A more realistic approach to nerve function can be found in Gilbert Ling's work. Ling has demonstrated in many ways that the ruling dogma of "cell membrane" function isn't coherently based on fact. He found that hormones such as progesterone regulate the energetic and structural stability of cells. Many people, unaware of his work, have felt that it was necessary to argue against the idea that there are anesthetic steroids with generalized protective functions, because of their commitment to a textbook dogma of "cell membrane" physiology.

I think the myelinating cells do have relevance to nerve conduction, but I don't think they serve primarily as electrical insulators. If the adrenal cortex were inside the heart, it would be obvious to ask whether its hormones aren't important for the heart's function. Since the oligodendrocytes are steroid-synthesizers, it seems obvious to ask whether their production of pregnenolone in response to stress or fatigue isn't relevant to the conduction processes of the nerves they surround.


A biologist friend of mine who was about 85 became very senile. His wife started giving him thyroid, progesterone, DHEA and pregnenolone, and within a few days his mental clarity had returned. He continued to be mentally active until he was 89, when his wife interfered with his access to the hormones.

In old age the brain steroids fall to about 5% of their level in youth. Pregnenolone and DHEA improve memory in old rats, and improve mood stability and mental clarity of old people. Pregnenolone's action in improving the sense of being able to cope with challenges probably reflects a quieting and coordinating of the "sequencing" apparatus of the forebrain, which is the area most sensitive to energy deprivation. This is the area that malfunctions in hyperactive and "dyslexic" children. Weakening of the sequencing and sorting processes probably explains the common old-age inability to extract important sounds from environmental noise, creating a kind of "confusion deafness." Insomnia, worry and "restless legs" at bedtime are problems for many old people, and I think they are variations of the basic energy-depletion problem.

The oligodendrocytes were reported (Hiroisi and Lee, 1936) to be the source of the senile plaques or amyloid deposits of Alzheimer's disease.(16) Hiroisi and Lee showed the cells in different stages of degeneration, ending with translucent "mucoid" spots that stained the same as amyloid, the material in the senile plaques. This type of cell also appears to form a halo or crown around degenerating nerve cells--possibly in a protective reaction to provide the nerve cell with any pregnenolone the oligodendrocytes are able to make. The oligodendrocytes, the source of the brain steroids (that people previously believed came from the adrenals and gonads, and were just stored in the brain), myelinate nerve fibers under the influence of thyroid hormone (17). Thyroid is responsible for both myelination and hormone formation. In old age, glial cells become more numerous, and nerve cells become structurally and functionally abnormal, but usually there is no problem with the formation of myelin. In MS, the problem is just with myelination, and there are no senile plaques or defects in the nerve cells themselves.

These differences suggest the possibility that Alzheimer's disease involves a specific premature loss of brain pregnen- olone production, but not of thyroid. Recent work suggests a central role for pregnenolone and progesterone in the regulation of consciousness (18), and possibly in the brain's detoxifying system. Elsewhere, I have suggested that vitamin A deficiency might cause the excessive production of the "amyloid" protein. A vitamin A deficiency severely inhibits steroid synthesis. (It is used so massively in steroid synthesis that a progesterone supplement can prevent the symptoms of vitamin A deficiency.) I suspect that vitamin A is necessary for the side-chain cleavage that converts cholesterol to pregnenolone. Iron-stimulated lipid peroxidation is known to block steroid formation, and vitamin A is very susceptible to destruction by iron and oxidation. Iron tends to accumulated in tissues with aging. Gajdusek has demonstrated that brain deterioration is associated with the retention of whatever metal happens to be abundant in the person's environment, not just with aluminum. (One type of glial cell is known for its metal-binding function, causing them to be called "metallophils."). According to Gajdusek, "calcium and other di- and trivalent elements" are "deposited as hydroxyapatites in brain cells" in brain degeneration of the Alzheimer's type.(19)

Even early forms of Alzheimer's disease begin at an age when the youth-associated steroids have begun to decline. If MS involves a deficiency of thyroid (or of T3 within the oligodendrocytes, where T3 normally can be made from thyroxine; many things, including protein deficiency, can block the conversion of T4 to T3), those cells would necessarily be deficient in their ability to produce pregenolone, but in young people the brain would still be receiving a little pregnenolone, progesterone, and DHEA from the adrenals and gonads. This relatively abundant youthful supply of hormones would keep most of the body's organs in good condition, and could keep the bodies of the major brain cells from deteriorating. But if proper functioning of the nerve fibers requires that they be fed a relatively high concentration of pregnenolone from their immediately adjacent neighbors (with the amount increasing during stress and fatigue), then their function would be impaired when they had to depend on the hormones that arrived from the blood stream.

For many years it has been recognized that the brain atrophy of "Alzheimer's disease" resembles the changes seen in the brain in many other situations: The traumatic dementia of boxers; toxic dementia; the slow-virus diseases; exposure of the brain to x-rays (20); ordinary old age; and in people with Down's syndrome who die around the age of thirty.

In menopause, certain nerve cells have lost their ability to regulate the ovaries, because of prolonged exposure to estrogen (6). The cells that fail as a result of prolonged estrogen exposure aren't the same cells that fail from prolonged exposure to the glucocorticoids (7), but they have in common the factor of excitatory injury.

Since people who experience premature menopause are known to be more likely than average to die prematurely, it is reasonable to view menopause as a model of the aging process. It is now well established that progesterone fails to be produced at the onset of menopause (the first missed period, increased loss of calcium, symptoms such as hot flashes, etc.), and that estrogen continues to be produced at monthly intervals for about four years. The essential question for aging, in the present context, is why the anesthetic steroids are no longer produced at a rate that allows them to protect tissues, including brain cells, from the excitotoxins. Using menopause as a model for aging, we can make the question more answerable by asking why progesterone stops being produced.

During stress, we are designed not to get pregnant, and the simplest aspect of this is that ACTH, besides stimulating the adrenals to produce stress-related hormones, inhibits the production of progesterone by the ovary. Other stress-induced factors, such as increased prolactin and decreased thyroid, also inhibit progesterone production. Stress eventually makes us more susceptible to stress. Menopause and other landmarks of aging simply represent upward inflections in the rate-of-aging curve. Individual variations in type of stress, hormonal response and diet, etc., probably govern the nature of the aging process in an individual.

The amphetamine-like action of estrogen, which undoubtedly contributes to the general level of stress and excitotoxic abuse of nerve cells, is probably the only "useful" facet of estrogen treatment, but a little cocaine might achieve the same effect with no more harm, possibly less. The toxicity of catecholamines has been known for over thirty years, and estrogen's stimulating effects are partly the result of its conversion to catechol-estrogens which increase the activity of brain catecholamines. Estrogen's powerful ability to nullify learning seems never to be mentioned by the people who promote its use. The importance of a good balance of brain steroids for mood, attention, memory, and reasoning is starting to be recognized, but powerful economic forces militate against its general acceptance.

Since the brain is the organ that can allow us to adapt without undergoing stress in the hormonal sense, it is very important to protect its flexibility and to keep its energy level high, so it can work in a relaxed way. It is the low energy cellular state that leads to the retention of calcium and iron, and to the production of age pigment, and other changes that constitute the vicious circle of aging. And mental activity that challenges obsession and rigidity might be the most important brain energizer. Pseudo-optimism, humor-as-therapy, has a certain value, but a deeper optimism involves a willingness to assimilate new information and to change plans accordingly.


Nutritional supplements that might help to prevent or correct these brain syndromes include: Vitamin E and coconut oil; vitamin A; magnesium, sodium; thyroid which includes T3; large amounts of animal protein, especially eggs; sulfur, such as magnesium sulfate or flowers of sulfur, but not to take continuously, because of sulfur's interference with copper absorption; pregnenolone; progesterone if needed. Bright light, weak in the blue end of the spectrum and with protection against ultraviolet, activates respiratory metabolism and quenches free radicals. Raw carrot fiber and/or laxatives if needed; charcoal occasionally for gas or bowel irritation. Coconut oil serves several purposes. Its butyric acid is known to increase T3 uptake by glial cells. It has a general pro-thyroid action, for example by diluting and displacing antithyroid unsaturated oils, its short- and medium-chain fatty acids sustain blood sugar and have antiallergic actions, and it protects mitochondria against stressinjury.

P.S.: In 1979, a woman whose husband was suffering from advanced Amyotrophic Lateral Sclerosis (ALS) asked me if I had any ideas for slowing his decline. I described my suspicion that ALS involved defective metabolism or regulation of testosterone. In some tissues, testosterone is selectively concentrated to prevent atrophy, and ALS is a disease of middle-age, when hormone regulation often becomes a special problem. In the late 1970s, there was discussion of a higher incidence of ALS in males, and especially in athletes. I told her about progesterone's general protective effects, its antagonism to testosterone, and its prevention of atrophy in various tissues. She decided to ask her doctor to try progesterone for her husband. Later, I learned that her husband had gone into a very rapid decline immediately after the injection, and died within a week; the physician had given him testosterone, since, he said, "testosterone and progesterone are both male hormones." Besides making me more aware of the problems patients have in communicating with physicians, this tended to reinforce my feeling that a hormone imbalance is involved in ALS. Although I haven't written much about testosterone's toxicity, Marian Diamond's work showed that prenatal testosterone is similar to prenatal estrogen, in causing decreased thickness of the cortex of the brain; both of those hormones oppose progesterone's brain-protecting and brain-promoting actions.


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GLOSSARY 1. Amyloid is the old term for the "starchy" appearing (including the way it stains) proteins seen in various diseases, and in the brain in Alzheimer's disease.
2. Cytochrome P450scc. The cytochromes are "pigments," in the same sense that they contain the colored "heme" group that gives hemoglobin its color. P450 means "protein that absorbs light at a wavelength of 450. The scc means "side-chain cleaving," which refers to the removal of the 6 carbon atoms that distinguish cholesterol from pregnenolone. Other Cyt P450 enzymes are important for their detoxifying oxidizing action, and some of these are involved in brain metabolism.
3. Glial means "glue-like," and glial cells are mostly spidery-shaped cells that used to be thought of as just connective, supportive cells in the brain.
4. Mitochondria (the "thread-like bodies") are the structures in cells which produce most of our metabolic energy by respiration, in response to the thyroid hormones.
5. Mucoid--refers to a mucoprotein, a protein which contains some carbohydrate. A glycoprotein; usually not intended as a precise term.
6. Myelination. Myelin is a multilayered enclosure of the axons (the long processes) of nerve cells, composed of proteins and complex lipids, including cholesterol. The layered material is a flat, thin extension of the cytoplasm of the oligodendroglial cells.
7. Oligodendrocytes are one of the kinds of glial (or neuroglial) cells, and structurally they are unusual in having sheet-like, rather than just thread-like processes; they have a sensitivity ("receptors") to stress and valium, and produce pregnenolone when activated. Under the influence of thyroid hormone, they wrap themselves in thin layers around the conductive parts of nerve cells, leaving a multilayered "myelin" coating. Their absorption of thyroid hormone is promoted by butyrate, an anti-stress substance found in butter and coconut oil.
8. Steroidogenesis is the creation of steroids, usually referring to the conversion of cholesterol to hormones.

Neurology. 1999 Sep 11;53(4):883-5.
Association of MS with thyroid disorders.
Karni A, Abramsky O.
Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel.
A controlled prospective study was conducted to determine whether thyroid disorders are present with increased frequency in patients with MS. We found that thyroid disorders were at least three times more common in women with MS than in female controls. This was accounted for mainly by the prevalence of hypothyroidism among the female MS patients. Because hypothyroidism is usually due to Hashimoto's thyroiditis, its association with MS may support the hypothesis of autoimmune pathogenesis for MS. Our findings might have therapeutic implications because interferon treatment can induce antithyroid antibodies and thyroiditis.

Hum Reprod. 2002 Oct;17(10):2715-24.
High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.
Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P.
Pediatric and Reproductive Endocrinology Branch, National Institute of Child
Health and Human Development, NIH, 10 Center Drive, Building 10, Room 9D42, MSC
1583, Bethesda, MD 20892-1583, USA.
BACKGROUND: Women with endometriosis may also have associated disorders related
to autoimmune dysregulation or pain. This study examined whether the prevalence
of autoimmune, chronic pain and fatigue and atopic disorders is higher in women
with endometriosis than in the general female population. METHODS AND RESULTS: A
cross-sectional survey was conducted in 1998 by the Endometriosis Association of
3680 USA members with surgically diagnosed endometriosis. Almost all responders
had pain (99%), and many reported infertility (41%). Compared with published
rates in the general USA female population, women with endometriosis had higher
rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus
3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001),
rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus
(0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001)
and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or
diabetes. Allergies and asthma were more common among women with endometriosis
alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with
fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001
respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001
respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue
syndrome, autoimmune diseases, allergies and asthma are all significantly more
common in women with endometriosis than in women in the general USA population.

J Neurol. 2003 Jun;250(6):672-5.
Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple sclerosis.
Niederwieser G, Buchinger W, Bonelli RM, Berghold A, Reisecker F, Költringer P,
Archelos JJ.
Department of Neurology, Barmherzige Brüder Hospital, Bergstrasse 27, 8021 Graz,
Since multiple sclerosis (MS) and autoimmune thyroiditis (AIT) are presumed to be
of autoimmune origin the correlation of these two diseases is of special
interest. The aim of this study was to determine whether there are differences in
the prevalence of thyroid disease with special emphasis on AIT compared with MS
and normal subjects and whether the presence of thyroid disease correlates with
disability, disease course, age, and disease duration. 353 consecutive patients
with clinically definite MS, without interferon-beta treatment and 308 patients
with low back pain or headache were extensively examined for the presence of
non-immune or autoimmune thyroid disease. We found a significantly higher
prevalence of AIT in male MS patients (9.4 %) than in male controls (1.9 %; p =
0.03). The prevalence of AIT in female MS patients (8.7 %) did not differ from
female controls (9.2 %). Hypothyroidism, caused by AIT in almost all cases,
showed a tendency to be more severe and more often present in patients with MS.
There was no association between relapsing-remitting and secondary progressive
disease course of MS and the prevalence of AIT. MS patients with AIT were
significantly older but did not differ in disease duration and expanded
disability status scale (EDSS). Further studies are warranted, to see if there is
a difference in sex-hormone levels between MS patients with and without AIT and
healthy controls. Longitudinal studies comparing MS patients with or without AIT
could show whether there is an influence of AIT on the disease course or

Neurologist. 2005 Sep;11(5):301-4.
Multiple sclerosis and Hashimoto thyroiditis: two cases.
Petek-Balci B, Yayla V, Ozer F.
Neurology Department, Haseki Educational and Research Center, Istanbul, Turkey.
Multiple sclerosis (MS) occurs with immune-mediated mechanisms, but its
pathogenesis is not accurately known. The coexistence of MS with other autoimmune
diseases has been reported. The hypothesis that MS coexists with other autoimmune
diseases has been supported by the reported association of MS with type I
diabetes mellitus and inflammatory disorders. Even though there have been only
rare reports of associations between Hashimoto thyroiditis and MS, this
association is important for its clinical and therapeutic aspects. Proximal
muscle weakness, myalgia, and fatigue are symptoms that are common in both MS and
hypothyroidism. When MS patients demonstrate these symptoms, thyroid function
tests should be performed. The thyroid hormone levels of MS patients being
treated with interferon-beta and Campath-1H also should be monitored. The authors
report the clinical data of 2 definite MS patients who also fulfilled criteria
for Hashimoto thyroiditis.

Eur J Neurol. 2007 Sep;14(9):1048-52.
Prevalence of autoimmune thyroid disorders in a Spanish multiple sclerosis
Munteis E, Cano JF, Flores JA, Martinez-Rodriguez JE, Miret M, Roquer J.
Neurology Service, Hospital Universitari del Mar, IMAS, Barcelona, Spain.
The aim of the study was to determine the prevalence of thyroid autoimmune
disorders in a cohort of untreated multiple sclerosis (MS) patients and compare
it with a stratified sample of an adult population. We prospectively studied 93
untreated MS patients. The control group included 401 healthy subjects selected
by stratified sampling in a non-iodine-deficient area. Antithyroid antibodies
(ATA) (antibodies against peroxidase and thyroglobulin) were considered positive
at titres > or =149 IU/ml. Antibodies were positive in 11 MS patients (11.8%; 95%
CI 5.3-18.4%). This prevalence was five times higher (P = 0.0001) when compared
with that in the control population. We found six cases with subclinical
hypothyroidism (6.45%; 95% CI 11.4-1.5) in contrast to 2.24% in the control
group. Comparing MS with positive and negative ATA, there was a non-significant,
slightly higher frequency of low Expanded Disability Status Scale (EDSS) score in
the ATA-positive group (81% vs. 73.2%). One year after start of interferon (IFN)
treatment, only one patient developed subclinical thyroid dysfunction. MS
patients have a higher prevalence of ATA compared with the general population. An
initial ATA and thyroid-stimulating hormone (TSH) determination is recommended in
all MS patients. A periodic assessment of thyroid function during IFN treatment
only seems to be justified in those cases where positive ATA or dysfunction is
present before treatment.

J Neurol Sci. 1984 Nov-Dec;66(2-3):217-21.
Multiple sclerosis co-existent with myxedema. An autopsy case report.
Nagashima T, Yamada K, Uono M, Nagashima K.
A 64-year-old woman developed impaired consciousness and vision, sensorimotor
paresis, hypothermia, bradycardia, and edema. Symptoms fluctuated with seasonal
exacerbations in winter and terminated in coma with respiratory insufficiency at
age 69. High CSF protein content and low serum T4 and TSH levels were noted.
Treatment with prednisolone and thyroxin considerably improved her consciousness
and edema. The patient suddenly expired of pulmonary embolism. Postmortem
examination revealed a marked atrophy of pituitary and thyroid glands, while
multiple demyelinating plaques were disclosed in the optic tract and cervical
cord. A review of the literature indicates that this is the first report of the
co-existence of two such disorders.

Ann Intern Med. 1981 Oct;95(4):431-5.
Thyroid disease in progressive systemic sclerosis: increased frequency of
glandular fibrosis and hypothyroidism.
Gordon MB, Klein I, Dekker A, Rodnan GP, Medsger TA Jr.
A series of patients with fatal progressive systemic sclerosis was reviewed with
regard to pathologic, clinical, and serologic evidence of thyroid disease.
Histologic evidence of severe fibrosis of the thyroid gland was found
significantly more frequently in 56 progressive systemic sclerosis cases (14%)
compared to an age and sex matched control autopsy series (2%) from the same
institution. Based on determination of serum free thyroxine, free
triiodothyroxine (T3), thyroid stimulating hormone, and reverse T3, 27 patients
were classified as euthyroid (11), euthyroid sick (9), and hypothyroid (7).
Patients with hypothyroidism more frequently had subcutaneous calcinosis.
Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and multiple
telangiectasias (the CREST syndrome variant of progressive systemic sclerosis);
all thyroid glands from the hypothyroid patients had fibrosis, but lymphocytic
infiltration was an infrequent finding. Six hypothyroid patients had high titers
of serum antithyroid antibodies, suggesting autoimmune thyroid disease. Thyroid
gland fibrosis and hypothyroidism, possibly of autoimmune pathogenesis, are thus
frequent and often unsuspected findings in progressive systemic sclerosis.

Zh Nevrol Psikhiatr Im S S Korsakova. 2009;109(1):10-5.
[Pathology of the thyroid gland and multiple sclerosis: a possible influence on
efficacy and tolerability of treatment]
[Article in Russian]
Bagir' LV, Batysheva TT, Bo ko AN, Gusev EI.
This paper reviews the literature and own data on prevalence of thyroid diseases
in patients with multiple sclerosis (MS). It has been shown that 20-25% of
untreated MS patients have autoimmune thyroiditis (AIT) and/or subclinical
hypothyroidism. No correlation was found between age, gender, disease course, MS
duration, disability status and prevalence of thyroid disorders.
Disease-modifying therapy (DMT) of MS can induce or worsen the thyroid pathology.
Female gender, pre-existing AIT, family history of thyroid disorders are
considered as risk factors of thyroid dysfunction and autoimmunity during
interferon- (IFN- ) therapy. Most cases of autoimmune hyperthyroidism require
discontinuation of IFN- therapy. The present study of thyroid status includes 43
MS patients, 42% of them with thyroid disorders such as thyroid nodes and
subclinical hypothyroidism. Thyroid dysfunction is revealed mostly in patients
treated with IFN- -1b; thyroid notes - in MS patients receiving copaxone. These
facts emphasize the significance of systematic thyroid assessment in patients
with MS especially during the long-term DMT.

J Neurol Sci. 2001 Dec 15;193(1):17-22.
Thyroid function and anti-thyroid antibodies in MS patients screened for interferon treatment. A multicenter study.
Durelli L, Oggero A, Verdun E, Isoardo GL, Barbero P, Bergamasco B, Brossa PC, Ghigo E, Maccario M, Faggiano F; Betaferon Safety Trial (BEST) Study Group. Clinica Neurologica, Dipartimento di Neuroscienze, Universita' di Torino, Via
Cherasco 15, Ospedale S. Giovanni Battista, 10121, Turin, Italy.
Interferon beta (IFNB) treatment for multiple sclerosis (MS) has been associated with thyroid disorders (TD), in particular in patients with subclinical TD or anti-thyroid (AT) autoantibodies (autoAb) before starting treatment. TD and AT autoAb frequency was reported increased in MS. To determine whether MS patients have subclinical thyroid function abnormalities or anti-thyroid autoimmunity predisposing to develop TD, we performed a prospective multicenter screening of thyroid function and autoimmunity in 152 relapsing-remitting (RR) MS patients selected to receive IFNB treatment and in 437 healthy normothyroidal controls. Thyroid-related hormones and anti-thyroid microsomal antigen (anti-TMA) autoAb were tested with sensitive immunoradiometric or chromatographic assays. Cases were stratified for different progressively decreasing or increasing cutoff values of thyroid-stimulating hormone (TSH) (0.3, 0.2, 0.1, 3 and 5 mIU/l), and odds ratios (OR) with 95% confidence intervals (CI) calculated using logistic regression adjusted for gender, age, and anti-TMA autoAb positivity. The frequency of cases below or above the TSH cutoff values was not significantly different in MS patients and controls, and the risk to have an abnormal TSH level was not significantly increased in MS patients (OR ranging 0.37-0.84; CI, 0.05-3.01), even if anti-TMA autoAb positive (OR ranging 0.35-0.85; CI, 0.04-3.00). Frequencies of subclinical hypothyroidism and of anti-TMA autoAb positivity were, however, trending higher in MS men (ranging 5-7%) than in controls (3%). MS patients do not have an increased risk of subtle thyroid function abnormalities, subclinical TD, or anti-TMA autoAb positivity that may predispose to develop thyroid dysfunction during IFNB treatment. The positive trend for subclinical hypothyroidism and anti-TMA autoAb positivity, however, advises a longitudinal study of thyroid function and autoimmunity during IFNB treatment to see whether patients with baseline subclinical thyroid dysfunction develop clinically significant alteration during treatment.

Endocr Res. 1999 May;25(2):207-14.
Prolactin secretion is increased in patients with multiple sclerosis.
Azar ST, Yamout B.
Department of Internal Medicine, American University Hospital-Medical Center, New York, NY 10022, USA.
Before the onset and during experimental allergic encephalomyelitis (EAE), the animal counterpart of multiple sclerosis (MS), prolactin levels were found to be elevated and bromocriptine was found to attenuate the attacks. This study was designed to determine whether patients with MS show evidence of hyperprolactinemia. Twelve patients with MS and twelve healthy controls were studied at baseline and with TRH stimulation, a provocative test for prolactin secretion. Compared to matched controls, patients with MS had slightly but significantly higher prolactin levels at baseline (10.2+/-1.6 vs 6.4 4+/-0.57 ng/ml, P=0.042), however, values were within the normal range. The prolactin levels post TRH were significantly higher in patients with MS: peak prolactin level was higher in patients than controls (57.08+/-6.144 vs 32.94+/-4.92 ng/ml, P=0.006). The area under the curve of prolactin was also higher in patients than in controls (3421.87+/-394.53 vs 2317.62+/-257.22 ng/ml, P=0.030). These findings are compatible with data from studies of experimental animals with MS and suggest that prolactin may play a role in the immunology of MS.


Sep 10, 2014
Not Uganda
A good review that agrees with some of Ray's points:

"Some recent efforts stand out as important milestones on the road to discovering the root cause of multiple sclerosis:
1. The observation of constricted blood vessels for the return venous blood from the brain and how this causes small lesions that allow blood and pathogenic material to leak into the brain through the compromised blood-brain barrier (Zamboni et al., 2003, 2005, 2006, 2007, 2008, 2009a,b,c, 2010, Francesci 2009, Zamboni 2009, @khan et al., 2010, Lee et al., 2009).
2. The discovery that multiple sclerosis is connected to accumulation of iron in the brain, creating large internal oxidative stresses in the brain (Hooper et al., 1998, 2000, Szabo et al., 2007, Szabo 2003, Gilun-Sherki et al., 2002).
3. The finding that multiple sclerosis not only affects white matter brain, but that it causes grey-matter necrosis and that this is an initially inflammatory process, proportional to the degree of micro-vascularisation of the grey-matter tissue."

"Free radicals promote the inflammation and retard the myelin sheath regeneration process. Several factors affect free radicals and the oxidants that are their precursors. Vitamin A, C, E, K, and D are all oxidant scavengers. Both NO and Fe2+/Fe3+ are involved in generation of peroxides, superoxide, peroxynitrite and free radicals (the Fenton reactions), all highly toxic to any living cells. In multiple sclerosis, oxygen deprivation is not very pronounced, but rather local and occurs through localized blood vessel lesions, and the damage associated with the iron accumulation. Free radicals are known to create blood vessel ulcers (Simka and Rybak 2008), and most probably establish a reinforcing link, keeping the pathway through the blood-brain barrier permanently or intermittently open, suggesting an explanation of the remitting/permanent types of the illness. Blood deposited in the brain generates NO* upon decomposition and leads to the deposits of iron in the brain. This is under reducing conditions transformed to free iron ions (Fe2+). These auto-catalyse degeneration of vitamin C, catecholamines and Vitamin E and may overcome the protection system against free radicals locally. When this happens, the metabolites will contain superoxides, further aggravating damages (Coyle and Puttefarcken 1993). The free radicals and Fe3+ in the brain interferes with the regenerative function of the oligodendrocytes. It is also suspected that they may have a role in changing harmless antibodies to a kind that initiate Th1 cell attack on the myelin sheaths of the brain."

"Multiple sclerosis has no simple cause-effect relationships that traditional methods will find. Multiple sclerosis is a whole system disease and must be seen as a system for any progress to be made. We can see that there are three important reinforcing feedback loops in the multiple sclerosis system that must be terminated in the treatment systemic process:
1. A feedback loop between minor vessel leaks and free radicals.
2. A feedback loop between immune system attacks, further production of iron and oxidants, triggering autoimmune response
3. A feedback loop between wrongly triggered antibodies and myelin damage from leukocyte attacks that produce more debris that further triggers attacks."

Members that might be interested: @burtlancast @PakPik @schultz
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Feb 24, 2016
What a beautiful paper! I love it. I only skimmed through most of its pages and got to read some paragraphs -it's quite lengthy-, but I will surely read every detail of it :) That's how papers aimed at understanding how disorders start and progress, with the goal of developing treatment strategies and management considerations, should be made. Not only that, but at the end of the paper they seemed to derive the conclusions that were begging to be made. Now I understand even more why my notebooks filled with similar diagrams of interactions and systems have been so fundamental to me. Awesome @Amazoniac


Mar 30, 2016
I've mentioned it before but that Swannk's protocol of copious amounts of pufa oils amongst other things healing his many MS
patients still lingers. Its brought up quite a few times here in this forum but no real answer to close that case.


Feb 24, 2016
I've mentioned it before but that Swannk's protocol of copious amounts of pufa oils amongst other things healing his many MS
patients still lingers. Its brought up quite a few times here in this forum but no real answer to close that case.
I'd like to point out that the original Swank protocol was designed as a ultra-fat diet -very low Sat. Fat, PUFA, MUFA-. That was the diet that yielded the great initial successes. The PUFA you are referring to was a later addition that Swank considered in order to help improve skin appearance/complexion of patients (I wonder if the increased metabolism from a very low fat diet/PUFA depletion may have led to some kind of nutrient/calorie deficiency if they didn't adjust to the new increased nutritional needs). This quote by Swank leads me to think that indeed these people weren't compensating the increased metabolic demands, they may have started feeling starved with signs of nutrient deficiencies since he also added the PUFAs a method to increase "reserve of calories" (just speculating, I don't know the specifics to how the original Swank diet was managed in term of nutrient and caloric intake):

"JM: What do you think about adding vegetable oils to your diet?

Swank: Well, I think it’s worthwhile. We have looked at this over a number of years, and have found that the skin and the hair seem better in women. There is also some reserve of calories for energy. Best of all, however, is the fact that the patients can follow the diet more easily if they can have some oil. It makes it more palatable for them."
Source: Dr. McDougall's Health & Medical Center » McDougall Interview with Dr. Roy Swank, MD

The Gerson diet, which is ultra-low fat, has also been promoted as a MS therapeutic diet (I don't have statistics on it, though).
So, all of the above lead me to conclude that PUFA doesn't seem to have much to do with their successful MS treatment. Moreover, I wonder why the high amounts of PUFA didn't undermine their success.


Nov 16, 2015
I'd like to point out that the original Swank protocol was designed as a ultra-fat diet -very low Sat. Fat, PUFA, MUFA-. That was the diet that yielded the great initial successes. The PUFA you are referring to was a later addition that Swank considered in order to help improve skin appearance/complexion of patients (I wonder if the increased metabolism from a very low fat diet/PUFA depletion may have led to some kind of nutrient/calorie deficiency if they didn't adjust to the new increased nutritional needs). This quote by Swank leads me to think that indeed these people weren't compensating the increased metabolic demands, they may have started feeling starved with signs of nutrient deficiencies since he also added the PUFAs a method to increase "reserve of calories" (just speculating, I don't know the specifics to how the original Swank diet was managed in term of nutrient and caloric intake):

"JM: What do you think about adding vegetable oils to your diet?

Swank: Well, I think it’s worthwhile. We have looked at this over a number of years, and have found that the skin and the hair seem better in women. There is also some reserve of calories for energy. Best of all, however, is the fact that the patients can follow the diet more easily if they can have some oil. It makes it more palatable for them."
Source: Dr. McDougall's Health & Medical Center » McDougall Interview with Dr. Roy Swank, MD

The Gerson diet, which is ultra-low fat, has also been promoted as a MS therapeutic diet (I don't have statistics on it, though).
So, all of the above lead me to conclude that PUFA doesn't seem to have much to do with their successful MS treatment. Moreover, I wonder why the high amounts of PUFA didn't undermine their success.
I too wonder this. Denise Minger speculates about it and says she will get to the mechanisms in another post, but that post hasn't come. I know @tyw also briefly discussed it in one post, but didn't elaborate. Terry wahls seems to favor saturated fat for her MS protocol, which makes swank more confusing
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