Among the number of causes that have been proposed in autism seemingly all have two common denominators, G-proteins and thyroid hormones. G-protein-coupled receptors and G-protein-mediated cell responses are of key importance in the processes of neurotransmission and intercellular signaling in the brain. Thyroid-stimulating hormone, thyrotrophin (TSH), stimulates the uptake of iodine into the thyroid, the conversion of diiodotyrosine to thyroxine (T4), and the secretion of thyroid hormones into the bloodstream. If not enough iodine is available in the diet, then not enough T4 will be made to shut off the release of TSH (high test numbers). Prolonged stimulation of the thyroid by TSH results in an abnormal enlargement of the gland, known as goiter. In normal circumstances, G-proteins are modulated by thyroid hormones. In the absence of TSH, the thyroid’s G-protein is totally inactive. The binding of TSH to its receptor activates G-protein, which stimulates the effector systems and then quickly becomes inactive. The end result of this signal-transduction process in the thyroid gland is stimulation of thyroid hormone synthesis and thyroid growth (Utiger, 1995). G-proteins direct information transfer from outside the cell to inside the cell. HIV infection, electromagnetic signals, and growth factors all use G-proteins to transmit their signals. G-proteins are found in cells throughout the body.
Here is a part of Dr. Mary Megson statement to US Congress on April 6, 2000 about vitamin A deficiency in Autism (edited slightly for clarity):
In the vast majority of these cases, one parent reports night blindness or other rare disorders that are caused by a genetic defect in a G-protein, where they join cell membrane receptors that are activated by retinoids, neurotransmitters, hormones, Secretin, and other protein messengers. G-proteins are cellular proteins that upgrade or downgrade signals in sensory organs that regulate touch, taste, smell, hearing, and vision. They are found all over the body, in high concentration in the gut and the brain. They turn on or off multiple metabolic pathways including those for glucose, lipid, protein metabolism, and cell growth and survival. Close to the age of “autistic regression,” we add the pertussis toxin that completely disrupts G-Alpha signals. The opposite G-proteins are now “on”, without inhibition, leading to:
1. Glycogen breakdown or gluconeogenesis. Many of these children have elevated blood sugars. There is a sixty-eight percent incidence of diabetes in parents and grandparents of these children.
2. Lipid breakdown that increases blood fats that leads to hyperlipidemia. One-third of families have either a parent or grandparent who died from myocardial infarction at less than 55 years of age and was diagnosed with hyperlipidemia.
3. Cell-growth differentiation and survival that leads to uncontrolled cell growth. There are cases of malignancies associated with ras-oncogene in 60 families of these autistic children. The measles antibodies cross react with intermediate filaments that are the glue that holds cells together in the gut wall. The loss of cell-to-cell connection interrupts apoptosis (the ability of neighboring cells to kill off abnormal cells). The MMR vaccine at 15 months precedes the DPT at 18 months, which turns on uncontrolled cell-growth differentiation and survival.
Most families report cancer in the parents or grandparents, the most common being colon cancer. The genetic defect, found in 30-50% of adult cancers, is a cancer gene (ras-oncogene). It is the same defect as that for congenital stationary night blindness. (Of significance is a study from England that found a pregnant mother’s allergies can be passed to her child, but that restricting her allergic reactions during pregnancy can help prevent this transfer—Dr. Jill Warner, Southhampton General Hospital. Dr. Rosemary Waring reports that the group with this hereditary background are the most likely to respond favorably to the gluten/casein free diet—WSL.)
G-protein defects cause severe loss of rod function in most autistic children. They lose night vision and light-to-dark shading on objects in the daylight. They sink into a “magic eye puzzle”, seeing only color and shape in all of their visual field, except for a “box” in the middle, the only place they get the impression of the three dimensional nature of objects. Only when they look at television or a computer do they predictably hear the right language for what they see. They try to make sense of the world around them by lining up toys, sorting by color. They have to “see” objects by adding “boxes” together, thus “thinking in pictures”. Their avoidance of eye contact is an attempt to get light to land off center in the retina where they have some rod function. Due to G-protein defects, mother’s touch feels like sandpaper on their skin. Common sounds become like nails scraped on a blackboard. We think they cannot abstract, but we sink these children into an abstract painting at 18 months of age, and they are left to figure out if the language they are hearing is connected to what they are looking at, at the time.
The defect for congenital, stationary, night blindness on the short arm of the X chromosome affects cell-membrane, calcium channels that, if not functioning, block (the action of—WSL) NMDA/glutamate receptors (preventing calcium from entering the neurons to activate a signal—WSL) in the hippocampus where pathways connect the left and right brain with the frontal lobe. Margaret Bauman has described a lack of cell growth and differentiation in the hippocampus seen on autopsy in autistic children. The frontal lobe is the seat of attention, inhibition of impulse, social judgment, and all executive function.
When stimulated, these NMDA receptors, through G-proteins, stimulate nuclear (of the nucleus) Vitamin A receptors discovered by Ron Evans, et al. Dec 1998. When blocked, in the animal model, mice are unable to learn and remember changes in their environment. They act as if they have significant visual perceptual problems and have spatial learning deficits.
Of concern is that the Hepatitis B virus protein sequence was originally isolated in the gene for a similar retinoid receptor (RAR beta) that is the critical receptor important for brain plasticity and retinoid signaling in the hippocampus.
I am using natural, lipid-soluble concentrated cis form of vitamin A in cod-liver oil (CLO now seems to be palmitate fortified – look for vitamin A from fish-liver oil - Willis) to bypass blocked G-protein pathways and turn on these central retinoid receptors. In a few days, most of these children regain eye contact, and some say their “box” of clear vision grows. After two months on Vitamin A treatment some of these children, when given a single dose of Bethanechol™ to stimulate pathways in the parasympathetic system in the gut, begin to focus, laugh, concentrate, show a sense of humor, and talk after 30 minutes as if reconnected.
This improves cognition, but they are still physically ill. When these children get the MMR vaccine, their vitamin A stores are depleted; they cannot compensate for blocked pathways. Lack of vitamin A, that has been called “the anti-infective agent,” leaves them immuno-suppressed. They lack cell-mediated immunity. T-cell activation, important for long-term immune memory, requires 14-hydroxy retro-retinol. Using cod-liver oil, the only natural source of this natural substance, the children get well.
The parasympathetic nervous system is blocked by the second G-protein defect. These children are unable to relax, focus, and digest their food. Instead, they are in sympathetic overdrive with a constant outpouring of adrenaline and stress hormones. They are anxious, pace, have dilated pupils, high-blood pressure, and a high, heart rate. These and other symptoms of attention deficit hyperactivity disorder are part of this constant “fright or flight” response. These symptoms improve on vitamin A and Bethanechol™. (Magnesium in 500 mg or more, and similar amounts of potassium tend to balance these pathways, and should be used with the CLO. Additionally, bicarbonate shuts off the adrenal response—WSL).
I live in a small, middle-class neighborhood with twenty-three houses. I recently counted thirty children who live in this community who are on medication for ADHD. One week ago, my oldest son, who is gifted but dyslexic, had twelve neighborhood friends over for dinner. As I looked around the table, all of these children, but one, had dilated pupils. After two-and-one-half months of taking vitamin A and D in cod-liver oil, my son announced, “I can read now. The letters don’t jump around on the page anymore.” He is able to focus and his handwriting has improved dramatically. In his high school, for college-bound-dyslexic students, 68 of 70 teenagers report seeing headlights with starbursts, a symptom of congenital stationary night blindness!
Dr. Wm. D. Padula, OD, F A A O, Padula Institute of
Vision Rehabilitation,
There’s a nutritionist in
Dr. Megson said, “These children are unable to relax, focus, and digest their food. Instead, they are in Sympathetic overdrive with a constant outpouring of adrenaline and stress hormones.” It is vital that one eat according to one’s metabolic function. If Sympathetic, then one must eat according to that type. Further, to shift to the more balanced state (moving back to a balance with Parasympathetic), it has been shown in many studies that magnesium suppresses Sympathetic function, while potassium stimulates Parasympathetic activity. Furthermore, a largely vegetarian diet tends to be very alkalinizing, and the neurophysiologic research documents that in an alkaline environment Sympathetic activity is reduced and Parasympathetic activity increased. So, if Sympathic, stressed-out kids will increase vegetable intake (or take “green drinks”, or P---------e™, a vegetable concentrate by M---------h™) and supplement with zinc picolinate, magnesium, potassium, vitamins A and D (cod-liver oil), vitamin B6, and lecithin, or any of a number of acetylcholine builders listed herein, they can achieve a more balanced state without B---------ol™.
Dr. Megson also suggests letting autistics have salt. Dutch researchers have just found that high levels of blood calcium is linked to a faster decline in cognitive ability. If there is a G-protein defect, three of the channels that remove calcium from the cells are blocked. The only other major means of removing calcium is with salt. Salt will also support the overworked adrenals. Without enough salt, there is a danger that an autistic will calcify his or her brain cells. I suggest sea salt rather than the processed table salts available. Additionally, I suggest drinking more water, taking a bit of salt after each glass.
While much has been said about congenital, night blindness, there are three nutrient deficiencies that produce night blindness: Dark adaptation has been used as a tool for identifying patients with subclinical vitamin A deficiency. With this functional test, it was shown that tissue vitamin A deficiency occurs over a wide range of serum vitamin A concentrations. However, serum vitamin A concentrations >1.4 micromol/L predict normal dark adaptation 95% of the time. Other causes of abnormal dark adaptation include zinc and protein deficiencies.
Aside from its well-known role in facilitating vision,
vitamin A is now recognized as an essential hormone for maintaining the
structural and functional integrity of epithelial membranes, such as the
cornea. It also has a role in inducing epithelial-cell differentiation in
mucus-secreting cells. Besides night blindness, severe deficiency of this
vitamin can cause keratinization of the corneal layer leading to permanent
blindness (xerophthalmia). Other organ systems that would be susceptible to
vitamin A deficiency include the respiratory (impaired breathing),
gastrointestinal (indigestion and diarrhea) and genitourinary systems
(calculi formation, impaired spermatogenesis and abortion). Deficiencies of
this vitamin also result in increased susceptibility to carcinogenesis of
epithelial tissues and to damage by the measles virus. I suspect
It’s significant to note that Secretin receptors, opioid receptors, oxytocin receptors, dopamine receptors, thyrotropin-releasing-hormone (TRH) receptors, thyroid-stimulating-hormone (TSH) receptors, stress inducers, etc., are all coupled to G-proteins. G-proteins function essentially as on-off switches for cellular signaling. They consist of three, non-identical, protein subunits (alpha, beta, and gamma) that are non-covalently associated. In the resting state, the nucleotide guanosine diphosphate (GDP) is tightly bound to the alpha subunit. This is the “off” position of the G-protein switch. When the binding of a hormone activates the membrane receptor—it interacts with the G-protein, causing GDP to dissociate from the alpha subunit. GDP is rapidly replaced by guanosine triphosphate (GTP), which activates the G-protein. This in turn, leads to its dissociation into alpha-subunit and beta-gamma-subunit complexes, either or both of which can activate effectors. The switch is now “on”. Within a few seconds the alpha subunit, which is a guanosine triphosphatase (GTPase), hydrolyzes GTP to GDP. This inactivates the alpha subunit, allows it to reassociate with the beta-gamma subunit, and resets the switch to the “off” position. Many different G-proteins mediate diverse physiologic effects by this mechanism.