OK, sometimes I “go places” via a chain of “What does THAT really mean?” and end up at something I already knew, but where I had no theoretical basis for it.
(This particular chain started from a general investigation of trans fat metabolism. Something I need to get back to after this posting).
One of the things I knew was that eggs, butter, and beef are all “good for you”. I was raised with this knowing. The Amish eat eggs, butter, heck even lard, by the ton. My Granddad lived to “90 something” and was active to the end on just such a diet. He lived on a farm in Iowa and had an Amish wife. (She lived longer than he did, I think). The Amish often have recipes that are about 1/2 lard and eggs, the rest similarly “forbidden foods” by the dictates of the modern world. “The English” in Amish-speak.
So I grew up with a typical breakfast being: Bacon (4 or more slices, thick and cooked as in England with a greasy finish not a crispy finish – that is, the fat left in), eggs (often fried in Bacon Grease in a fashion called “laced eggs”), toast soaked in butter (real butter, not that plastic crap called “margarine”. I’m with the French on that one, I’d rather die early and have butter than life long eating margarine, though it looks like, in fact, if you eat butter you life long…), and hash browned potatoes soaked in lard in the cooking. Dinner would often be things like fried chicken, mashed potatoes smothered in either butter or gravy (made with pan drippings – that is, a load of fat), and corn bread loaded with, yes, butter. My favorite dessert is either Flan / Custard or Custard Pie (that we always had in the restaurant and I often ate 2 slices a day. Basically it’s eggs and milk (with full fat level) on a pastry crust. My dad was fond of a local milk sold as “Guernsey” as it was advertised for its high butterfat level ( IIRC, about 7% though these folks say 5% http://guernseymilk.com/ )
You’d think I’d be dead by now. Yet I’m not. (Several of my friends have not fared so well…)
OK, is there a REASON for this? Is there some other thing going on here (other than the “farm country” life style in general) that might explain things?
Some Metabolic Chemistry
You need Vitamin A. Everyone knows that. What isn’t so well know is that it comes in many forms. There are a lot of things that you can turn into Vitamin A products that your body needs, but not all of them have the same effects, nor are they equally well metabolized at different stages of life.
We’re going to see several things with names of the form “Retin”-xxx so watch the endings. They matter. First up is Retinoic Acid. (Lots of things in food and life are acids, even things like lactic acid that makes yogurt yummy and sauerkraut tart, so it’s not a big deal to see “acid” in biochemistry). It gets made from “retinol” that is a common form of Vitamin A.
Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A required for growth and development. Retinoic acid is required in chordate animals which includes all higher animals from fishes to humans. During early embryonic development, retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.
The key role of retinoic acid in embryonic development mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin used for treatment of cancer and acne. Oral megadoses of pre-formed vitamin A (retinyl palmitate), and retinoic acid itself, also have teratogenic potential by this same mechanism.
“Teratogenic” means it screws up the development of a fetus. So a load of retinoic acid can help mitigate the damage from drugs like Acutane. But don’t take ‘megadoses’ of it. OK, I’m “good with that”.
Retinoic acid acts by binding to the retinoic acid receptor (RAR) which is bound to DNA as a heterodimer with the retinoid X receptor (RXR) in regions called retinoic acid response elements (RAREs). Binding of the retinoic acid ligand to RAR alters the conformation of the RAR which affects the binding of other proteins that either induce or repress transcription of a nearby gene (including Hox genes and several other target genes). Retinoic acid receptors mediate transcription of different sets of genes controlling differentiation of a variety of cell types, thus the target genes regulated depend upon the target cells. In some cells, one of the target genes is the gene for the retinoic acid receptor itself (RAR-beta in mammals), which amplifies the response. Control of retinoic acid levels is maintained by a suite of proteins that control synthesis and degradation of retinoic acid.
“Hox genes” are the genes that control other genes in things like development. They make sure all your parts end up forming where they are supposed to be. This matters. Rather a lot. It also gets into the act on other cellular differentiation and controlling the expression of other genes. This, too, matters a lot. This stuff is down in the basic most important layer of control chemistry in your cells.
That means that if you don’t have enough of it, all sorts of things may go very wrong.
Retinoic acid can be produced in the body by two sequential oxidation steps which convert retinol to retinaldehyde to retinoic acid, but once produced it cannot be reduced again to retinol. The enzymes that generate retinoic acid for control of gene expression include retinol dehydrogenases (i.e. Rdh10) that metabolize retinol to retinaldehyde, and retinaldehyde dehydrogenases (Raldh1, Raldh2, and Raldh3) that metabolize retinaldehyde to retinoic acid. Enzymes that metabolize excess retinol to prevent toxicity include alcohol dehydrogenase and cytochrome P450.
OK, so we need “retinol” and / or “retinaldehyde” to get this stuff made.
Interesting that alcohol dehydrogenase is used to limit the upper bound. Those of us with high levels of that enzyme; redheads in particular, but white males in general; may need to have some extra Vit-A in our diets to deal with a tendency to deplete. Yes, that is speculative. It may also be that using up that alcohol dehydrogenase with a glass of wine or two daily could be part of the life extending properties of those beverages. Again, speculative, and as life processes often have feedback loops, you would need to test this first to be sure. These folks have a great list of the health benefits of various types of Vit-A, but also reference a study that found alcohol levels lowered Vit-A levels (though the ‘dose’ was not well described):
The relationships between alcohol consumption and carotenoid metabolism are not well understood. There is some evidence that regular alcohol consumption inhibits the conversion of beta-carotene to retinol. Increases in lung cancer risk associated with high-dose beta-carotene supplementation in two randomized controlled trials were enhanced in those with higher alcohol intakes
So it may be that “a little is good, a lot of alcohol is bad” via this mechanism.
FWIW, the same article has some interesting observations on Macular Degeneration and Cataracts:
Age-Related Macular Degeneration (AMD)
In Western countries, degeneration of the macula, the center of the eye’s retina, is the leading cause of blindness in older adults. Unlike cataracts, in which the diseased lens can be replaced, there is no cure for age-related degeneration (AMD). Therefore, efforts are aimed at disease prevention or delaying the progression of AMD.
Dietary Lutein and Zeaxanthin
The only carotenoids found in the retina are lutein and zeaxanthin. Lutein and zeaxanthin are present in high concentrations in the macula, where they are efficient absorbers of blue light. By preventing a substantial amount of the blue light entering the eye from reaching the underlying structures involved in vision, lutein and zeaxanthin may protect against light-induced oxidative damage, which is thought to play a role in the pathology of age-related macular degeneration. It is also possible, though not proven, that lutein and zeaxanthin act directly to neutralize oxidants formed in the retina. Epidemiological studies provide some evidence that higher intakes of lutein and zeaxanthin are associated with lower risk of age-related macular degeneration (AMD)
A randomized controlled trial in patients with atrophic AMD found that supplementation with 10 mg/day of lutein slightly improved visual acuity after one year compared to a placebo.
The first randomized controlled trial (AREDS1) designed to examine the effect of a carotenoid supplement on AMD used beta-carotene in combination with vitamin C, vitamin E, and zinc because lutein and zeaxanthin were not commercially available as supplements at the time the trial began. Although the combination of antioxidants and zinc lowered the risk of developing advanced macular degeneration in individuals with signs of moderate to severe macular degeneration in at least one eye, it is unlikely that the benefit was related to beta-carotene since it is not present in the retina.
Which is then followed by various other combination studies that purported to not find a benefit. So some stuff “works” and some doesn’t. OK.
Dietary Lutein and Zeaxanthin
The observation that lutein and zeaxanthin are the only carotenoids in the human lens has stimulated interest in the potential for increased intakes of lutein and zeaxanthin to prevent or slow the progression of cataracts. Four large prospective studies found that men and women with the highest intakes of foods rich in lutein and zeaxanthin, particularly spinach, kale, and broccoli, were 18-50% less likely to require cataract extraction or develop cataracts. Additional research is required to determine whether these findings are related specifically to lutein and zeaxanthin intake or to other factors associated with diets high in carotenoid-rich foods.
Evidence from epidemiological studies that cataracts were less prevalent in people with high dietary intakes and blood levels of carotenoids led to the inclusion of beta-carotene supplements in several large randomized controlled trials of antioxidants. The results of those trials have been somewhat conflicting. Beta-carotene supplementation (20 mg/day) for more than six years did not affect the prevalence of cataracts or the frequency of cataract surgery in male smokers living in Finland. In contrast, a 12-year study of male physicians in the U.S. found that beta-carotene supplementation (50 mg every other day) decreased the risk of cataracts in smokers but not in nonsmokers. Note that use of beta-carotene supplements have been shown to increase the risk of lung cancer in smokers (see above). Three randomized controlled trials examined the effect of an antioxidant combination that included beta-carotene, vitamin C, and vitamin E on the progression of cataracts. Two trials found no benefit after supplementation for five years or more than six years, but one trial found a small decrease in the progression of cataracts after three years of supplementation. Overall, the results of randomized controlled trials suggest that the benefit of beta-carotene supplementation in slowing the progression of age-related cataracts does not outweigh the potential risks.
Ultraviolet light and oxidants can damage proteins in the eye’s lens, causing structural changes that result in the formation of opacities known as cataracts. As people age, cumulative damage to lens proteins often results in cataracts that are large enough to interfere with vision
OK, to me it’s pretty clear, though the researchers have the usual blinders on. Eat natural sources of Vit-A and you get something good that helps prevent AMD and Cataracts. Whatever it is gets removed in the process of making a synthetic extract that they used in the testing. Basically, they over simplified the test, then found “nothing happened” then concluded “nothing there” rather than “we screwed the pooch on what to test”.
So eat your cruciferous vegetables and carrots…
And avoid “plastic fats”:
In a controlled feeding study, consumption of 18 g/day of the fat substitute Olestra™ (sucrose polyester) resulted in a 27% decrease in serum carotenoid concentrations after three weeks. Studies in people before and after the introduction of Olestra-containing snacks to the marketplace found that total serum carotenoid concentrations decreased by 15% in those who reported consuming at least 2 g/day of Olestra. One study in adults found that those who consumed more than 4.4 g or Olestra weekly experienced a 9.7% decline in total serum carotenoids compared to those not consuming Olestra.
As it just sucks you dry of your carotenoids…
Back to the original wiki article:
Retinoic acid is responsible for most of the activity of vitamin A, save visual pigment effects which require retinal (retinaldehyde), and cell metabolism effects that may require retinol itself. Also, some biochemical functions necessary for fertility in vitamin A deficient male and female mammals originally appeared to require retinol for rescue, but this is due to a requirement for local conversion of retinol to retinoic acid, as administered retinoic acid does not reach some critical tissues unless given in high amounts. Thus, if animals are fed only retinoic acid but no vitamin A (retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A (including no xerophthalmia– dryness of the cornea). They do suffer retina degeneration and blindness, due to retinal (retinaldehyde) deficiency. They also suffer defects in reproducton: vitamin A-deprived but retinoic acid-supplemented male rats exhibit hypogonadism and infertility due to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due to fetal resorption caused by a lack of local retinoic acid synthesis in the embryo.
OK, a lot going on there. Basically, retinoic acid is needed for most of the “good stuff” that Vit-A does, but for a couple of key things, you simply MUST have the other forms of Vit-A. Retinal for your eyes and vision. And retinol directly for fertility.
We’ll come back to those two (retinol and retinal) in a bit. But first a digression into fat burning.
Burn Fat via Vit-A
But not just any Vit-A.
All-Trans Retinoic Acid Increases Oxidative Metabolism in Mature Adipocytes
J. Mercader; L. Madsen; F. Felipe; A. Palou; K. Kristiansen; L. Bonet
aLaboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca and CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, bDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense
Cell Physiol Biochem 2007;20:1061–1072
Background/Aims: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. […] Results: Treatment with RA resulted in decreased cellular triacylglycerol content and increased basal lipolysis and fatty acid oxidation rate. At the mRNA level, RA treatment led to a reduced expression of adipogenic/lipogenic transcription factors (peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, rexinoid receptor alpha) and two purported suppressors of lipolysis and oxidative metabolism (CIDEA and receptor-interacting protein 140), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). […] Conclusion: The results indicate that RA directly favors remodeling of mature 3T3-L1 adipocytes in culture toward increased oxidative metabolism.
Copyright © 2007 S. Karger GmbH, Freiburg
As an “Educational non-profit” uses I believe that quoting with parts left out is “fair use” under US law.
So what does this say? It says that rats fed extra retinoic acid burn a load more fat for fuel than rats that don’t get the RA. As human and rat metabolism are rather similar, one would expect similar results in people (but it would need testing to assure it).
OK, so if we eat Retinol (or retinal) it will be metabolized into retinoic acid. Where do we get them?
Retinal, also called retinaldehyde or vitamin A aldehyde, is one of the many forms of vitamin A (the number of which varies from species to species). Retinal is a polyene chromophore, and bound to proteins called opsins, is the chemical basis of animal vision. Bound to proteins called type 1 rhodopsins, retinal allows certain microorganisms to convert light into metabolic energy.
Vertebrate animals ingest retinal directly from meat, or produce retinal from one of four carotenoids (beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin), which they must obtain from plants or other photosynthetic organisms (no other carotenoids can be converted by animals to retinal, and some carnivores cannot convert any carotenoids at all). The other main forms of vitamin A, retinol, and a partially active form retinoic acid, may both be produced from retinal.
OK, we get it from meat products and from carotenoids. (I’ve not been able to find the reference, but I’ve seen a reference that infants were not able to convert carotenoids and so needed animal forms of Vit-A as in mother’s milk, basically, Mom needs to make it, or the kids need animal products. Butter provides it, but margarine uses a beta-caroteninoid so doesnt’ work for infants. Another reason not to eat margarine…)
In a pinch, we can back form Vit-A retinol from retinal, but clearly the preference if to go the other way.
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals.
When converted to the retinal (retinaldehyde) form, vitamin A is essential for vision, and when converted to retinoic acid, is essential for skin health and bone growth. These chemical compounds are collectively known as retinoids, and possess the structural motif of all-trans retinol as a common feature in their structure. […]
Retinol is produced in the body from the hydrolysis of retinyl esters, and from the reduction of retinal. Retinol in turn is ingested in a precursor form; animal sources (liver and eggs) contain retinyl esters, whereas plants (carrots, spinach) contain pro-vitamin A carotenoids (these may also be considered simply vitamin A). Hydrolysis of retinyl esters results in retinol, while pro-vitamin A carotenoids can be cleaved to produce retinal. Retinal, also known as retinaldehyde, can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid, which then cannot function as the vitamin in the eye.
So animal source Vit-A can be turned into any of the particular bits you need, and some limited back formation happens.
All sources of vitamin A can provide retinol, but retinoids are found naturally in some foods of animal origin. Each of the following contains at least 0.15 mg of retinoids per 1.75–7 oz (50–200 g):
Cod liver oil
Liver (beef, pork, chicken, turkey, fish)
OK, just the stuff I was raised on. (Mom loved liver and onions, as do it. She fed me cod liver oil when I was ill, or sometimes not… but she thought I might need some. We had butter galore. (I note that the wiki includes margarine and that is in error as it is typically made not with Vit-A but with a beta-carotene precursor). Eggs, cheese, milk. Yup. all that stuff.
As many in my family have headed down the vegetarian path, I need to be particularly aware of this. So far they have stopped at “ovo-lacto” so milk, cheese and eggs are still in the mix.
Turns out that to absorb it, you need some fats in your diet too:
Newer research has shown that the absorption of provitamin-A carotenoids is only half as much as previously thought. As a result, in 2001 the US Institute of Medicine recommended a new unit, the retinol activity equivalent (RAE). Each μg RAE corresponds to 1 μg retinol, 2 μg of β-carotene in oil, 12 μg of “dietary” beta-carotene, or 24 μg of the three other dietary provitamin-A carotenoids.
Though they don’t say why. Perhaps our recent fad of very low fat diets?
Because the conversion of retinol from provitamin carotenoids by the human body is actively regulated by the amount of retinol available to the body, the conversions apply strictly only for vitamin A-deficient humans. The absorption of provitamins depends greatly on the amount of lipids ingested with the provitamin; lipids increase the uptake of the provitamin.
The conclusion that can be drawn from the newer research is that fruits and vegetables are not as useful for obtaining vitamin A as was thought; in other words, the IUs that these foods were reported to contain were worth much less than the same number of IUs of fat-dissolved oils and (to some extent) supplements. This is important for vegetarians, as Night blindness is prevalent in countries where little meat or vitamin A-fortified foods are available.
Or maybe, just maybe, one could put a pat of butter on their carrots and “eat without guilt”!
So first they tell us to leave out the butter, then they tell us the carrots are not as good for us, then they say we need a pill with, yes, oil in it. Just crazy! Butter your veggies and enjoy.
Secondary vitamin A deficiency is associated with chronic malabsorption of lipids, impaired bile production and release, and chronic exposure to oxidants, such as cigarette smoke, and chronic alcoholism. Vitamin A is a fat soluble vitamin and depends on micellar solubilization for dispersion into the small intestine, which results in poor use of vitamin A from low-fat diets. Zinc deficiency can also impair absorption, transport, and metabolism of vitamin A because it is essential for the synthesis of the vitamin A transport proteins and as the cofactor in conversion of retinol to retinal. In malnourished populations, common low intakes of vitamin A and zinc increase the severity of vitamin A deficiency and lead physiological signs and symptoms of deficiency. A study in Burkina Faso showed major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children.
So get your zinc, and don’t overdo the cigarettes and avoid being an alcoholic.
So, when making all their extracts and doing their failed tests, did they maybe leave out anything?
Cryptoxanthin is a natural carotenoid pigment. It has been isolated from a variety of sources including the petals and flowers of plants in the genus Physalis, orange rind, papaya, egg yolk, butter, apples, and bovine blood serum.
In the human body, cryptoxanthin is converted to vitamin A (retinol) and is, therefore, considered a provitamin A. As with other carotenoids, cryptoxanthin is an antioxidant and may help prevent free radical damage to cells and DNA, as well as stimulate the repair of oxidative damage to DNA.
Recent findings of an inverse association between β-cryptoxanthin and lung cancer risk in several observational epidemiological studies suggest that β-cryptoxanthin could potentially act as a chemopreventive agent against lung cancer.
Oh, a form that we can easily convert to retinol (and on to all the other forms we need), that we can store, that acts as an oxidative stress “fix” and stimulates repair of damage to DNA (important to longevity, normal kids, preventing cancer, and radiation exposure repair). Oh, and it holds down lung cancer…
And what foods is it in?
Orange Marmalade (that English tradition I’ve eaten my whole life), eggs, butter, apple pie, and blood sausage.
My God Man, that sounds like the traditional diet we’ve all been told to avoid…
My take on it all?
The folks who think they know what we ought to eat are clueless. Take the plastic foods out of your mouth (and your diet). Put in the traditional foods people of eaten (and thrived eating) for generations. Make your pie crusts with chilled butter, not trans fat vegetable shortening, and have your eggs and toast (with butter and marmalade).
And that liverwurst or blood sausage sandwich for lunch? The Pâté de Foie Gras and the sardines? Go for it.
IMHO, of course.
Remember that the retinoic acid you gain will cause the fat metabolism to pick up the pace, leaving you feeling full, and energized, all day as you “burn with pride”…
So now I know why I don’t gain weight eating that traditional high fat (AND high Vit-A) diet.
End Note on Autism
There is a researcher who believes she has found the causal link to the “Autism Epidemic”. In her opinion, it turns on the fact that infants can not convert beta-carotene into the right form of retinol. When deficient in animal source Vit-A and simultaneously exposed to MMR vaccine, there is a bad interaction that leads to the Autism outcome.
My kids had an MMR type vaccine, and had no problems. Then again, we eat eggs and real butter every single day.
Here is a bit on her work:
Dr. Mary Megson
Vitamin A & Urocholine for Autism
Megson’s Research on Supplements for Autistic Spectrum Disorders
Jun 9, 2008
Studies undertaken by Dr. Mary Megson suggest that supplements of vitamin A and Urocholine may provide benefits for some autistic children.
Doctor Megson has put forward the theory that autism may result from “disruption of the G-alpha protein,” which affects the brain’s retinoid receptors. Retinoid receptors are critical for sensory perception, attention and language processing, all areas that are often deficient in those with autistic spectrum disorders. Autistic individuals are also more inclined to have relatives who suffer from night blindness (poor night vision) and other retinoid-based disorders.
Nutritional Basis for the Theory
There has been a dramatic increase in the autism rate in recent years combined with a decrease in the consumption of foods rich in natural cis forms vitamin A such as kidney, milk fat, liver, salmon and codfish. There are essentially two forms of vitamin A, which have molecular shapes that are cis-trans isomers of each other. The synthesis of rhodopsin, which promotes healthy eye functioning, requires a particular cis isomer of vitamin A. The commercial version of vitamin A – vitamin A palmitate – contains only the trans form, which is not as effective.
Most children now consume more of the trans form than the cis form of vitamin A. Vitamin A palmitate, derived from palm oil, can be found in many baby formulas and low-fat milk. Beta-carotene, found in dark orange and yellow vegetables and fruits such as carrots, cantaloupes and sweet potatoes, as well as dark green leafy vegetables such as spinach and kale, can be converted to vitamin A by the body. However, although they offer many important health benefits, fruit and vegetable sources provide the trans form rather than the more potent cis form of vitamin A. Additionally, absorption of this form of vitamin A can be compromised by damage in mucosal gut surfaces as a result of a wheat allergy or intolerance that is often undiagnosed, as well as a number of other health conditions. Overall, the cis form is far more effective.
As I remember it, one of the “other health conditions” was found to be MMR vaccine, but only for children already significantly low in the cis form of Vit-A.
To the extent that thesis has validity, one would expect to see various studies finding MMR is fine, or not fine, depending entirely on the individuals in whom it was tested. If the testing plan particularly screens out folks in poor nutritional status, it would fail to find this diet dependent for of failure.
(Please note: I am not saying MMR is causal. I am saying it needs a new kind of test to find out.)
Providing natural cis vitamin A supplements in the form of cod liver oil along with the alpha muscarinic receptor agonist Urocholine has generated dramatic, immediate benefits for some autistic children, including enhanced social interaction, improved attention and language usage, better vision and improved sleep.
Vitamin A supplements may be beneficial for children who engage in “sideways glancing,” as this may indicate improper function of the rods in the eye, a symptom of defective G-alpha protein. Case studies have indicated improved eye contact with supplementation.
Code liver oil resulted in 53% of the parents saying they saw improvement.
The testimony of Dr. Mary Megson to congress is reproduced on this page:
I’m going to reproduce all of it here. I have other, much more techincal, presentation of hers on video tape somewhere. It is very moving and you rapidly realize this lady knows what is going on down to the level of the individual molecules, then devised a test that confirmed it.
House Government Reform Committee on Autism and Vaccines
Representative Dan Burton, Chairman April 6, 2000
Mary N. Megson, MD
Mr. Chairman, Honorable Dan Burton and members of the committee; My name is Mary Norfleet Megson. I am a board-certified pediatrician, Fellowship trained in Child Development, a member of the American Academy of Pediatrics and Assistant Professor of Pediatrics at Medical College of Virginia.
I have practiced pediatrics for twenty-two years, the last fifteen years seeing only children with Developmental Disabilities, which include learning disabilities, attention deficit hyperactivity disorder, cerebral palsy, mental retardation and autism.
In 1978, I learned as a resident at Boston Floating Hospital that the incidence of autism was one in 10,000 children. Over the last ten years I have watched the incidence of autism skyrocket to 1/300-1/600 children.
Over the last nine months, I have treated over 1,200 children in my office. Ninety percent of these children are autistic and from the Richmond area alone. The State Department of Education reports that there are only 1522 autistic students in the state of Virginia.
MHMR agencies have created local infant intervention programs, and have had a hard time keeping up with the numbers of delayed infants and toddlers. I have served as advisor to the City of Richmond and the surrounding counties as they have established entire programs for autistic children that fill multiple classes in several schools in each district.
The segment of children with “regressive autism,” the form where children develop normally for a period of time then lose skills and sink into autism most commonly at 18-24 months of age, is increasing at a phenomenal rate. I am seeing multiple children in the same family affected, including in the last week four cases of “autistic regression” developing in four-year-old children after their MMR and DPT vaccination. In the past, this was unheard of.
In the vast majority of these cases, one parent reports night blindness or other rarer disorders which are caused by a genetic defect in a G protein, where they join cell membrane receptors, which 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: and 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 pertussis toxin, which completely disrupts G Alpha signals. The opposite G proteins are on without inhibition leading to:
1. Glycogen breakdown or gluconeogenesis. Many of these children have elevated blood sugars. There is sixty-eight percent incidence of diabetes in parents and grandparents of these children.
2. Lipid breakdown which increases blood fats that lead to hyperlipidemia. One-third of families has 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 which leads to uncontrolled cell growth. There are 62 cases of malignancies associated with ras-oncogene in 60 families of these autistic children. The measles antibody cross reacts with intermediate filaments which are the glue that hold cells together in the gut wall. The loss of cell to cell connection interrupts apoptosis or 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. 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.
Suddenly mothers touch feels like sandpaper on their skin. Common sounds become like nails scraped on a blackboard. We think they cannot abstract, but we are sinking these children into an abstract painting at 18 months of age and they are left trying to figure out if the language they are hearing is connected to what they are looking at, at the same time.
The defect for congenital stationary night blindness on the short arm of the X chromosome affects cell membrane calcium channels which, if not functioning, block NMDA/glutamate receptors 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 judgement and all executive function.
When stimulated, these NMDA receptors, through G proteins stimulate nuclear 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 the Hepatitis B virus protein sequence was originally isolated in the gene for a similar retinoid receptor (RAR beta), which is the critical receptor important for brain plasticity and retinoid signaling in the hippocampus. After the mercury is removed, I understand we will restart Hepatitis B vaccine at day one of life. Studies need to be done to determine if this plays an additive roll in the marked increase in autism.
I am using natural lipid soluble concentrated cis form of Vitamin A in cod liver oil 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, 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 can not compensate for blocked pathways. Lack of Vitamin A which 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.
On 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 heart rate. These and other symptoms of attention deficit hyperactivity disorder are part of this constant “fright or flight” response. These symptoms improve on bethanechol.
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.
I think we are staring a disaster in the face that has affected thousands of Americans. The children with autism or dyslexia/ADHD are lucky. There are many other children not identified, just disconnected.
We must direct all of our resources and efforts to establish multidisciplinary centers to treat these children. Insurance companies should pay for evaluations, both medical and psychiatric, and treatment.
These children are physically ill, immuno-suppressed with a chronic autoimmune disorder affecting multiple organ systems. Funding to look at etiology of autism, to identify children at risk prior to “autistic regression,” and to prevent this disorder is imperative. Implementing vaccine policies that are safe for all children should become our first priority.
Mothers from all over the country have brought pictures of their autistic children to Washington this weekend. Most of these children were born normal and lost to “autistic regression.” Look into their eyes and you will hear their silence.
Mary N. Megson, MD