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Researcher sees link between vitamin D, autism

December 1st, 2010

From AutismToday.com:

The growing prevalence of autism is one of the biggest scientific whodunits in the medical world, with few clues for its rising incidence.

But a U.S. researcher is advancing a controversial hypothesis: that autism is related to vitamin D deficiency during fetal development and early childhood.
Dr. John Cannell, a psychiatrist and prominent vitamin D advocate, says flagging levels of the vitamin in pregnant women and young children could be the elusive factor explaining the rising rate of autism.

The evidence for such a link is circumstantial, and autism experts describe the hypothesis as speculative. But Dr. Cannell, founder of the Vitamin D Council, a non-profit advocacy group, says autism rates have skyrocketed in lockstep with medical advice given to the public since the late 1980s to avoid all exposure to bright sunshine.

“If it’s true, I can’t think of another situation where medical advice was so damaging to such a large number of people,” says Dr. Cannell, who practises at Atascadero State Hospital in California.

The vitamin D link “is an interesting speculation,” says Dr. Wendy Roberts, a professor of pediatrics at the University of Toronto and one of Canada’s leading autism experts.

Because the cause of autism is such an enigma, Dr. Roberts says researchers should investigate vitamin D, but the public should treat the idea more cautiously.

“You like to be able to have something that is firm and clear before you get parents all excited and doing something and then, once again, being disappointed,” she said.

Although Dr. Cannell is something of a maverick in research circles, he has credentials. Last year, he published an important peer-reviewed paper linking low vitamin D levels to an increased susceptibility to influenza, based on research at his hospital.

But for his autism hypothesis, he is now jeopardizing his chances of publication in a scientific journal by e-mailing the Vitamin D Council newsletter outlining the idea to thousands of U.S. autism activists – a possible violation of the rules of publication.

Dr. Cannell said he decided to disseminate his hypothesis now to encourage the public to increase its sun exposure during the warmer part of the year.

“If only 10 pregnant women go outside and sunbathe a little bit, they may be saved a lifetime of misery,” he said.

The idea that vitamin D deficiency may have a link to autism isn’t as farfetched as it once might have seemed because the deficiency is also emerging as a possible cause of many diverse illnesses, ranging from multiple sclerosis to cancer.

Last month, the Canadian Cancer Society recommended adults start taking the sunshine vitamin to reduce their risk of cancer.

Autism refers to a spectrum of conditions that involve repetitive behaviours and difficulty communicating and interacting socially. Autism manifests itself in the first few years of life and is thought to be some kind of neurological disorder affecting brain function.

One discredited theory is that the mercury-containing preservative thimerosal once used in childhood vaccines causes autism. Studies have failed to find any link.

The cause of autism is further clouded because some scientists speculate that part of the apparent increase in incidence – in the United States it is being diagnosed about 10 times more frequently now than in the early 1990s – may reflect improved reporting by doctors more aware of the condition.

The current Canadian estimate is that about 60 children out of every 10,000, or about 1 in 165, have autism and related conditions. Up until the 1990s, the prevalence was thought to be far lower, at only 4 or 5 children in 10,000.

If there is a vitamin D link, incidence rates around the world would probably vary by latitude. Rates would be lower in equatorial areas, where sun exposure is higher, than in northern latitudes, but studies investigating geographical differences in diagnosis haven’t been done.

Dr. Cannell says some of the strongest evidence vitamin D may have a hand in the disorder is that the vitamin is converted in the body to a steroid hormone, which in animal experimentation has been found to influence brain development. If vitamin levels are low, whatever brain development it is linked to will be skewed.

Startling trend
The occurrence of autism spectrum disorders (the most sever of which is autism) has risen sharply during recent years.
Rate per 10,000
UNITED STATES
1980s: 4-5
1990s: 30-60
2000A: 67
CANADA
2001B: 60
SOURCES: ENVIRONMENTAL HEALTH PERSPECTIVES
A- CENTRES FOR DISEASE CONTROL
B-CAIRN

Too Much, Too Young – Excess brain growth may be the first sign of autism

August 9th, 2010

From ScientificAmerican.com:

The average age at which children are diagnosed with autism is between three and four, but scientists have long suspected that the disorder starts much earlier. A key piece of evidence is a phenomenon known as brain overgrowth. Autistic toddlers tend to have large brains for their age, and researchers have shown a correlation between the degree of excess growth and the severity of autism symptoms. Eric Courchesne, director of the Autism Center of Excellence at the University of California, San Diego, helped to pioneer the overgrowth hypothesis. Now he and his colleague Cynthia Schumann have published data that suggest the excess brain growth starts in the first year of life, if not sooner.

The study, published in a recent issue of the Journal of Neuroscience, is the first to evaluate brain growth and autism throughout early development. Using cross-sectional MRI scans, the U.C.S.D. researchers found overgrowth in autistic subjects as young as one and a half. At two and a half, the autistic subjects’ brains were 7 percent larger on average than the control group’s. Al though why, exactly, excessive brain growth is related to autism remains a mystery, the new work helps to confirm that signs of the disorder appear early—knowledge that could lead to detection and treatments, such as behavior therapy, at a younger age. “The earlier the intervention, the better the outcome,” Courchesne says.

Evolution determines infant brain growth

July 13th, 2010

From TheAutismNews.com:

The parts of the human brain that grow the most during infancy and childhood are nearly identical to the brain regions that have changed the most when humans are compared to primates, a recent study has shown.

Researchers made the discovery as they conducted a study to try to better understand abnormal brain development in premature babies and assess the long-term effects of premature birth on brain development.

The number of babies born before term in the United States has risen steadily to reach 12% of all births, said Terrie Inder from Washington University in St Louis and lead author of the study published in the Proceedings of the National Academy of Sciences.

Disorders due to brain structure

Babies born prematurely face a greater risk of having learning disabilities, attention deficits, behavioral problems and cognitive impairments, according to the researchers.

“This study and the data that we’re gathering now could provide us with very powerful tools for understanding what goes wrong structurally in a wide range of childhood disorders,” Inder said.

The researchers hope to gain insight into the after-effects of premature birth and even conditions such as autism, attention-deficit disorder or reading disabilities, they said.

Uneven growth points to evolution

The researchers used a technique called surface reconstruction to compare regions and structures in different brains.

In analysing the brain scans of 12 full-term babies and comparing them to the scans of 12 healthy young adults, the researchers found that the cerebral cortex – the wrinkled area on the surface of the brain responsible for higher mental functions – grew unevenly.

A quarter to a third of the cortex expanded around twice as much as other cortical areas during normal development.

The findings reveal “evolution’s imprint on the human brain” because the rapidly developing parts of the brain are also those that differ most when the human brain is compared to primates’.

Gaining the upper hand

High-growth regions have been linked to advanced mental functions such as language and reasoning and traits that make humans uniquely human.

Previous studies have shown that many of the brain’s high-growth regions “are expanded in humans as a result of recent evolutionary changes that made the human brain much larger than that of any other primate,” said David Van Essen, one of the study’s authors.

Brain growth dictated by early needs

Van Essen, who developed the surface reconstruction technique used to scan the brain regions, speculated that the full physical growth of the rapid-growth regions may be delayed somewhat to allow them to be shaped by early life experiences.

Inder hypothesised that certain regions of the brain might develop more quickly in young infants for evolutionary reasons.

For instance, the part of the brain responsible for vision, which is necessary to allow a baby to bond with his mother during nursing, develops early, while brain functions less important early in life come later.

Source: http://www.cosmosmagazine.com/news/3562/evolution-determines-infant-brain-growth

Autism and Vitamin D (more)

July 7th, 2010

From VitaminDCouncil.org:

n addition to the current epidemic of vitamin D deficiency, say another epidemic—an epidemic of autism—was upon our children? What if the autism epidemic began at the same time the epidemic of vitamin D deficiency began? What if both epidemics had worsened in unison? What if one theory explained all the unexplained facts about autism? What if both epidemics had the same root cause: sun avoidance? What if both were iatrogenic, that is, medical advice to avoid the sun had caused both epidemics?Be warned, what follows is not light reading—autism is not a light disease.DOES THE VITAMIN D THEORY BEST EXPLAIN AUTISM?The theory that vitamin D deficiency, during pregnancy or childhood, causes autism is just a theory. However, the theory has a plausible mechanism of action, explains all the unexplained facts about autism, subsumes several other theories, implies simple prevention, and is easily disprovable—all components of a useful theory.A genetic lesion (abnormality) in some component of the vitamin D system—a lesion vitamin D’s unique pharmacology could overcome—would explain why monozygotic (identical) twins are highly affected while fraternal twins are not. Varying brain levels of activated vitamin D during later life would explain why some identical twins get severe disease while others are barely affected.Falling vitamin D levels over the last 20 years due to sun-avoidance explain autism’s rapid increase in incidence during that same time. The very different effects estrogen and testosterone have on vitamin D metabolism may explain why boys are much more likely to get it than girls are. Lower vitamin D levels in blacks may explain their higher rates of autism. The vitamin D theory has tenable explanations for all the epidemiological features of autism.WHAT’S THE RISK OF GOING IN THE SUN?The window of opportunity to affect brain development is limited. Time is of the essence if the vitamin D theory of autism is correct. Ask yourself, what is the risk of taking your autistic child outside to play in the sun? What’s the risk of pregnant women sunbathing for a few minutes every day? Children always played in the sun before the epidemic of autism; your pregnant grandmother spent time in the sun as well. Physicians considered that sunshine was healthy before the sun-scare, that is, before autism became an epidemic.

What Is Autism?The Autism Society of America describes autism as “a complex developmental disability that typically appears during the first 3 years of life and is the result of a neurological disorder that affects the normal functioning of the brain, impacting development in the areas of social interaction and communication skills…One should keep in mind however, that autism is a spectrum disorder, and it affects each individual differently and to varying degrees.” They estimate that 1.5 million Americans and their families are now affected—a national health crisis, costing about $35 billion annually.After exhaustive metabolic and genetic evaluations, more than 60% of individuals with autism spectrum disorders are found to have idiopathic disease. Even after the most thorough medical evaluation possible, doctors simply cannot find the cause for their autism.WHAT ARE AUTISM’S FIVE UNEXPLAINED FEATURES?Any valid theory of autism must explain the following:
Significantly higher concordance (if one has it, the other is likely to have it) rates in identical, but not fraternal, twins.
Widely-varying symptoms, even among identical twins.
Striking 4:1 male to female sex ratio.
Increased rates in blacks.
Rapid increase in occurrence rates over the last 20 years.
Whatever its genetic roots—and they are strong—autism hardly follows classic genetic inheritance. What is clear is that the genes that control autism confer predisposition, not predestination.ARE AUTISM RATES INCREASING?Multiple scientific groups have reported greatly increasing rates of autism over the last 20 years. Dr. Hjordis Atladottir, of the University of Aarhus in Denmark, recently reported that hyperactivity and Tourette’s syndrome (two other childhood neurodevelopmental disorders) have increased dramatically right along with autism, while a third, childhood obsessive-compulsive disorder, has not changed at all. Why would some childhood neurodevelopmental disorders increase dramatically in such a short time, while another is entirely unchanged? Perhaps something is harming our children’s brains, and doing so with increasing frequency. Professor Gillian Baird, and his colleagues at Guy’s and St. Thomas’ Foundation Trust in England, recently discovered that about 1 in 88 English children will eventually develop autism. Families caring for autistic children are under more stress than those caring for a child with cystic fibrosis, a fatal illness. The lifetime cost of autism is $3.2 million per case. Not only is autism epidemic, it is catastrophic.

The Vitamin D ConnectionSix years ago, Professor John McGrath and his colleagues at the University of Queensland in Australia, pointed out that vitamin D, “the neglected neurosteroid,” was crucial for proper brain development. In the same paper, they reported that activated vitamin D increases nerve growth factor in the brain and the vitamin D receptor appears in a wide variety of brain tissue quite early in the development of the baby. These two facts alone led them to conclude that vitamin D deficiency “should be examined in more detail as a candidate risk factor for neurodevelopmental…disorders.” In 2006, Dr. Alan Kalueff and his colleagues went further, suggesting vitamin D offers “neuroprotection, possible interplay with several brain neurotransmitter system and hormones, as well as regulation of behaviors.” In 2007, Dr. Kalueff, now at the National Institutes of Mental Health, reviewed the nootropic (brain-enhancing) properties of vitamin D in even more detail and concluded that the scientific data stress the importance of the mother having enough vitamin D while she is pregnant and the child having enough vitamin D after birth for “normal brain functioning.” There is no doubt vitamin D affects the brain, and does so profoundly. PREDISPOSITION – WHAT GENE SHOULD WE BE LOOKING FOR?Given what we know about neurosteroids, in our search for the genetics of autism it is reasonable to search for a gene which:
is environmentally responsive.
codes for a systemic steroid that is also a potent neurosteroid.
profoundly affects brain development
has had its levels decrease over the same time that autism has increased.
is affected differently by estrogen and testosterone.
has levels that are much lower in blacks than in whites.
explains all the bizarre epidemiology of autism.
A tall order indeed.Two clues: rare genetic malformations of the vitamin D systemAn inborn error of metabolism that causes a rare form of rickets, pseudo-vitamin D deficiency rickets, involves the defective manufacture of activated vitamin D. While no one has assessed afflicted children for signs of autism, these children clearly display autistic markers such as hypotonia (flabby muscles), decreased activity, developmental motor delay, listlessness, and failure to thrive.Much more interesting is the fact that children with Williams Syndrome (rare congenital disorder due to a missing piece of chromosome seven) often have greatly elevated activated vitamin D levels for several months in early life. They usually present in later life with remarkable sociability, overfriendliness, empathy, and willingness to initiate social interaction—strikingly the opposite personality of autistic children. So, abnormally-low activated vitamin D levels produce infants with symptoms of autism while abnormally-high levels produce children with personalities the exact opposite of autism.What is the role of the vitamin D receptor in autism? Variations in the DNA sequence of vitamin D receptor are common and called vitamin D receptor (VDR) polymorphisms (many-shaped receptors). No one has studied them in autism, but a highly significant association exists between one VDR polymorphism and larger head size. Larger head sizes are common in autism, especially in childhood.

VITAMIN D INTAKE—ARE CHILDREN AND PREGNANT WOMEN GETTING AS MUCH AS THEY USED TO?No, because sun exposure is much less common today. Furthermore, perhaps because the term vitamin D contains the word “vitamin,” many people mistakenly assume it is a vitamin. Vitamin D is the only known precursor for a steroid hormone system that, until recent sun-avoidance, always began in the skin, not the mouth. Before the sun-scare, 90% of human vitamin D stores came from skin production, not diet. Large populations of pregnant women and autistic children ingesting small amounts orally, instead of generating large amounts through the skin, are novel to human brain development. Obviously, if people are going to put it in their mouths rather than make it in their skin, oral intake must be adequate enough to make up for decreased skin production. However, the skin’s production of vitamin D is rapid and robust, easily exceeding usual dietary sources by a factor of 10. For example, when fair-skinned adults sunbathe in the summer (one full-body exposure to ultraviolet light, enough to turn the skin slightly pink) they make about 20,000 units of vitamin D in 20 minutes. A pregnant woman would have to drink 200 glasses of milk or take 50 prenatal multivitamins to do the same. An autistic boy who plays inside the house, instead of outside, would have to take several thousand units of vitamin D to make up for what his skin would have produced had he played outside that day. When did medical organizations first tell us to avoid the sun?In 1989, around the time autism began to rise, the American Medical Association’s (AMA) Council on Scientific Affairs first warned about the dangers of sun exposure, advising mothers to “keep infants out of the sun as much as possible.” In 1999, when autism rates really exploded, the American Academy of Pediatrics went further, advising mothers always to keep infants out of direct sunlight, use sun-protective clothes and sunblock, and make sure children’s activities minimize sunlight exposure. Quite inexplicably, they said there was “no evidence” such “rigorous sun protection” would affect vitamin D levels. By 2002, the Centers for Disease Control (CDC) reported such efforts were quite successful: “protection from sun exposure is reported for a high proportion of children.” DID AUTHORITIES RECOMMEND COMPENSATORY VITAMIN D INTAKES?Medical organizations did not plan for the vitamin D deficiency such sun avoidance would predictably induce. For example, when the AMA warned about the dangers of sunlight, they did not even mention that sunlight triggers the formation of vitamin D. Furthermore, medical recommendations for infants, children, young women, and pregnant women, did not change during the decades of sun avoidance: 200 units/day for all infants, children, pregnant women, and young adults—regardless of weight. That is, they did, and still do, recommend the same 200 daily units for a 5-pound infant as they do for a 200-pound pregnant woman. In fact, in 2003, the American Academy of Pediatrics cut their long-standing 400 units/day recommendation in half—apparently to comply with government recommendations—and did so despite warnings from a prominent University of Wisconsin professor of pediatrics, Dr. Frank Greer, and despite their own advice 4 years earlier that infants and children should avoid sunlight. HAVE VITAMIN D LEVELS FALLEN AS AUTISM HAS INCREASED?Yes they have, although no linear studies of vitamin D levels over the last 20 years exist. That is, we don’t know how successful sun avoidance campaigns have been in lowering vitamin D levels. However, if one assumes that some Americans do follow their government’s and physician’s advice, then at least some must have had declining vitamin D levels over the last 20 years—unless they took enough supplemental vitamin D to make up for lack of sun exposure. Unfortunately, few take the thousands of daily units needed to do that. What we do know is that vitamin D deficiency, like autism, is now an epidemic.

About Vitamin DHOW IS VITAMIN D UNIQUE?Among the body’s steroid hormone systems, vitamin D certainly is unique. Unlike other steroids, the body cannot create the activated vitamin D it needs directly from cholesterol; all of the body’s activated vitamin D must come from simple vitamin D—either made in the skin or taken orally. Besides its endocrine role in maintaining blood calcium, activated vitamin D has multiple independent hormonal functions, if enough of its precursor is available. Like all steroid hormones, activated vitamin D binds to a member of the nuclear hormone receptor superfamily where the complex then acts as a molecular switch to signal its target genes. So far, we know 2,000 genes (about 10% of the human genome) are primary targets of activated vitamin D, and the list is steadily growing. If adequate precursor is available, most organs in the human body produce their own activated vitamin D, have a vitamin D receptor, and regulate their own needs independently. Thus, they do not depend on blood supply of activated vitamin D from the kidney. DOES HUMAN BEHAVIOR DETERMINE VITAMIN D LEVELS?The pharmacology contained in this paragraph may be a bit confusing to some, but it is vitally important in understanding vitamin D. It is so important that Professor Reinhold Vieth, of the University of Toronto, wrote an entire chapter about its implications in the most current textbook of vitamin D. Unlike any other steroid hormone, substrate (precursor) concentrations are absolutely rate-limiting for activated vitamin D production. The enzyme that first metabolizes vitamin D in the liver and the enzyme in tissue where activated vitamin D is made both operate below their respective Michaelis-Menten constants throughout the full range of their normal substrate concentrations, i.e. the reactions follow first-order, mass-action, kinetics. In English, this means the more vitamin D made in the skin or taken by mouth, the more vitamin D in your blood, and the more vitamin D in your blood, the more activated vitamin D in your brain. That is, levels of activated vitamin D during brain development directly depend on the mother’s vitamin D levels, which in turn, directly depend on the amount of vitamin D the mother makes in her skin or ingests orally. That is, the rate-limiting step for the production of activated vitamin D is totally dependent on human behavior, a situation that is unique among all steroids. Brain concentrations of activated vitamin D literally depend on one’s behavior—be it the step into the sun, to the supplements, into the shade, or to the sunscreen.

Vitamin D and the BrainIS VITAMIN D REQUIRED FOR NORMAL BRAIN DEVELOPMENT?Yes, Professor John McGrath and Dr. Darryl Eyles of the University of Queensland in Australia have repeatedly warned us that normal brain development depends on adequate amounts of activated vitamin D to orchestrate the cellular architecture of the brain. Both the vitamin D receptor and the enzyme necessary to make activated vitamin D are present in a wide-variety of human brain tissues very early in pregnancy. Production of the vitamin D receptor in the developing mammalian brain rises steadily beginning several weeks after conception where activated vitamin D induces the expression of nerve growth factor and stimulates brain cell growth. DOES MATERNAL VITAMIN D DEFICIENCY INJURE THE DEVELOPING BRAIN?We do not know what vitamin D deficiency during pregnancy does to human brains, but we know what it does to rat brains and it is not good. In a series of recent animal experiments, Professor John McGrath, Dr. Darryl Eyles and their Australian group found severe maternal vitamin D deficiency in mother rats produced babies with abnormal apoptosis (normal cell death) and abnormal brain cell proliferation, reduced production of proteins involved in nerve structure, and baby rats who have subtle abnormalities in both learning and memory. Several months ago, Dr. Almeras, Professor Feron, and their group at the University of the Mediterranean in Marseilles found developmental vitamin D deficiency disrupts 36 proteins involved in mammalian brain development. Severe maternal vitamin D deficiency leads to rat pups with increased brain size and enlarged ventricles (chambers in the brain), abnormalities very similar to those found in autistic children. Is autism an ongoing, destructive, inflammatory disease process?Abnormal inflammation is associated with both autism and vitamin D deficiency. For example, autistic individuals show increases in cytokines (inflammatory mediators) that show a striking similarity to the immune processes regulated by vitamin D. Both the brain and the blood of autistic individuals show evidence of ongoing chronic inflammation and oxidative stress. That is, the autistic disease process is progressive and probably increasingly destructive. If this ongoing inflammation could be interrupted, the symptoms might improve. Hope for a vitamin D treatment effect lies in activated vitamin D’s powerful anti-inflammatory properties. Its administration decreases production of inflammatory cytokines in the brain, which have consistently been associated with brain impairment. Activated vitamin D stimulates neurotrophin release (neurotrophins induce the survival of nerve cells), reduces toxic calcium levels in the brain, and inhibits the production of nitrous oxide (nitrous oxide destroys brain cells). Besides reducing inflammatory cytokines, vitamin D does one more thing: it increases concentrations of glutathione—the brain’s master antioxidant. DO BRAINS FUNCTION BETTER WITH HIGHER VITAMIN D?At least 5 studies have found significant associations between higher vitamin D levels and better intellectual functioning, but they all studied adults. However, a recent report found a very high incidence of vitamin D deficiency among 337 younger individuals with intellectual disabilities. The obvious explanation is that intellectually impaired individuals do not go outdoors as often as higher functioning individuals and thus have lower vitamin D levels. Two groups found the association after controlling for outdoor activities, making it likely that low vitamin D levels per se impair intellectual ability. DOES VITAMIN D EXPLAIN THE ROLE OF VACCINES, MERCURY, AND HEAVY METALS?Vitamin D’s role in increasing glutathione levels may explain the link between mercury and other heavy metals, oxidative stress, and autism. For example, activated vitamin D lessens heavy metal induced oxidative injuries in rat brain. The primary route for brain toxicity of most heavy metals is through depletion of glutathione. Besides its function as a master antioxidant, glutathione acts as a chelating (binding) agent to remove heavy metals such as mercury. Autistic individuals have difficulty excreting heavy metals like mercury. If brain levels of activated vitamin D are too low to employ glutathione properly, and thus unable to remove heavy metals, they may be damaged by heavy metal loads normal children easily excrete. That is, the mercury in Thiomerosol vaccines may have injured vitamin D deficient children while normal children would have easily bound the mercury and excreted it. These studies offer further hope that sun-exposure or vitamin D supplements may help autistic children by increasing glutathione and removing heavy metals. Not only do we have more clues that vitamin D is involved in autism, the vitamin D theory just did something else: it explained two other theories of autism, the mercury accumulation theory and the oxidative stress theory. It bears repeating that the amount of activated vitamin D in the brain directly depends on the amount of vitamin D made in the skin, or ingested orally.

Vitamin D Deficiency’s Role In AutismDO CHILDREN WITH COMMON RICKETS SHOW SIGNS OF AUTISM?If vitamin D deficiency caused autism, then children with vitamin D-deficient rickets would be at greater risk for the disease. To the best of my knowledge, no studies have looked at the psychiatric profiles of children with vitamin D deficient rickets to look for evidence of autism. However, children with rickets are more likely to be hypotonic (flabby muscle tone), display decreased activity, and have developmental motor delays. Hypotonia is common in children with autism, as is decreased activity, and developmental motor delays are the rule. DOES VITAMIN D EXPLAIN AUTISM’S FREQUENT INFECTIONS?Vitamin D deficiency in childhood is associated with an increased risk of infections so the vitamin D theory of autism predicts autistic children would be more prone to infections. A recent study found that children who went on to develop autism were not prone to increased infection in the first 2 years of their life but they looked at infection rates before the child was diagnosed with autism, not afterwards. Three earlier studies found an increased incidence of infections in children with autism. A Japanese study found a very strong positive correlation between the prevalence of infantile autism in 1-year birth cohorts (groups) and the total number of children hospitalized for pneumonia and bronchiolitis during that cohort’s birth year. DRUGS THAT INTERFERE WITH VITAMIN D METABOLISM—DO THEY CAUSE AUTISM?The vitamin D theory predicts medications that lower vitamin D levels, if taken during pregnancy, would increase the risk for autism. While little is known about the drugs that interfere with vitamin D metabolism, sodium valproate (Depakote) is one drug that lowers vitamin D levels and the drug has been associated with autism. DOES VITAMIN D EXPLAIN SEIZURES, WHICH ARE COMMON IN AUTISM?Seizures are very common in autism and activated vitamin D increases the seizure threshold, making brain tissue less likely to seize. A controlled study found vitamin D reduced the incidence of seizures in patients with intractable seizures.

Vitamin D Explains AutismWHY ARE BOYS AT HIGHER RISK?The reason for the striking 4:1 sex difference is totally unknown. However, there is a clue or two. Estrogen and testosterone have very different effects on vitamin D metabolism. In mid-pregnancy, when brains are rapidly developing, boy brains bathe in testosterone and girl brains bathe in estrogen. The majority of studies have found estrogen has multiple enhancing effects on vitamin D metabolism while testosterone does not. For example, in Feldman’s massive textbook on vitamin D, Dr. Epstein and Dr. Schneider report, “the majority of studies have found a positive effect of estrogen on activated vitamin D levels.” Yet, after reviewing similar studies on testosterone they conclude that “it is unlikely that testosterone is a major controlling factor in vitamin D metabolism.” If estrogen potentiates activated vitamin D, but testosterone does not, the differences in sex steroids during brain development may mean that estrogen protects developing female brains from vitamin D deficiencies, while testosterone exposes male brains to those same deficiencies. This is important because any good theory must be parsimonious (explain all known facts). DOES VITAMIN D-RICH FISH PREVENT AUTISM?The vitamin D theory of autism predicts that eating vitamin D-rich, fatty ocean fish during pregnancy would improve the offspring’s mental abilities—that is, as long as that fish did not contain a lot of mercury. Higher fish consumption during pregnancy was associated with better infant cognition, with the greatest effect for infants whose mothers consumed the most fish. Very recently in a Lancet article, Dr. Joseph Hibbeln and colleagues at the National Institutes of Health found low maternal seafood consumption was associated with infants with an increased-risk of lower verbal IQs and poor outcomes for social behaviors, fine motor skills, communication, and social development—outcomes eerily similar to autism. We don’t know what in ocean fish helped, omega-3 or vitamin D, but this evidence from a completely different source could support the vitamin D theory of autism. IS AUTISM LESS-COMMON AT THE EQUATOR?If vitamin D played a role in autism, the disorder should be less common at latitudes closer to the equator, at least before modern sun-avoidance. Dr. William Grant of SUNARC found a strong positive association between latitude and the prevalence of autism in children born in various countries born before 1985, but not after. Recently, the Centers for Disease Control (CDC) in Atlanta reported the autism rates from 14 states. The state with the highest prevalence, New Jersey, is the second most northern state. Alabama, with the lowest prevalence, is the most southern of the 14 states surveyed. Studies of season-of-birth and autism are contradictory, as would be expected if activated vitamin D deficiencies can impair brain development during either pregnancy or in early childhood. However, most studies show excessive autism births in the winter—especially March—when vitamin D levels are at their lowest. SUNSCREEN—DOES IT INCREASE RISK?If prenatal or postnatal vitamin D deficiency caused autism, then parents who rigorously used sun protection, both during pregnancy and for their children, would be more likely to have children with autism. Richer parents are more likely to apply sunscreen to their children, as are parents with a higher education. Although numerous studies—especially early ones—linked higher social class with autism, a certain kind of statistical problem (called ascertainment bias) confuses such associations. Despite identifying the source of the bias, Dr. Tanya Bhasin at the CDC recently again found wealthier parents and more highly educated parents were at higher risk for having an autistic child. It was not at all clear that ascertainment bias explained all her findings. It appears that people who bought into the sun-scare are more likely to have an autistic child. WHY DO CHILDREN FIRST DEVELOP SIGNS AROUND THE AGE OF WEANING?If children can develop autism after birth, and it’s not entirely a genetic brain injury before birth, then autism should be rare before weaning as infant formula contains significant amounts of vitamin D when calculated on a per-pound basis and breast fed babies are supposed to be supplemented with vitamin D. The disease should rapidly progress after weaning, unless the child takes vitamin D supplements or drinks significant amounts of vitamin D-fortified milk. A recent prospective study (the only such prospective study in the medical literature) of 87 children, some at high-risk for autism and some not, found that the children who later developed autism appeared entirely normal at 6 months of age. However, around the age of weaning, the children who later developed autism first showed signs of the disease with rapid additional impairments occurring between 14 months and 24 months—the same age many toddlers stop drinking vitamin D-enriched formula or milk and begin consuming lots of sodas and juice, which usually contain no vitamin D.

Evidence Autism Responds To Sunlight and Vitamin DDO VITAMIN D-CONTAINING MULTIVITAMINS HELP CHILDREN’S BRAINS?Evidence that vitamin D affects mental abilities comes from a series of 14 controlled studies evaluating the effect of vitamin D-containing multivitamins on childhood intelligence. All 14 studies they reviewed reported small (1–2%) to modest (5–6%) improvements, usually in nonverbal IQ. Lancet published the first study in 1988. More interestingly, most studies showed no effect on the majority of children but very significant effects (15% gains) in about 20% of children, perhaps the vitamin D-deficient subgroup. Something in the multivitamins helped some of the children’s brains quite a bit. Was it the vitamin D? DOES AUTISM IMPROVE IN THE SUMMER?If vitamin D was involved in autism, then symptoms might improve in the summer, when vitamin D levels are the highest. To the best of my knowledge, no controlled studies of such seasonality exist. A case study reported dramatic improvements in both sleep and behavioral problems in an autistic Japanese boy in the summer. Others reported significant improvements in autistic behaviors during a summer camp program that included swimming, hiking, boating, and other activities that would increase brain levels of activated vitamin D. CAN AUTISTIC CHILDREN GET BETTER?We don’t know although most do not. However, if vitamin D is involved in autism then young autistic children, whose brains have not been irreparably damaged, may improve if they move to sunnier latitudes, increase their sun exposure, or start consuming more vitamin D in their diet. Consistent with the theory, not all children diagnosed with autism keep that diagnosis in adulthood and a few children either improve spontaneously or improve after one of the numerous treatment programs available. Naturally, any reports of improvement generate suspicion that the initial diagnosis was incorrect—an obvious possibility. A controlled 3-month study of 20 autistic children found that multivitamins with even low doses of vitamin D (150 units) improved symptoms compared to placebo. What would physiological doses of vitamin D do?

The Black Community: A Tragic InjusticeIS AUTISM MORE COMMON IN DARK-SKINNED PEOPLE?Vitamin D deficiency discriminates based on race, or more precisely, the amount of melanin (pigment) in the skin, which is an effective and ever-present sunscreen. The vitamin D theory of autism predicts that autism is more common in children born to darker-skinned mothers. Such studies are difficult as they raise sensitive social issues, although 3 of 4 recent U.S. studies found a higher incidence of autism in black children—sometimes appreciably higher. In Europe, autism rates are higher in children of dark-skinned immigrants. Dr. Gillberg and colleagues reported that the incidence of autism in Sweden for children born to mothers who emigrated from Uganda was 15%—almost 200 times higher than the general population. The Centers for Disease Control in Atlanta and others report black children have significantly higher rates of mild mental retardation than white children do and socioeconomic factors cannot explain the differences. DO BLACKS HAVE A HIGHER RISK OF PREGNANCY PROBLEMS?Several studies indicate black mothers are more likely to give birth to infants who weigh less and low birth weight is a clear risk factor for autism. Black babies have lower Apgar scores. (Apgar tests are 10 point examinations done shortly after birth.) Low Apgar scores are associated with both poor vitamin D intake and with autism. ARE BLACK, PREGNANT WOMEN MORE LIKELY TO BE VITAMIN D DEFICIENT?Recent studies of vitamin D deficiency during pregnancy show striking racial inequities in maternal vitamin D levels. Professor Lisa Bodnar of the University of Pittsburg and her colleagues found that only 37% of white women, but only 4% of black women, in the northern United States were vitamin D sufficient in early pregnancy. That is, 96% of pregnant black women and 63% of pregnant white women did not have adequate vitamin D blood levels. Their infants fared little better and showed the same racial inequity. 45% of the pregnant black women and only 2% of the pregnant white women were severely deficient. Prenatal vitamins, virtually all of which contain only 400 IU of vitamin D, offered little protective effect for mother or infant; 90% of the women in the study reported taking them, to little or no effect. Unless infants take enough vitamin D after birth—either via direct supplementation or enriched formula—infant vitamin D levels are remarkably low, with black infants at highest risk. 78% of unsupplemented, breast-fed, Iowa infants had levels less than 11 ng/mL during winter. For those who wonder how vitamin D could be important for brain development—given its very low levels in breast milk—Professors Hollis and Wagner of the Medical University of South Carolina discovered that breast milk is a source of vitamin D that is rich enough to maintain healthy levels in infants—provided the mothers took at least 4,000 units/day. Pregnant women who do not go out into the sun need more vitamin D than is in their prenatal vitamin—much more. ARE BLACK CHILDREN AT A DISADVANTAGE, RIGHT FROM CONCEPTION?In 2002, Dr. Shanna Nesby-O’Dell and her colleagues at the CDC found that almost 50% of young, black women of childbearing age had vitamin D levels lower than 15 ng/mL. 12% of black women had levels less than 10 ng/mL, compared to 0.5% of white women. While it is unknown if such low levels approach those seen in the brain-injury animal studies reviewed above, the levels in these young black women are close to undetectable. It may be that white children have a huge, developmental advantage over black children—an advantage that begins immediately after conception. One that has nothing to do with innate ability and everything to do with environment.

What Should We Do Right Now?That is, what do we do while we wait for all the hundreds of studies that need to be done to see if the vitamin D theory is correct? The studies will take years. If we do nothing but just wait, we are continuing an unplanned naturalistic experiment on pregnant women, the brains of their unborn children, and upon autistic individuals. A risk/benefit analysis tells us the risk of doing nothing is potentially great while the risk of treating vitamin D deficiency is minimal, simply good medicine, and the better choice.So until we know for sure, pregnant women, infants, children, everyone—especially autistic children—should receive sensible sun exposure daily: around noon or 1:00 p.m., expose as much skin as possible, 10–30 minutes duration, depending on how easily one sunburns. In the winter, use a suntan parlor once a week, with the same precautions—or better yet, purchase an ultraviolet vitamin D lamp for home use.I PREFER TO AVOID SUNLIGHT, WHAT SHOULD I DO?You and your child should have a vitamin D blood test, called a 25-hydroxyvitamin D . Then take enough vitamin D to achieve adequate (natural summertime) levels. Given what we do know, adequate 25(OH)D levels are now thought to be somewhere above 40 ng/mL (100 nmol/L) and probably closer 50 ng/mL (125 nmol/L). Ideal levels are unknown but they are probably close to levels that were present when the human genome evolved. Natural levels (levels found in humans who live or work in the sun) are around 50–80 ng/mL (125–175 nmol/L). These levels are obtained by only a small fraction of modern humans. HOW MUCH VITAMIN D SHOULD I TAKE?The Food and Nutrition Board set the current Upper Limit for medically-unsupervised intake by infants and babies (up to the age of 1 years-old) at 1,000 units/day. This means the government says it is safe to give infants and babies up to 1,000 units a day without getting a blood test. Of course, with correct sun exposure in the summer this is not necessary, but it will be in winter. Children over 1 years of age, according to the Food and Nutrition Board, may safely take 2,000 units/day—again, without requiring a blood test.For adolescents, pregnant women, and other adults, the government’s Upper Limits are a problem. While a 2,000-unit Upper Limit is entirely appropriate for younger children, such limits in heavier adolescents, adults, and pregnant women limit effective treatment of vitamin D deficiency. However, these limits no more impair a physician’s ability to treat vitamin D deficiency with higher doses than comparable Upper Limits for calcium or magnesium impair their ability to treat calcium or magnesium deficiencies with higher doses, should those deficiencies be diagnosed. In the absence of sun exposure and in winter, heavier children, adults, and pregnant women may require doses above 2,000 units daily (depending on pre-existing blood levels, body weight, degree of skin pigmentation, age, and latitude of residence) in order to obtain and maintain levels of 50–80 ng/mL. For example, Professor Heaney at Creighton University has estimated that about 3,000 units/day is required simply to assure that 97% of adult Americans obtain levels greater than 35 ng/mL. Healthy adult men utilize up to 5,000 units of vitamin D per day, if present in the body. Professors Bruce Hollis and Carol Wagner, in South Carolina, have been giving pregnant women 4,000 units/day for years. Professor Vieth, at the University of Toronto, found that actual vitamin D toxicity, with systemic symptoms, is exceedingly rare and requires much higher doses than those discussed above. When exceeding the Upper Limit, periodic serum 25(OH)D and calcium levels will reassure both physician and patient that such amounts are safe as well as convince all concerned that the government should revise their 10-year-old (yet most current) recommendations—the sooner the better. IS AUTISM IATROGENIC?If the vitamin D theory of autism is correct, then to the extent it is correct, the current plague of autism is an iatrogenic disease, caused by modern sun-avoidance and the organizations that promulgated it. Long before we worshipped our current gods, primitive humans venerated an older god, the sun. Much as we have shunned our modern gods, 20 years ago we shunned the sun, hiding from it under buildings, cars, shade, and sunblock. We told the sun she was damaging us, and banished her from our lives—and from the lives of our pregnant women and our children. Tragically, we relied on medical knowledge instead of human traditions, government recommendations instead of common sense, the latest science instead of basic instincts. The ancient Greeks, who loved the sun, knew the gods seldom reward such hubris.

What If Vitamin D Deficiency Is a Cause of Autism?

July 2nd, 2010

A few researchers are turning their attention to the sunshine vitamin as a culprit, prompted by the experience of immigrants that have moved from their equatorial country to two northern latitude locations

From ScientificAmerican.com:

As evidence of widespread vitamin D deficiency grows, some scientists are wondering whether the sunshine vitamin—once only considered important in bone health—may actually play a role in one of neurology’s most vexing conditions: autism.

The idea, although not yet tested or widely held, comes out of preliminary studies in Sweden and Minnesota. Last summer, Swedish researchers published a study in Developmental Medicine and Child Neurology that found the prevalence of autism and related disorders was three to four times higher among Somali immigrants than non-Somalis in Stockholm. The study reviewed the records of 2,437 children, born between 1988 and 1998 in Stockholm, in response to parents and teachers who had raised concerns about whether children with a Somali background were overrepresented in the total group of children with autism.

In Sweden, the 15,000-strong Somali community calls autism “the Swedish disease,” says Elisabeth Fernell, a researcher at the Karolinska Institute in Stockholm and a co-author of the study.

In Minnesota, where there are an estimated 60,000 Somali immigrants, the situation was quite similar: There, health officials noted reports of autism among Somali refugees, who began arriving in 1993, comparable to those found in Sweden. Within several years of arrival, dozens of the Somali families whose children were born in the U.S. found themselves grappling with autism, says Huda Farah, a Somali-born molecular biologist who works on refugee resettlement issues with Minnesota health officials. The number of Somali children in the city’s autism programs jumped from zero in 1999 to 43 in 2007, says Ann Fox, director of special education programs for Minneapolis schools. The number of Somali-speaking children in the Minneapolis school district increased from 1,773 to 2,029 during the same period.

Few, if any, Somalis had ever seen anything like it. “It has shocked the community,” Farah says. “We never saw such a disease in Somalia. We do not even have a word for it.”

What seemed to link the two regions was the fact that Somalis were getting less sun than in their native country—and therefore less vitamin D. The vitamin is made by the skin during sun exposure, or ingested in a small number of foods. At northern latitudes in the summertime, light-skinned people produce about 1,000 international units (IUs) of vitamin D per minute, but those with darker skin synthesize it more slowly, says Adit Ginde, an assistant professor at the University of Colorado Denver School of Medicine. Ginde recommends between 1,000 to 2,000 IUs per day, calling current recommendations of 200 IUs per day outmoded.

It’s hard to definitively assess the extent to which Somali immigrant families in Sweden and Minnesota are experiencing increased rates of autism. Somalia doesn’t have great records of the condition, says Rebecca Berkowitz, who works for a United Nations–affiliated NGO called Global Education Motivators. “Children in Somalia may not even be getting diagnosed with autism due to the overall lack of awareness of the disorder,” Berkowitz says, in a nod to the fact that there is no Somalian word for it. And Swedish scientists have reported autism rates overall have risen since they began studying the epidemiology of the disorder in the mid-1980s—just as U.S. Centers for Disease Control officials have noted an increase.

Still, proponents of the vitamin D–autism link say there is biological plausibility to their theory. They cite a 2007 review by Allan Kalueff, a researcher now at Tulane University, in Current Opinion in Clinical Nutrition and Metabolic Care. That review—based on more than 20 studies of animals and humans—concluded that vitamin D during gestation and early infancy was essential for “normal brain functioning.”

At the same time, the theory needs a lot of data to back it before others will give it much credence, given how many other potential reasons there are for a climb in autism rates. Even Kalueff says he isn’t sure how vitamin D could be related to autism, even if it is an important player in the brain: “Discussions around autism specifically may be a right step or a wrong step, but they should not distract us from a much bigger picture.”

Catherine Lord, the director of the University of Michigan at Ann Arbor’s Autism and Communication Disorders Center, says she finds the Swedish study intriguing. “But it is going to be really important to replicate these findings,” says Lord, who has studied the disorder for 40 years and has been instrumental in developing autism diagnostic instruments used in practice and research worldwide. “We are talking about a small group of children with a lot of social factors, including that these kids are very conspicuously different from your average Swedish child, and being assessed by people who are from very different culture.” There is also the issue of consanguinity, she says, as many Somalis marry cousins. “This doesn’t mean the study is wrong,” she says. “But we need methodical testing.”

So Fernell and her colleagues are now measuring vitamin D blood levels in mothers and children with autism of both Somali and Swedish origin and comparing them with a control group of mothers and healthy children. She will not say how many subjects the study includes, describe any preliminary results nor say when it will be complete. Farah says Minneapolis researchers are now preparing to study the vitamin D levels of pregnant Somalis, other ethnic groups and Minnesotans of European stock. (That data is particularly hard to come by because Vitamin D levels are not typically screened in pregnancy in the U.S., says Stacy Brooks, a spokeswoman for the American College of Obstetricians and Gynecologists.)

The other potential reasons for a climb in autism rates: There is increased attention to the condition in the U.S., and Somalis are more likely to see a doctor after moving here. Also, genes, studies have found, may play a role; a number of papers, including a 1989 study of five Nordic countries and a 1995 British study, found that the concordance rate among identical twins was as high as 90 percent. (Then there is the much-ballyhooed but ultimately disproved link to vaccines.)

Somali refugees, in particular, faced multiple stressors as they adjusted to their new lives in Sweden and Minnesota: They had fled civil war, lost a supportive tribal culture, and replaced a diet of fruit, fresh meat and grains with processed food. Perhaps, most importantly, they had traded family compounds and regular exposure to the equatorial sun for cloistered high-rise apartments.

But some of those potential cultural reasons could also point to vitamin D. Surrounded by strangers, the predominantly Muslim women covered themselves almost continuously when outdoors, says Gregory A. Plotnikoff, medical director of the Penny George Institute for Health and Healing in Minneapolis. Plotnikoff, an internist, speaks Somali and has many Somali patients. That meant less exposure to the sun for pregnant women, who would have worn less modest dress in private areas of their own family compounds.

And there is other evidence for a vitamin D link: Last November, Cornell University researchers published a study in Archives of Pediatrics & Adolescent Medicine showing that children in rainy (and therefore more overcast) counties of Oregon, Washington and California were two times more likely to be diagnosed with autism than their counterparts in drier parts of the state. “Our research is sufficiently suggestive of an environmental trigger for autism associated with precipitation, of which vitamin D deficiency is one possibility,” says study co-author Michael Waldman, a professor of management and economics at Cornell’s Johnson Graduate School of Management. “Further research focused on vitamin D deficiency is clearly warranted.” His research on environmental links to autism are ongoing; he plans to publish in the coming months but will not disclose any of his studies until they are accepted by a journal.

Gene Stubbs, an associate professor emeritus of psychiatry and pediatrics at Oregon Health & Science University, says the preliminary research is already intriguing. “We don’t have proof, but I am certainly leaning in the direction that this hypothesis could be correct for a proportion of kids,” says Stubbs, who has been studying autism for 30 years. He is launching a pilot study of 150 pregnant women who have at least one child diagnosed with the disorder. The women will receive 5,000 IUs of vitamin D3 during gestation and 7,000 IUs during lactation. “If we find that we are able to reduce the recurrence rate of autism within families substantially enough, others will want to study this in larger groups with larger controls.”