Autism, Sulphate, Sunshine, and Nutrition

First off, a h/t to Verity Jones who pointed me at two interesting articles about sulphate / sulfate metabolism.

They give an overview of the importance of sulphate to metabolism and the epigenetic influence it may have, plus look at using Epsom Salts as an easy way to get sulphate and the benefits it may bring.

That eventually lead to some “digging around” that resulted in finding this particularly interesting article:

Download PDF here:

A fairly technical paper that goes into the full Monty of genetics, epigenetics, metabolic pathways, the works. It ties together, in oh so genteel and circumspect a way, the elusive impacts of environmental insults such as vaccination, heavy metal exposure, Bis-Phenol-A, and even some high fructose corn syrup and sunscreen use. All leading back to a common metabolic function (sulphates) and the myriad impacts it can have.

I’m going to quote some of the more attainable bits here, but the whole paper is worth the read (at least if you have some genetics and biochem background). I’ve bolded bits of particular interest.

Entropy 2012, 14(10), 1953-1977; doi:10.3390/e14101953

Impaired Sulfate Metabolism and Epigenetics: Is There a Link in Autism?

Samantha Hartzell and Stephanie Seneff* email

Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge 02139, MA, USA
* Author to whom correspondence should be addressed.
Received: 28 September 2012; in revised form: 16 October 2012 / Accepted: 16 October 2012 / Published: 18 October 2012
(This article belongs to the Special Issue Biosemiotic Entropy: Disorder, Disease, and Mortality)

Abstract: Autism is a brain disorder involving social, memory, and learning deficits, that normally develops prenatally or early in childhood. Frustratingly, many research dollars have as yet failed to identify the cause of autism. While twin concordance studies indicate a strong genetic component, the alarming rise in the incidence of autism in the last three decades suggests that environmental factors play a key role as well. This dichotomy can be easily explained if we invoke a heritable epigenetic effect as the primary factor. Researchers are just beginning to realize the huge significance of epigenetic effects taking place during gestation in influencing the phenotypical expression. Here, we propose the novel hypothesis that sulfates deficiency in both the mother and the child, brought on mainly by excess exposure to environmental toxins and inadequate sunlight exposure to the skin, leads to widespread hypomethylation in the fetal brain with devastating consequences. We show that many seemingly disparate observations regarding serum markers, neuronal pathologies, and nutritional deficiencies associated with autism can be integrated to support our hypothesis.

Keywords: autism; epigenetics; cholesterol sulfate; DNA methylation; sulfotransferases; heparan sulfate; folate; cobalamin; zinc

Folks from MIT are usually pretty good about getting things figured out right. They manage to integrate many disparate observations into a coherent whole package at the level of enzyme systems and biochemistry.

While many different markers have been observed to be abnormal in association with autism, reduced levels of plasma sulfate and subsequent reduced sulfation capacity are among the most consistent findings in autism research [3]. A recent interest in sulfated glycosaminoglycans (GAGS) has spurred investigations highlighting the importance of sulfate in the developing brain [4]. It is proposed here that sulfate depletion, caused by a combination of various environmental factors and genetic predispositions, is an important contributor to the development of ASD, and that epigenetics plays an important role in readjusting the phenotypical expression to cope with a sulfate deficiency.

The idea that impaired sulfate metabolism is a key factor in autism is not new [5–7]. An excellent review chapter [6] discusses several abnormal factors related to sulfate chemistry that have been found in association with autism. Observed serum imbalances include low plasma levels of free sulfate, abnormally high ratios of plasma cysteine to sulfate, and high loss of sulfite, sulfate and thiosulfate through the kidneys, as well as reduced levels of urinary thiocyanate [6]. Additionally, many sulfatedependent neurodevelopmental processes have been found to be defective in association with autism.

The sulfate pathways matter, it shows up in lab tests, the developmental pattern of the brain is changed with low sulfate levels, and it is related both to the mother and child level of sulphate as there is an epigenetic component to the process.

In the remainder of this paper, we will first discuss the importance of sulfation in biology. We will then look specifically at the role of sulfate in the developing brain, focusing on serotonin and the glycosaminoglycans. We next turn our attention towards evidence of abnormal sulfate metablism in association with autism, including impaired sulfoconjugation capacity and increased sulfate excretion. We will then discuss available theories concerning possible causes of this impairment, including genetic effects and environmental effects. In particular, we will emphasize the effect of insufficient sunlight exposure to the skin and will argue that this issue goes beyond vitamin D3 deficiency. We further discuss how other known characteristics of children on the autism spectrum, such as gastrointestinal problems, increased androgen levels, and increased inflammation, can be explained by the sulfate deficit, and we will show that treatments aimed at repairing sulfate metabolism have shown some benefit. Finally, we will discuss the evidence for an epigenetic effect related to genomic hypomethylation in the fetus in association with autism. We conclude with a discussion section where we elaborate on our hypothesis and demonstrate how it can explain all of the complex factors associated with autism. Finally, we discuss simple lifestyle changes that could be implemented to address the problem.

That “addressing the problem” is mostly about eliminating the development of new cases, only a little bit about small improvements in present cases.

Of particular interest to me was the sun connection. Sunlight does more than just make Vitamin D. It also forms cholesterol sulphate and make sulphate available to the body. Or recent life style habits of hiding indoors and being covered in clothes or slather on sunscreen may well be partly causal in a sulfate deficit and some of the resulting risk of autism.

I’m skipping over a lot of the evidence and specific discussions of metabolic pathways and biochem. For that, read the article. Mostly I’m quoting bits with interesting observations and conclusions in them.

Sulfate is a vital nutrient required for proper development, and as such, normally flows in abundant supply from the mother to the fetus. The developing child receives sulfate from the mother through the placental villi and later through colostrum, the mother’s first milk [28]. Especially during the third trimester, renal reabsorption of inorganic sulfate increases in the mother, increasing serum sulfate levels. This causes an increase in inorganic sulfate concentrations in the mother’s amniotic fluid and an enrichment of cholesterol sulfate in the placental villi. It has been hypothesized that sulfation of cholesterol, making it amphiphilic, allows it to penetrate the placental barrier [29]. It also then becomes a potential source of sulfate to the fetus. Cholesterol sulfate levels in the villi rise dramatically throughout pregnancy. The concentration of cholesterol sulfate increases from 3.93 to 18.35 to 23.75 pmol/mg dry mass over the course of the three trimesters, a six-fold increase from the first trimester to the third trimester [30]. During this same period, serum inorganic sulfate in the fetus is even higher than serum inorganic sulfate in the mother [20].

Within the brain, sulfate transporters are expressed most strongly in the cerebellum and the hippocampus, implying that these two regions carry out important processes requiring sulfate regulation [31]. Interestingly, both of these brain regions have been implicated in the pathogenesis of autism

There is a huge rise in suphate demand in the developing child and the mother provides that if available. So staying out of the sun, slathering on sunscreen, not eating sulphur rich foods (i.e. the present fad of avoiding meats, eggs, cheeses, etc.) all challenge this need for extra sulfate. The result may well be epigenetic changes if sulfate is low.

Of special interest is a recent discovery that a postnatally induced heparan sulfate deficiency in the brain is capable of causing autistic behavior in mice, including impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, all without causing detectable changes in cellular arrangement in the brain [38].

They’ve done it in mice.

Consistent with the idea that excess levels of serotonin are involved in the pathogenesis of autism is the fact that prenatal cocaine exposure, which increases serotonin, is heavily associated with autism at a rate of 11.4% [46]. A strong connection exists between autism and Smith-Lemli-Opitz Syndrome (SLOS), which is caused by a defect in the enzyme catalyzing the last step in cholesterol synthesis. Fifty three of those with SLOS develop autism [47], which might also be explained through serotonin, as cholesterol depletion has been shown to cause a loss of serotonin transporter (SERT) activity [48].

Don’t do coke, and you need cholesterol, so being on hyper low cholesterol diets might not be a bright idea.

There are two routes for the metabolism of homocysteine in the body, the first of which leads to methionine through the methionine synthase reaction, and the second of which leads to cystathionine, catalyzed by cystathionine beta synthase (see Figure 1). The methionine synthase route enables methylation, while the cystathionine route protects from oxidation. Thus, low methionine levels will lead to reduced methylation and low cysathionine levels will lead to increased oxidative stress. Due to the fact that the methionine synthase reaction relies on B12, folate, and the reduced folate carrier, a lack of any one of these components will ultimately impair methylation. Zinc deficiency may also play a role.

You need your vitamins and minerals. Especially B12, folate, and zinc. Genetic defects in their metabolism may also be a problem (that was in the next paragraph that I left out. ;-)

This suggests that the consequence of less effective methionine metabolism might be more relevant during the period when the fetus is developing in utero. Given that hyperhomocysteinemia, along with reduced levels of B12 and folate, is associated with obesity [61], this might help to explain the association between obesity in the mother and autism risk in the child [62].

Along with folate, cobalamin is also a critical cofactor in the methionine synthase reaction. One protein of interest in this process is transcobalamin II (TCN2), the transport protein which mediates the cellular uptake of B12 [63]. In this case, the TCN2776GG variant, which has a decreased binding affinity for B12, reduces its cellular uptake. This allele was found to increase the risk of autism 1.7-fold [55]. Indeed, it has been observed that B12 deficiency is associated with developmental regression that in many ways parallels the observed pathology associated with autism [64].

Cobalamin too. If prone to obesity, this might indicate a genetic problem with those vitamin pathways so special care is in order.

hydrolyzes homocysteine thiolactone [65], thus participating in its conversion to sulfate [66]. An association between reduced PON1 activity and autism in the United States was reported in [67]. Factors which might have contributed to this deficiency that were considered included excess dietary high fructose corn syrup (HFCS), insufficient dietary magnesium, and exposure to mercury. An association between PON1 deficiency and HFCS exposure has been confirmed in rats [68].

Overall, low methionine levels are observed in many children diagnosed with autism. As oxidative stress reduces methionine synthase activity [57], a combination of genetically impaired folate transport, B12 transport, and oxidative stress might work in tandem to produce this outcome.

Rats fed high fructose corn syrup have their enzymes (PON1) shift in the same direction as that seen in autism and in a way that interferes with sulphate metabolism. Exposure to oxidative stress and mercury not helpful (and can be contributory) and keep your magnesium levels good too.

In short get some sun and avoid the crap foods and HFCS laden sodas and crap packaged junk foods. Keep toxin exposure down.

Certain genetic tendencies related to the uptake of folate and B12 increase the risk of autism substantially, but they do not act alone. It has been found that three genetic risk factors for autism: variants in catechol-O-methyl transferase (COMT), methyl tetrahydrofolate reductase (MTHFR), and cystathionine beta synthase (CBS) act in tandem with vitamin depletion to increase autism risk [74]. This is an especially important issue for the many Americans who do not meet the RDA of these vitamins.

Increased use of sunscreen and decreased exposure to the sun may also play a role in the development of autism.
One possible mechanism is through vitamin D, which appears to regulate the sodium-sulfate cotransporter NaSi-1. Mice lacking the vitamin D receptor (VDR) had NaSi-1 expression in the kidney which was reduced by 72%, causing urinary sulfate excretion to increase by 42% and serum sulfate concentration to decrease by 50%.

Individual genetics play into enhanced risks, so some folks need to be more careful than others. If an at risk type (relatives with issues or family history) be especially careful with nutrition levels.

Mice models demonstrate that the sun induced sulfate and Vit-D is important since knocking out the receptor for Vit-D caused a lot of sulfate dumping from the kidneys. Get your sun, don’t be over using sunscreen. (And think about adopting a mouse ;-)

In [29] and [76], we proposed that sunlight exposure to the skin is essential not only for vitamin D3 synthesis, but also for the synthesis of sulfate in the skin, and subsequently its combination with cholesterol to form cholesterol sulfate. The skin synthesizes an abundance of cholesterol sulfate, and it has been proposed that the skin is the major supplier of this nutrient to the tissues [77]. In fact, many sunscreens contain a form of retinoic acid (vitamin A) which is a known inhibitor of cholesterol sulfate synthesis by squamous cells in the epidermis [78]. Cholesterol sulfate supply would likely be severely impaired in SLOS–over half of SLOS children are diagnosed with autism, and it is likely that impaired synthesis of cholesterol sulfate in the skin leads to impaired sulfate supply throughout the body. We propose that a similar impairment in the supply of cholesterol sulfate due to the impaired sunlight stimulated synthesis of sulfate in the skin may be implicated in many other cases of autism.

There is a known defect that causes some autism by impairment of cholesterol sulphate, so it is highly likely that other impairment of cholesterol sulphate formation could also cause autism. Sunshine is good. Cholesterol is good.

In fact, there are several epidemiological clues that sunlight exposure in the mother, proposed here to protect against sulfate deficiency, is preventative of autism in the child. Pregnancies which occur in northern latitudes and births timed so that the third trimester corresponds with the late winter or early spring months are more likely to produce a child with autism [79]. In Nordic countries, mothers from foreign backgrounds, who often have darker skin, wear more conservative clothing, and consume reduced amounts of protective foods such as meat and fish, are more likely to have children with autism [80].

Especially in the third trimester when sulfate demand is highest in the fetus, get your sun or use a UV “Lizard Lamp” of the kind prescribed for Seasonal Affective Disorder. Avoid wearing a burka. Get out there in the sun and show some skin. Enjoy your meat and fish.

Another increasingly common condition associated with a vitamin D deficiency [82] is diabetes, which has recently been shown to be the most important prenatal maternal risk factor for the development of autism [62]. Interestingly, vitamin D3 in the mother is also a risk factor for the development of preeclampsia [83], which, in turn, is also a strong risk factor for future autism in the fetus [84].

I just have to wonder how much of the “Diabetes Epidemic” is due to sucking down quarts of high fructose corn syrup and sitting inside way from the sun, or covering up in paranoia with excess clothes and sunscreen when going anywhere near outdoors…

In those individuals already compromised by a reduced sulfation capacity, postnatal administration of acetaminophen (branded as androsten, paracetamol or tylenol) could be partially responsible for the rise in autism. Acetaminophen is a xenobiotic which is neutralized and metabolized by the body largely through sulfation, and administration of acetaminophen to rats has been shown to dramatically reduce sulfation capacity to the point of saturation [85]. In fact, acetaminophen use following the measles-mumps-rubella (MMR) vaccine in children has been shown to increase the subsequent risk for autism, and particularly for regressive autism [86].

Shoving Tylenol into your kid at every cry or red spot is a bad idea. Not only does acetaminophen risk blowing out the liver of adults; it screws up your sulfate metabolism and coupled with the stress of a vaccination could be a Very Bad Idea for infants.

As I recall it, our pediatrician was fond of pushing Tylenol at the kids for any discomfort, and offered it after our MMR vaccine and we declined (partly due to my “paranoia” about it… that is looking ever more justified…)

Methionine synthase (MS) activity has been shown to be significantly susceptible to deactivation by numerous environmental toxins [87]. Both heavy metals and the ethylmercury-containing vaccine preservative thimerosol potently interfere with MS activation and impair folate-dependent methylation. Further, it has been demonstrated clinically that elevated mercury body-burden in subjects diagnosed with autism was associated with transsulfuration abnormalities, likely arising from increased oxidative stress and decreased detoxification capacity [88].

In a multi factor causality, you don’t want to be adding factors. Heavy metals, like mercury, are another factor. So thimerosol alone may not be a problem, and vaccination alone may not be a problem and Tylenol alone may not be a problem, and low cholesterol sulphate from sunscreen use may not be a problem, but stack them all up you can have a problem… So just say no to each of them. Then put back in the vaccinations on a schedule that does not increase risks.

Each is shown to have a contributory effect to the sulfate availability suppression. Removing each will help get normal sulfate.

Depleted cysteine stores, as in the case of autism, stress both sulfate and glutathione synthesis, since both processes compete for cysteine. As expected, this leads to low levels of glutathione (GSH) in autism. Low GSH results in an increase in inflammation, microglial activation, neuro inflammation, and expression of nitric oxide (NO) through inducible nitric oxide synthase (iNOS), all pathologies found in autism [100–102].

In addition to the ‘gut’ effects (leaky gut, various sensitivities) it looks like low sulfate can also cause excess inflammation. Along with other effects. I wonder to what extent getting sulfate levels up can help with generic inflammation related diseases. Get some sun, soak in a mineral bath, suck down a mineral water, and have a bit of BBQ. See if that arthritis lets up…

I found this next bit particularly encouraging. While not a cure, it can be helpful:

7. Increasing Sulfate Levels Can Help Alleviate Autistic Symptoms

Although much of the pathology associated with autism seems, unfortunately, to be related to brain development during the critical period and is irreversible, an increase in sulfate levels has, in fact, been shown to alleviate symptoms in some children diagnosed with autism. In one study, a reduction in urinary sulfate excretion achieved through supplementation with molybdenum, an essential metal catalyst in sulphite oxidase, correlated with improvement in autistic symptoms in patients [7]. Oral and transdermal glutathione supplementation, administered to children on the ASD spectrum, led to significant increases in plasma reduced glutathione, sulfate, cysteine, and taurine [103]. In the case of autism, which is hard to pin to one definite cause, it is becoming clearer that many different pathologies lead to the sulfate deficiency which in turn contributes to neurological damage.

Depending on the root cause of the sulfate deficiency, different dietary supplements may be beneficial in treating autism. These include, specifically, the vitamins and minerals involved in the transsulfuration pathway (Figure 1): B12, B6, folate, magnesium and zinc.
While several of these nutrients have been proposed for the alleviation of autism, findings have been generally inconsistent [104,105]. It is likely that the dysfunctional intestinal epithelium impairs uptake of these nutrients [106].

So getting the sulfate levels up can be helpful. I’m surprised they didn’t mention the direct absorption via a bath in Epsom Salts or just taking a bit of Epsom Salts in water. Dasani Water, IIRC, has MgSO4 in it. Correcting specific vitamins and minerals can also be helpful.

The article then goes on into a discussion of epigenetics that is quite interesting, and the potential that low sulfate in the mother may lead to epigenetic changes in the child to adapt to low sulfate availability (via methods that cause other problems…). So it is important for Mom to get some sun, not suck down too much HFCS, and have good sulfate levels.

DNA methylation is the first layer of epigenetic effects, and environmental toxins negatively impact DNA methylation globally [11]. Maternal supplementation of folate, particularly in the month before gestation and the first two months of pregnancy, has been demonstrated to have a strong protective effect against autism in the fetus. This could be directly attributed to the important role that folate plays in the methylation pathway. However, one has to be cognizant of the effect that folate will have in redirecting methionine towards methylation pathways rather than towards sulfation pathways, thereby introducing further strain on the sulfation system under conditions of sulfur deprivation.

Keeping maternal folate levels up is important, but increases the need to keep maternal sulfate levels high as it creates a competition between two pathways that can show up in epigenetic methylation changes.

The paper then goes on for quite a while admiring the particular genetic / epigenetic changes observed in various rodents and people and drawing the connections… It gets a bit thick then, but here is an example.

We have previously proposed that endothelial nitric oxide synthase (eNOS) is a moonlighting enzyme whose main product is sulfate, catalyzed by sun exposure, and, further, that the sulfate is combined with cholesterol to produce cholesterol sulfate in the skin, which is then transported to all the tissues. The enzyme’s physical structure suggests that cobalamin may facilitate the reaction, as it fits snugly into the heme pocket of NOS isoforms, and is known to inhibit nitric oxide synthesis [126]. eNOS switches to nitric oxide (and hence nitrate) synthesis following calcium entry, calmodulin binding and phosphorylation [127], which we view as a pathological response. eNOS is membranebound in caveolae in its so-called “inactive” state, and caveolin suppresses nitric oxide synthesis. Nitrate can substitute for sulfate for ionic buffering in the blood, but the resulting global sulfate deficiency has pathological consequences [76]. Indeed, autism is associated with excess nitrite and nitrate in the blood [128,129]. We hypothesize that the 1,047 genes that were upregulated and the 444 genes that were downregulated as a consequence of hypomethylation during embryogenesis [108] have to do with adjusting system-level parameters to account for severe sulfate deficiencies.

The basic idea being that you can shift to a nitrate buffer instead of a sulfate buffer in emergencies, but it has costs. So you can still have a viable child during conditions of severe sulfate shortage, but not an ideal one. So better to avoid those epigenetic gene regulatory changes and keep the sulfate levels proper to begin with.

Specific experiments involving the agouti mice are compelling and supportive of our hypothesis. In [123], it was demonstrated that prenatal exposure to the estrogenic environmental toxin, bisphenol A (BPA), induced non-specific gene hypomethylation, leading to favored expression of the yellow phenotype. However, concurrent supplementation with folate, cobalamin, betaine and choline, important nutrients for the supply of methyl groups, abolished this effect.

Again with the mice… poor dears… but this time demonstrating an epigenetic impact on them from Bisphenol-A causing hypomethyltion (a bad thing). But enough vitamins and supplements could prevent it. Lending some credence to the Bisphenol-A as yet another cofactor / partial factor. So best to just avoid it in plastic baby bottles and plastic soda bottles and plastic can liners and…

And folks wonder why I like to eat food that is not packaged in plastic nor heated in plastic…

And then there is this bit. A rather complex interaction of the mother taking added folate, but being low on sulfate, leading to a worse result. I wonder how many mothers were taking their added folate, but avoiding the sun and using a lot of sunscreen… and on a low cholesterol diet.

While folate deficiency is recognized as a risk factor in autism, folate supplementation has met with varied success [135]. Interestingly, these authors propose that there may be a specific relationship between regressive autism and poor response to folate therapy. Furthermore, others have found an autoimmune reaction to folate in the central nervous system in association with autism, which prevents its transport across the blood brain barrier, even when levels are sufficient in the blood stream, associated with the so-called cerebral folate deficiency (CFD) syndrome [136]. In a study of 93 children with autism, over 75% were found to have CFD syndrome, and 44% of the parents who were tested also had the condition.

We hypothesize that all of these observations can be explained if we envision a scenario where the mother is supplemented with folate during gestation, but is severely deficient in supplying cholesterol sulfate to the fetus.
The folate will redirect methionine towards methylation pathways rather than sulfotransferase pathways, thus further depleting the already dangerously low sulfate levels. However, the bioavailability of methyl groups will result in a false sense of security, whereby hypermethylated DNA sets up a phenotype that anticipates sulfate sufficiency. It is only after birth and continued subjection to factors that further deplete sulfate, such as lack of sun exposure and toxic environmental chemicals, that the autoimmune reaction to folate develops to spare methionine for its urgent need as a source of sulfate in the brain.

Their ‘wrap up’ reads to some extent like a list of things to do that doctors have been telling folks NOT to do for the last few decades… Gee, I wonder…

If our hypothesis is correct, then there is some optimism that reversing the epidemic would not be difficult. If people can be made aware of the importance of sun exposure to the skin to health, then they can alter their lifestyle habits to spend additional time outdoors without sunscreen. Dietary changes involving increases in foods that are good sources of sulfur, such as animal-based proteins and cruciferous vegetables, will help to assure an adequate supply of sulfur, the substrate for sulfate synthesis. Foods that are rich in choline, betaine, folate, cobalamin and zinc would also be encouraged, as these nutrients play an important role in the methylation and sulfotransferase pathways. People should also be encouraged to consume cholesterol-rich foods, as this lessens the burden for cholesterol synthesis, and will likely increase the bioavailability of cholesterol sulfate. Finally, people should make a conscious effort to minimize exposure to xenobioics, which deplete sulfate supplies. Whether the damage can be repaired in individuals already on the autism spectrum is doubtful, but enrichment along these lines would surely be of benefit to them as well.

Xenobiotics is a “polite” way of saying “foreign chemicals” like Bisphenol-A, Tylenol, and all that laundry list of chemical soup on most processed packaged foods…

So avoid the chemical soup. Get some sun on bare skin without sunscreen. Eat your cholesterol rich foods like eggs, sea food, and meats. Animal foods. Oh, and your cabbages and kales and turnips.. you know, all those ‘stinky vegetables’ that trendy folks like to avoid…

For completeness, here is the conclusion entire:

10. Conclusion

In this paper, we have presented the novel hypothesis that there is a strong link between DNA hypomethylation and sulfate deficiency, both of which have been proposed as key factors associated with autism spectrum disorder. Methionine sits as the crossroads of the methylation and transsulfuration pathways, and thus a deficiency in methionine supply impacts both systems. We hypothesize that insufficient sun exposure to the skin compromises the supply of cholesterol sulfate both to the fetus and to the infant postnatally, and that the concurrent exposure to environmental toxins further depletes sulfate and sulfur metabolites. We further hypothesize that hypomethylation during gestation implements a switch towards the production of nitrate rather than sulfate for ionic buffering in the blood stream, and that this has huge negative consequences due to the critical need for sulfate in neuronal maturation. Confirmation of the hypothesis awaits further studies. If our hypothesis is correct, then increased dietary sulfur and increased sun exposure for both the mother and the infant should be strongly encouraged, along with avoidance of exposure to sulfate-depleting environmental toxins.

“Methionine” is found in meats… So we have here a statement to eat some meat, do it in the sun, avoid the chemical crap, keep your cholesterol intake at a good level, and make sure you have a good sulfate intake. (My preference would be some time in the mineral bath and drinking mineral water, but YMMV.)

In other words, ignore the advice to slather on loads of sunscreen. Don’t be paranoid about sun exposure. Tell the folks nagging you about meat and eggs and cholesterol to go stuff it, and treat yourself so some well deserved time at the spa. Be a bit of a hedonist and enjoy life and the rich foods it offers. Kind of the exact opposite of some of the paranoid self flagellatory advice from the “usual suspects”… Oh, and toss the chemical factory foods and keep you and the kid off of Tylenol and away from plastic packaging with Bisphenol-A and similar substances. Have real foods, prepared at home from whole ingredients and in a natural setting. Roast a chicken, or mash some potatoes, and put butter on them. It’s Fine.

That’s what this is saying to me. But as I could be wrong, please read the whole paper yourself. You might well pick up something I’ve missed or gotten wrong. Me? I’m going to go have a ham and cheese omelet for breakfast… with buttered toast on home made bread. Washed down with a bit of sulfate rich mineral water and coffee.

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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
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17 Responses to Autism, Sulphate, Sunshine, and Nutrition

  1. Petrossa says:

    I wrote this about nutrition and autism:
    This annoying article cropped up and irritated the hell out of me. Why? Because Autism is a catchall for anybody with autistic symptoms, so is so diverse it’s totally impossible to say if ANY treatment effectively prevents/heals/lessens TRUE autism. True Autism being a genetic neurological disorder, and DSM defined Autism being whomever passes the DSM autism test. As with most definitions in the DSM, whichever version, the relation between the tests for the definition are wholly based on the assumption that the definition is correct in the first place. Which is a remarkable circular (lack of)logic since the DSM contains mostly observationally based selfconfirming definitions. There is no objective way to determine if they hold water.

  2. P.G.Sharrow says:

    Thank you for the above post. As one that is somewhat autistic any insight on minimizing it’s effects is welcome. As I age, over the last few years it seems to be getting worse. Loud busy crowds are getting more difficult for me to tolerate. Autism does have a benefit, I can pick up more details from the world around me then normal people. This often leads to distraction and overload. A few drinks reduce the sensitivity, but I hate being drunk and the next days aftermath. I will try increasing sulfates. More turnips and cabbage! And garlic of course! 8-) pg

  3. E.M.Smith says:


    In some ways it is worse than that… At schools, they are now combining what were different “diagnoses” into one catch all and tossing nearly anyone with ‘behaviour issues’ into it. ADHD, Aspergers, Autism now all just “ASD” Autism Spectrum Disorder.

    I’m sorry, but true Autism is so incredibly different from a “High function Aspergers” and both are orthogonal from the ADHD guy running around banging into the walls….

    They really need to keep these distinct, and with distinct paths of ‘treatment’.

    As to “cause”:

    Yes, some is ‘genetic predisposition’. But a lot is environmental triggers as well.

    Just saying “Genetic” doesn’t cover it. (In fact, for most “genetic” diseases there is still an environmental component; genes give a predisposition but are not the end of the story.)

    There are also many genes involved; and, as shown in the article, epigenetic changes that are not coded into the genes, but still modify the expression of them.

    Furthermore, just slapping the “genetic” label on something does not remove the ability to treat it environmentally nor prevent it via environmental changes.

    The most direct example I can think of is Favism. Clear genetic determination of who gets it and who doesn’t. Yet the eating of Fava beans is needed as the environmental trigger. (They raise oxidative stress in red blood cells, as does the Favism gene, and the ‘double dose’ causes the disease as the red blood cells start failing.) So you can ‘cure’ it by just not eating Fava beans.

    So ought we to ‘breed out’ the Favism “defective” gene? Well, no. It is an adaptation that provides better resistance to Malaria (that are killed by oxidative stress in the red blood cells). It is neither ‘good’ nor ‘bad’ but a bit of both. (Like many genes).

    Oh, and there are several variations on that gene, so different degrees of Favism and malaria resistance. Nature is trying to evolve a malaria cure and it is a work in progress…

    Now autism / ASD is much more complex. (As shown in the article) with many contributor genes as “possibles” and many environmental risk factors as potential triggers / cofactors / causal. All interacting.

    So ought we just ‘breed out’ the genes that tend toward the occasional Austistic / Aspberger’s kid? Well, no. “Some” of the trait leads to much higher mental performance. It is only ‘too much’, or when pushed by “too much environmental insult”, that the “problem” shows up. It would be a bit dumb to throw away genes that improve some mental functions in order to accommodate more “crap” in the environment.

    You have clearly demonstrated a desire to “bucket” things into “genetic” and be done. Dismissing environmental from that point on. That is a mistake. Genes only matter in the context of the environment. (Actually, worse than that, the PAST environment of both the individual and the mother can have epigenetic control of the genes causing more changes and dependency on past exposures. Read the part in the article about “agouti” mice… )

    So we can change the coat color of agouti mice via environmental changes. Based on a particular gene. Similarly we can ‘turn on’ or ‘turn off’ various genes via environmental triggers. This is all “old hat”. At a very basic level, for many “genetic” diseases it is flat out wrong to think of that as the end of the story. It is often only the beginning. That is why genetic studies are so careful to say “genetic predisposition”; as that is all it may be.

    (There is an interesting disease caused by exposure to a particular grain contaminant weed seed. Modest amounts cause some folks with ‘genetic predisposition’ to become ill. Higher exposures push more ‘normal’ folks into illness. That’s the more common model. Genes make a modest bias on which the environmental factors play out.)

    So, irritate you or not, foods we eat are an environmental trigger for all sorts of diseases, including ASD. Avoiding some foods and adding others can have real and significant benefits. This is not a hypothetical and not speculative. It is clearly demonstrable and often known down to the particular enzymes and pathways involved. ( PKU and aspartame are a stellar example – don’t drink Nutrasweet soda if you are PKU genetics.)

    In particular, just being ‘dismissive’ as in ‘it is genetic so food does not matter’ completely misses the ability to adapt and treat via accommodation of what is consumed. So in the following quote from the article, they find minor defects in folate transport may be partially contributor. Yes, genetic ’cause’. Yet an obvious treatment of having excess folate so slow transport is less important immediately suggests itself. (There are likely other modes of treatment available as well, perhaps even modification of diet to reduce the body demand for folate in other uses).

    Another gene involved in the transport of folate is methyltetrahydrofolate reductase (MTHFR). The MTHFR 677T allele, which is associated with reduced synthesis of metabolically active folate, also confers a higher susceptibility to autism, especially when paired with the RFC1 G allele. In fact, a combination of the RFC-1 80GG allele and the MTHFR 677CT genotype was found to increase the risk of autism three fold [55]. Overall, these data seem to support the idea that a genetic tendency toward a folate deficiency induced by impaired folate transport may alter methionine metabolism and cause a predisposition towards autism.

    As genetics are often a ‘spectrum’ of variations on their own, I’d expect some genotypes to have different degrees of folate transport efficiency. (Nature does not like wasting energy on overly perfect systems…) This, then, implies that in addition to folks with “broken” folate transport who would have a very high degree of risk of autism, there would be some folks with “reduced” transport where they are at low or no risk on high folate diets, but under marginal or deficient folate intake would be at high risk. Would you condemn them to high autism rates as it is “genetic” rather than say “take a vitamin with folate in it when pregnant”? Or even just “eat high folate foods”?

    That is the much more common “genetic’ model. Folks on one end who have a ‘broken’ gene and a disease. Folks on the other end with genetics that don’t lead to the disease under “normal” environmentals. Some folks in the middle who can go either way depending on environment. All natural and all inside normal human genetic variation.

    So some folks with Favism can eat some fava beans and be OK. Some eat fava beans and die. Some “normal” folks don’t feel good if they eat fava beans. Other folks don’t have any problem at all with fava beans (but likely are not as able to recover from malaria). Who is “normal” and who is “broken”? (Personally, as I don’t like fava beans, I’d be happy to put them on the ‘avoid’ list in exchange for malaria resistance…)

    In ASD kids, what they eat can ‘send them around the bend’ far more than “normal” kids. There are several parts of this that are known (some details in the article) including ‘leaky gut’ that looks to also be partly caused by low sulfate levels. “Leaky gut” is also implicated in various folks who get ‘reactions’ to foods as larger protein fragments can get through the gut into the blood where the immune system then attacks them as ‘foreign’ (some times after being incorporated into body parts, leading to ‘auto immune diseases’). As I’m prone to arthritic “problems” when eating “cow stuff” I likely have a slightly ‘leaky gut’. That added sulfate in the diet could “fix that” is rather important to me. I don’t really care if the “cause” is low sun exposure (as I hide inside in winter), a ‘different’ genetic predisposition, epigenetic from something Mom did, or didn’t do, reflecting in my gene methylation status, or just that I’ve not eaten much sulfate rich foods. No, what matters to me is that some added MgSO4 in my diet could very well increase gut lining sulfate levels and fix that problem.

    Just dismissing it as “genetic” also dismisses the potential ‘easy cures’.

    So like it or not, irritated at it or not: Diet can directly modulate “genetic” diseases including ASD and “spectrum” disorders.

    Oh, I probably ought to add that you do not go from 10,000 : 1 ratio of disease to 56 : 1 ratio in one generation based on a ‘genetic’ cause. That’s something (or things) environmental that have changed. Likely now impacting nearly “normal” genetic types. I’d expect lack of sun, avoidance of ‘animal foods’ and cholesterol, and too many xenobiotic chemicals all in combination. Easy to fix by just going back to the environment type in which we evolved…


    Glad to have offered some ideas on things that might help.

    FWIW I’ve found that Bendaryl can also reduce the ‘sensitivity’ some. (It also increases the ‘punch’ of alcohol, so you will get ‘medicinal effect’ or ‘drunk’ on less, which can reduce next day aftermath ;-) I’d be careful about prolonged use, since it does suppress some of the immune response and might increase risks of some bad bugs moving in, but it has been helpful to have some on the keychain pill box. Out in a crowed at a late ‘social event’ and wanting to escape or tune it down… well, it’s a quick and easy patch. Does cause some drowsiness, so best when feeling a bit ‘hyper’. Instead of hitting the bar and downing a bottle of wine, one pill and a glass in hand is often enough. Just be ready to find some espresso if you think you will be driving home later ;-)

    I’m also going to be experimenting with ‘trivial’ levels of Epsom Salt intake. Like putting a fractional gram in my coffee or some such. As a spoon full is used as a laxative, the risk from a 1/8 tsp is near nill. (Hmmmm…. many autistics have constipation… perhaps an indicator of low sulphate levels in the gut?…. )

    It also looks like making sure specific vitamins are at high levels can be helpful. So experimentation with B12, Folate, etc. might be in order, even going to above normal levels.

    I find it very encouraging that folks are getting down to the level of particular enzymes, genes, cellular mechanism, et. al.

    I wonder if your choice of profession (being in the sun a lot) was partly from the ‘feel better’ from the sun mediate cholesterol sulfate production. BBQ in the sun and all… Folks tend to gravitate to where they feel better. And that’s a good thing. ;-)

    Well, in the spirit of this article, I’m going out to get some sun …

  4. P.G.Sharrow says:

    @EMSmith says;Bendaryl before a loud party.
    I will have to try that the next time I have to do a large party. I always have it on hand for histaminic attacks. It is embarrassing to have to flee from a party where everyone is having a great time and I feel as if I am going to EXPLODE! pg

  5. Tim Clark says:

    {There is an interesting disease}

    You mean ricin from castor bean?

  6. Tim Clark says:

    {Loud busy crowds are getting more difficult for me to tolerate}

    That’s just age. I’m not autistic and I’ve lost tolerance. ;~)

  7. Verity Jones says:

    Ooooh! I will have to come back and read this properly tomorrow. I’m traveling again (when am I not these days? – or at least it feels that way). I spent part of the long car journey wondering about sulphate and hydrogen sulphide as detox mechanisms. I wonder if it is to do with the type of metabolism that is generating the free radicals – H2S is a reducing agent and ought to mop up oxidised products (we hear so much about antioxidants these days). The sulphation I remembered poorly and not helped by the quick read when I found the ref last night. Perhaps there is a sulphur cycle in cells…. I did of course remember your Mg / Epsom salts stuff.

    Here’s another one I’ve started to investigate – fructose (especially high fructose corn syrup) and leptins.

  8. adolfogiurfa says:

    IRON SULFATE (Ferrous Sulphate) is mandatory added to flours in many countries.

  9. Petrossa says:

    I just avoid crowds. Avoid people in general actually. Avoid noise, light. I’m a quite happy recluse. No need for all kinds of placebo’s.

  10. jradig says:

    A bit of a tangent to the autism focus of the article, but here’s an interesting presentation of another reason why more exposure to the Sun is probably a good thing. One factor that ties in with the article here is the idea that sun exposure triggers synthesis in the skin of beneficial chemicals.

  11. nemesis says:

    My Dad was very keen on growing Roses, that is until the ‘Clean Air Act’ (UK) came into force. After that time he found that his Roses suffered from ‘Black spot’ and other diseases and he gave up growing them. He put it down to the subsequent lack of sulpher in the air. If sulpher or lack of it can have such an effect on plants, should it not also have an effect on humans? Does it also tie in with the increase in Autism?

  12. E.M.Smith says:


    Maybe sulphur in particular, or might just be that the rain was a bit acidic and the “Black Spot” doesn’t like acid.

    As a key element in many metabolic pathways, sulphur is critical and defects (in metabolism or in cofactors or in availabillity) will have “bad things” happen. That most of the time for most people the available sulphate is enough just means lots of folks don’t notice what happens when it is broken.


    Nitric Oxide too, eh? So that’s three compounds from sun on skin… ( Vit-D, Cholesterol Sulphate, Nitric Oxide). One wonders how many more are made, and not noticed… None of those account for the S.A.D. issue either. Looks like sunlight in general, and “Enough UV” in particular, are very important…


    It isn’t a placebo. It is a neurological depressant / anesthetic. Very real effect. FWIW, you can use benadryl powder as an emergency topical anesthetic for minor surgery. Dump a capsule of the dust into the mouth and “things go very numb”. Only for a couple of minutes, though, so you need to work fast.

    While I’m happy to be a ‘recluse’ some times; I’m also fond of the occasional “night out” and have learned to enjoy the odd party. Then there are things like “The Kid’s Graduation”… and once you are in a place (like the trip with the spouse to Disneyland) it’s kind of hard to ‘back out’. So having a ‘fall back’ is nice when “things get more than expected”…

    Though, yeah, I’d often rather just curl up with a good book on the couch… ;-)


    While that is added for the iron, I wonder how much benefit comes from the sulphate…

    @Tim Clark:

    No, not ricin. It was a weed common in some grain crop in a Eastern European country. Some folks were tolerant of it, and some more reactive. I need to find that thread again…

  13. Tim Clark says:

    Poison hemlock?

  14. 9/10 post, 10/10 if you could explain how HFCS ties into this sulphate thing

  15. hillrj says:

    EM Have you ever considered the possibility that the autism spectrum extends theough normality to an extreme in the other direction?
    Definition of autism…
    The condition, which can range from mild to severe, is characterized by impaired communication and social interaction./quote.
    I was recently at a social function and overheard a conversation about a local athletic coach.
    “X is very good because X coaches each individual in the squad and understands how to contact them”
    I have met a Hindu Guru who seemed to give every person in a large gathering a feeling of personal contact.
    I postulate a new condtion called tua-ism
    Definition of tua-ism…
    The condition, which can range from mild to severe, is characterized by enhanced communication and social interaction.
    If we find out what causes tua-ism we could get a clue about aut-ism.

  16. E.M.Smith says:

    @Tim Clark:

    You will never guess it as it was some strange Latin species name and nothing ever heard of outside wheat growers… I’ll dig it up again ‘some day’… maybe… (Or you can search endlessly on European outbreaks of disease from odd weeds in grain in small farms and isolated cities… with a genetic predisposition link for some folks…)


    OK, I’m working on it… but since the HFCS link is somewhat new / speculative it is likely going to be a partly ‘hand waving’ link explanation (when I get one ;-)


    It’s called ‘charisma’ and folks like Mr. Clinton have it. I’ve seen a couple of exec types go at it “schmoozing” and oozing on each other. I can spot it a mile away. It also makes me a bit sugar-nauseated to see it in full rut… It’s just so damned transparent that they are trying to stroke each other into a frenzy… Part of why I “can’t do it” is that it IS so transparent a manipulation… at least to me.

    Oh Well…

    But yes, it exists. It is a continuum of the traits. Don’t know if it is ‘related’ though. (kind of like coat color where the gene for black is not necessarily the same as the one for red…)

  17. Pingback: A facinating Ted Talk on UV and heart attacks | Musings from the Chiefio

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