The Autism Metabolism

by Dan@cowseatgrass · Published December 10, 2017 · Updated February 13, 2019

What do hypothyroidism, inflammation, intestinal distress, lipid peroxidation, bacterial endotoxin, oxidative stress, high cortisol, high serotonin, low vitamin D, mitochondrial dysfunction, low cholesterol, iron accumulation, and high nitric oxide, lactate and histamine, all have in common? If you guessed autism, congratulations, you are right.

Ok, yes, you’re also right if you said that these are indicators of stress and metabolic energy suppression. But really, you’d be hard pressed to find a disease or condition that isn’t related to metabolic stress. That doesn’t detract from the argument, because physiology is physiology, even if it’s popular to say otherwise.

“The autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in communication and social interactions along with restrictive and repetitive behaviors…studies support evidence that metabolic disturbances, immune dysregulation, oxidative stress, and toxicant exposures…linked to ASD…Understanding the interaction between ASD and GI symptoms in the context of mitochondrial dysfunction can provide a greater understanding of…biological abnormalities…related to…behavioral manifestations…of ASD…”

But if you look at Wikipedia, you might conclude that nobody really understands anything about ‘autism’. It looks like one big vague and confused – genetically deterministic, lacking in relevant experimental evidence – mess. I’m not going to go into why I think that is…at least not right now.

To be fair, autism gets referred to as ASD (Austism Spectrum Disorder) for a reason. You could say that the severity of the symptoms vary from person to person, and that in reality, they are continuously fluctuating.

Why is that? What makes symptoms worsen or improve? If you believe all the hype about genetics, it doesn’t really make sense for that to be able to happen. Unless interactions between biology as a whole and the environment, is what really matters.

So what, you might ask, does any of this have to do with sugar and the polyunsaturated fats? Well, that’s what I’m going to tell you.

When stress of any kind is high – or goes on for a long time – it tends to go hand in hand with thyroid function suppression. And when thyroid is interfered with, like it or not, that impacts upon biological function in general, including brain development and performance.

“Severe maternal hypothyroxinemia…was associated with an almost 4-fold increase in the odds of having a probable autistic child…We found a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring.”

You can’t really talk about stress and thyroid without also considering energy metabolism. Stress, thyroid and the supply of energy are constantly interacting in a manner which determines overall function.

The biochemical changes common in the etiology of autism, are directly involved with mitochondrial energy systems.

“…multiple biomarkers of mitochondrial dysfunction are elevated in a significant portion of children with autism spectrum disorder and lend support to the notion that disorders of energy production may affect a significant subset of children with autism…”

The ubiquitous consumption of polyunsaturated fats (PUFAs) is a major factor contributing to the rising prevalence of conditions which relate to energy system dysfunction.

When blood sugar supplies run low due to ongoing exposure to stress, PUFAs stored in tissue are released into circulation as free fatty acids, damaging cellular energy systems and causing the release of numerous stress substances known to worsen symptoms of autism.

The breakdown products of PUFAs (due to lipid peroxidation) interfere with mitochondrial function and have been consistently demonstrated to rise alongside increasing severity of ASD symptoms.

“We compared lipid peroxidation status in the plasma of children with autism, and their developmentally normal non-autistic siblings by quantifying the levels of malonyldialdehyde [MDA – breakdown product of PUFA]…Lipid peroxidation was found to be elevated in autism indicating that oxidative stress is increased in this disease.”

“The majority of autistic subjects showed a moderate increase in isoprostane levels while a smaller group of autistic children showed dramatic increases in their isoprostane levels…results suggest that the lipid peroxidation biomarker is increased in this cohort of autistic children…”

“In children less than 6 years of age…MDA was significantly higher among patients than controls…children with autism are more vulnerable to oxidative stress in the form of increased lipid peroxidation and deficient antioxidant defense mechanism especially…younger children.”

“We determined the urinary levels of oxidative stress markers like thiobarbituric acid-reacting substances, lipid hydroperoxides, 4-hydroxy nonenal…observed a significant elevation in the level of oxidative stress markers in autistic children when compared with normal children…when correlated with the degrees of severity, oxidative stress markers showed positive correlation with increasing order of severity…”

There are many good reasons to think that oxidative stress ties in – in a logical, predictable manner – with a number of related physiological changes, causing the so called autistic behaviors and symptoms.

PUFAs directly suppress thyroid function and limit the ability of sugar to be used as energy, leading to rising levels of cortisol (as a means to providing alternative fuel), and high cortisol is another indicator shown to be related to ASD.

“A significantly higher serum cortisol response was found in the group of children with autism. Analysis showed significantly higher peak cortisol levels and prolonged duration and recovery of cortisol elevation…evidence for dysregulation of the HPA stress response in individuals with autism.”

When stress rises and thyroid function is inhibited, digestion is directly effected. You don’t need to look very far to find out that digestive issues always go together with autism, and this is not just some weird coincidence.

“…we found that greater lower GI tract symptoms were significantly associated with cortisol concentration after exposure to stress. This relationship between cortisol response to stress and GI functioning was greatest for children who had a history of regressive autism…significant relationships were observed between the cytokines and irritability, socialization, and intelligence.”

Stress combined with exposure to greater amounts of PUFAs, interferes with digestive function, promoting overgrowth of bacteria as well as a reduction in intestinal barrier function.

This allows for rising levels of the byproducts of bacteria – such as endotoxin/LPS – to pass into circulation in the main system, directly interfering with organ function and escalating symptoms related to autism.

“Compared with healthy subjects, serum levels of endotoxin were significantly higher in autistic patients and inversely and independently correlated with Socialization scores…”

“LPS [endotoxin] serum levels were significantly higher in autistic patients compared to heathy individuals and correlated with socialization scores in an inverse and independent manner. These evidences support a role of microbiota and, generally, of an alteration of the gut barrier in its integrity, in the genesis of ASD.”

To make matters even worse, the combination of PUFAs and endotoxin is well known to cause chronic inflammatory issues, and there is no shortage of information showing the relationship between low level inflammation and ASD.

Looking at these issues independently is one thing, but the truth is you cannot logically separate inflammation and endotoxin and PUFAs and blood sugar instability, or any of the other biological issues I am talking about. Not without creating confusion.

“…present data indicate that an inflammatory response, coupled with increased lipid peroxidation, is present in subjects with ASDs…new insight into the identification of potential plasma protein biomarkers in autism.”

“The significant positive correlations recorded between 8-isoprostan, Leukotriene and PGE2…confirmed the association between the impairment of LCPUFA [long-chain polyunsaturated fatty acids] metabolism together with pro-inflammation and oxidative stress in the etiopathology of autism.”

“Chronic low-grade inflammation is an eminent feature…studies report increased…endotoxin levels and…gut permeability in patients suffering from these conditions….stress-induced increases in intestinal permeability…raise the possibility of translocation of bacteria and/or their toxins across the…gut barrier. The resulting, long lasting, endotoxemia should be considered much more than just a risk factor for chronic disease; it could be a cause.”

“…experimentally-induced inflammation [endotoxin-induced inflammation] can lead to decreases in the ability to accurately and reliably comprehend emotional information from others, which is a critical aspect of social interaction that is altered in neuropsychiatric disorders such as schizophrenia and autism.”

Stress, thyroid suppression and rising bacterial issues have another thing in common, and that is they promote a rise in levels of the substances of stress, nitric oxide (NO) and Serotonin.

Rising levels of NO and mitochondial dysfunction also go together. NO directly interferes with oxidative metabolism and this has been shown to be a factor which is involved in the progression of ASD symptomology.

“…several recent studies proposed that NO may have a pathophysiological role in autism…total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite…levels in the autistic group were significantly higher than control values…”

“Plasma levels of NOx were significantly higher in the autistic subjects…NOx and IFN-gamma levels were positively correlated in the autistic subjects…”

When metabolic energy systems are suppressed and stress is rising, lactate levels are also known to go up, and it is not by chance that lactic acid, NO and lipid peroxidation have been seen rising together in the development of autism and numerous other conditions related to interference with cellular energy performance.

“Plasma oxidative stress indicators such as nitric oxide (NO), malondialdehyde (MDA), protein carbonyl, and lactate to pyruvate ratio were quantified…significant elevation was observed in the levels of NO, MDA, protein carbonyl, and lactate to pyruvate ratio in the plasma of…autistic children as compared to their age-matched controls. These oxidative stress markers are strongly associated with major cellular injury and manifest severe mitochondrial dysfunction in autistic pathology…”

“…children with ASD, as a group, have significantly abnormal values for direct (that is, lactate, pyruvate and ubiquinone) and indirect (that is, carnitine) biochemical markers of mitochondrial dysfunction compared with controls…”

“Lactate as an important energy metabolite for the brain was significantly higher in autistic patients compared to control showing about 40% increase…The present study confirmed the impairment of energy metabolism in…patients which could be correlated to the oxidative stress previously recorded in the same investigated samples…”

PUFAs, and all of the other things that interfere with oxidative metabolism and digestive function, promote the release of serotonin, and it is almost impossible to separate autism from a high serotonin state.

“Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research…our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD…”

“The involvement of…5-HT [serotonin] has been suggested…in autistic disorder. Increased platelet 5-HT levels were found in 40% of the autistic population, suggesting that hyperserotonaemia may be a pathologic factor in infantile autism…it is of interest to assess the efficacy of cyproheptadine, a 5-HT2 antagonist in the treatment of autistic disorder.”

“Mean whole blood serotonin (5-HT) levels were elevated in groups of autistic and severely retarded children. Eight of 27 (30%) individual autistic children, 13 of 25 (52%) severely retarded children, two of 23 (9%) mildly retarded children, and none of the control children had statistically significant blood 5HT levels elevations (hyperserotonemia).”

“In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels.”

I don’t want to go on too much, but there is also the relationship between high serotonin and low vitamin D, toxic levels of iron accumulation in the tissue, rising excitotoxicity and low GABA, low cholesterol and subsequently low progesterone.

All have been shown to result from – or be exacerbated by – exposure to PUFAs (and a number of other stress promoting things), and all can be approached holistically once dietary and other issues responsible, are properly understood.

“It has been previously reported that there is vitamin D deficiency in autistic children…The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group.”

“…evidence of an inverse relationship between maternal 25(OH)D and foetal serotonin concentrations…vitamin D deficiency increases foetal serotonin concentrations and thereby contributes to longer-term neurocognitive impairment in infants and children.”

“The ‘neurodegeneration with brain iron accumulation’ (NBIA) disease family entails movement or cognitive impairment…Abnormalities in brain iron may contribute to various psychiatric disorders, including major depression, bipolar disorder and autism…”

“Since elevated glutamate is coupled with decreased GABA…in…brain of autistic individuals, so elevated PGE2 reported in the present study could be related to the reduced GABA level previously recorded in…autistic patients…”

“…up to 20% of children from a sample of mostly multiplex ASD sibships have substantial hypocholesterolemia…the study of hypocholesterolemia and its predicted effects on neurosteroid metabolism may offer important insights into the cause and treatment of ASD.”

“…low progesterone may be responsible for both obstetrical complications and brain changes associated with autism…ensuring adequate levels of progesterone may decrease the likelihood of autism.”

So stress, PUFA consumption, and blood sugar dysregulation, play a big part in promoting thyroid insufficiency, inflammation and digestive distress. This goes together with rising levels of cortisol, nitric oxide, serotonin, lactic acid, lipid peroxidation, mitochondrial energy system dysfunction, low cholesterol, low vitamin D, low progesterone, iron dysregulation and a few other things.

Sugar, on the other hand, lowers cortisol and limits exposure to polyunsaturated free fatty acids. Sugar promotes cholesterol and thyroid energy metabolism, increasing pregnenolone production, improving digestion, and lowering endotoxin, serotonin, nitric oxide, lactic acid, as well as overall inflammation.

“The fact that the younger children manifested higher levels of the inflammatory marker suggests that inflammation could be a trigger that initiated the mitochondrial dysfunction and damage…”

“…role of mitochondrial function in the GI mucosa and the relationship to GI symptoms observed in children with ASD…many of the GI symptoms have been noted in children with mitochondrial disease, such as gastroesophageal reflux, dysmotility, constipation, enterocyte dysfunction, pancreatic dysfunction and vomiting…”

There are many proven, cheap and safe ways to deal with all of these things, and all of these things have been connected to the progression of autism, yet nobody seems to know about it. Interesting.

I wonder if it could have anything to do with the sale of products which market the often misleading idea that the things that rise under stress are safe to promote or use? No need to answer that.

Many foods consumed today have been shown to be able to create bacterial issues and suppress thyroid function, worsening stress.

Insufficient consumption of low iron, high quality protein, from dairy [also high in calcium relative to phosphorous], helps promote inflammation and thyroid dysfunction. Excessive intake of grains, beans and legumes, as well as under cooked vegetable matter, leads to digestive stress and bacterial issues, as well as being a source of PUFAs and inflammatory levels of phosphorous.

A pro-metabolic diet avoiding PUFAs and excess iron, limiting too many starches and fibrous materials, and providing sufficient protein and other nutrients from milk, cheese and gelatin, and plenty of sugar from sweet ripe fruit, fruit juice, white sugar and honey, is a logical way to reduce ASD symptoms.

There are many other things that can be helpful. I’m not a doctor but it makes sense to me that anything that does help, helps by supporting thyroid metabolism and energy system performance, and by reducing stress and digestive dysfunction. There is no way that I know about to get around that.

“A mechanism linking oxidative stress with…lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.”

“Reduced serum NAD+ and ATP levels and lower NAD+:NADH ratio were observedin patients with autism compared to controls… a significant inverse correlation was observed between…serum NAD+ and ATP levels…and autism severity…”

“This more oxidized cytosolic redox state in autism could favor anaerobic glycolysis over oxidative phosphorylation as a source of adenosine triphosphate…consequences for brain function could be devastating due to its heavy reliance on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes.”

Proper thyroid metabolism is also probably the most important overall factor which enables the detoxification of harmful substances trapped in the body, and this includes heavy metals and other toxic things people are increasingly exposed to today, in a manner which may be unavoidable.

Some other things which are known to protect against stress include cyproheptadine, famotidine, thyroid hormone, pregnenolone, progesterone, methylene blue, increased exposure to daylight and red light, aspirin, raw carrot salad, activated charcoal, vitamin E, coconut oil, minocycline, niacinamide and a number of other metabolism supporting things.

All that’s needed now, is for dietary and lifestyle advice to be based on a more logical view of biological changes underpinning ASD symptoms. The supporting scientific evidence can help demonstrate ways that the relationships hold true, and all of this can be used to monitor improvements and setbacks. There’s a big part of the problem solved.