A Clear Biomarker for Autism? – The Question of Alterations in Lipid Metabolism.
By Kent Heckenlively, Esq.
(Author’s note – I’m indebted to Professor Richard Deth of Northeastern University for sending me this article.)
The title may be long and confusing, but the findings are what many have been hoping to discover for years. (Novel Plasma Phospholipid Biomarkers of Autism: Mitochondrial Dysfunction as a Putative Causative Mechanism, Prostglandins Leukotrines Essent. Fatty Acids (2009) (HERE).
Given the profound differences in behavior and cognition in children with autism it's only reasonable to believe there must be some trace in the body of what makes these children so different.
Researchers in Canada working for Phenomenome Discoveries, Inc. and the Jonty Foundation out of Saint-Paul, Minnesota believe they may have found the answer.
In prefacing their study the researchers noted, “Neuropathological studies in autism have shown increased microglial activation, decreased cerebellar Purkinje cell density and abnormal brain swelling, particularly in white matter. Biochemical studies have shown increased oxidative stress, abnormal glutathione metabolism, decreased melatonin, and increased docosahexaeonic acid (DHA) in autistic subjects. Although there is debate as to whether autism has a pre- or post-natal origin, it is generally accepted that the symptoms and pathology persist through the life of the subject. These studies suggest that there is an underlying and ongoing biochemical abnormality in autism, regardless of its origin.”
The study conducted by the researchers was designed to find evidence of metabolic dysregulation and toxicity, regardless of the initial cause. Their plan was to collect three plasma samples over the course of a year from 15 autistic and 12 non-autistic age-matched controls. 8 out of the 12 controls were siblings of autistic children, some of whom had impairments in social relations not rising to the level of autism.
The researchers found “consistent alterations in the levels of very long chain fatty acid (VLCFA)-containing phosphatidylethanolamines (PtdEtns) and in DHA-containing ethnalomine plasmalogens (PlsEtns). . . These findings are reported herein and suggest a possible disruption of fatty acid metabolism due to compromised mitochondrial function. Mitochondrial stress was assessed through measurements of reduced glutathione (GSH) and related metabolites. In addition, we investigated and compared the in vitro effects of glutamate toxicity on neuronal, astrocyte and hepatocyte cell cultures to biomarker changes observed in the autistic subjects. Impaired mitochondrial fatty acid oxidation as the underlying cause of elevated plasma levels of VLCFA-containing PtdEtn is hypothesized.”
In plain English, what does this mean? First, the researchers found abnormal levels of very long chain fatty acids in children with autism. Second, it may be due to the mitochondria not working as well as it should (I'd also suggest involvement of the peroxisome). Last, the glutamate derangement which would result from this situation would have different effects on different parts of the brain.
All of the autistic subjects had significantly elevated plasma levels of long chain fatty acids A curious finding was also uncovered in relation to the siblings of the children with autism. “In all eight sibling pairs in which a non-autistic sibling was available for comparative analysis, the autistic child had more pronounced VLCFA lipid changes than the non-autistic sibling. Out of these controls, five showed some impairment in social cognition. When studied as a separate group, they displayed higher levels of lipid markers relative to non-impaired controls. These results suggest that the lipid biomarkers are also indicative of risk in that siblings of autistic subjects are considered to be “high-risk” controls and may share some phenotypic traits of the syndrome.”
In their discussion the researchers observed that their results “indicate that chronic mitochondrial stress is pervasive in autism and that elevated levels of fatty acid elongation and desaturation products are useful metabolic biomarkers of both mitochondrial stress and autism.”
The question of how glutamate may adversely affect the brain was addressed by the researchers. “Glutamate was used for the following reasons: it plays a major role in microgliosis, which is pervasive in autism; its ability to deplete glutathione is well-documented; and it has been reported to impair mitochondrial beta-oxidation, which is central to our hypothesis.”
In their experiments with glutamate on various brain cells they found “In all cell culture assays performed on hepatocytes, neurons and astrocytes, glutamate exposure resulted in a decreased 16:0 mitochondrial beta-oxidation, an increased peroxisomal processing of 16:0 and cytosolic fatty acid elongation/desaturation, as evidenced by an increased DHA-PlsEtn to 18:3-PtdEtn ration. Based upon these studies, the origin of the biomarkers we observed in autism plasma is hypothesized to be the result of impaired mitochondrial function.”
In their conclusion the authors stated, “the data presented herein indicate that a common metabolic phenotype is present in autism, and that this phenotype can be easily measured from a blood sample. This metabolic phenotype is characterized by elevated plasma levels of VLCFA-containing lipids arising from impaired mitochondrial fatty acid beta-oxidation. We further speculate that the elevated plasma VLCFA could be causal to the pervasive microglial activation observed in autism via a mechanism previously established in X-ALD. (X-linked adrenoleukodytrophy is a disease which has been studied extensively by the Peroxisomal Disease Laboratory of the Kennedy-Krieger Institute/Johns Hopkins.) Glutamate, a known neurotoxin that is excreted by activated microglia was shown by direct experimentation to reproduce the observed metabolic phenotype in liver, neuron, and astrocyte cultures. A thorough literature review of autism and glutamate revealed that glutamate toxicity arising from neuroinflammation is consistent with all known biochemical, pathophysiological and epidemiological data in autism.”
Although this study was small in nature and leaves many questions unanswered, such as the cause of the neuro-inflammation, it provides potentially breakthrough information. If the level of very long chain fatty acids can provide a clear biomarker for autism we will not only have a way to diagnose, but we'll also know the direction that research should proceed to find a cure.
For further information on the possible connection of autism to very long chain fatty acids you can look at my previous article on the subject HERE.
Kent Heckenlively is Legal Editor for Age of Autism
Gee,I wonder why there maybe an increase in autism due to dysregulation of lipid metabolism? Could it be that infant formulas now contain interesterified sources of fatty acids only? Rearranged fatty acid triacyglycerols that the human body does not recognize. Will cause serious digestive issues. Yes the DHA/ARA added are also randomly esterified. What you get is saturated fatty acids found in the wrong position-leading to malabsorption and constipation. Then increased oxidative instabilty from free DHA/ARA found in the wrong positions. One may expect alterartions in s-acylation of signaling proteins as well as increases in oxidative damage. This ties in well with hyper-activated protein signaling and mitochondrial dysfunction. Alterations in calcium and cholesterol homeostasis. Loss of antioxidant protection and redox imbalances. Of note, these changes in fatty acid triacylglycerols have been made since the 1980s. If you want to alter neurodevelopment, alter the fatty acids used as the sole source of nutrition for some infants. By the time the symptoms manifest, the connection to infant formula will not be made. How many infants were diagnosed as lactose intolerant because of serious digestive issues associated with these garbage formulas? My guess is that in most cases the infant just couldn't tolerate the structural changes made to the fats.
Posted by: Mike Pescatore | July 25, 2010 at 10:58 AM
It's interesting that the researchers observed "Alterations in Lipid Metabolism" in children with autism.
An "Inborn error of lipid metabolism" is called "Dyslipidemia"
http://en.wikipedia.org/wiki/Dyslipidemia
One effect of mercury is DYSLIPIDEMIA:
"The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction."
www.ncbi.nlm.nih.gov/pubmed/17405690
Posted by: CM | September 03, 2009 at 01:59 PM
Mito testing is now being done in CFIDS
http://www.ijcem.com/812001A.html
Posted by: Beta | August 04, 2009 at 01:32 PM
Marni,
You may find this article helpful:
"Studies show that aluminum can activate microglia for long periods of time, meaning that the aluminum in your vaccine is triggering your microglia to overreact.
The next vaccine you get will trigger the enhanced inflammatory reaction and release the excitotoxins glutamate and quinolinic acid. Excitotoxins kill nerve cells and damage cell structures. If you come down with an infection, are exposed to more toxins, or have a stroke or head injury of any kind, this will magnify the inflammatory reaction occurring in your brain due to the vaccines.
Research suggests that the more your immune system stays activated, you increase your risk of suffering from neurodegenerative diseases. The aluminum hydroxide used in many vaccines has been clearly linked to symptoms associated with multiple sclerosis, Parkinson’s disease, ALS (Lou Gehrig’s disease), and Alzheimer’s disease."
http://doctormercola.com/2009/01/27/aluminum-%E2%80%93-another-reason-why-vaccines-are-unsafe/
Other information:
MMR and MMRV contain Glutamate
And Kent's article states, “Glutamate was used for the following reasons: it plays a major role in microgliosis, which is pervasive in autism; its ability to deplete glutathione is well-documented; and it has been reported to impair mitochondrial beta-oxidation, which is central to our hypothesis.”
Just to repeat from the comments to his previous article, valproic acid (a substance already known to cause autism) impairs beta-oxidation. So I think these researchers are definitely on the right track.
Also, most of the other vaccines contain(ed) thimerosal and/or aluminum.
Aluminum compounds have been shown to effect microglial function:
"We have previously observed in vivo that chronic AlCl3 exposure in young adult New Zealand white rabbits induces a reversible motor neuron degeneration. ...Both organic and inorganic aluminum decreased the extent of LPS-activated microglia-mediated death of a motor neuron hybridoma cell line (NSC 34). These findings demonstrate that aluminum compounds can directly affect microglial in vitro"
http://www3.interscience.wiley.com/journal/96516277/abstract?CRETRY=1&SRETRY=0
And since previous articles have mentioned that Alzheimer's disease may provide some clues, this may be beneficial:
"Injury to glia, including oligodendrocytes and astrocytes, may be mediated through hypertension and ApoE epsilon4 allele effects on endothelial vessel walls; metal toxicity from aluminum, which may be toxic to glia; and aging, which is noted to be a prominent risk factor for Alzheimer's disease.
Measures which reduce toxicity to vascular endothelium and glia, such as fish oil, may have potential for reducing the likelihood of development of the disease, while medicines such as some anticonvulsants, which increase carnosine-like substances such as homocarnosine, may be able to reduce the effects of the disease on neuronal structures. "
http://www.alzforum.org/res/adh/cur/brenner/default.asp
Posted by: CM | July 30, 2009 at 09:53 PM
I think there is no damage untill after the vaccine is given. How can they test for that? Maybe they do the first vaccine and then stop with the boosters if it test out with these very long chain markers? That would be good for it would have save all three of my family members.
Today, We went to the neurologist at the Univerisity of KY. I always thought if we could get there, things would be better; they would be in the KNOW. I was not going for my son who has autism and seizures- no I was driving my husband who was dignosed 20 years ago with oxidation Phosphorlation complex one, environmental induced not inherited, with very low oxygen.
I already told the neurologist from the last visit- it was the vaccines,and I ask if they had anything for it? SO, today he sent in the nurse practionery. Might as well, she knows about as much as he does.
I told her (because I can't help myself as you all can tell by the amount of blogging I do here) about all three of my family members starting with my daughter who had Kawaskis. The nurse practionery, with amazement in her eyes, said her son had Kawaskis in the mid 80's. She said they gave him only asprin at the time, and she thought it was caused by an after effect of a virus, even though at the time it was suggested to be carpet cleaner. Don't that sound stupid: carpet cleaner! I told her that the DPT shot caused my daughter to have a 105 temp and then she ran these rhuematoid like fevers for six weeks till she came down with Kawaskis. She said her son too had a 105 temp with his DPT shot.
I told her about peroximes, and long chain fatty acids, oxidation phosphoration, Atkins diet. Her eyes crossed. The only thing she knew about the Atkins diet was when it was trendy and all the supporting staff was trying to lose weight on it. Never mind that it was in the epilepsy magazine in their very office! Now you would think her chosen field is neurology she could explain or at least look like she comphrended something? Too bad we have to go to ,and pay the neurologists and then tell them the latest stuff. She was thinking hard when I left, I bet she is going home and looking up the amount of time between her son's latest vaccine and his bout wiht Kawaskis.
She was really wanting to know how my daughter was doing. I told her she was a nurse now and had to take the Hib B, and she was fine for the first two shots, but then the third one really caused her to be really stiff and hurt, and her SED rates were high. The rhuemotologist said she had inflammatory disease unspecfied. I warned her that her son had better be careful with vaccines and esp the boosters.
There are a lot more illness out there tied to the vaccines than just autism. The medical profession from the ground up to the sky scrappers seem somewhat dense.
Posted by: Benedetta Stilwell | July 30, 2009 at 01:39 PM
Thimerosal has has an affinity for fat.
The brain is made up of fat.
Vaccines contain both metals, fats and MSG.
Mercury, as Dr. Don Colbert writes in "What you don't know may be killing you!", constipates the cell not letting nutrients in or toxins out.
Pat Kane and Paris Kidd both extol phophalipids because they heal cell membranes and restore the cell membrane.
My son has done fantastically with mito and phospha-lipid support together daily.
Both the missing link for us.
Posted by: karenatlanta | July 30, 2009 at 02:02 AM
Kent- I've been saying for a while now that there should be a test for infants to see whether or not they would be susceptible to vaccine-injury. I'm wondering if they would find the same results in an infant not yet showing signs of autism? Could this be the screening tool the autism community is looking for?
Posted by: Jen Radcliffe | July 29, 2009 at 11:00 PM
fish oil that is right - all three types of omega three oils are a very long chain triglycerides
and corn is a long chain triglyceride. Am I right on this?
Posted by: Benedetta Stilwell | July 29, 2009 at 10:42 PM
To Marni, Many of us would suspect that the changes described in this article are a result of damage done by ingredients in the vaccines. As I understand it many people might want to look also for indicators in babies or fetus that would predict the possibility of that kind of damage. (Of course, Im putting my bets on mercury :) - be it in vaccines, air, water, dental amalgams,corn syrup,fish ,dust from China, that only takes 3 days to reach the US- and all the other sources that we havent thought of yet)
Posted by: Cherry Sperlin Misra | July 29, 2009 at 10:18 PM
Inside each cell is peroxisome which lays outside the mitochondria. It like the mitochondria is involved in production of energy. Peroxisome main purpose is to break down carbon chains longer than 22 carbons. It breaks down these long chains with the help of L-carnitine. This is beta oxidation. L-carnitine is made by our own bodies with the help of vitamin C in our liver and kidneys, and is stored in the skeletal muscles. We can also eat it, plenty is found in beef and a really high source is in lamb.
My three most precious family members have low carnitine levels. Why is this happening, what damage did the vaccine do? Is that too much to ask for?
Posted by: Benedetta Stilwell | July 29, 2009 at 08:39 PM
huh....
I would like to mention the whole swelling of white matter and Chiari Malformation. On the word of a doctor studying this, but no actual "study" it is more common in autism cases.
My son and I both have Chiari (--and we both have Juvenile Myoclonic Epilepsy.)
just something else to think about in all of this.
Posted by: Jenny Webster | July 29, 2009 at 08:27 PM
WHY ARE WE HAVING TO TRY TO THINK ABOUT THIS? Why is there not some big lab running full time finding out exactly why, where, and what the energy cycle is not working. I have been doing this for the last two decades.
Roger, corn syrup is what a mother in Cinn., Ohio told me long ago that set off her son's seizures.
Posted by: Benedetta Stilwell | July 29, 2009 at 06:58 PM
Okay;
what about this: I feel like Goldie Locks,
our metabolism works best with triglyerides not too long or not too short but just right- MEDIUM Chain! As a matter of fact I read some where they did a study were they put MCT in IVs for brain truama patients.
Coconut oil was the thing we use to eat. It is mostly medium chain. In the late 70's they claimed it was causing heart attacks and got rid of it and soy bean oil took its place. I think soy bean is longer? Did you know that soy is trying to take the place of milk too? Read it in the Lexington Herald Leader, Monday.
My hobby is making soaps, and fats makes all the difference in the soap. Palm oil and coconut oil makes the very best soap that lathers ups. (Olive oil,and castor oil) makes tiny little bubbles, lard slimes, and tallow is very hard like wax. I really hated it when they traded coconut for soy because that soap is useless. Could the trading of coconut to soy caused some people- babies to be more something to vaccines???
Posted by: Benedetta Stilwell | July 29, 2009 at 05:08 PM
Oxidative phosphorlation (I know I can not spell) the Krebs cycle is one of the favorite things to target when you want to make a poison to kill an insect. They usually use a metal; Al, Cadium, Cu, they don't use Hg or Pb though,(probably been banned) but I suppose any of the metals would target it too. I can see why many here believe it is the mercury or Al in the vaccines.
Somebody else read Blaylock agian and see what you think about what he said about repeated vaccines and boosters?
Dawn one more question: SCAD is inherited?
Posted by: Benedetta Stilwell | July 29, 2009 at 04:11 PM
Kent - are they still doing studies? My identical twins - one ASD and one not - do show clear differences when testing metabloic differences - though haven't done all in depth ones (cost issues!) I've been searching high and low to get them studied - they only want siblings!
Posted by: Diane | July 29, 2009 at 04:02 PM
Dawn;
You have got to answer me. I have to know??
1) What happens if your son fast?
2) Does your son have epileptic seizures
3)Did you notice your son regressed or had a reation to a vaccine?
Posted by: Benedetta Stilwell | July 29, 2009 at 03:39 PM
Hello Dawn,glad to see you here.
Kim,I strongly suggest you contact Dawn Melton here,and try to convince her to become a regular contributor to Age of Autism.I first met Dawn in a Yahoo! group for mitochondrial disease last fall,and she was very helpful in helping me sort things out.As you can see,she has a wealth of knowledge about this stuff.
Like me,her son,has had serious regressions as an adult.This was the first time,I had found someone else this had happened to.Dawn is a treasure,she really is one of the original "warrior mothers".
I wouldn't call it a biomarker for autism,but a cause,or contributing cause for one subpopulation of those with autism. Based on my own case,I can definitely believe this.I have a form of "idiopathic" lipodystrophy.I have no fat in the upper half of my body,no abdominal muscles,preadolescent arm muscles,and only small,partial pieces of pectoral muscles.I am also hypermetabolic,and nobody could ever figure out why.
I have come across a number of parents online ,whose autistic children have metabolic syndrome,and are obese,in spite of the parent's best efforts.Clearly metabolic problems can go both ways.There is definitely a subgroup of those with autism who have metabolic disease.Metabolic disease that may not be mitochondrial in origin,but metabolic all the same.
Corn intolerance is one gut issue with autism that has been greatly overlooked.I am corn intolerant,any form of corn syrup is the worst.I am convinced that going off anything remotely corn related,and high dose omega3 has grealy decreased the severity of this last fever induced setback of mine.
It may be corn and not wheat gluten that is causing a lot of your child's problems.It was Dawn who helped point this out to me last year.
Posted by: Roger Kulp | July 29, 2009 at 03:28 PM
Curious then what effect the glutamate in vaccines or MSG in foods has on these children who have this VLCAD deficiency...Thanks for posting the very interesting article, Kent.
Posted by: Lisa | July 29, 2009 at 02:33 PM
Although this is amazing news, it would be ridiculous to say that only VLCAD deficiencies exist in children with autism.
I can say this with great confidence because my son who is now 25 has been diagnosed with one "common" SCAD mutation and he in fact suffered for many years from an autistic regression which was misdiagnosed as Schizo-affective disorder.
Since 2006/2007, he has been on a low-fat/high carb diet and high doses of carnitine supplements. We have also discovered intolerance to Omega-3's, whole corn products and dried beans (which produce an enormous supply of short chain fatty acids in the gut).
Before treatment, he was psychotic, aggressive, socially inappropriate, had audio hallucinations, was obsessively repetitive, had severe delayed response and could literally only do one thing at a time. For example: while eating he could not talk; while playing video games he could not hear, so on and so forth. And he did not learn anything new during his regression.
In the past year, he has far surpassed my expectations in recovery. He is no longer mentally ill, he is socially appropriate, he can make decisions and simple plans, he can cook safely, he is learning to pay bills, he has an understanding of boundaries, he has learned compassion and he is very gentle and kind.
There is still a possibility that there is yet another mitochondrial dysfunction involved, but as for fatty acid oxidation, his defect is SCAD.
I do hope that our story will encourage others to have hope of discovery and recovery.
God bless you all,
Dawn Melton
Posted by: Dawn Melton | July 29, 2009 at 01:44 PM
Keith, the measurements may be subjective, but if the observation is glaringly obvious and can be observed by another then it is no longer subjective.
What this study does is identify the markers for autism so that your "subjective judgements" are null.
The potential is there to use these simple identifiers noted in this study to help those who are possibly predispositioned to metabolic "disaster" at a young age. I quoted "disaster" because breakdown wasn't sufficient enough.
Posted by: Kevin D | July 29, 2009 at 11:59 AM
Question: does this also mean a newborn screen could identify a vulnerable child before h/she is injected with lifesaving/NOT toxic vaccines as the adjuntives would cause neurological damage.
Mother of an uncounted vaccine injured child
uncounted=not fd-up enough - joining the ranks of special ed life-dom
Posted by: Renee Tag | July 29, 2009 at 11:56 AM
This study doesnt show what did the damage but rather it specifies, in a universal way, what damage is done biochemically. So far nothing so universal has been found other than behaviors which are subjective measurements.
If you can find what specific things were done it can help direct future studies of how it was done.
I don't know if that helps you Marri but drawing a conclusions from this study would just be speculation.
Posted by: Keith | July 29, 2009 at 09:25 AM
Sounds like all this is proving
Dr. Blaylock right all along. It IS the vaccines causing autism. He has great information at his website www.drblaylockmd.com
I wonder what new disease the squalene containing swine flu vaccine was cause. I guess we will soon find out.
Posted by: It's the vaccines | July 29, 2009 at 09:15 AM
Could someone explain in plain English if/how this relates to the regression my son and may suffered post-vaccination?
Thank you
Posted by: Marni | July 29, 2009 at 08:38 AM