Preventing Auto-Immune Disease and some Autism

Today’s post is another one filling in some gaps in this blog.

I think it is common sense to say that preventing a problem from developing is much wiser than trying to solve it later on.  This is a recurring issue in both life and medicine.

In the research we now see preventative measures developed to reduce the risk of cancer, we also see how some interventions are only effective when started very early.

In the case of autism we have seen than often it is caused by a myriad of factors that by themselves might have been harmless but when taken together are the multiples hits that caused the brain to develop differently.

Much research looks individually at these factors that increase the risk of autism.  In the wider media much disdain is directed to these findings as if each factor is THE cause of autism and how can so many things cause autism.  But by understanding these factors you can then set about countering them.

I did create my simplified schematic to explain classic autism a while back.  It is not perfect but it does illustrate much of what is going on.

I do get occasional questions about reducing the risk of autism.  For example, Monty now aged 13 with ASD, has a big brother and he wants to know.  Our reader, Kritika from India, has also raised this issue.  If you have autism in your family you may well decide you would like to minimize the risk of more cases.

In practical terms, you cannot change your genes or those inherited epigenetic markers.  Maybe this will change in future.  But there are things you can do.

We know that oxidative stress is a driver of much disease including autism.  This can be minimized by lifestyle changes and indeed with a little pharmacological help.

I was interested to see a study that used NAC to treat mothers who suffer unexplained pregnancy loss, the antioxidant showed a “significant increase in the take-home baby rate”.  I was really just looking for safety information.

N-acetyl cysteine for treatment of recurrent unexplained pregnancy loss 

Pregnancy could be associated with a state of oxidative stress that could initiate and propagate a cascade of changes that may lead to pregnancy wastage. This process of oxidative stress may be suppressed by the antioxidant effect of N-acetyl cysteine (NAC). The current study aimed to evaluate the effect of NAC therapy in patients diagnosed with unexplained recurrent pregnancy loss (RPL). The study was a prospective controlled study performed in the Women's Health Centre, Assiut University, Egypt. A group of 80 patients with history of recurrent unexplained pregnancy loss were treated with NAC 0.6 g + folic acid 500 microg/day and compared with an aged-matched group of 86 patients treated with folic acid 500 microg/day alone. NAC + folic acid compared with folic acid alone caused a significantly increased rate of continuation of a living pregnancy up to and beyond 20 weeks [P < 0.002, relative risk (RR) 2.9, 95% confidence interval (CI) 1.5-5.6]. NAC + folic acid was associated with a significant increase in the take-home baby rate as compared with folic acid alone (P < 0.047, RR 1.98, 95% CI 1.3-4.0). In conclusion, NAC is a well-tolerated drug that could be a potentially effective treatment in patients with unexplained RPL.

This then made be recall a US fertility clinic, that our reader Roger once mentioned in a comment.

http://www.preventmiscarriage.com/

http://www.preventautism.com/

“At Braverman Reproductive Immunology, we believe Autism Spectrum Disorder (ASD) and various pregnancy and infertility complications (listed below) appear to have the same cause. In fact, we have found that a large number of patients who present to our center with the below complications already have a child with ASD.

This discovery started us on the journey to see if ASD itself could be prevented while treating other associated conditions. We believe treatment for these common issues will not only prevent the pregnancy complications listed below, but may also prevent ASD in the group of patients that have already had a child with ASD.”

Dr Braverman does not mention oxidative stress, but perhaps he should.

So step one would be to reduce oxidative stress during pregnancy, via lifestyle changes and taking antioxidants.

Step two would be to avoid inflammation, Dr Braverman refers to the link to auto-immune disease and miscarriage/autism.

We know that maternal inflammation is one of the easiest ways to cause autism in mouse models (the MIA model - Maternal Immune Activation).

  

We have some research to show that the risk of auto-immune disease can indeed be reduced and indeed that the risk of progression from minor to more major auto-immune disease can also be minimized.

We even have a tiny study showing that immuno-modulatory therapy using a probiotic during pregnancy can reduce incidence of ADHD and autism. For me ADHD is just a case of autism-lite.

A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood: a randomized trial

Background:

Recent experimental evidence suggests that gut microbiota may alter function within the nervous system providing new insight on the mechanism of neuropsychiatric disorders.

Methods:

Seventy-five infants who were randomized to receive Lactobacillus rhamnosus GG (ATCC 53103) or placebo during the first 6 mo of life were followed-up for 13 y. Gut microbiota was assessed at the age of 3 wk, 3, 6, 12, 18, 24 mo, and 13 y using fluorescein in situ hybridization (FISH) and qPCR, and indirectly by determining the blood group secretor type at the age of 13 y. The diagnoses of attention deficit hyperactivity disorder (ADHD) and Asperger syndrome (AS) by a child neurologist or psychiatrist were based on ICD-10 diagnostic criteria.

Results:

At the age of 13 y, ADHD or AS was diagnosed in 6/35 (17.1%) children in the placebo and none in the probiotic group (P = 0.008). The mean (SD) numbers of Bifidobacterium species bacteria in feces during the first 6 mo of life was lower in affected children 8.26 (1.24) log cells/g than in healthy children 9.12 (0.64) log cells/g; P = 0.03.

Conclusion:

Probiotic supplementation early in life may reduce the risk of neuropsychiatric disorder development later in childhood possible by mechanisms not limited to gut microbiota composition.

The issue, as with NAC during pregnancy, is whether immuno-modulatory therapy is safe.

The study on ADHD and autism was actually a study looking at whether a certain probiotic if given during pregnancy could reduce eczema later on in the child.

  

We also have the studied effect of having a pet dog at home.

House dust exposure mediates gut microbiome Lactobacillus enrichmentand airway immune defense against allergens and virus infection

 

Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched for Lactobacillus johnsonii, which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.

One of my views is that by early treatment of autism you may indeed reduce the risk of epilepsy.  The key here is “reduce the risk”, it does not mean there is no risk.  There are likely hundreds of causes of epilepsy, but if you can reduce the incidence by 30+% that would look like a big success to me.

I recall another study that looked at treating people with eczema to see if you could reduce the chance of progression to asthma.  Using Ketotifen the trial showed that it was indeed possible.

Prevention of asthma by ketotifen in infants with atopic dermatitis. 

To evaluate the prophylactic effect of ketotifen against the onset of asthma we selected 121 infants with atopic dermatitis, without any history suggestive of asthma (cough and/or wheezing). Sixty-one children received ketotifen twice daily. Those who weighed less than 14 kg received 0.8 mg; 14 kg or more, 1.2 mg. Sixty children, a placebo syrup indistinguishable from the active syrup. Both groups were followed for 1 year, with bimonthly evaluations. The criteria for onset of asthma were two different episodes of wheezing treated with bronchodilator drugs. Both groups were comparable regarding age, sex, weight, onset, and duration of atopic dermatitis and age at the onset of asthma. During the 1 year study, asthma was observed in eight children of the ketotifen group (13.1%) and in 25 children of the placebo group (41.6%) (P less than .001). Side effects were negligible and routine laboratory tests disclosed no significant alterations. Ketotifen is a very useful drug for prevention of asthma in children with atopic dermatitis and total IgE more than 50 IU/mL.

Somali Autism Clusters

This then takes me back to that issue I looked at long ago, which was the reason for the Somali immigrants to Sweden and US having so many children with autism.  This even got termed the Swedish Disease by the migrants, they claimed to have never seen autism back home in Somalia.

Then we have the hygiene hypothesis which in effect says that, within limits, a little dirt is good for you.

Hormonal Dysfunction

We know that gestational diabetes increases the risk of autism and we also known that the mother being hypothyroid increases the risk.  In some cases the hormone dysfunction is a consequence of the auto-immune dysfunction.

We also know the female hormone progesterone is extremely neuro-protective.  The level of this hormone is supposed to rise during pregnancy.

  

In past times hormones were given to some pregnant mothers, but this went out of fashion.  Perhaps this should be revisited?

Then we have the surge of the hormone oxytocin that the baby is supposed to receive at birth.  This surge may be relevant to the GABA switch when shortly after birth this neurotransmitter is supposed to switch from excitatory to inhibitory as the neurons mature. If the baby is born by Caesarian there will be no oxytocin surge for the baby.   

Preventing Regressive Autism Secondary to Mitochondrial Disease (AMD)

It is on open secret that doctors at Johns Hopkins have identified a variant of regressive autism called Autism secondary to Mitochondrial Disease (AMD).

It remains unclear how rare this is and absolutely nobody serious is going to research this, if they ever want to receive a research grant in the future.

We saw that in people with a genetic predisposition to mitochondrial dysfunction, an immune over-reaction to an insult like multiple vaccinations can trigger mitochondrial disease.  This will present itself as autism and quite possibly severe autism in a previously unaffected child.

Those doctors treating AMD use mild immuno-suppressing drugs before any future vaccinations.

How do you minimize the chance of AMD? 

The first thing is to never use paracetamol/acetaminophen in a baby or child, particularly just after vaccination.  This drug may kill the pain but it depletes GSH the body’s main antioxidant, just when it needs it most.   Use something like Ibuprofen.

Vaccines are given in multiples so as to save time and money and I suppose improve compliance. You might expect giving them one-by-one would actually make them more effective as well minimizing any collateral damage to a small percentage of kids.

Conclusion

As I keep reminding readers, I am not a doctor, but it would be nice if a few more doctors other than Braverman took preventing autism seriously.

I would like to know if progesterone is an effective therapy in the MIA model of autism.  In this model they trigger the mother’s immune system during pregnancy which leads to offspring with autism.  What would be the effect of giving progesterone?  Would it protect the pups?

Are progesterone levels reduced in mice that will become autistic?

So I suppose I would trial NAC and progesterone in the mother mouse.

For everyone else it is case of choosing whether or not to make lifestyle changes to reduce oxidative stress.  Improving gut bacteria can be done via probiotics, eating more (slightly dirty) fruit and vegetables, having a pet dog, spending some time in the nature.  

As for vaccine risk, however small it might indeed be, there will never be a serious investigation of this, for understandable reasons. 

Minimizing Summertime Autism Flare-ups in 2015

When I first connected histamine to autism, I did not realize that this might be a common problem.  The most frequently viewed post on this blog is one on histamine and autism; so at least 10,000 people out there have googled “autism and histamine”.

Two years later, the therapy is still evolving and it should be said that, what works best for one person may not help in another person.  The main point is that in some people with autism, they face a summertime regression due to the effect of allergy.  So bad behaviours and aggression increase and good behaviours and indeed cognitive function decrease.  This appears to be the result of histamine and a pro-inflammatory cytokine called IL-6.

For the 2015 pollen season, which started early where we live, this is what we are using:-

Azelastine nasal spray, this is an H1 antihistamine that is also inhibits mast cells from “degranulating” and emptying their load of pro-inflammatory substances.  Once a day.

Quercetin is a cheap flavonoid that has numerous actions including on histamine H1 receptors, mast cells, and inflammation. 125mg two or three times a day.

Verapamil is an L-type calcium channel blocker and also a mast cell stabilizer. 40mg three times a day

Fluticasone propionate 50 µg (micrograms) – see below.  It is a steroid that has recently been shown to have some unexpected effects on mast cells.  

I have found that oral antihistamines were effective for only a couple of hours, but their effect varies widely from person to person.

In theory, Rupatadine should be the most effective anti-histamine, since it is also a potent mast cell stabilizer.  The old first generation antihistamines (that make you drowsy) could in theory be better than the new ones like Claritin, Zyrtec, since they can also cross the blood brain barrier (BBB).

Ketotifen and cromolyn sodium should also be useful, but if the allergy is pollen related, you really need the nasal spray (nasalcrom etc) to get the most effect.  In some countries they sell eye drops and not the nasal spray.  Usually the eye drops are more diluted than the nasal spray.  For example, the Azelastine eye drops contain 50% less Azelastine than the nasal spray, but are otherwise the same.  Where we live they have run out of the nasal spray but not the eye drops, so you could refill the spray with eye drops and double the number of sprays to get the same dose.

Drugs like Claritin and Zyrtec are H1 antihistamines and also partial mast cell stabilizers; they have a positive behavioral effect in some people with ASD, who are apparently allergy free.

New for 2015

I expect that two recent anti-inflammatory therapies, the Tangeretin flavonoid and the Miyairi 588 bacteria/probiotic may have a beneficial, indirect, effect on our usual summertime regression.

A more convention approach is to add fluticasone propionate to reduce the inflammation caused by allergy.  This drug is a steroid and widely used either as an inhaler to control asthma and COPD, or as a nasal spray to treat allergies.

As Flixotide inhaler, Monty, aged 11 with ASD and asthma, has already been taking fluticasone propionate for a few years.  We now use a tiny dose (50 µg), since his autism therapies have greatly reduced any asthma tendencies.

Fluticasone propionate nasal spray (Flixonase, Flonase etc) is widely sold as a treatment for hay fever and rhinitis and was recently combined with Azelastine (see above) as a treatment for moderate to severe allergies in a product call Dymista.

The combination of H1 antihistamine, mast cell stabilizer and anti-inflammatory all in one spray does seem a good idea.  The steroid dose using Dymista is actually lower than the usual dose of steroid when using Fluticasone propionate nasal spray alone.  You want to minimize the amount of steroid absorbed in the blood. When used as a spray/inhaler the amount is tiny, but still should be considered.

Dymista (Azelastine + Fluticasone propionate) does indeed work better than Azelastine alone.  There is no sign of allergy at all (no red eyes, sneezing, itchy nose), with Azelastine you still have an itchy nose.

In our case, the allergy symptoms, even minors ones, do correlate with the change in behaviour and cognitive function; so the target is no allergy symptoms at all.

If anyone has other therapies for summertime flare ups, feel free to share them.

Autism Flare-ups - News on Allergy Drugs

I wrote earlier posts about the role of histamine in summertime autism flare-ups.  I ended up using a combination of a regular antihistamine like Claritin with Ketotifen, which though also an antihistamine, is a partial mast cell stabilizer.
 

I recently found a very useful table which shows different regimens that can be used for just this problem:-

 

The table is from a paper, again by Dr Theoharides, called:
 Autism: an emerging ‘neuroimmune disorder’ in search of therapy

Rupatadine is a safe and cheap antihistamine mainly sold in Europe.  The science appears to show that it is more effective at stabilizing the mast cells involved in allergies than Ketotifen.

The problem I found with Ketotifen is that it has very little immediate effect, unlike Claritin, so I ended up using both.  By the looks of things, Rupatadine may indeed do the job of both.

The table also mentions Periactin, which is an old first generation antihistamine.  It has a secondary antiserotonergic properties.  It was trialed in Iran for autism, apparently with some success.

Cyproheptadine in the treatment of autistic disorder: a double-blindplacebo-controlled trial.

 

Conclusion

Not all antihistamines are the same and some have very interesting secondary effects.  It looks like science has given up on investigating this further, which is a pity; but you don't have to.

 

Autism Flare-Ups & Leaky Blood Brain Barrier

As I discussed in an earlier post, autism flare-ups occur regularly in the lives of many autistic children.  The cause might be a pollen allergy, food allergy or indeed an illness that does not cause a fever.

That last part might sound odd, but fever actually reduces autistic behaviours.  This has been noted and documented by many, but never conclusively explained.  Lots of parents have noticed and one even created a blog about it, but they have not explained it.

To investigate the fever effect, you first need to understand thermoregulation, the process by which the body sets and maintains its temperature and the role played by of the HPA axis (hypothalamic-pituitary-adrenal axis).  The simplified explanation is that the body initiates a fever as part of its defence mechanism to the threat that has been detected, like an infection of some kind.  Certain hormones are released so as to raise and then maintain a steady higher temperature; they include TRH, ACTH, AVP, PRL and TSH. It occurred to me that if you could identify which hormone increase was behind the reduction in autistic behaviours during fever, you would be on to something really useful.  This is something that is very poorly covered in the literature and so it is very difficult to prove anything.  My hunch is that TRH is the one and I am looking into ways to prove it.  I wrote an early post all about TRH, which I believe, for other reasons could have great therapeutic value in autism. 

The Peter Hypothesis of TRH-induced Behavioural Homeostatis in Autism

Back to flare ups …

 

Sickness involving stress/inflammation, but without fever, makes autistic behaviours worse.  Stress and inflammation have been shown in research to make the Blood Brain Barrier (BBB) more permeable.  In an earlier post we discovered that histamine itself increases the permeability of the BBB.

If you want to read up on the BBB, here is some heavy reading:-

The Blood-Brain Barrier/Neurovascular Unit in Health and Disease

The other observation that seems not to get documented in the literature is the effect of a new cause of stress/inflammation on any previously existing or dormant ones.  This is very relevant in autism since part of the brain is known to be in a near permanent state of inflammation/stress.  So if a new site of inflammation/stress elsewhere in the body will “re-ignite” other weak sites around the body (including the brain) then we have a problem.  Just as we showed that pollen and food allergies sparked autism flare ups, so can a viral infection.

Because there is no temperature, you may hardly notice the virus. Most parents think their kids are only really sick if they have a temperature.

These observations actually apply to all of us.  My son Monty, aged 10 with ASD, currently has a virus that does not cause a fever.  I know all about it, because I subsequently caught it from him.  Having caught it myself, I see why it would affect Monty’s behaviour.  It goes on far longer than a common cold, but outwardly after a day sneezing and a runny nose there is little to notice.  Since I am now focused on autism flare up and comorbidities, I am taking a lot of notice.  I can see that in my own body sites of previous inflammation do indeed flare up.  Like many people, I occasionally suffer from GERD, which you might know better as “heartburn”.  This causes inflammation to the oesophagus and when it occurs you can actually feel it, as I can while writing this.

Imagine you have a brain with chronic neuroinflammation, even if you are taking steps to put out that fire (NAC and statins) along comes a wave of inflammatory cytokines released elsewhere in the body and they act to reignite the inflammation in the brain again.

In healthy neurotypical people the brain is better protected from such inflammatory cytokines due to a more effective Blood Brain Barrier (BBB).  In autism there is plenty of evidence pointing to a more permeable BBB.

You cannot stop your child getting pollen allergies, though you might well adjust diet to avoid food allergies; but can you do anything to keep those pro-inflammatory cytokines out of the brain?

We know for a fact that certain substances weaken the BBB; we just need to find the neuro-protective ones that can strengthen the BBB.  Such substances do indeed exist.  A common issue than arises is that what works in the test tube (in vitro) does not always work in humans (in vivo) and also what works in rodents (the typical laboratory test subject) may not apply to humans.

Other diseases linked to leaky BBB - Multiple Sclerosis & Alzheimer’s

The best known disease long thought to be caused by a breakdown in the BBB is multiple sclerosis.  People with MS and those trying to help them have a big interest in what might protect the BBB.

I found it interesting that recent research shows that Alzheimer’s disease is also triggered by a failure in the BBB.  

Alzheimer's protein damages blood brain barrier

Alzheimer's disease: A breach in the blood–brain barrier

Alterations in brain blood vessels in mice precede the neural dysfunction associated with Alzheimer's disease. The finding highlights potential targets for drug development.

Alzheimer’s disease (AD) is well researched/funded since it is the leading cause of dementia.  It is characterised by both oxidative stress and neuroinflammation, as is autism.  Drugs developed for AD that target strengthening the BBB or reducing stress/inflammation in the brain would be good targets to trial in autism.

Substances neuro-protective to the BBB.

If you look in the literature you struggle to find much research on strengthening the BBB.  Much more frequent reference is made to “neuro-protective” ,which is something good but subtly different.

  

Mast cell stabilizers.

                         

Mast cell stabilizer drugs work to prevent allergy cells called mast cells from breaking open and releasing chemicals that help cause inflammation.

 

Commonly used mast cell stabilizers in medicine include  the drugs Cromoglicic acid and   Ketotifen.  These drugs are used in treating allergies and asthma. Both these drugs have been covered in earlier posts and at least Ketotifen is used in autism. Some researchers suggest that truly effective mast cell stabilizers for humans do not exist.  It is suggested that mast cell stabilizers would be highly protective of the BBB.

Lipoic Acid

It has been stated that Lipoic acid is protective of the BBB, also known as  Alpha lipoic acid and thioctacid; it is another antioxidant.  I have also mentioned it previously in this blog.

Thioctacid is prescribed by doctors to patients with diabetic polyneuropathy in Germany and most East European countries.  It not only reduces symptoms of neuropathy but it also reduces the amount of insulin patients require.  It is given both intravenously and orally.  I am told that oral administration is effective, but research showed that IV has the strongest effect.

In autism some people in the US take advantage of its metal-chelating properties.  All anti-oxidants have should have metal-chelating properties, by the way.

 

Here is a study from the world of Multiple Sclerosis, into the protective properties of Lipoic Acid.

Lipoic Acid Affects Cellular Migration into the Central Nervous System and Stabilizes Blood-Brain Barrier Integrity

In the following research NAC was combined with Lipoic Acid to reverse memory impairment and oxidative stress in the brain.

The antioxidants α-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8  mice

These results support the hypothesis that oxidative stress can lead to cognitive dysfunction and provide evidence for a therapeutic role for antioxidants

From Iran, I found a hypothesis about lipoic acid reducing inflammation in autism. 

Gold nanoparticles and lipoic acid as a novel anti-inflammatory treatment for autism, a hypothesis

Anti-oxidants as neuroprotectors

Anti-oxidants will indirectly strengthen the BBB, since they reduce the oxidants that damage the BBB.  Are all anti-oxidants equal?  There is an argument that you should match the anti-oxidant to the oxidant.  The most powerful anti-oxidant available seems to be NAC, and I am already using it.  My second choice would be L-carnitine, since there has been at least one positive clinical trial in autism.

A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders

It works in a quite different way to NAC and it also has an effect on the mitochondria.  As you saw above, there is also a case to be made for alpha lipoic acid (ALA), as an antioxidant.  In the research combinations of antioxidants have been trialled, just not for autism.  In an ideal world, some research would be carried out comparing the effectiveness of different combinations of NAC, Carnitine and ALA.

Interestingly as with lipoic acid, L-carnitine improves insulin response in diabetics.

I found this Alzheimer’s research interesting.  It tested NAC, carnitine and SAMe.  SAMe is used in to treat many neurological conditions, including ADHD, which I view as autism-lite.  It is also used to treat seizures, a major comorbidity of autism.

Effects ofdietary supplementation with N-acetyl cysteine, acetyl-L-carnitine andS-adenosyl methionine on cognitive performance and aggression in normal miceand mice expressing human ApoE4.

In addition to cognitive impairment, behavioral changes such as aggressive behavior, depression, and psychosis accompany Alzheimer's Disease. Such symptoms may arise due to imbalances in neurotransmitters rather than overt neurodegeneration. Herein, we demonstrate that combined administration of N-acetyl cysteine (an antioxidant and glutathione precursor that protects against A beta neurotoxicity), acetyl-L-carnitine (which raises ATP levels, protects mitochondria, and buffers A beta neurotoxicity), and S-adenosylmethionine (which facilitates glutathione usage and maintains acetylcholine levels) enhanced or maintain cognitive function, and attenuated or prevented aggression, in mouse models of aging and neurodegeneration. Enhancement of cognitive function was rapidly reversed upon withdrawal of the formulation and restored following additional rounds supplementation. Behavioral abnormalities correlated with a decline in acetylcholine, which was also prevented by this nutriceutical combination, suggesting that neurotransmitter imbalance may contribute to their manifestation. Treatment with this nutriceutical combination was able to compensate for lack of dietary folate and vitamin E, coupled with administration of dietary iron as a pro-oxidant (which collectively increase homocysteine and oxidative damage to brain tissue), indicating that it provided antioxidant neuroprotection. Maintenance of neurotransmitter levels and prevention of oxidative damage underscore the efficacy of a therapeutic approach that utilizes a combination of neuroprotective agents.

Statins

Statins are claimed to increase the integrity of the BBB.  I am already convinced of the benefit of Atorvastatin, for other reasons.

Flavonoids:  luteolin, Quercetin, Rutin

Dr Theoharides from Tufts University in Boston where he is Professor of Pharmacology, Internal Medicine (Allergy) and Biochemistry is a proponent of flavonoids to stabilize mast cells,  He favours a mix of luteolin, Quercetin, Rutin all mixed up in olive kernel oil.  He says it works far better than Ketotifen and cromolyn.  His mixture is marketed under the name Neuroprotek.

Mast stabilizers are claimed to reduce BBB permeability, so as a consequence these flavonoids should help

I initially found it odd that such a scientist was favouring natural extracts,  so I thought I would see what other neuro-protective extracts might be out there.

Naturally occurring neuro-protectants

The internet is full of natural remedies and most have little supporting evidence.  Here are two that I found interesting.

Blueberries

These are both very tasty, available and remarkably good for you; nobody is exactly sure why.  They seem to slow down cognitive decline in older people, reduce neuroinflammation and promote cell survival.

Antioxidant and neuroprotective properties of blueberry polyphenols: a critical review

Over the last 10 years an increasing scientific interest has developed about polyphenols, which are very abundant in blueberries, as they have been seen to produce favourable effects related to neuroprotection and linked to a possible decrease of age-related cognitive and motor decline, as shown by the improvement of such functions in animal models with a supplemented diet. Such effects could not only be explained through a purely antioxidant action but also through more complex mechanisms related to inflammation, genic expression, and regulation of cell survival

Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection.

Withania Somnifera, also known as Ashwagandha

On the surface, this ages old Indian medical remedy looks interesting, not least because one study showed it could reverse Alzheimer’s Disease.  It is claimed to do many things, including protecting the BBB.

Withania somnifera reverses Alzheimer's disease pathology

Indeed it is an ingredient used in some supplements used for autism and if you Google it, you will parents recommending it.

Not being a regular to such types of “medicine” I did some research and found that you should buy the actual root rather than the ground up bits available in capsules.  The logic being that they put the leftovers in the capsules and that the capsules may give an overly concentrated dose, as compared to the tea version. 

With root you make a kind of herbal tea.  It is actually very easy and quite inexpensive; indeed the root seems easier to find than the capsules.  In keeping with my self-experimentation approach, I brewed up a batch of Withania somnifera tea and gave it a try.  Well there genuinely is an effect; you do feel different, although I would not call it “better”.  The problem is, as I learnt a couple of hours later, that it can, and does, irritate the gastrointestinal tract.  Maybe my brew was too strong or maybe I am just sensitive to it.  On WEBMD they list the following side effects:-

ASHWAGANDHA Side Effects & Safety

Ashwagandha is POSSIBLY SAFE when taken by mouth short-term. The long-term safety of ashwagandha is not known. Large doses of ashwagandha might cause stomach upset, diarrhoea, and vomiting.

It’s not known whether it’s safe to apply ashwagandha directly to the skin.

Special Precautions & Warnings:

Pregnancy and breast-feeding: Do not use ashwagandha if you are pregnant. It is rated LIKELY UNSAFE during pregnancy. There is some evidence that ashwagandha might cause miscarriages. Not enough is known about the use of ashwagandha during breast-feeding. Stay on the safe side and avoid use.

Stomach ulcers: Ashwagandha can irritate the gastrointestinal (GI) tract. Don’t use ashwagandha if you have a stomach ulcer.

“Auto-immune diseases” such as multiple sclerosis (MS), lupus (systemic lupus erythematosus, SLE), rheumatoid arthritis (RA), or other conditions: Ashwagandha might cause the immune system to become more active, and this could increase the symptoms of auto-immune diseases. If you have one of these conditions, it’s best to avoid using ashwagandha.

Surgery: Ashwagandha may slow down the central nervous system. Healthcare providers worry that anaesthesia and other medications during and after surgery might increase this effect. Stop taking ashwagandha at least 2 weeks before a scheduled surgery.

Since Ashwagandha can make the immune system more active, it would seem unsuitable for autism, which we have established in this blog is linked to an already overactive immune system.

Conclusion

Finding a remedy to permeability of the blood brain barrier (BBB), was never going to be simple, if it was, then multiple sclerosis and Alzheimer’s disease would have already  become curable.  But, knowing what weakens the BBB does help explain why autism flare-ups occur, and in turns this helps us to minimize them.

I think I will stick with the blueberries and steer clear of the Ashwagandha, at least until I have to worry about Alzheimer’s.  The L-carnitine is getting a trial as a supplemental anti-oxidant and mitochondria protector, as will Dr Theoharides’ somewhat expensive Neuroprotek.  Alpha lipoic acid is now in third position in my anti-oxidant league table and will be studied further.   NAC remains in pole position as antioxidant proven to reduce autistic behaviours.  The very inexpensive Ketotifen may have capabilities above and beyond those accepted by Theoharides, as suggested by the fact that it has the remarkable ability to prevent the onset of asthma in the at risk group.

I wrote an earlier post on flavonoids.  These are good parts of fruits that you usually miss out on in juices, since they are concentrated in the skins.  Indeed though olive oil contains beneficial flavonoids, many remain in the stone/kernel in the centre,  It was of interest to me that Theoharides uses olive kernel oil rather than regular olive oil to bind his Neuroprotek together.  All berries seem to be particularly good for you, including cranberries, blackberries, blueberries, billberries and raspberries. I think these flavonoids are likely more about promoting your general health than any autism breakthrough.