Betahistine is in the Pipeline for ADHD, but will it help Autism? Maybe for some, but not for others

 Will Betahistine provide a benefit?

Today’s post is the logical follow on from the post showing that the new drug compound E-100 gives a benefit in two models of autism.

Another Potential Autism Therapy - novel compound E100 from Krakow, a combined histamine H3 receptor blocker (H3R antagonist) and an acetylcholine esterase inhibitor (AChEI)

We saw that E-100 has two modes of action, thought to be complementary:-

·        Acetylcholinesterase inhibitor (AChEI)

·        Histamine H3 antagonists (H3R antagonist)

I think our reader Rene is thinking along the lines I suggested that you might achieve the same effects with existing generic drugs.  One combination would be Donepezil plus Betahistine.

Donepezil has long been studied in autism, a recent example is here:

Improvement of Language in Children with Autism with Combined Donepezil and Choline Treatment

The safety and efficacy of a novel combination treatment of AChE inhibitors and choline supplement was initiated and evaluated in children and adolescents with autism spectrum disorder (ASD). Safety and efficacy were evaluated on 60 children and adolescents with ASD during a 9-month randomized, double-blind, placebo-controlled trial comprising 12 weeks of treatment preceded by baseline evaluation, and followed by 6 months of washout, with subsequent follow-up evaluations. The primary exploratory measure was language, and secondary measures included core autism symptoms, sleep and behavior. Significant improvement was found in receptive language skills 6 months after the end of treatment as compared to placebo. The percentage of gastrointestinal disturbance reported as a side effect during treatment was higher in the treatment group as compared to placebo. The treatment effect was enhanced in the younger subgroup (younger than 10 years), occurred already at the end of the treatment phase, and was sustained at 6 months post treatment. No significant side effects were found in the younger subgroup. In the adolescent subgroup, no significant improvement was found, and irritability was reported statistically more often in the adolescent subgroup as compared to placebo. Combined treatment of donepezil hydrochloride with choline supplement demonstrates a sustainable effect on receptive language skills in children with ASD for 6 months after treatment, with a more significant effect in those under the age of 10 years.

I was not aware that a lot of money is being spent preparing to bring Betahistine to the US as a treatment for ADHD (Attention Deficit Hyperactivity Disorder).

Outside the US, Betahistine is cheap generic drug that is widely available.  It is used in adults for vertigo and tinnitus etc.  It is not approved for use in children, but that just means its use was never studied in children.  It was envisaged as a drug for older people.

In the US, Betahistine is not an approved drug, so if the promoter gets it approved for ADHD they will not have any cheap competition.  They might even make it in the form of nasal spray, which they say makes Betahistine much more bioavailable.  It would also make it look like a modern drug, rather than just an old drug sold for a high price.

48 mg Oral dose vs varying intranasal doses

Source: https://ir.aurismedical.com/static-files/093ed1ec-9744-4144-92d3-7f6faca3a18a

The promoter’s idea is to use a lower dose of Betahistine intranasally and yet be more potent/effective than the oral tablet now used to treat vertigo.  They also want to use it to treat antipsychotic-induced weight gain, which seems to be a huge problem and a $600 million a year market they suggest.  It appears after this they want to use Betahistine to treat ADHD and depression.

Life on an anti-psychotic, without Betahistine

Betahistine might start as a drug for young adults with ADHD, but ADHD is normally seen as a childhood disorder (something like 7% of US school children have taken ADHD drugs) the promoter will have to carry out studies to show it is safe for pediatric use.  They are actually trialing quite high doses orally for ADHD.

Betahistine in autism, without ADHD

I am not sure that Betahistine, or E-100, is going to have a good overall effect in autism in humans.  E-100 does look good in two mouse models of autism.

Acting via the histamine H3 receptor, Betahistine will increase the levels of neurotransmitters histamine, acetylcholine, norepinephrine, serotonin, and GABA.  In any specific case of idiopathic autism, some of these effects may be beneficial, but quite possibly not all.

If you have GABA still working in reverse, as in some Bumetanide-responsive autism, increasing the level of GABA will cause agitation and aggression, just like taking Valium does.

The active metabolite of Betahistine is something called 2-PAA and the level peaks in your blood about an hour after taking the pill. There certainly is potential for a negative reaction, but it would fade gradually over the next few hours.  The half-life is 3.5 hours.

In the ADHD trials of Betahistine agitation was listed as a possible side effect. The promoter does say that overall the drug is very well tolerated.

Auris Medical Announces Closing of Two US Patent Acquisitions Related to the Use of Betahistine for the Treatment of Depression and ADHD

 Betahistine is a small molecule structural analog of histamine, which acts as an agonist at the H1 and as an antagonist at the H3 histamine receptors. Unlike histamine, it crosses the blood-brain-barrier. It is known to enhance inner ear and cerebral blood flow, increase histamine turnover and enhance histamine release in the brain, increase release of acetylcholine, dopamine and norepinephrine in the brain and to result in general brain arousal. Betahistine for oral administration is approved in about 115 countries, with the US being a notable exception, for the treatment of vertigo and Meniere’s disease. The compound has a very good safety profile, yet it is also known that its clinical utility is held back by poor bioavailability. Intranasal administration of betahistine has been shown to result in 4 to 26 times higher bioavailability.

Safety first

Safety, tolerability and pharmacokinetics of 2-pyridylacetic acid, a major metabolite of betahistine, in a phase 1 dose escalation study in subjects with ADHD

Betahistine, a potent histamine H3 receptor antagonist, is being developed for the treatment of attention deficit hyperactivity disorder (ADHD) that manifests with symptoms such as hyperactivity, impulsivity and inattention. This study describes the pharmacokinetics of betahistine in ADHD subjects at doses higher than 50 mg. These assessments were made during a randomized, placebo-controlled, single blind, dose escalation study to determine the safety, tolerability and pharmacokinetics of once daily doses of 50 mg, 100 mg and 200 mg of betahistine in subjects with ADHD. Plasma levels of 2-pyridylacetic acid (2-PAA), a major metabolite of betahistine were quantified using a validated LC-MS/MS method and used for pharmacokinetic analysis and dose proportionality of betahistine. A linear relationship was observed in Cmax and AUC0-4 of 2-PAA with the betahistine dose (R2 0.9989 and 0.9978, respectively) and dose proportionality coefficients (β) for the power model were 0.8684 (Cmax) and 1.007 (AUC0-4). A population pharmacokinetic model with first-order absorption of betahistine and metabolism to 2-PAA, followed by a first-order elimination of 2-PAA provides estimates of clearance that underscored the linear increase in systemic exposure with dose. There were no serious adverse events reported in the study, betahistine was safe and well tolerated at all the dose levels tested.

Pharmacokinetics and Dose Proportionality of Betahistine in Healthy Individuals

Betahistine dihydrochloride is widely used to reduce the severity and frequency of vertigo attacks associated with Ménière’s disease. Betahistine is an analogue of histamine, and is a weak histamine H1 receptor agonist and potent histamine H3 receptor antagonist. The recommended therapeutic dose for adults ranges from 24 to 48 mg given in doses divided throughout the day. Betahistine undergoes extensive first-pass metabolism to the major inactive metabolite 2-pyridyl acetic acid (2PAA), which can be considered a surrogate index for quantitation of the parent drug due to extremely low plasma levels of betahistine. The aim of the present investigation was to assess the pharmacokinetics and dose proportionality of betahistine in Arabic healthy adult male subjects under fasting conditions. A single dose of betahistine in the form of a 8, 16, or 24 mg tablet was administered to 36 subjects in randomized, cross-over, three-period, three-sequence design separated by a one week washout period between dosing. The pharmacokinetic parameters C_max, AUC_0–t, AUC_0–∞, T_max, and T_half were calculated for each subject from concentrations of 2-PAA in plasma, applying non-compartmental analysis. The current study demonstrated that betahistine showed linear pharmacokinetics (dose proportionality) in an Arabic population over the investigated therapeutic dose range of 8–24 mg

Conclusion

I think Rene is right to be curious about whether the benefit of E-100 in autism models can be replicated today with cheap generic compounds.  Our readers who are doctors outside the US will be familiar with Betahistine, a cheap drug sitting on the shelf in their local pharmacy.

In my N=1 case of autism I am not so optimistic, because I did once follow up on another idea in the published literature.  That idea was to “fix” GABA_A receptors with bumetanide/bromide and then “increase GABA”, in lay-speak. It was in this post from 2015:  “More GABA” for Autism and Epilepsy? Not so Simple

Combined effect of bumetanide, bromide, and GABAergic agonists: An alternative treatment for intractable seizures

GABA is not supposed to cross the blood brain barrier (BBB), but when combined with niacin the Russians discovered it does, the result was the prodrug Picamilon (until recently sold in the US as a supplement). Some people with autism do take Picamilon.

In my case of autism, a single small dose of Picamilon had a pronounced negative effect, which I interpreted as GABA still acting as excitatory (it should be inhibitory).  It is possible that the niacin part of Picamilon was the problem.

Taurine is an agonist of GABA_A receptors, so it will also act like “increasing GABA”

Taurine and GABA neurotransmitter receptors, a relationship with therapeutic potential?

Very many people with autism take Taurine. Some people with autism who take Leucovorin (calcium folinate) also take Taurine to reduce its side effects.

Some people take Bumetanide and Taurine, which is surprising.

The original intended use of Leucovorin is for people undergoing chemotherapy, to reduce its side effects. Taurine is also used to reduce the side effects of chemotherapy. So not a surprise to see that Leucovorin is often together prescribed with Taurine, but that is in people fighting cancer.

In autism, there is no chemotherapy and so what is the rational to prescribe Taurine with Leucoverin?

Perhaps, by chance more than anything else, Taurine does reduce the aggression that is a common side effect of Leucovorin.  I hope it does.

My conclusion is that for plenty of people with autism, and particularly those who tolerate/use Taurine or Picamilon,  Betahistine’s effect on GABA should not cause a problem. When Betahistine gets FDA approval for pediatric use in ADHD, parents in the US will likely have little difficult getting a prescription for their child with autism. ADHD is highly comorbid with autism.

If Betahistine gives a benefit and is well tolerated, all you have to do is add Donepezil or Galantamine and you have something very similar to the research drug E-100, that shines in those two mouse models of autism.

I think the effect of Betahistine  increasing the levels of neurotransmitters histamine, acetylcholine, norepinephrine, serotonin, and GABA released from the nerve endings is likely to be occur from the first dose. It makes sense that the effect on your inner ear takes weeks/months to develop.

I think the ADHD version of betahistine will be a much more potent dose than current generic tablets and it will be achieved intranasally.

Betahistine was withdrawn from sale in the US many years ago because it was thought not to be effective;  the chart further below shows otherwise. 

If you are an adult outside the US, with some hearing loss, it looks like you might want to ask your doctor for a trial of Betahistine.  It is safe and very cheap.  While researched for Ménière's disease, you can have sudden onset reduction in hearing caused by an inflammatory response due to a virus or bacteria, that produces something very similar in the inner ear to what gets diagnosed as Ménière's disease, as I discovered myself. 

Sudden onset hearing loss (SOHL) is a 30 dB or greater hearing loss over less than 72 hours, it is usually idiopathic (you never get to know what caused it).  It is thought that most people do not go to their doctor – big mistake. If you treat SOHL immediately with steroids, hearing loss should be temporary. For people with the inner ear disease Ménière's, it looks like they should benefit from Betahistine, and then be able to hear sounds 6 decibels quieter.  Is Betahistine going to benefit SOHL that was not treated in time?  It might be worth finding out.

 

 Hearing function after betahistine therapy inpatients with Ménière's disease

Betahistine, acting via H3 receptors, reduces the pressure of the fluid that fills the labyrinth in the inner ear; it also is thought to improve blood supply.  The diuretic acetazolamide, covered in this blog because of its effects on ion channels relevant to autism, is also used to reduce fluid build-up in the inner ear in Ménière's disease.

When I had sudden onset hearing loss (SOHL), it was initially misdiagnosed and steroid therapy started very late, so I added some acetazolamide from my autism stock pile.  It all worked out well.

If someone reading this post goes on to try Betahistine off-label for:-

·        ADHD

·        Depression

·        Autism

·        Weight gain associated with antipsychotics, particularly Olanzapine

·        Previously untreated, sudden onset hearing loss (SOHL)

it would be interesting to know your results.

Take note that Betahistine is also a mild agonist of H1 receptors, which explains why it may cause mild nausea (H1 blockers are used to reduce nausea) for a short while after taking it.  This side effect seems not to appear if Betahistine is taken with or after a meal. Betahistine may also reduce the H1 histamine receptor effect of any H1 antihistamine drugs being taken.

Ultimately the new E-100 drug may well be the best solution.  Hopefully the UAE researchers will persevere to human trials, but that is something that would need a lot of time and money and probably will not happen.

Anorexia, Orthorexia, PCOS, Fertility and Elevated Autism Risk (and don't forget Paternal Obesity)

 Super skinny is a poor role model and another

driver of autism risk via ensuing endocrine problems

While some types of autism cannot easily be prevented, those that relate to the lifestyle of future parents clearly can be reduced.

Rather than just be shocked about an “autism epidemic”, with ever increasing prevalence, why not start doing something about it?  People are staying at home to reduce the incidence of Covid-19; the risk of autism can also be reduced.

Today’s post is about the young females who, under peer pressure and Instagram pressure, choose to starve themselves in the pursuit of looking “good”.

School lunches are a daily subject of conversation in our house, since I always ask Monty, now aged 16 with autism, what he had for lunch at school.  Monty’s assistant tells me that even though the lunches at school are not bad, he is one of the few to eat them all.  The boys generally just eat the meat and potatoes and do not touch the fruit, vegetables and of course not any salad.  The girls eat next to nothing.  Why do the already skinny girls at school eat nothing?  It's cool to be super skinny and the popular role model is Billie Eilish. So, the girls want to be skinny and feel depressed.

In schools in rich Western countries, the perceived eating problem is usually too much, rather than too little.  When I drop off Monty, aged 16 with autism, at school all I see is skinny kids.  Some do a lot of sport and athletic should not be confused with anorexic.

Anorexia is nearly always an issue in young females, rather than males.  It is also very common in females with Asperger’s type autism, who are naturally prone to obsessions.

For most people the skinny look is just a passing issue, does it do any long-term harm?  Apparently, it does.

This post was prompted by reading about a “celebrity” mother with all 3 kids diagnosed with autism.  She is clearly an Instagram type, even in middle age.

She looks healthy (thin), had her children young, she is not one of those high IQ types of autism parent; the Dad is not a maths professor.  Why are all the kids diagnosed with autism?  Fortunately for her, it is not severe autism; the children can talk, her  six year old son is asking about corona virus and they play together for Instagram. They are fussy eaters and do not like loud noises.  

Being a former model and now a “celebrity”, it should not be a surprise that she reveals having had anorexia for ten years, then was diagnosed with PCOS, had the consequential fertility problems, but wanted a large family.  Now she has 3 children with autism; she seems not to have made the connection between PCOS and autism. (Clearly endocrine dysfunction may not be the only contributing factor)

The Mum is an Ambassador for the UK’s National Autism Society (NAS).  I think the most useful role she could perform would be to go into schools and tell skinny girls to eat more, rather than keep pushing her look good (i.e. skinny) and exercise more image on social media.  Perhaps the NAS needs to learn more about autism.

Orthorexia is another common eating disorder. It is characterized by a fixation to eat only healthy foods, or to avoid entire food groups. It is often accompanied by exercise addiction, where exercise is foremost in life, rather than including exercise in a balanced lifestyle. 

I am quite sure you could make an algorithm to identify people with Orthorexia or Anorexia, with or without exercise addiction, based on their Instagram posts. Perhaps they should get sent a warning of likely endocrine disorders later in life, including fertility problems and a substantially higher risk of having children with autism. Perhaps, “You too could become an Ambassador for the UK’s National Autistic Society”, might shock some skinny girls into eating more. These are likely the very same "cool" girls who make their female classmates with Asperger's type autism feel socially excluded. 

      Instagram use is linked to increased symptoms of orthorexia nervosa

PCOS

Polycystic ovary syndrome (PCOS) is a set of symptoms due to elevated androgens (male hormones) in females.

Not everyone with PCOS has polycystic ovaries (PCO), nor does everyone with ovarian cysts have PCOS.

Women diagnosed with PCOS have increased risk of having a child with autism.

Women diagnosed with PCOS have an increased chance of being autistic themselves.  This not surprising since elevated male hormones in women is associated with autism, as in Turner Syndrome, where one of the X chromosomes is missing, or partially missing.

People with Turner syndrome have a lifelong endocrine disorder, that was not of their making; they are almost always infertile.

People with anorexia have given themselves endocrine problems that may lead to a diagnosis of PCOS.

PCOS is associated both with being overweight and with being malnourished/anorexic.

There are different criteria used to diagnose PCOS, but it affects about 5-10% of females.

Anorexia and Endocrine Disorder

For the easy to read version, here is a good article: -

Anorexia nervosa can cause lifelong endocrine problems

Overweight and obese patients are not the only patient group that needs lifestyle modification

Warren said that the incidence of fractures in this population when they are younger is up to eight times that of the normal population. “There is a high incidence of vegetarianism along with anorexia nervosa that may also contribute to osteoporosis because of fat avoidance and low protein, calcium and vitamin D intake,” Warren said. This problem is best treated nutritionally. With a return to a normal weight significant increases in bone density are seen and fractures will also stop, she said.

In addition, a lack of estrogen may also contribute to this extensive bone loss. Hormone replacement or oral contraceptives can be used as a secondary measure but appear to help only if that patient is eating well and near a normal weight.

Another common problem in women with anorexia nervosa is infertility. Many patients with eating disorders will not ovulate. Warren said that although patients may present with a fertility problem, endocrinologists should be sure that any underlying nutritional problem is resolved before a patient is encouraged to conceive. “You can help patients to conceive using drugs, but it is really not recommended until they have a normal BMI,” she said. “There is a higher incidence of miscarriage in these patients and higher incidence of low-weight babies due to intrauterine growth retardation.”

If the return to a normal weight does not solve the fertility problems, endocrinologists should also consider a premorbid hormonal imbalance. Warren said that some patients who have had anorexia nervosa may also have an anovulatory disorder like polycystic ovary syndrome. “Patients are overweight and then lose too much weight,” she said. “As they gain back weight, they return to their premorbid anovulatory state and although they may be making estrogen, they are not ovulating on a regular basis.”

Patients with anorexia nervosa may also present with symptoms that appear to be endocrine disorders but may in fact be a result of altered nutritional intake.

“Sometimes patients have low thyroxine and triiodothyronine,” Warren said. “They present with pseudo-hypothyroidism. It may be very mild, but endocrinologists have to be aware that this syndrome may present and it is not really hypothyroidism. It is just a reaction to severe nutritional deprivation.”

In addition, because patients with eating disorders may be compulsive water drinkers, they may also develop hyponatremia. “You have to look very carefully at how much [water] they are drinking,” she said.

The endocrine manifestations of anorexia nervosa: mechanisms and management

Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotrophic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia, and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5–15% of those affected by anorexia nervosa are men, only limited data exists regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.

Autism four times likelier when mother's thyroid is weakened

Pregnant women who don't make nearly enough thyroid hormone are nearly 4 times likelier to produce autistic children than healthy women, report scientists from the Houston Methodist Neurological Institute and Erasmus Medical Centre in an upcoming Annals of Neurology.

Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory

Elevated levels of prenatal testosterone may increase the risk for autism spectrum conditions (autism). Given that polycystic ovary syndrome (PCOS) is also associated with elevated prenatal testosterone and its precursor sex steroids, a hypothesis from the prenatal sex steroid theory is that women with PCOS should have elevated autistic traits and a higher rate of autism among their children. Using electronic health records obtained from the Clinical Practice Research Datalink (CPRD) in the UK between 1990 and 2014, we conducted three matched case-control studies. Studies 1 and 2 examined the risk of PCOS in women with autism (= 971) and the risk of autism in women with PCOS ( n = 26,263), respectively, compared with matched controls. Study 3 examined the odds ratio (OR) of autism in first-born children of women with PCOS ( n = 8588), matched to 41,127 controls. In Studies 1 and 2 we found increased prevalence of PCOS in women with autism (2.3% vs. 1.1%; unadjusted OR: 2.01, 95% CI: 1.22–3.30) and elevated rates of autism in women with PCOS (0.17% vs. 0.09%, unadjusted OR: 1.94 CI: 1.37–2.76). In Study 3 we found the odds of having a child with autism were significantly increased, even after adjustment for maternal psychiatric diagnoses, obstetric complications, and maternal metabolic conditions (unadjusted OR: 1.60, 95% CI: 1.28–2.00; adjusted OR: 1.35, 95% CI: 1.06–1.73). These studies provide further evidence that women with PCOS and their children have a greater risk of autism.

Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis.

There is evidence showing a positive correlation between prenatal androgens and their effect on the development of central nervous system and the autistic spectrum disorder (ASD) phenotype in offspring of mothers with polycystic ovary syndrome (PCOS). We applied a systematic review to investigate whether women with PCOS have increased odds of having a child with ASD, while, secondarily, if these women themselves are at high risk of having the disease. Major databases from inception until 14th October 2018 were searched. The primary outcome measure was the odds of an ASD diagnosis in children of mothers with diagnosed PCOS, while the secondary outcome was the odds of ASD diagnosis in women with PCOS. Scheduled subgroup analyses were according to the time of birth and maternal age.Ten studies were eligible for inclusion, including a total of 33,887 ASD children and 321,661 non-ASD children. Diagnosed PCOS was associated with a 1.66 times increase in the odds of ASD in the offspring [95% CI: 1.51, 1.83, p = 1.99 × 10^-25, 7 studies, I² = 0%, τ² = 0]. Women with PCOS were 1.78 times more likely to be diagnosed with ASD (95% CI: 1.10, 2.87, p = 0.0179, 5 studies, I² = 85.4%, τ² = 0.2432). Additional analyses did not change the initial result. The overall quality of the evidence was high. The pooled effects size displayed low heterogeneity for the primary outcome. While the heterogeneity in the secondary outcome appears to attenuate when only high quality studies are synthesized, still the result exhibits significant heterogeneity. Τhe available data allowed a subgroup analysis only for classification system for PCOS diagnosis and showed a significant increase of ASD diagnosis in the offspring of women with Read Code and ICD diagnosed PCOS. In conclusion, the available evidence suggests that women with PCOS have increased odds of having a child with ASD, an effect size estimate based on a large number of patients from studies of good quality. Regarding the evidence on the prevalence of ASD in PCOS women, results suggest that women with PCOS are more likely to be diagnosed with ASD.

As I have pointed out in earlier posts there is an association between parents who experience fertility problems and those who have children with autism.  PCOS is only one risk factor, auto-immune conditions affect both fertility and autism risk.  This was noted by one American fertility clinic, which decided to create a prevent autism website.

http://www.preventautism.com/

As specialists in reproductive immunology, we treat numerous patients who have suffered previous miscarriages and other pregnancy complications. Many of these women have had at least one child on the autism spectrum.

The most common question we encounter from our patients is, "Are the two outcomes connected?" Our patients want to know if diagnosis and treatment for the immune-related causes of miscarriage may also lessen the chance of a having a second child diagnosed with Autism Spectrum Disorder (ASD).

The Centers for Disease Control & Prevention (CDC) recently reported that about 1 in 68 children are diagnosed with autism. Accordingly, there are millions of couples asking the question, "Can we reduce our chances of a second child with ASD?"

In an effort to discover the answers my patients and countless other families are seeking, we have created this informational website. Our practice is currently investigating the following:

·         Can autism be prevented by treating immune-related issues during pregnancy?

·         Can we identify those babies that are most susceptible to these inflammatory responses from women with known or as yet unknown underlying autoimmune issues?

What We Know So Far

For some time now, we have noticed a trend among patients: Mothers with autoimmune disorders who experience an inflammatory flare during the second trimester appear to have an increased risk of having a child on the autistic spectrum. The correlation seems stronger in mothers who have had previous miscarriages and / or a previous child with ASD. Recent studies have also noticed the connection, citing data gathered from the CDC.

Because the second trimester is when critical brain development takes place, it seems logical to conclude that any hindrance to fetal growth at this time, including a trigger of the baby's autoimmune issues due to an overactive immunological response from the mother, could potentially be detrimental to the cognitive progression of the child.

Autism rates are on the rise, and it is our belief and experience that this is due to the many "triggers" present in our diets, as well as the medications that our "at-risk population of women" (women with underlying or known autoimmune syndromes) are exposed to.

Conclusion

If girls need a role model, best not to choose a skinny one. What about one that smiles (sorry, Billie Eilish) and eats.

Athletic good looks are not the same as being malnourished.

Undereating can be as harmful as over-eating and can cause permanent damage.

Autism is multifactorial, which means a long list of different things, either by themselves, or in combination can cause it.  Since the severity of symptoms needed to warrant a diagnosis of autism has fallen dramatically over the years, issues like PCOS are likely behind many people’s autism diagnosis. Some cases of PCOS are likely genetic, but some are self-induced and so preventable.

Not all people with an endocrine disorder will get a PCOS diagnosis.

All endocrine disorders in mothers are linked to autism.  For example, Type 1 diabetes (T1D), Type 2 diabetes (T2D) and Gestational Diabetes (GDM) all increase autism odds.

Unadjusted average ASD incidence rates per 1000 children in Southern California were:

·         4.4 for exposure to T1D

·         3.6 for T2D

·         2.9 for GDM by 26 weeks

·         2.1 for GDM after 26 weeks

·         1.8 for no diabetes

Source: https://jamanetwork.com/journals/jama/fullarticle/2685775
Data is from Southern California

If you are worried about an “autism epidemic” do something about it.  Encourage healthy eating and a healthy body image; some may need to revise what they think of as healthy.  Models and pop stars are generally a bad example.

There are numerous other preventable factors that increase autism prevalence/severity, some come from the mother, some from the father and some from the environment. (Recreational drug use, alcohol consumption, lack of exposure to the expected bacteria from pets and other domesticated animals etc). 

This post was really about elevated male hormones in females affecting their offspring, but of interest is that obesity in fathers (and as we already knew, in mothers) appears to have a major impact on autism incidence. 

Obesity among fathers appears to have a greater effect on severe autism incidence than obesity in mothers.  "Normal" BMI is often quoted as being 18-25.

Parental body mass index also seems to affect different severity of autism to different degrees.  I did rather suggest this when I wrote about PCOS above, meaning since autism is multifactorial, if you have no genetic predispositions to autism, being super skinny is adding just one set of risks. You are adding one bale of straw to the camel's back, so to speak.  

Here is the effect of body mass index of both parents on the risk of offspring later being diagnosed with Asperger's type autism. OR = Odds Ratio, so greater than one is increased risk and less than one is reduced risk.

Asperger's

Here (above) the skinny mother increases the odds ratio that her children will have mild autism, but this is not severe non-verbal autism. The same risk increase effect applies to skinny fathers.

The effect is not the same when you look at who later gets diagnosed with Autistic Disorder (Severe Autism)

Autistic Disorder (Severe autism)

In the above chart, being an anorexic mother has almost no effect on the odds that her child will have severe autism.  Having a skinny father is associated with a reduced chance of severe autism.

The real takeaway point from the study is don't forget about Paternal Obesity, it is not just about the mother.

Source: Parental Obesity and Risk of Autism Spectrum Disorder

"Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies."