The Ketone D-BHB as a Medical Food for Heart, Kidney and Brain Disease (Alzheimer’s, some Autism …)

 Nestle’s research centre in Lausanne, Switzerland

I did write extensively about the potential to treat some autism using the ketone BHB (beta hydroxybutyrate). This can be achieved either by following a strict ketogenic diet or just by eating medical foods that contain/produce BHB.

Some readers are now big consumers of BHB supplements and anyone taking BHB should be interested in today’s paper, that I assume was paid for by Nestlé.

Nestlé make everything from baby milk formula to George Clooney’s Nespresso.  You may not be aware that they also have a business selling medical food; they have been looking at ketones to treat Alzheimer’s for some time.  This is quite similar to Mars developing Cocoa flavanols to improve heart and brain health.

Most ketone supplements are sold to help you lose weight or boost athletic performance.  The military also uses ketones in survival rations. 

We saw that you can increase the level of ketones in your body by supplementing: -

·        MCT oil (medium chain triglyceride oil, which usually contains about 60% caprylic C8 acid and 40% capric C10 acid).  This is a product already sold by Nestlé

·        Neat caprylic acid, C8

·        BHB salts (potassium, sodium, calcium etc)

·        BHB esters (also called ketone esters KE)

These products range from expensive to very expensive.

People requiring ketones as an alternative fuel to glucose, like those with Alzheimer’s need quite large amounts of the supplements.  In Alzheimer’s a glucose transporter at the blood brain barrier is restricting the flow of glucose in blood and so the brain is starved of “fuel”.  Mitochondria in the brain can be powered by both ketones and glucose, so if not enough glucose cannot get through, you have the option to increase the amount of ketones.

Babies fed with mother’s milk are on a high ketone diet.  You can safely combine both glucose and ketones as a fuel for your body.

The news from today’s paper has already been translated to a usable therapy. 

Metabolism of Exogenous D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart and Kidney

There is growing interest in the metabolism of ketones owing to their reported benefits in neurological and more recently in cardiovascular and renal diseases. As an alternative to a very high fat ketogenic diet, ketones precursors for oral intake are being developed to achieve ketosis without the need for dietary carbohydrate restriction. Here we report that an oral D-beta-hydroxybutyrate (D-BHB) supplement is rapidly absorbed and metabolized in humans and increases blood ketones to millimolar levels. At the same dose, D-BHB is significantly more ketogenic and provides fewer calories than a racemic mixture of BHB or medium chain triglyceride. In a whole body ketone positron emission tomography pilot study, we observed that after D-BHB consumption, the ketone tracer ¹¹C-acetoacetate is rapidly metabolized, mostly by the heart and the kidneys. Beyond brain energy rescue, this opens additional opportunities for therapeutic exploration of D-BHB supplements as a “super fuel” in cardiac and chronic kidney diseases.

One of the main benefits of ketones is their ability to act as an alternative energy source to glucose or fatty acids for production of ATP by mitochondria. Caloric restriction and intermittent fasting also produce transient mild-moderate ketosis (6, 7).

While a high dose of MCT can provide a moderate increase in blood ketones (+0.5–1.0 mM), gastrointestinal intolerance and high caloric load limit their use. Second, ketone esters (KE) made of a BHB ester linked to butanediol provide one molecule of D-BHB after digestion, with the butanediol being further metabolized by the liver to D-BHB (9). KE increase blood ketones above 1 mM but are also limited at high dose by their gastric tolerability and severe bitterness (10).

Third, perhaps the most physiologic way to raise blood ketones is via the oral intake of D-BHB itself. Exogenous D-BHB is directly absorbed into the circulation, with some of it being converted to AcAc by the liver, and both ketones being distributed throughout the body. Until recently, only racemic mixtures of dextro (D) and levo (L) BHB (D+L-BHB) were available and oral human studies with them have been reported (9, 11–14). As L-BHB is not metabolized significantly into energy intermediates and is slowly excreted in the urine (9, 15), D+L-BHB would be anticipated to be less ketogenic than pure D-BHB. 

Levo, Dextro and Racemic

When certain chemicals are manufactured, they usually contain an equal mixture of the left-handed and right-handed version, this is called a racemic mixture. These versions are called enantiomers.

One enantiomer is an optical stereoisomer of another enantiomer. The two molecules are mirror images of each other, which are not superimposable - much like your left and right hand.

In the case of the chemical BHB, only the right-handed version has an effect on your body.  If you take the salt potassium BHB, half of the product has no effect other than raise your level of potassium.

Zyrtec is an antihistamine made of Cetirizine, but it is a racemic mixture.  If you want pure L-Cetirizine, you would buy Xyzal not Zyrtec.

Arbaclofen/ R-baclofen is the right-handed version of baclofen

Rezular/R-verapamil is the right-handed version of verapamil.

Back to the study:

The study compared three therapies: -

D-BHB

14.1 g of pure salts of the D enantiomer of D-BHB were used. The D-BHB supplement tested was formulated as a mixture of three salts: sodium D-beta-hydroxybutyrate, magnesium (D-beta-hydroxybutyrate and calcium (D-beta-hydroxybutyrate). Each oral serving provided 12 g D-beta-hydroxybutyric acid, 0.78 g sodium, 0.42 g magnesium, and 0.88 g calcium, citrus flavouring and sweetener (Stevia), dissolved in 150 mL of drinking water.

D+L-BHB

14.5 g of an equimolar mixture of commercial D and L beta-hydroxybutyrate salt was used (KetoCaNa, KetoSports, USA). Each serving provided a mixture of 12 g D+L-Beta-hydroxybutyric acid, 1.3 g sodium, 1.2 g calcium, orange flavoring and stevia, dissolved in 150 mL of drinking water.

MCT oil

Fifteen grams of medium chain triglyceride (MCT) (60% caprylic C8 acid and 40% capric C10 acid) emulsified in 70 mL of a 5% aqueous milk protein solution.

This chart shows the concentration of ketones in your blood plasma after taking either of the three therapies.

This chart shows the concentration of just the ketone D-BHB in your blood plasma after taking either of the three therapies.

 This chart shows the concentration of the ketone ACAc in your blood plasma after taking either of the three therapies.

  

This chart shows where the ketones are going; the chart shows the distribution of the ketone “tracer” acetoacetate (AcAc) by organ after D-BHB oral intake.  The effect is greatest on the heart and kidney, but some does reach the brain.

From the dynamic brain scan, CMR_AcAc and K_AcAc could be determined for all main regions of the brain and compared to baseline values previously determined in healthy young adults. Overall and compared to baseline, each region demonstrated an increase in CMR_AcAc and K_AcAc of ~4.7 and 2.3-fold, respectively, about 1 h after taking D-BHB. This indicated that AcAc is effectively taken by the brain and by other organs particularly the heart and the kidney.

Ketone production from an exogenous dietary source has been traditionally achieved by MCT. This requires a bolus intake to saturate the liver with MCFA, producing excess acetyl-CoA which is then transformed to AcAc and BHB, which are released into systemic circulation. The C_max achieved with MCT is usually between 300 and 600 μM, with higher values being difficult to reach due to GI side effects and liver saturation. Here we show that D-BHB, a natural and biologically active ketone isomer, raises blood ketone C_max above 1 mM without noticeable side effects. In comparison, an equivalent dose of D+L-BHB or MCT only achieved half this ketone level, with similar T_max at 1 h. Thus, compared to D+L-BHB, D-BHB significantly reduces the salt intake needed to achieve the same plasma ketone response.

Results from a previous study (9) comparing KE to D+L-BHB showed that at the same dose of D-BHB equivalent, the increase blood ketone iAUC had the same magnitude, suggesting that exogenous D-BHB and KE produce similar ketosis.

Note that KE means Ketone Ester and the study (9) is this one: -

On the Metabolism of Exogenous Ketones in Humans

Ketone esters are available, but horribly expensive and taste really bad.

Conclusion

In previous posts the numerous possible beneficial modes of action of BHB were outlined. The summary post is here: -

Ketone Therapy in Autism (Summary of Parts 1-6)

In practise some people with autism seem to benefit a lot, some moderately and some not at all.

Monty, aged 16 with ASD, fits in the “moderately benefits” category.  The combination of about 20ml of caprylic acid (C8) plus a scoop of Potassium BHB powder does produce more speech.

It is not a cheap or very convenient therapy, compared the others I use.

I would agree with Nestlé that the limiting factor with BHB salts is the “salt”.  As they comment in their paper 

“compared to D+L-BHB, D-BHB significantly reduces the salt intake needed to achieve the same plasma ketone response”

Giving someone with heart disease "sodium anything" is not a good idea. A potassium salt would be safer, but even then, your heart is the limiting factor on potassium use.  Calcium salts are unwise in people with autism, because it appears to be able to upset calcium ion signalling, which would also be a potential risk in heart disease.

As I mentioned to one parent who is a big time user of BHB salts, if you switch to D-BHB you can either produce twice the ketones of regular potassium BHB, with the existing potassium load, or reduce your dosage by half and keep the same effect and save some money.

I think potassium D-BHB is good choice.  If you are taking bumetanide you may no longer need a potassium supplement (K-BHB becomes your potassium supplement).

I think people with autism and genuine mitochondrial disease are highly likely to benefit from D-BHB.  These are people who show symptoms in their entire body, i.e. lack of exercise endurance. For these people, eating (or producing via diet) large amounts of ketones will increase the production of ATP in their brains and so improve cognitive function.  D-BHB undergoes a different process to glucose, as it “converted” to ATP by the process called OXPHOS
(Oxidative phosphorylation). Some people with autism lack the enzyme complexes needed to complete OXPHOS, these people who should try D-BHB.

BHB has other beneficial effects, some relating to inflammation that seem to explain its benefit in other types of autism.  The effects were investigated here.

In the brains of people with Alzheimer’s there is decreased expression of glucose transporter 1 (GLUT 1) at the blood brain barrier. This starves the brain of glucose, which is fuel for the brain. D-BHB is an alternative fuel for mitochondria that is not dependent on GLUT 1.  People with early onset Alzheimer's would seem the best ones for this therapy, that would include many people with Down Syndrome. 

Life with Autism under Lockdown

I thought there should be at least one post about how life has changed during Covid-19.  Where we live, Monty’s life goes on pretty much as before, now we are back to home schooling - but that is nothing new for us.

School starts at 9am, there are 3 or 4 classes a day online from school and then activities and exercises till 3.30pm. 

We have PE, art and music like at school.  Piano practice continues most days.

Monty’s latest addition to his routine is reading 30 pages a day of a novel in the evening.  Now that he has started, he insists on doing it every day.  Having finished the (boring) books from school, he is going to start reading his brother’s collection of Biggles novels. They are about a fictional fighter pilot, the series starts in 1916 and continues for 50 years (the author got old, but Biggles did not).  We are going to set the scene with one of the old epic films about fighter aces from 1914-18.

The parks are closed and we have a curfew starting at 5pm weekdays and now across the entire weekend.  If you live in a small apartment, as many people do in the areas with the most strict lockdowns, life clearly will be difficult for people who do not understand why their movements have suddenly been restricted.

In many countries parents have asked for special treatment for those with autism, so that they can go outside more often. This has just been implemented where we live.

Parents are now going outside to walk their child with autism during the curfew and then neighbours are calling the police to report them.  In some countries you can get a special paper confirming your right as a disabled person to be taken outside, when everyone else has to stay at home.

In our case, Monty accepts that schools, parks, restaurant and cafes are all closed, but he expects that come September life will return to normal and his brother will go back to University.  Monty is lucky to live in a house with a garden, so he has plenty of space and lots of things to do.

Life with autism under control is not so demanding, even under lockdown.

When Monty was eight years old, we had nine months of autism out of control, which then results in a self-imposed lockdown.  That period ended just before Monty started his Polypill therapy in 2012.

I would not want to be in lockdown with an adult-sized person with untreated severe autism.

The Big Issue

Recently I was asked for some advice by Monty’s assistant; her friend works publishing a magazine homeless/disadvantaged people sell on the street.  One of their best “sellers” is a young man with mild autism.  He actually lives with his parents – he is not homeless.  He is struggling under the lockdown, because the magazine is not being published; he still turns up at the office to collect his copies to sell, even though there are none.

The young man became very anxious and so his parents gave him something to calm his nerves (which turned out to be Valium).

I was told that he had been given some pills, but in spite of these pills he got worse and started being aggressive, which is totally out of character.  This was all (falsely) attributed to the Corona virus changes to life.

As usual you do have to double check the facts.  Where we live a man with “mild autism” does not mean a person with Asperger’s, it means a person with Autistic Disorder (i.e. severe autism), but not such a bad case, so the young man can walk to work by himself and has some speech. 

I was asked what pills the parents could ask for, to calm him down. I explained that for anxiety people with autism often get prescribed benzodiazepines, but for aggression and self-injury they might get antipsychotics.  Neither are a good choice in most cases.

“And … there should not be any side effects.

The pills he currently takes are just something very mild”

So, what pills had he been given? It was a local brand name I did not know, so I looked it up and it was Valium/Diazepam, the benzodiazepine.

Adult with autism going crazy after Valium? that sounds familiar.

You don’t want Valium, you want 2mg of Bumetanide.

People who show a negative reaction to benzodiazepine drugs, usually prescribed to calm you down, are very likely to be bumetanide responders.

Benzodiazepine drugs increase the effect of the neurotransmitter GABA. In most people GABA is inhibitory, so increasing its effect will calm you down and ultimately sedate you.

In people with GABA working in reverse, it acts as excitatory.  This will reduce cognitive function and affect mood and behavior.  If you “turn up the volume” of GABA by taking a Benzodiazepine drug like Valium, you will make such people go crazy, with aggression and self-injury.

Hopefully the parents of the young man will get my message and stop giving Valium.  It would be nice to think they will also start to give Bumetanide, but that is their choice and I assume they most likely will not.  A diuretic for autism? How crazy is that.

How crazy is an anti-malarial for Covid-19?

How are the French doing with an antimalarial and an antibiotic for Covid-19, that I referred to in an earlier post? Say farewell to Covid-19 in just five days, it appeared.

By now the French have treated thousands of people with their new off-label therapy.  Also being developed in Marseille is Bumetanide as an off-label autism therapy by Neurochlore.  It looks like free thinking is flourishing on the Cote d'Azur.   

The data below is from the Marseille University Hospital Institute for Infectious Diseases (IHU Méditerranée Infection) and the wider hospital group in Marseille called APHM, which means Assistance Publique-Hôpitaux de Marseille.

The public hospitals in Marseille have treated 4,337 Covid-19 patients and 78 died (1.8%).

Within that group 2,671 were treated at the specialist IHU hospital with the antimalarial hydroxychloroquine (and some with azithromycin in addition) and of those that received at least 3 days of treatment 11 died (0.4%).

I think we can infer that 1,666 patients did not have hydroxychloroquine and 67 died (4%).

So if taken sick with Covid-19 in Marseille, tell the ambulance:

         "IHU Méditerranée Infection et vite !!"

If needed you can add:

        "Appuyez sur le champignon!"

Source :  https://www.mediterranee-infection.com/covid-19/

As I suggested in my post on Covid-19, hydroxychloroquine looks a very good bet.  The supposedly fact-based media (CNN, BBC etc) continues to say there is no hard evidence to support the use of hydroxychloroquine.  How much evidence do you need?

To measure the success of hydroxychloroquine, you just count the bodies.

If this is such a struggle, what hope is there to ever prove a drug can work for such an ill-defined condition as autism?

Until you have been vaccinated against Covid-19, it appears that what you need is hydroxychloroquine + azithromycin and some potassium, to treat the hypokalemia caused by Covid-19. Ideally you would also have a home test for Covid-19, which are getting much cheaper, so you do not take the drugs unnecessarily.

Fortunately where we live hospitals are routinely giving hydroxychloroquine + azithromycin, but ideally you would start the antiviral therapy before getting ill enough to go to hospital.

Tom Hank’s wife was complaining recently in the media about the side effects (nausea, vertigo etc) of the chloroquine she was given in hospital in Australia for Covid-19.  I think that is a little ungrateful. Untreated Covid-19 can have a pretty terminal side effect.

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."