Friday 8 December 2023

Walnuts for Brain Health in Aging and ADHD, but in Autism?


Source: Ivar Leidus - Own work, CC BY-SA 4.0,


Diet does seem to be the most popular intervention for autism and it does appear to give benefits, particularly in those with milder autism.

There are lessons to be learnt from healthy aging, when looking at how to optimise brain function in those with a neurodevelopmental disorder like autism.

As we age, multiple processes in the body start to function sub-optimally and this pretty much determines our healthy life expectancy. There are overlaps between features of this sub-optimal function (oxidative stress, mitochondrial dysfunction, neuroinflammation etc) and what is present in people with level 3 autism and/or intellectual disability.

The dietary keys to healthy aging:

A healthy varied diet rich in fruits, berries, vegetables, whole grains, legumes and nuts.

Healthy fats and lean protein.

To this we have to add all those herbs and spices.

Herbs, in large quantities, are a key element of the Mediterranean diet and are often omitted by people trying to copy this diet. I still remember meeting our reader Petra in Greece and receiving her gift of olive oil and oregano – it was a huge bag of oregano, not the size you might find in a supermarket in Northern Europe.

The healthy Okinawa diet is distinguished by low-calorie intake, fish, very little meat, fermented food (like natto), not to forget the seaweed. They also consume large amounts of a purple sweet potato. Okinawan sweet potatoes, also known as purple sweet potatoes, are a type of sweet potato that is native to Okinawa. They are characterized by their deep purple flesh, which is due to the presence of anthocyanins, a type of antioxidant.

I have to say that having visited an island in the Okinawa archipelago they also have some very unhealthy food adopted from US military bases. Spam sushi was everywhere, as are US style fast food outlets, with over-sized burgers. I found it hard going eating fish three times a day, albeit those small amounts.


Greece is no different, there are older Greeks with healthy traditional diets, but no shortage of giros and souvlaki joints catering to the locals and the tourists alike.



Nuts!  Not just at Christmas

Nuts are on the list of healthy foods, but I think most people neglect them.

It is difficult to incorporate sufficient nuts into your diet unless you are going to spend time eating them by the handful.

Incorporating large amounts of herbs like oregano, basil, sage, rosemary, thyme, parsley, mint etc is not so hard and you end up with much tastier food. They provide numerous health benefits. 

I was very surprised to find that there was so much evidence to support the humble walnut.

I was also surprised where some of the evidence comes from.

I did exchange emails many years ago with Abha Chauhan, a well-known researcher at the Institute for Basic Research in Developmental Disabilities in New York. She has written some very cutting edge research about oxidative stress.

She turns out to be a fan of walnuts.

She does actually list nutrition among her research interests:-

Alzheimer's disease, amyloid, free radicals, glutathione, mitochondria, nutrition, oxidative stress, protein kinases

 Her paper is here:-

Beneficial Effects of Walnuts on Cognition and Brain Health

I did previously wonder why New York has a research center into intellectual disabilities. Here is some information.


The Institute for Basic Research in Developmental Disabilities (IBR) is a proud part of New York State’s long history of caring for its citizens with developmental disabilities. It was in the 1940s and 1950s that the idea of creating an institute dedicated to studies in mental retardation was first discussed. In 1958, enabling legislation was passed for the creation of the Institute for Research in Mental Retardation within the New York State Department of Mental Hygiene. Ground was broken for the Institute’s research tower in 1964, and when its first laboratories opened in 1968, IBR was the first large-scale institute in the world with the mandate to conduct basic and clinical research into the causes of mental retardation. IBR became part of OPWDD, then known as the New York State Office of Mental Retardation and Developmental Disabilities (OMRDD) in 1979; a year later, it was renamed the Institute for Basic Research in Developmental Disabilities to reflect OMRDD’s broader focus on many developmental disabilities.  

Research is always good, but what really matters is translating it to therapy. How about actually getting kids with autism treated for oxidative stress? This I recall discussing with Abha and her response was that the funding is lacking for clinical trials. My response was that she could always give Mike Bloomberg a call.  How much money do you really need? 

Abha, Alzheimer’s and the walnut

As we saw Alzheimer’s was number one on Abha’s research interests. Here we have her paper suggesting walnuts for Alzheimer’s.


Benefits of a diet with walnuts in Alzheimer’s disease

Alzheimer’s disease is a severe neurodegenerative disorder, responsible for 60-70% of cases of dementia. The most common symptoms are memory loss, disorientation and loss of cognition. To date, there is no known cure for this disease, but Dr Abha Chauhan, based at the New York State Institute for Basic Research in Developmental Disabilities, New York, USA, has shown how supplementation with walnuts in the diet can help Alzheimer’s mice slow down the development of the disease. Her research demonstrates that walnuts can limit the oxidative stress characteristic of this condition, as well as promote the body’s natural antioxidant defence mechanisms. 

Based on these results, it’s reasonable to suggest that supplementation with walnuts may help in reducing the risk of developing Alzheimer’s disease, delaying its onset and/or slowing its progression due to the antioxidant and anti-inflammatory effects of different components of walnuts. At the very least, these results indicate that it may be worth conducting similar studies in humans.


It’s difficult to say at this stage what exactly in the walnut is responsible for these benefits, but in addition to antioxidants in walnuts, ALA (omega-3 fatty acid) may also be a contributing factor. While most nuts contain monounsaturated fats, only walnuts consist primarily of polyunsaturated fat, of which ALA is the main constituent. This fatty acid is the precursor of vital fatty acids, important for regulating serotonin and dopamine concentrations, as well as modulating key inflammatory and immune functions.


Beneficial Effects of Walnuts on Cognition and Brain Health

Oxidative stress and neuroinflammation have important roles in the aging process, mild cognitive impairment (MCI), Alzheimer’s disease (AD), and other brain disorders. Amyloid beta protein (Aβ) is the main component of amyloid plaques in the brains of people with AD. Several studies suggest that Aβ increases the generation of free radicals in neurons, which leads to oxidative damage and cell death. Aβ can also induce neuroinflammation by increasing pro-inflammatory cytokines and enzymes. Walnuts contain several components that have antioxidant and anti-inflammatory effects. Animal and human studies from our and other groups suggest that supplementation with walnuts in the diet may improve cognition and reduce the risk and/or progression of MCI and AD. In the transgenic AD mouse model (AD-tg), we have reported the beneficial effects of a diet with walnuts on memory, learning, motor coordination, anxiety, and locomotor activity. Human clinical trials have also suggested an association of walnut consumption with better cognitive performance and improvement in memory when compared to baseline in adults. Our recent study in AD-tg mice has shown that a walnut-enriched diet significantly improves antioxidant defense and decreases free radicals’ levels, lipid peroxidation, and protein oxidation when compared to a control diet without walnuts. These findings suggest that a diet with walnuts can reduce oxidative stress by decreasing the generation of free radicals and by boosting antioxidant defense, thus resulting in decreased oxidative damage to lipids and proteins. An in vitro study with synthetic Aβ showed that walnut extract can inhibit Aβ fibrillization and solubilize the preformed Aβ fibrils, suggesting an anti-amyloidogenic property of walnuts. Because it takes many years for cognitive impairment and dementia to develop, we suggest that early and long-term dietary supplementation with walnuts may help to maintain cognitive functions and may reduce the risk of developing, or delay the onset and/or slow the progression of, MCI and dementia by decreasing Aβ fibrillization, reducing oxidative damage, increasing antioxidant defense, and decreasing neuroinflammation. Furthermore, several animal and human studies have suggested that walnuts may also decrease the risk or progression of other brain disorders such as Parkinson’s disease, stroke, and depression, as well as of cardiovascular disease and type 2 diabetes. Together, these reports suggest the benefits of a walnut-enriched diet in brain disorders and in other chronic diseases, due to the additive or synergistic effects of walnut components for protection against oxidative stress and inflammation in these diseases.


Walnuts for teenagers? 

That’s Nuts! Eating Walnuts Regularly Improves Cognitive Development and Psychological Maturation in Teens

Summary: Teens who added walnuts to their diet for 100 days showed improvements in attention function, and for those with ADHD, frequent walnut consumption was associated with improvements in behavior. Researchers also noted an increase in fluid intelligence in those who frequently consumed walnuts as part of their daily diet.


Walnuts May Help Teens with Maturity, Thinking, and Attention


Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial


Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear.


We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain ( Identifier: NCT02590848). A total of 771 healthy teenagers aged 11–16 years were randomised into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socio-emotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations.


In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p < 0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was −11.26 ms (95% CI = −19.92, −2.60; p = 0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI = 0.90, 2.67; p < 0.0001), and reduction of ADHD symptom score was −2.18 (95% CI = −3.70, −0.67; p = 0.0050).


Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents.  

Walnuts for Autism? 

I did find a case study from the Middle East putting forward reasons why walnuts and pumpkin may benefit some types of autism.  It was not a robust study, but I was surprised to find anything at all on this subject. 

Effects of Walnut and Pumpkin on Selective Neurophenotypes of Autism Spectrum Disorders: A Case Study

Special diets or nutritional supplements are regularly given to treat children with autism spectrum disorder (ASD). The increased consumption of particular foods has been demonstrated in numerous trials to lessen autism-related symptoms and comorbidities. A case study on a boy with moderate autism who significantly improved after three years of following a healthy diet consisting of pumpkin and walnuts was examined in this review in connection to a few different neurophenotypes of ASD. We are able to suggest that a diet high in pumpkin and walnuts was useful in improving the clinical presentation of the ASD case evaluated by reducing oxidative stress, neuroinflammation, glutamate excitotoxicity, mitochondrial dysfunction, and altered gut microbiota, all of which are etiological variables. Using illustrated figures, a full description of the ways by which a diet high in pumpkin and nuts could assist the included case is offered.

This case study does not support broad food treatments as a treatment for ASD, but it does imply that specialized dietary interventions over time may play a role in the management of certain ASD symptoms, functions, and clinical domains. The pumpkin/walnut healthy diet improved nutritional status, presumably increasing the brain’s ability to function and learn by reducing oxidative stress, neuroinflammation, glutamate excitotoxicity, mitochondrial dysfunction, and altered gut microbiota, all of which are etiological mechanisms behind the clinical presentation of ASD.   

Impact of Nut Consumption on Cognition across the Lifespan 

Cognitive health is a life-long concern affected by modifiable risk factors, including lifestyle choices, such as dietary intake, with serious implications for quality of life, morbidity, and mortality worldwide. In addition, nuts are a nutrient-dense food that contain a number of potentially neuroprotective components, including monounsaturated and polyunsaturated fatty acids, fiber, B-vitamins, non-sodium minerals, and highly bioactive polyphenols. However, increased nut consumption relates to a lower cardiovascular risk and a lower burden of cardiovascular risk factors that are shared with neurodegenerative disorders, which is why nuts have been hypothesized to be beneficial for brain health. The present narrative review discusses up-to-date epidemiological, clinical trial, and mechanistic evidence of the effect of exposure to nuts on cognitive performance. While limited and inconclusive, available evidence suggests a possible role for nuts in the maintenance of cognitive health and prevention of cognitive decline in individuals across the lifespan, particularly in older adults and those at higher risk. Walnuts, as a rich source of the plant-based polyunsaturated omega-3 fatty acid alpha-linolenic acid, are the nut type most promising for cognitive health. Given the limited definitive evidence available to date, especially regarding cognitive health biomarkers and hard outcomes, future studies are needed to better elucidate the impact of nuts on the maintenance of cognitive health, as well as the prevention and management of cognitive decline and dementia, including Alzheimer disease.



We are told in dietary advice from public health authorities that we should include nuts in our daily diet. The suggested daily amount is about 30 grams (1 ounce).

If you had to choose one nut, it looks like the walnut is the one most likely to help the brain.

Teenagers with ADHD are suggested to benefit in the research from Spain.

Abha Chauhan over in New York is a proponent of walnuts for potentially slowing down Alzheimer’s disease.

Whether walnuts may benefit some with autism is an open question, but there are reasons to believe that it should. Over in Abu Dhabi one autism practitioner is suggesting combining walnuts with pumpkin for optimal effect. 

Ensuring healthy aging with diet and exercise is actually very straight forward, but most people still choose not to do it.

Treating severe autism is much more hit and miss, but many of those who persevere see good results.

Tuesday 21 November 2023

Transit Training / Travel Instruction


Monty coming home by himself, at night, from a trip to see his friend Vera, who proudly sent me the photo - not nervous at all.


Today’s post is a practical one, it is all about developing independent travel skills. This is all part of what is called “adaptive behavior,” which are the skills you need to function independently in life.

I still recall one mother’s reaction from years ago when a teenager with autism traveling by bus was mentioned:-

“I’d be petrified I’d never see him again”

Your success in mastering life skills matters much more than your IQ, or any academic results.

Depending on where you live, there may be free services available to teach both children and adults, with some kind of special need, how to safely use public transport. There may be group classes, but some even provide a 1:1 helper to ride with the learner to teach the travel route until they can manage unassisted. We followed this latter model with Monty, now aged 20.  It did not take so long, but we encountered many disruptions along the way that provided key learning opportunities – more of that later.

In North America it is the transit authority or school that may offer this training, whereas in the UK it seems to be the municipal authority.



Example from the UK – Essex County Council

 Transit training in Vancouver


There are video training courses and apps for smart phones.

It is apparent that a wide range of people, from low IQ to high IQ are using these services.  It is quite well known that some Aspies struggle with travel by plane, but others may not like sitting next to strangers on the bus.

As with all trainings, they range from the superficial, like how to buy the ticket, to the comprehensive where many of the possible disruptions are planned for.

This is very similar to learning how to buy food/groceries - there is more to it than just learning how to stand in line and pay for your shopping. 

In the jargon this is all part of “adaptive behavior.” I think it would be much clearer if it was called “adaptable behavior.” Many people with autism are not adaptable at all and when things change, or go wrong, they can fall apart.


When things go wrong  it’s also called “life”

In my brief research I came across quite a lot from the US and just a small amount from the UK. Many of the anecdotes from the US are very upbeat, with parents happy that their child has achieved travel independence.  Some of the children / young adults do not appear very disabled, I should point out.

There remains the issue of what happens when things go wrong.

I always told Monty’s 1:1 school assistants not to worry if something went wrong it’s when things go wrong that you actually learn something useful.  The same is true with independent travel, inevitably things are going to go wrong – more of that later.

Here is a comment I found on the UK’s National Autism Society’s website:-



“My local authority is reviewing the cost of providing specialised transport for disabled adults and children. This is quite a widely reported issue nationally, as it affects vital transport links for people on the spectrum, especially those having to travel long distances to use support services and day centres.

One clever wheeze my local council has come up with is that they are going to train people with learning disabilities or autism how to travel independently by bus or train.

Yep, if you haven't heard this idea before, if my council are pushing this, sure enough lots of councils will be trying the same thing.

Seems they haven't factored in change. If the bus route changes. If the train leaves late or there's a confusing on train announcement. If the driver of the bus doesn't understand the difficulty. 

So for local authorities to come up with the clever saving, oh we'll teach disabled people how to go by bus or train. It is truly tragic how badly served we are.”


Clearly there are some people who will never be able to safely travel independently.  If you cannot master being out as a pedestrian unaccompanied, you are not ready for public transport training.

Given how broadly autism is now diagnosed with 1 in 25 (four percent) of seven to 14 year old Australians now having an autism diagnosis, it is only a very small proportion who cannot be helped.  Many will not need any help at all.


Getting used to things going wrong

Things rarely go exactly to plan and it is these unexpected events that can be hard for some people with autism, or intellectual disability, to deal with.

How do you build resilience to change? By being exposed to it, not being hidden from it.

Many things can go wrong when traveling independently, some are quite predictable, like forgetting to get off the bus at the correct stop, some are not.


Bad news can be good news

Since starting independent travel a couple of years ago, Monty has experienced his share of surprises/upsets.

Early on in his bus training he was getting used to traveling by himself on a small local bus and we had his former school assistant following in her car. He was supposed to go from near our house to the park. A lady riding in the bus, who had previously seen Monty practising with his assistant, thought he must have forgotten to get off and so she led him off the bus in what was the middle of his planned journey.  We had not expected that, but no harm done.

A bigger issue occurred recently when Monty took his regular two bus journey to his “work” – about an hour door to door. After getting off the first bus as usual and walking to another bus stop, the second bus had its route modified, due to a road closure, and Monty ended up at a big shopping mall.  He then headed off back towards his work on another bus, but again got stuck because of the road closure.  He could not fully explain what was going on by telephone, so I told him to go to a specific McDonalds, buy a cheeseburger and fries and wait for Dad.  This clearly was a stressful experience, but it is important to complete your activity, so after he finished eating I took him to his work by car.

Fortunately, with a tracking app on your smartphone, you cannot really lose your adult child. I use Google’s Family Link app.

You do need to always pack your phone, remember to charge it and not turn the ringer volume down to zero. Being able to answer your phone and use it to make calls have to be already mastered. Many children with autism hate the sound of a phone ringing and so just turn it off. If your house has poor cell phone coverage you need to teach calling via WhatsApp as well as by phone.

Monty has been taught "if you have a problem, call Dad" and call me he does. At every stage of his bus travels he calls to update me, so the tracking App is really just for emergencies. 


The broader concept of Adaptive Behavior, for those interested

Adaptive behavior is the technical term used for daily living skills.

 You might wonder why it is called adaptive behavior. The term "adaptive behavior" is used because it emphasizes the ability of individuals to adapt to their environment and meet the demands of everyday life. It goes beyond simply having basic skills like walking, talking, and eating; it encompasses the ability to learn, solve problems, interact with others, and manage one's personal life.

The word "adaptive" highlights the dynamic nature of these skills, as they are constantly being modified and refined to fit the changing circumstances of an individual's life. As we grow and develop, we learn new ways of coping with challenges, navigating relationships, and achieving our goals.

In addition, the term "behavior" emphasizes the active and intentional nature of these skills. It's not just about having the potential to perform certain actions; it's about actually using those skills in a functional and purposeful way.

Overall, the term "adaptive behavior" captures the essence of what it means to be able to function effectively in the world around us. It's about having the skills and abilities to adapt to new situations, solve problems, and build meaningful relationships, all of which are essential for a fulfilling and independent life.

Adaptive behavior is the collection of conceptual, social, and practical skills that all people learn in order to function in their daily lives. It encompasses a wide range of abilities, from basic self-care skills to more complex problem-solving and social interaction skills. Adaptive behavior is essential for individuals to live independently and to participate fully in their communities.

Conceptual skills are the ability to understand and apply information and concepts. They include:

  • Literacy: The ability to read and write at a level that is appropriate for one's age and environment.
  • Self-direction: The ability to set goals, make decisions, and manage one's own time and behavior.
  • Concepts of number, money, and time: The ability to understand and use basic mathematical concepts, to handle money responsibly, and to manage one's time effectively.

Social skills are the ability to interact with others in a positive and productive way. They include:

  • Interpersonal skills: The ability to communicate effectively, build relationships, and resolve conflict.
  • Social responsibility: The ability to follow rules, be considerate of others, and contribute to the community.
  • Self-esteem: A positive sense of self-worth and value.
  • Gullibility or naïveté: The ability to recognize and avoid being taken advantage of.
  • Social problem-solving: The ability to identify and solve social problems in a constructive way.
  • Following rules: The ability to understand and follow rules and expectations.
  • Obeying laws: The ability to understand and obey laws and regulations.
  • Avoiding being victimized: The ability to protect oneself from harm or exploitation.

Practical skills are the ability to perform the tasks of everyday living. They include:

  • Activities of daily living (personal care): The ability to take care of oneself, such as bathing, dressing, eating, and using the toilet.
  • Occupational skills: The ability to perform the tasks of a job or other productive activity.
  • Use of money: The ability to manage money responsibly, including budgeting, saving, and spending.
  • Safety: The ability to stay safe from harm, including fire, traffic, and other hazards.
  • Health care: The ability to manage one's health, including taking medication, seeing a doctor, and understanding one's health conditions.
  • Travel/transportation: The ability to travel from place to place safely and independently.
  • Schedules/routines: The ability to manage one's time and follow schedules and routines.
  • Use of the telephone: The ability to use a telephone to communicate with others.

Adaptive behavior skills develop gradually over time, from infancy to adulthood. Children with disabilities may develop these skills more slowly or with more difficulty than children without disabilities. However, with appropriate intervention and support, children can learn to develop the adaptive behavior skills they need to succeed in life.


Conclusion - creating dependence vs creating independence

A recuring theme in dealing with a child who has special needs is to what extent you accommodate those needs, versus trying to overcome them.

If your child struggles at the dentist, do you simply resort to sedation for every visit? or at least try and learn how to be treated like a typical patient?

It is fashionable these days to exaggerate smaller problems to try and get some benefits, or maybe some ADHD meds. A case in point is in Australia with a ballooning budget for those with a disability. In order to access financial support via their NDIS (National Disability Insurance Scheme), some clinicians have been exaggerating the severity of autism, only level 2 and 3 gets you financial benefits.  The end result will be a completely unaffordable scheme and some children/adults held back by a diagnosis they do not warrant. Ultimately there will be insufficient money to support those that need it the most.

In Australia a record 11.5 per cent of boys aged between five and seven are now receiving funding from the NDIS.  Not surprisingly this has put immense pressure on the program’s $42 billion annual budget.


Save money on specialist transport by investing in transit training!

A problem the Aussies have is that once someone joins their NDIS disability scheme, they apparently are likely never to leave it. So most of those 5-7 years olds will still likely be on it in 10, 20 and 50 years’ time. The average recipient receives over $30,000 a year.

We recently learnt from the US that about a third of children diagnosed with autism before 36 months of age no longer have symptoms qualifying for an autism diagnosis by the age of 7 years.


Persistence of Autism Spectrum Disorder From Early Childhood Through School Age

Key Points

Question:  What is the frequency with which children diagnosed clinically with autism spectrum disorder (ASD) at 12 to 36 months of age continue to meet criteria for ASD based on functioning at 5 to 7 years of age, and what factors are associated with ASD persistence?

Findings:  Of the 213 children in this cohort study, 79 (37%) had nonpersistent ASD. Higher baseline adaptive functioning and female sex were associated with nonpersistent ASD.

Meaning:  These findings suggest that an ASD diagnosis in a child younger than 3 years may not persist, and child-specific factors may be associated with persistence.


A big shake up will have to occur down under, or they will go broke.


IQ vs Adaptive Behavior as predictors for success

The interesting thing is that plenty of people with low IQ travel by bus every day, with no need for transit training.  Some higher IQ autistic teens and adults seem to struggle and many of them are fully verbal.

Adaptive behavior is the predictor of future independence/semi-independence.

You may well need your IQ to do some kind of office job, but without some adaptive behavior you will not be able to get to and from it.

If you are lucky, adaptive behavior is taught at school, but for many it will have to learnt outside school.

What about those unable to move towards transit training because they cannot safely cross a road? Try and raise IQ pharmacologically where possible, so that basic concepts of danger and self-preservation can be mastered.  Remarkable success is possible if you persist.


“I’d be petrified I’d never see him again”

This undoubtedly is a concern many parents of an adult or child with special needs will have.

Plenty of people thought Monty couldn't, or shouldn't, travel independently. There are always a hundred good reasons not to. It's too hot, it's too cold, it might rain, what if he gets lost, what if someone mistreats him ... and the list goes on. 

At least the training option already exists in many countries to move towards travel independence. Perhaps there should be courses for nervous parents too!

Wednesday 8 November 2023

Glycine-NAC for longevity, but for Autism? and Ketogenic “Autistic” Fish

Fish taking a ketone ester

Lonesome fish


Baylor College of Medicine in the US have a patent on the combination of glycine and the anti-oxidant NAC to promote healthy aging, which they licensed to Nestle. You can easily make it yourself - just buy both separately. 

GlyNAC supplementation reverses mitochondrial dysfunction, oxidative stress and aging hallmarks to boost strength and promote health in aging humans

One of the intriguing questions from this trial is why so many improvements occur toward promoting health. We believe that this is due to the combined effort of three separate components – glycine, cysteine (from NAC) and glutathione, and not just due to glutathione itself. Glycine and cysteine are both very important for cellular health on their own, and GlyNAC provides both. 

We believe that the improvements in this trial and in our previous studies are the result of the combined effects of glycine and NAC and glutathione, and we refer to this combination as the "Power of 3" said Sekhar.

You need cysteine and glycine to make the body's key antioxidant, glutathione (GSH).  Older people and people with autism are likely to lack GSH.

If you add the precursors via supplementation, you will hopefully increase the production of GSH.


GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage

Determinants of length of life are not well understood, and therefore increasing lifespan is a challenge. Cardinal theories of aging suggest that oxidative stress (OxS) and mitochondrial dysfunction contribute to the aging process, but it is unclear if they could also impact lifespan. Glutathione (GSH), the most abundant intracellular antioxidant, protects cells from OxS and is necessary for maintaining mitochondrial health, but GSH levels decline with aging. Based on published human studies where we found that supplementing glycine and N-acetylcysteine (GlyNAC) improved/corrected GSH deficiency, OxS and mitochondrial dysfunction, we hypothesized that GlyNAC supplementation could increase longevity. We tested our hypothesis by evaluating the effect of supplementing GlyNAC vs. placebo in C57BL/6J mice on (a) length of life; and (b) age-associated GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage in the heart, liver and kidneys. Results showed that mice receiving GlyNAC supplementation (1) lived 24% longer than control mice; (2) improved/corrected impaired GSH synthesis, GSH deficiency, OxS, mitochondrial dysfunction, abnormal mitophagy and nutrient-sensing, and genomic-damage. These studies provide proof-of-concept that GlyNAC supplementation can increase lifespan and improve multiple age-associated defects. GlyNAC could be a novel and simple nutritional supplement to improve lifespan and healthspan, and warrants additional investigation.


Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial

GlyNAC supplementation for 24‐weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin‐resistance and endothelial dysfunction, and genomic‐damage, and improved strength, gait‐speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation.




Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review

Glycine is most important and simple, nonessential amino acid in humans, animals, and many mammals. Generally, glycine is synthesized from choline, serine, hydroxyproline, and threonine through interorgan metabolism in which kidneys and liver are the primarily involved. Generally in common feeding conditions, glycine is not sufficiently synthesized in humans, animals, and birds. Glycine acts as precursor for several key metabolites of low molecular weight such as creatine, glutathione, haem, purines, and porphyrins. Glycine is very effective in improving the health and supports the growth and well-being of humans and animals. There are overwhelming reports supporting the role of supplementary glycine in prevention of many diseases and disorders including cancer. Dietary supplementation of proper dose of glycine is effectual in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. Glycine also has the property to enhance the quality of sleep and neurological functions. In this review we will focus on the metabolism of glycine in humans and animals and the recent findings and advances about the beneficial effects and protection of glycine in different disease states. 

As glycine is a very successful immunomodulator that suppresses the inflammation, its action on arthritis is investigated in vivo through PG-PS model of arthritis. PG-PS is a very crucial structural component of Gram-positive bacterial cell walls and it causes rheumatoid like arthritis in rats. In rats injected with PG-PS which suffer from infiltration of inflammatory cells, synovial hyperplasia, edema, and ankle swelling, these effects of PG-PS model of arthritis can be reduced by glycine supplementation [66].


Glycine has a wide spectrum of defending characteristics against different injuries and diseases. Similar to many other nutritionally nonessential amino acids, glycine plays a very crucial role in controlling epigenetics. Glycine has much important physiological function in humans and animals. Glycine is precursor for a variety of important metabolites such as glutathione, porphyrins, purines, haem, and creatine. Glycine acts as neurotransmitter in central nervous system and it has many roles such as antioxidant, anti-inflammatory, cryoprotective, and immunomodulatory in peripheral and nervous tissues. Oral supplementation of glycine with proper dose is very successful in decreasing several metabolic disorders in individuals with cardiovascular disease, various inflammatory diseases, cancers, diabetes, and obesity. More research investigations are needed to explore the role of glycine in diseases where proinflammatory cytokines, reperfusion or ischemia, and free radicals are involved. Mechanisms of glycine protection are to be completely explained and necessary precautions should be taken for safe intake and dose. Glycine holds an enormous potential in enhancing health, growth, and well-being of both humans and animals.


Ketogenic Fish – rebuilding social affinity 

Regular readers will have noted that some people with autism, but normal IQ, are deeply troubled by their lack of social affinity and seek out ways to improve it.

Perhaps we can learn something on that subject from Masato Yoshizawa, an evolutionary developmental biologist and neurobiologist at the University of Hawaii. Yes, that’s right, an evolutionary developmental biologist – they exist! Back in 2018 he published a paper called “The evolution of a series of behavioral traits is associated with autism-risk genes in cavefish”.

“Many people first doubted that the fish have an autism-like state; I also doubted it at first,” said Yoshizawa. But as he soon found out, even patterns of gene regulation resembled autistic patients.

His recent paper uses his cavefish to look at how the ketogenic diet affects behaviour. 

In the experiment, cavefish where fed the same ketogenic milk provided to human patients, albeit with a few modifications for fish consumption, and their behavior was monitored. As a comparison, a type of A. mexicanus fish that lives in rivers and not caves were also tested.

The surface fish do not display the same autism like behaviors as their cave dwelling relatives. In the presence of other surface fish, individuals will begin to follow each other and swim together, something rarely seen in cavefish, Yoshizawa said. The surface fish also do not do the repetitive behavior of swimming in circles.


Using these fish as a comparison, Yoshizawa and his students watched and waited. Amazingly, after a month of the ketogenic diet, the cavefish began to act like the more social surface fish. They would follow each other in groups and ceased going round in circles. There were some other behaviors, such as attention to a specific task and sleeping, that were unaffected, but overall the results were promising and according to Yoshizawa, suggest dopamine could be key to how the diet affects behavior.


According to Yoshizawa, there are two plausible ideas as to how the ketones produced by a ketogenic diet are acting on behavior. The first involves the mitochondria, which use either carbs or fat to produce energy in our cells, and the other involves epigenetics, which simple refers to any non-genetic influence which turns genes on and off.


Ketones are known to create detectable increases in gene expression in cells. Pulling apart exactly how things like, diet, environment, genes and neurotransmitters are linked is incredibly difficult but could reveal which pathways are best to target for autism treatments or could identify a specific ketone which works more efficiently than others.



Cavefish provide clues to the keto diet's effect on autism-like behavior 


Metabolic shift toward ketosis in asocial cavefish increases social-like affinity



Social affinity and collective behavior are nearly ubiquitous in the animal kingdom, but many lineages feature evolutionarily asocial species. These solitary species may have evolved to conserve energy in food-sparse environments. However, the mechanism by which metabolic shifts regulate social affinity is not well investigated.


In this study, we used the Mexican tetra (Astyanax mexicanus), which features riverine sighted surface (surface fish) and cave-dwelling populations (cavefish), to address the impact of metabolic shifts on asociality and other cave-associated behaviors in cavefish, including repetitive turning, sleeplessness, swimming longer distances, and enhanced foraging behavior. After 1 month of ketosis-inducing ketogenic diet feeding, asocial cavefish exhibited significantly higher social affinity, whereas social affinity regressed in cavefish fed the standard diet. The ketogenic diet also reduced repetitive turning and swimming in cavefish. No major behavioral shifts were found regarding sleeplessness and foraging behavior, suggesting that other evolved behaviors are not largely regulated by ketosis. We further examined the effects of the ketogenic diet via supplementation with exogenous ketone bodies, revealing that ketone bodies are pivotal molecules positively associated with social affinity.


Our study indicated that fish that evolved to be asocial remain capable of exhibiting social affinity under ketosis, possibly linking the seasonal food availability and sociality.


Are these behavioral and growth changes induced by ketosis? The KD contains high amounts of fat, sufficient levels of proteins, and a minimum amount of carbohydrates. This question motivated us to test the molecular basis of the effects of KD feeding by supplementing major ketosis metabolites, ketone bodies, to the standard diet.


In humans, KD feeding induces ketosis, in which the liver releases beta-hydroxybutyrate (BHB) and acetoacetate via beta-oxidation of fat [63].


Instead of supplying a massive amount of fat using the KD, BHB might be responsible for the majority of effects observed after KD feeding. With this idea, the ketone ester (D-b-hydroxybutyrate-R 1,3-Butanediol Monoester; delta-G® [64]) was provided as a supplement to both surface fish and cavefish for 5 weeks. The ketone ester (KE) was expected to undergo complete hydrolysis by the gut esterases, resulting in two BHB molecules (and acetoacetate) [64]. It does not contain any salt ions, unlike the sodium or potassium salt forms of BHB, nor does it has the racemic L-form, where only the D-form is considered to be biologically active [65]. Since we were unsure whether gut esterases were available in juvenile-adolescent fish at 3 months old, we used 6–7-month-old fish that have a mature gut system but are in the young adult stage. The results indicated that the KE supplementation significantly reduced the serum GKI (Additional file 2: Fig. S8), while promoting nearby interactions in cavefish (Fig. 7A, B). Swimming distance was slightly reduced in cavefish (Fig. 7C). Turning bias was not reduced by KE supplementation in cavefish (Fig. 7D). There was no detectable difference between CD and KE supplemental diets in sleep duration or VAB (Additional file 2: Fig. S9A and B, respectively).


We also tested the supplemental feeding of the BHB salt form (sodium salt form of racemic BHB: 50% L-form and 50% D-form). We used 11–12-month-old fish in this study since the younger fish seemed to suffer from the high-salt-containing diet. The 4-week feeding result was essentially the same as the KE-supplemented diet feeding: the BHB salt supplemental diet significantly reduced GKI in the serum of surface and cavefish (Additional file 2: Fig. S10), while promoting nearby interactions in cavefish but reduced the duration of nearby interactions in surface fish (Additional file 2: Fig. S11A, B). No major change in response to the BHB feeding was detected in swimming distance (Additional file 2: Fig. S11C), turning bias (Additional file 2: Fig. S11D), sleep (Additional file 2: Fig. S12A), and VAB (Additional file 2: Fig. S12B) in cavefish, while the BHB salt reduced growth (standard length and weight) in surface fish (Additional file 2: Fig. S12C, D). In contrast, cavefish did not show any detectable negative effects on growth under the BHB salt supplemental feeding (Additional file 2: Fig. S12C, D).


In summary, BHB (KE and BHB salt) treatment encompassed the effect of the KD treatment—promoting social interactions. BHB, particularly KE, had a no-detectable negative effect on growth. These facts suggest that ketone bodies can be responsible factors for the positive effects on social behaviors of KD feeding. BHB treatment also indicated that older-age cavefish (6–7 months or 11–12 months old) were still capable of responding to ketone bodies, not only younger age groups (3–4 months old).


You can treat an old-fish new tricks!

Indeed, some of our adult readers are treating themselves with ketone esters.

Both ketone esters and ketone salts were trialed in the fish. In humans ketone esters are the clear winner because they provide a much longer lasting effect.

There is no reason why they have to be so expensive, the bulk chemical is not expensive.



For longevity and, more importantly, healthy life expectancy it has long been clear that high doses of anti-oxidants are beneficial.

The question is how best to get this effect.

The most potent way is via intravenous infusion of something like ALA (alpha lipoic acid). In some countries intravenous ALA is a mainstream therapy for people with diabetes, not surprisingly thanks to the ALA some of these people also overcome their other health conditions, like heart disease, and increase their healthy lifespan.

Most people will not have this option and probably do not want intravenous therapy anyway.

Oral supplementation with NAC is cheap, effective and available.

Is adding glycine going to have any incremental effect?  Quite possibly it will. If you are lacking glycine, this will hold back your production of GSH (glutathione). Glycine itself might well provide a health benefit.

Dr Sekhar, over at Baylor College in Houston, refers to the “power of three” (NAC, glycine and glutathione/GSH). The immediate, short-lived, beneficial effect is directly from the anti-oxidant effect of NAC itself.

If, like me, you have chosen to take NAC you are experiencing the “power of two” (NAC and Glutathione/GSH).  Glycine is really cheap and so why not take the extra step and add it? You may increase Glutathione/GSH and glycine has its own direct antioxidant and anti-inflammatory properties.

When it comes to young people with autism who take NAC, is the benefit from the immediate antioxidant effect of NAC, or is it from the increase in GSH?  Here I think we know the answer.  The behavioral effect of NAC is quite short-lived and it matches the short half-life of NAC.  Is there a secondary effect from NAC releasing cysteine that gradually increases GSH (glutathione)? Quite possibly, but in autism you really do need to give NAC 3-4 times a day, so the direct effect of NAC itself looks to be key.

Is Glycine NAC going to be better than NAC for young people with autism? Glycine has its own interesting properties and glycine is cheap. It even can help some of those with sleep problems (3g one hour before bed time).

There are plenty of anecdotal reports on the internet of Aspies finding glycine supplementation helpful - some find it makes them more social.

There is a potential problem for bumetanide-responders. In these people if GABA is operating "in reverse", due to high intracellular chloride, the same may be true of glycine. You would then expect a negative reaction

GABA and glycine in the developing brain

GABA and glycine are major inhibitory neurotransmitters in the CNS and act on receptors coupled to chloride channels. During early developmental periods, both GABA and glycine depolarize membrane potentials due to the relatively high intracellular Cl concentration. Therefore, they can act as excitatory neurotransmitters. GABA and glycine are involved in spontaneous neural network activities in the immature CNS such as giant depolarizing potentials (GDPs) in neonatal hippocampal neurons, which are generated by the synchronous activity of GABAergic interneurons and glutamatergic principal neurons. GDPs and GDP-like activities in the developing brains are thought to be important for the activity-dependent functiogenesis through Ca 2+ and/or other intracellular signaling pathways activated by depolarization or stimulation of metabotropic receptors. However, if GABA and glycine do not shift from excitatory to inhibitory neurotransmitters at the birth and in maturation, it may result in neural disorders including autism spectrum disorders.


And those ketone esters (KE)?

Well they are really expensive, when packaged up for humans, but they should be helpful to a sub-group within autism.

Will ketone esters (KE) make our reader Stefan feel more social? Quite possibly, but they are likely too expensive to take every day. Glycine is cheap and worth a try for social affinity, based on the anecdotes from other Aspies.

Some readers are already big fans of ketone esters.  They do not need any further proof from those cavefish in Hawaii.