Alpha-lactalbumin Whey Protein – Treating Neurological Dysfunction, including Epilepsy and Autism, via the Gut (Eubiosis)

 

Moo! α-Lactalbumin is a whey protein constituting 22% of the proteins in human milk and 3.5% of those in cow milk.

 

Most parents love the idea of treating their child with autism or epilepsy with diet.

Diet is so popular because you do not need a doctor - no drugs, no prescriptions, just healthy food.

This blog is about the science, which often takes us to drugs that need a prescription, but when talking about using the gut to fine-tune how the brain works, much can be achieved with nutraceuticals.

We previously saw how the ketogenic diet, which has been reducing epilepsy for one hundred years, actually works by modifying which bacteria grow in the gut.  The super high fat diet encourages specific bacteria to flourish and it is these bacteria which indirectly cause the cessation in seizures. You can replicate the effect with probiotic bacteria, without needing the highly restrictive diet at all.

Today I will introduce Alpha-lactalbumin, which is a commercially available whey protein found in mother’s milk and to a lesser extent in cow milk. 

Alpha-lactalbumin when combined with another regular in this blog, sodium butyrate, has been shown to improve autism, epilepsy and indeed depression.

The research also suggests that Alpha-lactalbumin may improve sleep and mood disorders.

  

Whey protein vs NAC

I recall reading about whey protein as an antioxidant back in 2013, when I was deciding what to try next after Bumetanide, as I developed by son's personalized polytherapy for autism. I did choose NAC, but I still recall the surprising option of whey protein.

Whey protein is popular among athletes and body builders.

Whey protein is a mixture of proteins isolated from whey, the liquid material created as a by-product of cheese production. The proteins consist of α-lactalbumin (ALAC), β-lactoglobulin, serum albumin and immunoglobulins.

 

Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein

We sought to increase glutathione levels in stable patients with cystic fibrosis by supplementation with a whey-based protein.

 After supplementation, we observed a 46.6% increase from baseline (P<0.05) in the lymphocyte GSH levels in the supplemented group. No other changes were observed. 

Conclusion: The results show that dietary supplementation with a whey-based product can increase glutathione levels in cystic fibrosis. This nutritional approach may be useful in maintaining optimal levels of GSH and counteract the deleterious effects of oxidative stress 

 

The Antioxidant Effects of Whey Protein Peptide on Learning and Memory Improvement in Aging Mice Models

The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1β) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein.

These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.

 

 

 α-lactalbumin (ALAC)

Today we are really focused on one specific whey protein, α-lactalbumin (ALAC), which is actually sold commercially as a nutraceutical.

 

https://www.arlafoodsingredients.com/health-foods/our-ingredients/alpha-lactalbumin/?downloadUrl=%252F4908eb%252Fglobalassets%252Frestricted%252F2017%252F_ho_alpha20_wellbeing_0317_v2.pdf

 

 

Applications for α-lactalbumin in human nutrition

α-Lactalbumin is a whey protein that constitutes approximately 22% of the proteins in human milk and approximately 3.5% of those in bovine milk. Within the mammary gland, α-lactalbumin plays a central role in milk production as part of the lactose synthase complex required for lactose formation, which drives milk volume. It is an important source of bioactive peptides and essential amino acids, including tryptophan, lysine, branched-chain amino acids, and sulfur-containing amino acids, all of which are crucial for infant nutrition. α-Lactalbumin contributes to infant development, and the commercial availability of α-lactalbumin allows infant formulas to be reformulated to have a reduced protein content. Likewise, because of its physical characteristics, which include water solubility and heat stability, α-lactalbumin has the potential to be added to food products as a supplemental protein. It also has potential as a nutritional supplement to support neurological function and sleep in adults, owing to its unique tryptophan content. Other components of α-lactalbumin that may have usefulness in nutritional supplements include the branched-chain amino acid leucine, which promotes protein accretion in skeletal muscle, and bioactive peptides, which possess prebiotic and antibacterial properties. This review describes the characteristics of α-lactalbumin and examines the potential applications of α-lactalbumin for human health.

 

α-Lactalbumin constitutes approximately 22% of total protein and approximately 36% of the whey proteins in human milk and approximately 3.5% of total protein and approximately 17% of whey proteins in bovine milk (Figure 1)¹,². It has an amino acid composition that is high in essential amino acids and comparatively rich in tryptophan, lysine, cysteine, and the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine.³ (Table 1)⁴. Because of its unique amino acid profile, α-lactalbumin has potential for multiple uses: (1) as a component of infant formulas, to make them more similar to breast milk; (2) as a supplement to promote gastrointestinal health or modulate neurological function, including sleep and depression; and (3) as a therapeutic agent with applications in conditions or diseases such as sarcopenia, mood disorders, seizures, and cancer. 

 

Intestinal inflammation increases convulsant activity and reduces antiepileptic drug efficacy in a mouse model of epilepsy

We studied the effects of intestinal inflammation on pentylenetetrazole (PTZ)-induced seizures in mice and the effects thereon of some antiepileptic and anti-inflammatory treatments to establish if a link may exist. The agents tested were: alpha-lactoalbumin (ALAC), a whey protein rich in tryptophan, effective in some animal models of epilepsy and on colon/intestine inflammation, valproic acid (VPA), an effective antiepileptic drug in this seizure model, mesalazine (MSZ) an effective aminosalicylate anti-inflammatory treatment against ulcerative colitis and sodium butyrate (NaB), a short chain fatty acid (SCFA) normally produced in the intestine by gut microbiota, important in maintaining gut health and reducing gut inflammation and oxidative stress. Intestinal inflammation was induced by dextran sulfate sodium (DSS) administration for 6 days. Drug treatment was started on day 3 and lasted 11 days, when seizure susceptibility to PTZ was measured along with intestinal inflammatory markers (i.e. NF-κB, Iκ-Bα, COX-2, iNOS), histological damage, disease activity index (DAI) and SCFA concentration in stools. DSS-induced colitis increased seizure susceptibility and while all treatments were able to reduce intestinal inflammation, only ALAC and NaB exhibited significant antiepileptic properties in mice with induced colitis, while they were ineffective as antiepileptics at the same doses in control mice without colitis. Interestingly, in DSS-treated mice, VPA lost part of its antiepileptic efficacy in comparison to preventing seizures in non-DSS-treated mice while MSZ remained ineffective in both groups. Our study demonstrates that reducing intestinal inflammation through ALAC or NaB administration has specific anticonvulsant effects in PTZ-treated mice. Furthermore, it appears that intestinal inflammation may reduce the antiepileptic effects of VPA, although we confirm that it decreases seizure threshold in this group. Therefore, we suggest that intestinal inflammation may represent a valid antiepileptic target which should also be considered as a participating factor to seizure incidence in susceptible patients and also could be relevant in reducing standard antiepileptic drug efficacy.

  

Increased efficacy of combining prebiotic and postbiotic in mouse models relevant to autism and depression

Highlights 

·        Prebiotic/postbiotic combination is a suitable approach in manipulating the Microbiota Gut Brain Axis. 

·        Prebiotic/postbiotic combination is more effective than single drug administration. 

·        α-lactalbumin/sodium butyrate combination improves animal behaviour in autistic (BTBR) mice. 

·        α-lactalbumin/sodium butyrate combination improves animal behaviour in the depression chronic unexpected mild stress model.

   

Conclusion

It is not by chance that mother’s milk has evolved to be rich in Alpha-lactalbumin (ALAC).

ALAC has wide-ranging health benefits. People with gut dysbiosis would seem likely to benefit from it, particularly if they have co-occurring neurological symptoms (epilepsy, ASD, depression) that are made worse by GI inflammation.

NaB (Sodium Benzoate) has some overlapping benefits with ALAC and the research shows that the combined effect is better than either alone,

The increase in production of glutathione (GSH), the body’s main antioxidant is clearly a benefit of whey protein in general and we assume its effect extends to ALAC.

NaB seems to have an effect that can be very dose dependent.  Too little has no benefit and, at least in some people, too much and you lose the benefit.

NaB is producing butyric acid and depending on your fiber intake and gut bacteria you are already producing your own butyric acid.  As a result, it makes sense that the effective dose of NaB will vary from person to person.

This continues the earlier subject of eubiosis vs dysbiosis.  The graphic below looks nice, but really is an oversimplification.  You can modify the microbiome to produce a specifically targeted change in the brain, which has nothing to do with allergic diseases.  All  very clever and a little hard to believe at first.

 

 

Source : The Role of Prebiotics and Probiotics in Prevention of Allergic Diseases in Infants

I think ALAC is an interesting choice for autism and hopefully one day there will be a clinical trial.  In that trial do not exclude those with epilepsy, but collect data of the impact of ALAC on the frequency/intensity of seizures.

 

Cesarian Delivery and Autism – another inconvenient truth?

Brasil is the C-section capital of the world, with rates in the public sector of 35–45%, and 80–90% in the private sector.

A recent study from the Karolinska Institute in Sweden, analysing 61 previous studies, has again shown a connection between birth by Cesarian Section and an increased risk of autism or indeed ADHD. 

C-sections account for just 16% of births in Sweden, but 32% in North America.

This of course prompted a reaction to reassure future mothers that they have nothing to fear, from experts in obstetrics who of course know nothing about the etiology of autism.  Mothers should be reassured, but trashing the study helps nobody.  Instead of a 1% risk of non-trivial autism, it rises to 1.3%. You still have more than a 98% chance of having a neurotypical child, all other factors being equal.  Without a medically necessary C-section, death is a real possibility.

It was a couple of years ago that the Karolinska Institute highlighted the fact that those with severe autism currently have a life expectancy of under 40 years.  Another inconvenient truth.

Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring 

Question  Is birth by cesarean delivery associated with an increased risk of neurodevelopmental and psychiatric disorders in the offspring compared with birth by vaginal delivery?

Findings  In this systematic review and meta-analysis of 61 studies comprising more than 20 million deliveries, birth by cesarean delivery was significantly associated with autism spectrum disorder and attention-deficit/hyperactivity disorder.

Meaning  The findings suggest that understanding the potential mechanisms behind these associations is important, especially given the increase in cesarean delivery rates for nonmedical reasons.

Abstract

Importance  Birth by cesarean delivery is increasing globally, particularly cesarean deliveries without medical indication. Children born via cesarean delivery may have an increased risk of negative health outcomes, but the evidence for psychiatric disorders is incomplete. 

Conclusions and Relevance  The findings suggest that cesarean delivery births are associated with an increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder, irrespective of cesarean delivery modality, compared with vaginal delivery. Future studies on the mechanisms behind these associations appear to be warranted. 

Very many things are known to slightly increase the odds of a person having autism and the more risk factors you have the more severely autistic you may be.  This ranges from maternal stress (anything from experiencing a hurricane, work stress, life trauma) to maternal/paternal age, obesity, gestational diabetes, alcohol/drug abuse, illness during pregnancy etc. This combines with whatever is in the parents’ DNA and random mutations that are bound to occur.    

A more rational reaction might be to investigate further why there might be a link and how you could counter any risk to children born by cesarian section.  You only have to read the existing research, or this blog.

There are 2 very good reasons why there should be a link between autism and C section, both have been covered in this blog.

1.     The microbiome comes from the mother. Science is only recently starting to understand the role of bacteria in health, but we know that it plays a key role in conditioning/calibrating the immune system of babies.  Once the immune system has been calibrated it is set for life.  Early exposure to bacteria is necessary and humans evolved to expect it.  If your immune system is over/under sensitive there will be consequences. Birth via C-section avoids exposure to bacteria in the birth canal, unless the newly arrived baby is “seeded” with bacteria from the mother. Mother’s milk is another key source of transferring the mother’s microbiome to the baby. 

2.     We saw that the birthing hormone Oxytocin plays a key role in triggering the “GABA switch” in new-borns. This is the process which transforms immature neurons with high chloride to mature neurons with low chloride shortly after birth.  During natural birth there is a surge in the hormone Oxytocin that is transferred to the baby, this causes the chloride transporter KCC2 to be further expressed and the “opposing” transporter NKCC1 to fade away.  In many people with severe autism their neurons remain in the immature state their entire life.  Just as you can replace the bacteria transfer lost in birth via C-section, there would be absolutely no reason why you could not replicate the surge in Oxytocin to "flip the GABA switch".

The recent study showed that elective C-sections (where the baby is in perfect health and not distressed) are associated with the elevated risk of both Autism and ASD.

Regular readers of this blog would probably be surprised if C-section did not increase autism prevalence.

The important thing is to acknowledge this likely connection and mitigate it, rather than try and fault the numerous studies that have shown the same effect.

The same of course applies to reducing the very small risk from vaccines, rather than construct new studies in a contrived way to show there is zero risk.   If you can safely and cheaply reduce the risk of a negative reaction to vaccines, why wouldn’t you?  Just follow Johns Hopkins example and give Ibuprofen or Montelukast (Singular) for a few days before and after and remember to never give Paracetamol/Acetaminophen (Tylenol) in response to fever after a vaccine. Paracetamol/ Acetaminophen reduces the body’s key antioxidant GSH just when the baby/child may need its neuroprotection most.

Some conditions are associated with preterm births, a good example is Cerebral Palsy (CP), which is twice as common in babies born very early. CP is rarely genetic and is usually considered to be caused by a complication during pregnancy, birth or shortly thereafter. I think you would find a correlation between C-sections and CP, but in this case I doubt you would find it in elective C-sections.   In other words C-sections do not “cause” CP, but they may be associated with it. The ID/MR often found in CP might be elevated by C-section and, if so, would be treatable.

Conclusion

In order to halt the rise in incidence of the disabling kinds of autism there should be steps taken to reduce some of the very many factors that are driving the increase, albeit each one sometimes by a tiny amount.

This would be a good application of all those thousands of autism research papers, many of which have shown what factors contribute to increased risk, that now sit gathering dust.

We are not at the stage of wide scale gene editing, but many simple steps can be taken today to improve future health.  This does not mean do not vaccinate, or avoid medically necessary C-sections; vaccinations and C-sections have saved millions of lives. But, why would you not want to take a good thing and make it even better?  That is what we humans tend to be good at, like the Swedes and their Volvos.

Perhaps take your C-section with a generous smear of Mum's bacteria and a shot of synthetic oxytocin?  

There will be more on Cerebral Palsy in a later post on D-NAC (Dendrimer N-Acetyl Cysteine). 

                                                               

Refining Antioxidant (ROS & RNS) Therapy in Autism - Selenium and Molybdenum

Today’s post is about further refining antioxidant therapy.

As we saw in a recent post, oxidative and nitrosative stress is a very common feature of autism and is treatable with OTC products.

The cheapest antioxidant, N-acetylcysteine (NAC), looks to be the best one, but there are numerous others with exotic names and equally exotic prices.

Today we just look at selenium and molybdenum.  Selenium was on my to-do list for a long time because it affects some key enzymes call GP_X (glutathione peroxodases).

Molybdenum was enthusiastically recommended in a recent comment and this blog has previously touched on Molybdenum Cofactor Sulfurase (MOCOS).

Rather surprisingly, there is a commercial product that contains NAC, Selenium and Molybdenum. 

Selenium and GP_X (glutathione peroxodases)

There are eight different glutathione peroxodases, but GPx1, GPx2, GPx3, and GPx4 are all made from selenium.

GP_X speeds up the antioxidant reactions that involve glutathione (GSH).

In autism we know that both GSH and GP_X are lacking.

We know how to make more GSH, just take some NAC.  But what about the catalyst GP_X? 

There may be an equally easy way to increase that. 

Selenium and Thyroid  Enzymes

Selenium is also part of the three deiodinase enzymes D1, D2 and D3.

The active thyroid hormone is called T3, but most of what is circulating in your body is the inactive pro-hormone form called T4.

Deiodinase 1 (D1)  both activates T₄ to produce T₃ and inactivates T₄. Besides its increased function in producing extrathyroid T₃, its function is less well understood than D2 or D3.

Deiodinase 2 (D2), located in the ER membrane, converts T₄ into T₃ and is a major source of the cytoplasmic T₃ pool.  It looks like some people with autism may lack D2 in their brain.

Deiodinase 3 (D3) prevents T₄ activation and inactivates T₃. It looks like some people with autism have too much D3 in their brain.

D2 and D3 are important in homeostatic regulation in maintaining T₃ levels at the plasma and cellular levels.

·        In hyperthyroidism D2 is down regulated and D3 is upregulated to clear extra T₃

·        in hypothyroidism D2 is upregulated and D3 is downregulated to increase cytoplasmic T₃ levels

Serum T3 levels remain fairly constant in healthy individuals, but D2 and D3 can regulate tissue specific intracellular levels of T3 to maintain homeostasis since T3 and T4 levels may vary by organ.  

It appears that some people with autism may have central hyperthyroidism, meaning in their brain.

Regular readers may recall this post:-

Central Hypothyroidism or Low Brain D2 Levels in Autism

The major source of the biologically active hormone T3 in the brain is the local intra-brain conversion of T4 to T3, while a small fraction comes from circulating T3. 

As evidence derived from in vitro studies suggests, in response to oxidative stress D3 increases while D2 decreases (Lamirand et al., 2008; Freitas et al., 2010).  As we know in the autistic brain we have a lot of oxidative stress.

Furthermore, in ASD, the lower intra-brain T3 levels occur in the

Absence of a systemic T3 deficiency (Davis et al., 2008), most likely due to the increased activity of D3.

So in some autistic brains we have too much D3 which is inactivating T3 and preventing T4 being converted to T3.

Reduced D2 is reducing the conversion of T4 to T3. 

We would therefore want to increase D2 in some autism.

This can be achieved by:-

·        Reducing oxidative stress, which we are already sold on. 

·        We can also potentially upregulate the gene that produces D2 using some food-based genetic therapy. Kaempferol (KPF) appears to work and may explain why broccoli sprout powder makes some people go hyper and some others cannot sleep  

The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone Activation

The cAMP-responsive gene for type 2 iodothyronine deiodinase (D2), an intracellular enzyme that activates thyroid hormone (T3) for the nucleus, is approximately threefold upregulated by KPF

·        Perhaps low levels of selenium differentially affect the synthesis of D1, D2 and D3?

  

Where does selenium come from? 

We know from Chauham/James that selenium levels are reduced in autism, but we also know that selenium levels vary widely by geography.  

You get selenium from your diet and the level of selenium in the soil varies widely.  It is widely held that most healthy people should have plenty selenium in their diet. 

In the following paper there is an analysis of Selenium status in Europe and the Middle East.

Since we have plenty of Polish readers I have included the chart with the Polish data (on the left).  It shows that Polish people may be a little deficient in selenium.

You can see the level of selenium in Poland is below that needed to optimise plasma GPx activity.

So if you already have reduced GPx activity, because of autism, and you really need to make the most of your limited glutathione (GSH) because you have oxidative/nitrosative stress, then a little extra selenium could be just what the doctor should have ordered.

  

A Review of Dietary Selenium Intake and Selenium Status in Europe and the Middle East

Se is an essential non-metal trace element [3] that is required for selenocysteine synthesis and is essential for the production of selenoproteins [4]. Selenoproteins are primarily either structural or enzymatic [2], acting as catalysts for the activation of thyroid hormone and as antioxidants, such as glutathione peroxidases (GPxs) [5]. GPx activity is commonly used as a marker for Se sufficiency in the body [6], where serum or plasma Se concentrations are believed to achieve maximum GPx expression at 90–100 μg/L (90.01 μg/L as proposed by Duffield and colleagues [7] and 98.7 μg/L according to Alfthan et al. [8]). However, plasma selenoprotein P (SEPP1) concentration is a more suitable marker than plasma GPx activity [9]. Prospective studies provide some evidence that adequate Se status may reduce the risk of some cancers, while elevated risk of type 2 diabetes and some cancers occurs when the Se concentration exceeds 120 μg/L [10]. Higher Se status has been linked to enhanced immune competence with better outcomes for cancer, viral infections, including HIV progression to AIDS, male infertility, pregnancy, cardiovascular disease, mood disorders [2] and, possibly, bone health [11–14].

  

Selenium and NAC for Rats with TBI

Perhaps not surprisingly, selenium and NAC have been found beneficial for Rats unfortunate enough to have sufferred a traumatic brain injury (TBI).

 N-Acetylcysteine and Selenium Modulate Oxidative Stress, Antioxidant Vitamin and Cytokine Values in Traumatic Brain Injury-Induced Rats

It has been suggested that oxidative stress plays an important role in the pathophysiology of traumatic brain injury (TBI). N-acetylcysteine (NAC) and selenium (Se) display neuroprotective activities mediated at least in part by their antioxidant and anti-inflammatory properties although there is no report on oxidative stress, antioxidant vitamin, interleukin-1 beta (IL)-1β and IL-4 levels in brain and blood of TBI-induced rats. We investigated effects of NAC and Se administration on physical injury-induced brain toxicity in rats. Thirty-six male Sprague–Dawley rats were equally divided into four groups. First and second groups were used as control and TBI groups, respectively. NAC and Se were administrated to rats constituting third and forth groups at 1, 24, 48 and 72 h after TBI induction, respectively. At the end of 72 h, plasma, erythrocytes and brain cortex samples were taken. TBI resulted in significant increase in brain cortex, erythrocytes and plasma lipid peroxidation, total oxidant status (TOS) in brain cortex, and plasma IL-1β values although brain cortex vitamin A, β-carotene, vitamin C, vitamin E, reduced glutathione (GSH) and total antioxidant status (TAS) values, and plasma vitamin E concentrations, plasma IL-4 level and brain cortex and erythrocyte glutathione peroxidase (GSH-Px) activities decreased by TBI. The lipid peroxidation and IL-1β values were decreased by NAC and Se treatments. Plasma IL-4, brain cortex GSH, TAS, vitamin C and vitamin E values were increased by NAC and Se treatments although the brain cortex vitamin A and erythrocyte GSH-Px values were increased through NAC only. In conclusion, NAC and Se caused protective effects on the TBI-induced oxidative brain injury and interleukin production by inhibiting free radical production, regulation of cytokine-dependent processes and supporting antioxidant redox system.

  

Dietary selenium stabilizes glutathione peroxidasemRNA in rat liver

  

And now to Molybdenum 

Molybdenum (Mo) is a trace dietary element necessary for human survival.

Low soil concentration of molybdenum in a geographical band from northern China to Iran results in a general dietary molybdenum deficiency, and is associated with increased rates of esophageal cancer.  Compared to the United States, which has a greater supply of molybdenum in the soil, people living in those areas have about 16 times greater risk for esophageal cancer.
So you would not want to have molybdenum deficiency.

Four Molybdenum-dependent enzymes are known, all of them include molybdenum cofactor (Moco) in their active site: sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase.

Moco cannot be taken up as a nutrient, and thus it requires to made in your body from molybdenum.

If your body cannot make enough Moco you may develop what is called molybdenum cofactor deficiency, which would ultimately kill you. It is ultra rare.

Symptoms include early seizures, low blood levels of uric acid, and high levels of sulphite, xanthine, and uric acid in urine.


When caused by a mutation in the MOCS1 gene it is called the type A variant.

Molybdenum cofactor deficiency may indeed be extremely rare, but MOCS1 is a known autism gene.  Perhaps there exists partial molybdenum cofactor deficiency, which is not rare at all?

Source:-  Identification of candidate intergenic risk loci in autism spectrum disorder

MOCOS (Molybdenum cofactor sulfurase)


Molybdenum cofactor sulfurase is an enzyme that in humans is encoded by the MOCOS gene.

MOCOS sulfurates the molybdenum cofactor of xanthine dehydrogenase (XDH) and aldehyde oxidase (AOX1), which is required for their enzymatic activities.

MOCOS is downregulated in autism and is suggested to induce increased oxidative-stress sensitivity, which would not be good.

So it looks like we need a clever way to upregulate MOCOS.

You need adequate molybdenum cofactor (Moco), for which you do need adequate molybdenum.

You need the genes MOCS1 and MOCOS to be correctly expressed.

SIRT1 activation, which is a future therapy for Alzheimer’s, is suggested to increase MOCOS, as may NRF2.

Sirtuin-activating compounds (STAC) are chemical compounds having an effect on sirtuins, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are molecules able to prevent aging related diseases like Alzheimer's, diabetes, and obesity.  There is quite a long list that includes ranges from polyphenols such as resveratrol, the flavonols fisetin, and quercetin also butein, piceatannol, isoliquiritigenin,

Fisetin is found in strawberries, cucumbers and supplements.  In normal animals, fisetin can improve memory; it also can have an effect on animals prone to Alzheimer's.

Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice

Here is the excellent French paper on MOCOS:-

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders

With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.  

Lately, a diminished seric expression of glutathione, glutathione peroxidase, methionine and cysteine has been highlighted in a meta-analysis from 29 studies on ASD subjects.⁴⁵ Along this line, purines and purine-associated enzymes are recognized markers of oxidative stress. ROS are generated during the production of uric acid, catalyzed by xanthine oxidase and XDH.⁴⁶ Conversely, uric acid is nowadays recognized as a protective factor acting as a ROS scavenger.^{47, 48} Interestingly, allopurinol, a xanthine oxidase inhibitor, was found efficient in reducing symptoms, especially epileptic seizures, in ASD patients displaying high levels of uric acid.⁴⁹ However, in our cohort, only 3 out of 10 patients exhibited an abnormal uric acid secretion. It can therefore be postulated that still unknown other MOCOS-associated mechanisms may have a role in the unbalanced stress response observed in ASD OSCs.

Identifying and manipulating downstream effectors of MOCOS will be the next critical step to better understand its mechanisms of action. In parallel, we plan to ascertain some of its upstream regulators. For example, bioinformatic analyses revealed that the promoter region of MOCOS includes conserved binding sites for transcription factors such as GATA3 and NRF2. In addition, other putative interactors, such as the NAD-dependent deacetylase sirtuin-1 (SIRT1), may have a regulatory role on MOCOS expression. Interestingly, these three genes have been associated with ASD, fragile X syndrome, epilepsy and/or oxidative stress.^{54, 55, 56, 57} In conclusion, our study opens an unexplored new avenue for the study of MOCOS in ASD, and could set bases for the development of new diagnostic tools as well as the search of new therapeutics.

Conclusion

It looks like a little extra selenium may be in order to increase those GPx enzymes that are need to speed up aspects of the antioxidant activity of GSH.

When it comes to molybdenum, things get much more complex. You certainly do not want to be deficient in molybdenum and you do not want Molybdenum cofactor deficiency; you also do not want molybdenum cofactor Sulfurase (MOCOS) mis-expression.

It is fair to say that quite likely there is a problem related to molybdenum that affects oxidative stress in autism; but it is not yet clear what to do about it.  I rather doubt the solution is as simple as just a little extra molybdenum, but it is easy to try.

On the plus side, we see that if you have autism, epilepsy and high uric acid you are likely to benefit from allopurinol, which also seems to help in COPD.

There is nothing new about allopurinol possibly be effective in some autism, as from this 25 year old book, Diagnosis and Treatment of Autism.

Again we see that activating NRF2 looks a good idea, that applies to both autism and COPD.

One thing to note is that NRF2 activators are good for cancer prevention, but if you have a cancer you want NRF2 inhibitors.

NRF2 activators include sulforaphane (SFN), R-alphalipoic acid (ALA), resveratrol and curcumin.  SFN is by far the most potent.  Resveratrol and curcumin have a problem with bioavailability.