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Friday 8 October 2021

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-CaMK 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.

 







28 comments:

  1. Whey protein as an antioxidant? Wow.
    So whey protein might be doubly beneficial for older people, a source of extra protein, and with an antioxidant effect? Interesting.

    ReplyDelete
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    1. Whey protein is rich in cysteine and cysteine is the rate-limiting amino acid for synthesis of the body's antioxidant glutathione (GSH).

      NAC is n-acetlycysteine and by the time you swallow it has often degraded to cysteine and other substances.

      They even sell cysteine-rich whey protein:

      IMMUNOCAL® Nutraceutical Glutathione precursor

      Indeed it is interesting.

      Delete
  2. I would love to try this. Is there a recommended formulation ad it looks like there are lots of options.
    Also BCAAs (using XTend as recommended by Tyler) is a must-have for my son's mood disorder. Would I stop that since ALAC seems to have BCAAs also?
    Thanks
    Nancy

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    1. Nancy, the particular advantage of ALAC relates to GI inflammation. If you suspect GI inflammation you would look for ALAC content in the product. If you want to make more glutathione (GSH) you would want to maximize cysteine.

      Whey protein does contain BCAAs and so you might indeed want to keep an eye on the total amount of BCAAs you give.

      Whey protein naturally contains calcium, which in some people is problematic if absorbed quickly.

      Whey protein can effect how some antibiotics are absorbed.

      I would see what is available where you live and then decide what to do. Start with a small dose.

      Delete
    2. Roger they start with cows milk and extract the alpha-lactalbumin (ALAC). This is sold in bulk as a neutraceutical.

      This is sold to help make things like:

      Protein-fortified beverages
      Lactose-free and reduced carbohydrate/fat/calorie foods
      Nutritional and dietary supplements
      Infant formula
      Medical foods

      It is marketed as being:

      Uniquely high in these amino acids:
      Tryptophan, a precursor to serotonin and melatonin
      Leucine, the trigger for muscle protein synthesis
      Cysteine, a glutathione precursor
      High protein quality; a complete amino acid profile with high digestibility and delivery
      A clean, neutral taste
      Lactose and fat-free

      This is a US producer:

      https://www.agropur.com/us/ingredients/branded-ingredients/bipro-alpha-9000

      Delete
  3. Hi Peter

    My son is currently following the milk free high dose calcium folinate plan at the moment following a positive binding antibody result, is there an alternative to this probiotic.

    I’m not sure the difference between milk & lactose if it’s something different or the same thing that creates these antibodies.

    ReplyDelete
    Replies
    1. Ross, cows milk is suggested to contain folate receptor antibodies. When they make ALAC, or other whey protein products from cows milk, does this contain some folate receptor antibodies? Nobody probably can tell you for sure 100%.

      People will GI inflammation can use sodium benzoate (NaB), referred to in the paper above. People with low glutathione can use NAC.

      Delete
  4. Hi Peter,

    It might be a coincidence, but I just read that low Glutathione has also been implicated in Cystic Fibrosis. One symptom of Cystic Fibrosis is wrinkled hands after short term contact with water. My daughter’s hands after even a 2 minute shower look like she’s been swimming for hours. Is there a possible connection?

    ReplyDelete
    Replies
    1. Kei, aquagenic wrinkling of the palms (AWP) has a strong association with cystic fibrosis. It looks dramatic. If your daughter has it as severely as in the paper below, you should take a picture and show it to your doctor.

      https://www.contemporarypediatrics.com/view/girls-hands-shrivel-when-exposed-water

      All chronic medical conditions are likely to feature oxidative stress and therefore low glutathione.

      Delete
    2. Thanks for your reply Peter,

      Sometimes her hands are worse than the girl in the link, but for instance now when I try to get a photo for the doctor it’s not that bad at all, so it depends on the day.

      I will definitely check it with the Dr, although I have no other reason to suspect cystic fibrosis. There are no other symptoms evident.

      However I’m still interested to see if low glutathione is an issue as she does have some of the general symptoms of low levels. Can I administer supplements via trial and error or should we get a blood test first ?

      Delete
    3. The research tells us that if someone has autism they will very likely have oxidative stress. Many people with autism respond well to a wide range of possible OTC antioxidants. Personally I use NAC, but there are many options.

      I doubt your doctor will know about these tests. A good one would be the GSH GSSG ratio.

      Delete
  5. So ALAC would probably not be necessary for a 3 y/o with ASD who does not appear to have gut issues and does not have any difficulty sleeping?

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    1. Ronald, the only point of ALAC or a more easy to obtain whey protein would be to increase glutathione and so reduce stereotypy and anxiety in the same way as NAC.

      Delete
  6. Hello , have u researched oral colostrum MAF?
    Lots of research done by Bradstreet prior to his death?

    ReplyDelete
    Replies
    1. No there is nothing in this blog about MAF. Some people do think it is beneficial, it certainly is contraversial.

      Delete
  7. Our dietitian has recommended this whey protein based drink for faltering growth.. we will start it soon.. hopefully it will help with other symptoms. https://www.nestlehealthscience.co.uk/brands/peptamen/peptamen-junior-1-5

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    Replies
    1. Rahul, your product is sold for kids with GI problems.

      An altered growth trajectory is a feature of some autism. My son went from 80th percentile for height to the 20th. As long as it is not caused by lack of nutrition, I doubt you can safely change it.

      One autism therapy is IGF-1 injections. That might well also increase growth of the body.

      Delete
  8. Dear Peter, we have introduced Ketotifen at a small introductory dose, with the idea to go up. It was recommended for her specifically, based upon her history and extensive bloodwork, by a russian doctor who is both a neurologist and an immunologist. However, since we introduced it, a week ago, she has been consistently worse. I will stop it for a few days to see how she fares without it and then introduce it again. But, what would be the cause for her worsening - less attention, more anxiety, more scripting? aka probably more inflammation. we also introduced sodium cromoglycate (oral) per his recommendation 3 weeks ago, and that had a nice stabilizing effect.

    ReplyDelete
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    1. Tatjana,

      Ketotifen is an antihistamine and a mast cell stabilizer.

      Cromolyn sodium is a mast cell stabilizer but not an antihistamine.

      Antihistamine drugs always affect some receptors other than H1 histamine and this is usually what causes the side effects.

      https://www.mayoclinic.org/drugs-supplements/ketotifen-oral-route/precautions/drg-20064435

      This medicine may cause some people to become excited, irritable, or nervous or to have trouble in sleeping. These are symptoms of central nervous system stimulation and are especially likely to occur in children.

      Delete
  9. Yes, I read thay very same link. I thought there might be informational value in that - as in, why she reacts like that when on it.

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    Replies
    1. Ketotifen has a mild effect on muscarinic acetylcholine receptor (mAChRs) and on the serotonin receptor 5-HT2A. 5-HT2A and other serotonin receptors are implicated in autism and so this might be a factor.

      Delete
  10. we took her off and she side effects went away and she is a showing more dialogue. i am thinking that maybe tje good effects of ketotifen stayed for a few days. maybe she just needs something similar to replace it?

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    1. Tatjana, mast cell stabilizers take a while to show effect and so quite possibly the effect continues a while after cessation.

      Cromolyn sodium is the popular one, that you have also been trialing.

      Rupatadine is another one that some people find beneficial. You may have to buy it abroad. It is sold in Italy, for example.

      Quercetin is OTC and is worth a try. It has many effects including on mast cells.

      You already tried Verapamil and it will affect the calcium channels in the mast cells and inhibit degranulation.

      I think you also have used Azelastine.

      There is a lot written by Prof Theoharides on this subject. He has his own supplement Neuroprotek.

      Delete
  11. Azelastine only worked in the regular allergy ways, neuroprotek and wuercetin might as well be water as to how they did with her. The cromolyn is really a nice stabilizer. Verapamil was amaaaaaazing for a short period and then caused I think aggression or something bad - could be the same effect we got with ketotifen, now I think of it. I will look into Rupatadine and also run my question by the russian immunologist. One more thing I’d like to do is repeat this so I can check out rhe effect one more time, so to make sure its not random. The increase in dialogue lasted less than 24h but was pretty remarkable.
    Interestingly, this is a muscarinic antagonist. In spring we did the vit a/myocholine protocol because my daughter fits the profile of dr Megson who thought that loading of vit a and then doing myocholine would bring on speech. We did not see that but now with an antagonist we did. we’ll see.

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    1. Hello Tpes, I have experience with Ketotifen, Clemastine and Verapamil. My son was in a bad mood at first with any antihistamine and he couldn't sleep without verapamil, I gave Ketotifen time and then I stopped giving him Verapamil to see the changes, and I guess he is a bit more hyperactive, and had a bit of trouble getting to the toilet on time, but he slept well. With Clemastine I have kept it at a low dose .5 so it mainly works as for myelination, I tried to give it twice a week like I read in one of the Peter's Post but it was easier to remember to give it every day and I give it at night and the mood changes are gone. I myself have experience with Verapamil in low doses and it was amazing for my rhinosinusitis and also my mood, I read it is prescribed in Bipolar too, but I've been having other health problems and the Dr said to discontinue it since it interacts with other meds. I'm taking loratadine, but nothing compares to the relief I've gotten from Verapamil for my allergies.

      Delete
  12. I will introduce clemastine 2x per week again but at the time honestly she is in so many meds, its scares me. she is however also doing very well.

    ReplyDelete
  13. Hi, Peter I want to tell you that barberine only went very well for a few days, and then I didn't see anything, but we are doing very well on bacoflen 10 mg a day, he is very calm, he realizes very well what is with him, he has hurry until we feed them, the memory is improved and a lot of affection and love, he is very affectionate, he kisses us and tells us that he loves us, he stays outside for hours, he is no longer anxious, we thank those who made bacoflen, I don't know if riluzole would have several benefits

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    Replies
    1. Hi Dragos, great news that your son responds so well to Baclofen.

      Baclofen is a great intervention for those who are responders because it is very well tolerated and it is not expensive. Some people use the Russian equivalent called Pantogam, but many people report having to take breaks from it and then restart later. Baclofen dose not usually have these issues.

      Riluzole also affects the excitatory/inhibitory imbalance, like Baclofen, but in a different way. Most people do not respond to Riluzole and it is much more expensive than Baclofen.

      Many people find interventions that work for just a few days, as you found with Berberine. The body has feedback loops which can counter the effect you are trying to make.

      One interesting thing about Baclofen is that the responders include people with all severity of autism, so everyone should trial it.

      I also wonder if non-responders in early childhood, might become responders when they get older. I think this might well happen as the disease progresses.

      Delete

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