Casein Contains Opioid Receptor Agonists + Removal Methods

Elephanto

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Here are 2 studies on the subject.

Study # 1 :
Hydrolysis of casein accelerates gastrointestinal transit via reduction of opioid receptor agonists released from casein in rats. - PubMed - NCBI

BACKGROUND:
Protein hydrolysate accelerates gastrointestinal transit (GIT) and feeding advancement in preterm infants compared to native protein. In rat pups, opioid receptor agonists released from casein during digestion such as beta-casomorphins slow down GIT. We hypothesized that hydrolysis of casein reduces the opioid activity released during digestion thereby accelerating GIT compared to native casein.

OBJECTIVE:
The aim of the present study was to investigate whether casein hydrolysate accelerates GIT compared to native casein and whether pretreatment with naloxone, an opioid receptor blocker, abolishes this difference in rat pups.

RESULTS:
GIT was significantly higher with hydrolyzed casein compared to native casein formula
(77.4 +/- 17 and 51.2 +/- 20%), but there was no difference after naloxone pretreatment (77.1 +/- 16 and 76.5 +/- 17%).

DISCUSSION:
The present data suggest that hydrolysis of casein accelerates GIT via reduction of opioid activity released during digestion. Further studies are required to investigate to which extent these rat pub data apply to preterm infants.

So what we have here is that 1) hydrolysis of casein removed the latency in gastrointestinal transit by undenatured casein and 2) the same result is achieved by blocking opioid receptors with naloxone. Hence, this is proof that the only variable affecting gastrointestinal transit in casein is the presence of opioid receptor agonists.

Conclusion : Casein Hydrolysate (protein powder) has no opioid receptor agonist property.


Study # 2 :
Isotope dilution liquid chromatography-tandem mass spectrometry for simultaneous identification and quantification of beta-casomorphin 5 and beta-c... - PubMed - NCBI

The method limits of detection (MLDs) in yoghurt extracts were found to be 0.5 and 0.25ng/g for BCM5 and BCM7, respectively.

The validated isotope dilution LC-MS/MS method was used to measure BCM5 and BCM7 in ten commercial and laboratory prepared samples of yoghurt and milk. Neither BCM5 nor BCM7 was detected in commercial yoghurts. However, they were observed in milk and laboratory prepared yoghurts and interestingly their levels decreased during processing.

BCM5 decreased from 1.3ng/g in milk to 1.1ng/g in yoghurt made from that milk at 0day storage and <MLQ at 1 and 7days storage. BCM7 decreased from 1.9ng/g in milk to <MLQ in yoghurts immediately after processing. These preliminary results indicate that fermentation and storage reduced BCM5 and BCM7 concentration in yoghurt.

Here we see that transforming milk into yoghurt immediately reduces the betacasomorphins content, and it reduces below their detection limits after 1 day of storage, and so after 7 days when it was tested again. In other words, bacterias digest it for us.

BCM7 is referred in other studies as the most inflammatory type and exclusively present in A1 milk, and it is hypothesized that it explains its more troublesome nature compared to A2 milk. A2 milk also contains various betacasomorphins.

It is interesting to note that their detection limits are quite high (0.5 and 0.25, still being an half and a quarter of the original content of BCMs in milk). This means that a physically relevant opioid effect could still be found in yoghurts.

Conclusion : Yoghurt has a lower content of opioid receptor agonists compared to milk.
 

Terma

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Very interesting, I see this backward because it's impossible for me to get constipation, my problem is exclusively loose stools and diarrhea as it's always been; opioidness should help as loperamide does. Unfortunately I never got dairy products to do that for me, so the opioid activity must be magnitudes less than loperamide.
 
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Elephanto

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Very interesting, I see this backward because it's impossible for me to get constipation, my problem is exclusively loose stools and diarrhea as it's always been; opioidness should help as loperamide does. Unfortunately I never got dairy products to do that for me, so the opioid activity must be magnitudes less than loperamide.

Personally it was a diet centered on quark cheese (100% casein, whey is removed) that made me feel the effects. I can feel the fatigue settling but it's not euphoric or anything, it's more of a lethargic feeling and of clouded thinking. And it adds up over the weeks, at first I didn't notice. It took the removal of it to see how I was doing in the precedent weeks. Especially when I went cycling and trained, it was a day and night difference for me. There's also an interesting hypothesis that it affects people with autism more. Now I don't have autism, but I come from the generation that saw a statistical explosion in the number of cases, probably because we all got vaccinated with the same toxins; and it may be that interaction (or ensuing immune sensibility) that does it.

Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity. - PubMed - NCBI

A naturally occurring opioid peptide from cow's milk, beta-casomorphine-7, is a direct histamine releaser in man. - PubMed - NCBI

It's also and importantly, an histamine releaser, which of course makes thinking calmly more difficult and pretty much reflects the way autists think and react.
 

chispas

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This is interesting. I've recently replaced daily casein shake with cheddar cheese and noticed better mental clarity / memory and a few other benefits.

At the same time, I've also replaced OJ mixed with salt, with Powerade. I wouldn't have thought salt would give mental benefits.

I always thought casein was superior to whey due to the lack of heating.
 

Travis

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Casein also has a lower tryptophan ratio.
 
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Elephanto

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This is interesting. I've recently replaced daily casein shake with cheddar cheese and noticed better mental clarity / memory and a few other benefits.

At the same time, I've also replaced OJ mixed with salt, with Powerade. I wouldn't have thought salt would give mental benefits.

I always thought casein was superior to whey due to the lack of heating.

It is superior in terms of amino acids. That is why the findings of the first study are exciting to me, it makes casein hydrolysate pretty much the perfect protein source.

Also, it's really not surprising that salt has mental benefits. It opposes serotonin and adrenaline.
 

Filip1993

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It is superior in terms of amino acids. That is why the findings of the first study are exciting to me, it makes casein hydrolysate pretty much the perfect protein source.

Also, it's really not surprising that salt has mental benefits. It opposes serotonin and adrenaline.

What do you think about micellar casein?
 
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Elephanto

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What do you think about micellar casein?

The hydrolysis of casein is what makes casomorphins disappear. Micellar casein is in a way less denatured state, so I'd tend to think it will have the same effect as quark cheese.
 

Travis

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The hydrolysis of casein is what makes casomorphins disappear.
Not necessarily always. Casomorphins exist because of the proline's are very resistant to enzymatic proteolysis. You would have too see if they used the right procedure or the right enzymes.

It's certainly possible to break apart these small peptides. I think the smallest one is 5 amino acids long (or is it 7?). The enzymes in the intestines, and in cheese, cleave casein into casomorphins. You need a prolypeptidase enzyme or strong acid to break them down completely.

I would check with the manufacturer to see what procedure they used. Some of them might sell not-opiate casein hydrolysate, but some might not.
 
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Elephanto

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Not necessarily always. Casomorphins exist because of the proline's are very resistant to enzymatic proteolysis. You would have too see if they used the right procedure or the right enzymes.

It's certainly possible to break apart these small peptides. I think the smallest one is 5 amino acids long (or is it 7?). The enzymes in the intestines, and in cheese, cleave casein into casomorphins. You need a prolypeptidase enzyme or strong acid to break them down completely.

I would check with the manufacturer to see what procedure they used. Some of them might sell not-opiate casein hydrolysate, but some might not.

I'll be the lab rat for you guys then, ordered some from canadianprotein.com. They don't really answer emails though so I'll just test it. I saw that it has 0 fat, and some brands have 0,5g of fat so I guess the process is more thorough. Generally, protein hydrolysate is done with a strong acid, though.
 
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Elephanto

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@Travis I think you're right, I got my casein hydrolysate and the opioid effect is potent at 20g of protein.

Soon I will test greek yogurt made from jersey cow's milk which is A2. Greek yogurt from goat's milk should lend similar results too.
 

tara

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I'm interested in your results.
I have trouble with too much milk, and of my suspects is the betacaseins.
I don't do better with yogurt or cheese, but that could be the histamines from fermentation.
Goat milk and A2 cow milk also give same trouble, though I can't say if it takes the same quantities to bother me.

No noticable gut distress, just head/brain symptoms that I am aware of, though affects energy flow in rest of system too - possibly via head.
 

Travis

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@Travis I think you're right, I got my casein hydrolysate and the opioid effect is potent at 20g of protein.
This is always why I cut the heroin with hydrolyzed casein. (The junkies can never tell the difference!)

Just kidding.

Casomorphin-7 is buried in the sequence for bovine β-casein:

MKVLILACLV ALALARELEE LNVPGEIVES LSSSEESITR INKKIEKFQS
EEQQQTEDEL QDKIHPFAQT QSLVYPFPGP IPNSLPQNIP PLTQTPVVVP
PFLQPEVMGV SKVKEAMAPK HKEMPFPKYP VEPFTESQSL TLTDVENLHL
PLPLLQSWMH QPHQPLPPTV MFPPQSVLSL SQSKVLPVPQ KAVPYPQRDM
PIQAFLLYQE PVLGPVRGPF PIIV

The goat sequence is: YPFTGP I

The goat sequence should digest completely because of the tyrosine-for-proline, which keeps bovine β-casein from breaking-down. Goats also have a more Peat-friendly fatty acid profile. The fatty acids caprylic, capric, and caproic were all named after goats.
 
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Elephanto

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This is always why I cut the heroin with hydrolyzed casein. (The junkies can never tell the difference!)

Just kidding.

Casomorphin-7 is buried in the sequence for bovine β-casein:

MKVLILACLV ALALARELEE LNVPGEIVES LSSSEESITR INKKIEKFQS
EEQQQTEDEL QDKIHPFAQT QSLVYPFPGP IPNSLPQNIP PLTQTPVVVP
PFLQPEVMGV SKVKEAMAPK HKEMPFPKYP VEPFTESQSL TLTDVENLHL
PLPLLQSWMH QPHQPLPPTV MFPPQSVLSL SQSKVLPVPQ KAVPYPQRDM
PIQAFLLYQE PVLGPVRGPF PIIV

The goat sequence is: YPFTGP I

The goat sequence should digest completely because of the tyrosine-for-proline, which keeps bovine β-casein from breaking-down. Goats also have a more Peat-friendly fatty acid profile. The fatty acids caprylic, capric, and caproic were all named after goats.

Very interesting, thanks. Your joke was funny, I guess I shouldn't call it a "potent opioid effect" because I don't get euphoric, it just makes me feel fatigued and "autistic". BCM-7 has other inflammatory properties that makes up its effect.

Now I want to find greek yogurt from goat milk instead of straight up goat milk though, to avoid the whey portion and precisely beta-lactoglobulin.
 

Travis

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... it just makes me feel fatigued and "autistic".
You know, I think exomorphins are the best theory for autism. These are commonly found elevated in the cerebospinal fluid, and gluten-free and casein-free diets have been shown to help.

But not all cases. I think autism is a too-broad of a category. It seems like they lump too many people under this umbrella.

Researchers also commonly report finding serotonin imbalances, but these are found nearly everywhere they look. If you pay too much attention to all of the weak correlations you would have to conclude that serotonin both causes and prevents every known psychological condition.
 
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Elephanto

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You know, I think exomorphins are the best theory for autism. These are commonly found elevated in the cerebospinal fluid, and gluten-free and casein-free diets have been shown to help.

But not all cases. I think autism is a too-broad of a category. It seems like they lump too many people under this umbrella.

Researchers also commonly report finding serotonin imbalances, but these are found nearly everywhere they look. If you pay too much attention to all of the weak correlations you would have to conclude that serotonin both causes and prevents every known psychological condition.

Yeah I can differentiate the serotonin symptoms of autism, since I've been on bcaa+tyrosine, zinc and carbonated water as dopaminergic substances and a diet low in tryptophan. To me those symptoms would be social anxiety, fear and the feeling of being socially dominated. Though that can apply to a lot of people who don't necessarily look/feel autistic.. I think the "always on opioid" look is more common of all autists. But since adrenaline is high in autism, I think that serotonin definitely plays a part too and is responsible for some symptoms.

It seems that even beta-lactoglobulin and therefore the whey fraction of milk, has opioid properties :
Milk protein-derived opioid receptor ligands. - PubMed - NCBI

With respect to the proteins, which they are derived off these peptides have been named alpha-casein exorphins or casoxin D (alpha-casein), beta-casomorphins or beta-casorphin (beta-casein), casoxin or casoxin A, B, or C (k-casein), alpha-lactorphins (alpha-lactalbumin), beta-lactorphin (beta-lactoglobulin) or lactoferroxins (lactoferrin). Only casoxins and lactoferroxins display antagonistic properties; the other peptides behave like opioid receptor agonists.
 

Travis

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Lactoglobulin is also the protein which is highest in tryptophan. This comes in the whey fraction.

Egg albumin comes in second.
 
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I think someone said the activity is negligible.
 
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Elephanto

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I think someone said the activity is negligible.

For almost anything that is harmful, you'll find someone on the net to brush it off and say it's negligible. I guess the only way to know is 1) to have a decent ability of introspection, 2) to have a standard way of benchmarking yourself (I find cardio-extensive physical training to be relevant when it comes to this opioid effect) and 3) to go through a period of abstention.

edit :

Also, to isolate the effect you should probably not be on stimulants like caffeine or nicotine. I often get the urge to drink a coffee after a dairy meal and it's successful at removing the fatigue.
 
Last edited:
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For almost anything that is harmful, you'll find someone on the net to brush it off and say it's negligible. I guess the only way to know is 1) to have a decent ability of introspection, 2) to have a standard way of benchmarking yourself (I find cardio-extensive physical training to be relevant when it comes to this opioid effect) and 3) to go through a period of abstention.

edit :

Also, to isolate the effect you should probably not be on stimulants like caffeine or nicotine. I often get the urge to drink a coffee after a dairy meal and it's successful at removing the fatigue.
He brought up figures, but I don't remember who it was.
 
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