Casomorphin

Casomorphin is a particular type of peptide, i.e protein fragment, that can be derived from the digestion of casein proteins in milk and milk products. The distinguishing characteristics of casomorphins are that they have opioid (i.e narcotic) effects. There is a range of casomorphins whose effects range from weak to strong. There are also other peptides in milk that can have an ameliorating effect on the opioid effects of the casomorphins.

The most important casomorphins from bovine milk are those released from the digestion of β-casein (beta-casein). These are known as β-casomorphins, sometimes written as BCM followed by a numeral indicating the number of amino acids in the sequence. The most important casomorphins appear to be BCM5, BCM7, and BCM9. BCM7 in particular has been implicated in a number of medical conditions including diabetes, heart disease, and the symptoms of autism and schizophrenia. However, it appears that only some individuals are susceptible.

In cattle the amount of β-casein, and hence the potential release of β-casomorphins, varies between species and breeds. Typically, beta-casein comprises about one third of the casein, or about 12 grams per litre of milk. However, there are at least 13 different variants of the β-casein protein in cattle, with any one cow producing milk that will contain either one or two of these 13 variants.

The variants fit into one of two main categories known as A1 and A2. In cattle, A1-type β-caseins have the amino acid histidine at position 67 whereas the A2-type β-caseins have the amino acid proline at position 67. Laboratory experiments show that the casomorphin known as BCM7 is only released from the A1-type β-caseins (Jimsmaa and Yoshikawa 1999) (ref Jinsmaa Y, Yoshikawa M, 1999. 'Enzymatic release of neocasomorphin and beta-casomorphinfrom bovine beta-casein', Peptides 20:957-962). The potential release of BCM7 is about 0.4 grams per litre of milk (assuming as above that there are 12g of β-casein per litre).

There is also the potential for release of casomorphins from human milk. However, human BCM7 (Tyr-Pro-Phe-Val-Glu-Pro-Ile)has two out of seven amino acids different to the bovine form (Tyr-Pro-Phe-Pro-Gly-Pro-Ile) and the opioid effects are much weaker.

Scientific understanding of the biochemistry and pharmacology of casomorphins is incomplete. A recent scientific review is provided by Kaminski et al (2007),:

In the human body casomorphins may be broken down to inactive dipeptides by the enzyme dipeptidyl peptidase-4. This enzyme is found in the digestive tract and in some endocrine cells.

Health

Casein has been documented to break down in the stomach to produce the peptide casomorphin, an opioid that acts as a histamine releaser.

Diets that eliminate foods containing casein are promoted at conferences for parents of children with ASD, and many books, web sites, and discussion groups contain testimonials describing benefits in autism-related symptoms, notably social engagement and verbal skills. Studies supporting these claims have had significant flaws, so the data are inadequate to guide treatment recommendations. Even if they do not help, changes in diet are expected to be harmless aside from their bother and cost.

Some known casomorphins

β-Casomorphin 1-3

• Structure: H-Tyr-Pro-Phe-OH
• Chemical formula: C₂₃H₂₇N₃O₅
• Molecular weight: 425.48 g/mol

Bovine β-casomorphin 1-4

• Structure: H-Tyr-Pro-Phe-Pro-OH
• Chemical formula:
• Molecular weight: 522.61 g/mol

Bovine β-casomorphin 1-4, amide

• Structure: H-Tyr-Pro-Phe-Pro-NH₂
• Chemical formula: C₂₈H₃₉N₅O₇
• Molecular weight: 557.64 g/mol

Bovine β-casomorphin 5

• Structure: H-Tyr-Pro-Phe-Pro-Gly-OH
• Chemical formula: C₃₀H₃₇N₅O₇
• Molecular weight: 594.66 g/mol

Bovine β-casomorphin 7

• Structure: H-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-OH
• Chemical formula: C₄₁H₅₅N₇O₉
• Molecular weight: 789.9 g/mol

Bovine β-casomorphin 8

• Structure: H-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-OH
• Chemical formula: C₄₆H₆₂N₈O₁₀
• Molecular weight: 887.00 g/mol

(Note there is also a form of bovine β-Casomorphin 8 that has Histideine instead of Proline in position 8, with this depending on whether it is derived from A1 or A2 beta-casein)