Beta-casomorphin Research Articles

Modeling the hybrid seedling performance of forage sorghum and silage corn under Jordan irrigation conditions

The beta casein gene (CSNS2) has 12 genetic variants divided into two groups: the first group (A1, B, and G) which differ from the second group (A2, A3 C, D, E, F, H, H2 and I) where A base replaces C base, this leads to potential liberation of a bioactive peptide, b-casomorphin, upon digestion where a histidine replaces a proline at position 67. The allele specific polymerase chain reaction (AS-PCR) was evaluated to distinguish between the beta casomorphin releasing variants (A1 and B) and the non-releasing variants. The sequence analysis was used to determine these variants and confirm it in goat, sheep and cattle. The results showed that cattle carrying allele A1 either homozygous or heterozygous more than sheep and goats. The allele frequency of A1 and A2 is 0.44, 0.56 in goats, 0.43, 0.57 in sheep and 0.54, 0.46 in cattle, respectively. The sequence results reported changing of C base to A base in goat, sheep and cattle. Therefore, this study reported that goat and sheep milk was more safe than cattle milk.

Evaluation of b-casein variants in Egyptian goat, sheep and cattle by allele specific PCR and relevance to b- casomorphin

The beta casein gene (CSNS2) has 12 genetic variants divided into two groups: the first group (A1, B, and G) which differ from the second group (A2, A3 C, D, E, F, H, H2 and I) where A base replaces C base, this leads to potential liberation of a bioactive peptide, b-casomorphin, upon digestion where a histidine replaces a proline at position 67. The allele specific polymerase chain reaction (AS-PCR) was evaluated to distinguish between the beta casomorphin releasing variants (A1 and B) and the non-releasing variants. The sequence analysis was used to determine these variants and confirm it in goat, sheep and cattle. The results showed that cattle carrying allele A1 either homozygous or heterozygous more than sheep and goats. The allele frequency of A1 and A2 is 0.44, 0.56 in goats, 0.43, 0.57 in sheep and 0.54, 0.46 in cattle, respectively. The sequence results reported changing of C base to A base in goat, sheep and cattle. Therefore, this study reported that goat and sheep milk was more safe than cattle milk.

Protein intake from dairy food increases bovine beta‐casomorphin 7 in human mature milk

Bovine beta casomorphin 7 (BCMb‐7) is an opioid peptide that increase the risk to develop cardiovascular disease, type 1 diabetes, sudden infant death syndrome, autism and schizophrenia. It has been found in milk, cheese, yogurt and some biological samples such as infant's blood, urine from autistic children and human milk. The aim of this cross‐sectional study was to investigate whether dairy food intake is associated with the presence of BCMb‐7 in breast milk in Mexican women. Three human milk samples from 78 women from a rural area in Querétaro Mexico were obtained between 3 and 16 weeks postpartum. BCMb‐7 was determined by Ultra Performance Liquid Chromatography Mass Spectrometry (UPLC‐MS). Dairy food intake was evaluated using three 24 hr‐recalls and a food frequency questionnaire. Intake of dairy food evaluated included whole milk, different types of cheese and yogurt. All women consumed any dairy products at least once a day. BCM‐7 concentration in mature human milk was 0.84±1.01 ng/mL. Women had a total protein intake of 68.5 ± 21 g per day. Women with higher protein intake from dairy food (>40g) had significantly higher concentration of bovine BCMb7 (> 0.90 ng/mL) compared with women with lower protein intake from dairy food (<33g) (p = 0.029). For every 10 grams of dairy protein consumed, the probability of increasing the concentration of BCMb‐7 increased 1.18 times (p=0.034). In conclusion, high intake of dairy food increases the concentration of BCMb‐7 in human milk in Mexican women.Support or Funding InformationThis work was funded by Conacyt and FOPER 2015 (UAQ)

Milk proteins and human health: A1/A2 milk hypothesis

Sir, Milk from dairy cows has been regarded as nature’s perfect food, providing an important source of nutrients including high quality proteins, carbohydrates and selected micronutrients. More than 95% of the cow milk proteins are constituted by caseins and whey proteins. Among the caseins, beta casein is the second most abundant protein and has excellent nutritional balance of amino acids. Different mutations in bovine beta casein gene have led to 12 genetic variants and out of these A1 and A2 are the most common. The A1 and A2 variants of beta casein differ at amino acid position 67 with histidine (CAT) in A1 and proline (CCT) in A2 milk as a result of single nucleotide difference. This polymorphism leads to a key conformational change in the secondary structure of expressed β-casein protein. Gastrointestinal proteolytic digestion of A1 variant of β-casein (raw/processed milk) leads to generation of bioactive peptide, beta casomorphin 7 (BCM7). [1] Infants may absorb BCM-7 due to an immature gastrointestinal tract whereas adults gather the biological activity locally on the intestinal brush boarder. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk. Initial studies on indigenous cow (Zebu type), buffalo and exotic cows (taurine type) have revealed that A1 allele is more frequent in exotic cattle while Indian native dairy cow and buffalo have only A2 allele, [2] and hence are a source for safe milk. Recently, a relationship between disease risk and consumption of a specific bovine β-casein fraction with either A1 or A2 genetic variants has been identified. BCM7 is suggested to be associated as a risk factor for human health hazards as it can potentially affect numerous opioid receptors in the nervous, endocrine and immune system. It is also known to be an oxidant of low dietary lipoproteins (LDL) and oxidation of LDL is believed to be important in formation of arterial plaque. Epidemiological evidences claim that consumption of beta-casein A1 milk is associated as a risk factor for type-1 diabetes, coronary heart disease, arteriosclerosis, sudden infant death syndrome, autism, schizophrenia etc. [3,4] A broad range of studies from American and European investigations has shown reduction in autistic and schizophrenic symptoms with decrease in A1 milk intake. [5] Further, animal trials have also supported the linking of type-1 diabetes to milk exposure in general and A1 beta-casein in particular. Populations, which consume milk containing high levels of β-casein A2 variant, have a lower incidence of cardiovascular disease and type-1 diabetes. The A1/A2 hypothesis is both intriguing and potentially very important for public health if it is proved correct. It should be taken seriously and deeper research is needed to verify the range and nature of BCM7 interactions with the human gastrointestinal tract and whole organism. This requires more of animal trials and generation of data on human subjects having the problems related to A1/A2 beta-casein milk consumption.

Beta-casomorphin (BCM) and human colonic lamina propria lymphocyte proliferation

BCM is a milk-derived peptide with opiate-like properties which is absorbed through the gastrointestinal mucosa. It has been shown to affect gastrointestinal motility, absorption and secretion. Recently, modulation of the immune system by BCM was also reported. In this study we investigated the in vitro effect of BCM on the human mucosal immune response as represented by lamina propria lymphocyte (LPL) proliferation. Results show that BCM significantly inhibited concanavalin A (ConA) stimulated LPL DNA synthesis. BCM also inhibited ornithine decarboxylase activity (ODC) in ConA-stimulated LPL. Although BCM also inhibited 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulated LPL DNA synthesis, the degree of inhibition was much lower than in ConA-stimulated LPL. The anti-proliferative effect of BCM was reversed by the opiate receptor antagonist, neloxone. Our results suggest that BCM may affect the human mucosal immune system, possibly via the opiate receptor.

Linear and cyclic β-casomorphin analogues with high analgesic activity

We investigated the antinociceptive efficacy of casomorphin (CM) derivatives using the vocalization test. Male Wistar rats received chronic microcannulae into the right lateral ventricle. One week later we examined the analgesic effect of CM derivatives 10, 30, 60, and 90 min after intraventricular injection (5 μl). The analgesic effect was calculated as the individual percent increase in the pain threshold and was compared to controls (saline treatment). The substitution of d-lysine and d-ornithine in position 2 in connection with a cyclization through ring closure of the 2 position side chain amino group to the C-terminal glycine-COOH group resulted in high analgesic potency. The substitution of d-Pro 4 was without any effect in the ineffective linear derivatives and decreased the effectiveness in the highly effective cyclic derivatives. The cyclic [ d-Orn 2]CM-5 and the cyclic [ d-Lys 2]CM-5 are the CM derivatives with the highest antinociceptive activity. The cyclic [ d-Orn 2]CM-5 is greater than 1000 times more effective than morphine. We conclude, on the basis of studies of receptor binding and in vitro investigations, that μ receptor activity alone is not responsible for the analgesic activity. The δ receptor and possibly also the κ receptor could modulate the nociceptive effectiveness.

Influence of modified casomorphins on yawning behavior of rats

Apomorphine-induced yawning was completely suppressed in animals treated with 5 nmol [D-Pro 4]casomorphin (CM) (ICV), 10 nmol [D-Phe 3]CM (ICV) or 10 nmol [D-Pip 4]CM (ICV). The apomorphine-induced yawning was also decreased, by des-Tyr analogs, but only by about 50%. Physostigmine (0.15 mg/kg, IP) induced yawning. The physostigmine-induced yawning was suppressed by 5 nmol [D-Pro 4]CM and 10 nmol [D-Phe 3]CM. Both [des-Tyr-D-Phe 3]CM and [des-Tyr-D-Pip 4]CM were without effect, whereas [des-Tyr-D-Pro 4]CM increased significantly the physostigmine-induced yawning. The results suggest that dopaminergic transmission can be modulated by β-casomorphin derivatives, thus resulting in a decrease in yawning. In the case of the des-tyrosine derivatives, we can assume a dopaminergic modulation, too. An increase in serotonergic activity might be supposed for [des-Tyr-D-Pro 4]CM.