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Milk Allergies and The Paleo Diet

Does Non-Allergenic Milk Exist? | The Paleo Diet

Dear Paleo Diet Team,

In the 1997 work entitled “Food and Low Incidence of Insulin Dependent Diabetes Mellitus (IDDM) in Iceland” (L. Thorsdottir and O. Reykdal) have suggested that the incidence of IDDM is lower in Iceland than in other human genetic related nations of Scandinavia.

Since milk proteins alleles frequencies in the Nordic cattle breeds varies and preliminary (at that time) results indicated that Beta Casein A1 was particularly low in Iceland milk, they have speculated that IDDM was caused by Beta Casein A1 and its bioactive peptide BCM-7.

My opinion is that Diabetes mellitus is not caused by one single factor alone, but perhaps there are also other factors involved.

I would like to know your opinion on that matter if possible, since cattle breeding association in Brazil, of a particular breed that produces A2 milk, is applying to official agencies to market their milk with the allegation of “non-allergenic milk.”

One of their main allegations is based on data that BCM-7 alone would be the “villain” in the milk, with which I totally disagree, since milk allergies are a multifactorial health problem.

Your attention would be greatly appreciated.

Jose Luiz M Garcia

Pedro Carrera Bastos’ Response:

Dear Mr. Garcia,

Cow’s milk (CM), as you know, has several proteins, but we can group these proteins into two major ones: whey proteins and caseins. 1 Caseins represent about 80% of the total protein content of CM, as seen in this table. 1

6.12.14-table1Caseins in CM (and also in goat’s milk) are divided into: alphaS1, alphaS2, beta and kappa.2

Following digestive proteolysis of beta-caseins in the human gut (and also after food processing, such as milk fermentation and microbial cheese ripening) there will be a release of bioactive peptides called beta-casomorphins (BCMs). 3 BCMs contain 4-11 amino acids and, more importantly, they are resistant to further proteolysis and express opioid like activity. This means they could potentially bind various opioid receptors in the human nervous system, and also in the gastrointestinal, immune and endocrine systems.3

Beta caseins (as well as the other caseins in CM) are encoded by genes found on bovine chromosome 63 and there are 12 recognized genetic variants of beta-casein: A1, A2, A3, B, C, D, E, F, H1, H2, I and G. A1 and A2 are the most common forms of beta-casein found in dairy cattle in western countries.3

Beta-caseins are proteins with 209 amino acids and the difference between A1 and A2 lies in just one amino acid at position 67: histidine in A1 and proline in A2.3, 4 Apparently, “ancestral cattle” (as well as goats, yak and most sheep) contained the A2 version of beta-casein gene and not the A1 version, which is a single nucleotide polymorphism (SNP) that appeared 5,000 to 10,000 years ago only in Bos taurus, being present today in breeds, such as Holstein, Friesian and Ayrshire.4, 5

The main premise behind the A1/A2 hypothesis is that beta-casein A1, but not A2, will originate the opioid like peptide beta-casomorphin-7 (BCM-7).3, 4 BCM-7 (which contains 7 amino acids) resists further digestion in the human gut, could be absorbed by some individuals, like babies and people with intestinal hyperpermeability, and can influence gut function without being absorbed into the bloodstream.3, 4 The proponents of this hypothesis claim that after being absorbed, BCM-7 could increase low-density lipoprotein oxidation and bind to opioid receptors in the nervous, immune and endocrine systems.3-6

This in vitro and animal data combined with epidemiological studies led to the hypothesis that beta-casein A1 is implicated in Autism and Schizophrenia,3, 4 Type 1 Diabetes,3-5 Cardiovascular Disease,3-6 Sudden Infant Death Syndrome,3 and perhaps even in Metabolic Syndrome (because it could cause insulin resistance).6

In the last years, some important scientific papers have been published criticizing the epidemiological and animal data, and particularly the lack of intervention studies supporting the above causality.5, 7, 8

Having said that, I believe the A1/A2 hypothesis should not be readily dismissed. It deserves to be better studied in animal models and, more importantly, in randomized controlled trials. Nevertheless, when it comes to Type 1 Diabetes (T1D), multiple lines of evidence strongly suggest various CM proteins, and not just beta-casein (which could yield BCM-7), are involved.

Beta-lactoglobulin (BLG)

BLG is a protein found in the whey fraction of CM (but apparently not in the whey of human’s milk) that has structural homology with the human protein glycodelin, which is responsible for the modulation of T-lymphocytes.9 This means that BLG could generate antibodies to glycodelin, and indirectly lead to autoimmunity in genetically susceptible children,9 especially if introduced early in life when there is increased intestinal permeability.9, 10

Bovine serum albumin (BSA)

This is another protein present in the whey fraction of CM. Antibodies against a specific peptide derived from BSA, called ABBOS, have been found repeatedly in the majority of patients with T1D.11-13 This is relevant because there is molecular mimicry between the peptide ABBOS and a beta-cell surface protein p69, one of the autoantigens attacked by T cells in T1D patients.11

Bovine insulin (BI)

CM, human’s milk, and presumably milk from all mammals contains insulin.10 Immunity to BI is common in children who consume cow’s milk or who have been exposed to infant formulas containing cow’s milk.10 Because BI differs from human insulin by only three amino acids, it can generate antibodies against human insulin in genetically susceptible individuals with increased intestinal permeability and other gut dysfunctions10 and/or enteral virus infections in their early years.10, 14

A recent randomized controlled trial (RCT) confirmed the role of BI in T1D.15 In this pilot trial, infants with genetic susceptibility for T1D were assigned to either a “normal” CM based formula, a whey-based hydrolyzed formula, or a whey-based formula “essentially free of bovine insulin” and it was found that the insulin-free formula reduced the cumulative incidence of autoantibodies by age 3 years.15

Interestingly, the RCT gives more support to the role of CM proteins in T1D. In this trial, 230 infants with genetic susceptibility to T1D and at least one family member with T1D received either a casein hydrolysate formula or a conventional, CM-based formula (control) whenever breast milk was not available during the first 6 to 8 months of life. The casein hydrolysate formula, as compared with the control, was associated with a decreased risk of positivity for at least one diabetes-associated autoantibody.16

In conclusion, the available evidence cannot firmly confirm or refute a causal role of BCM-7 in T1D. Nevertheless, even if a causal role is confirmed, drinking CM without beta-casein A1 could still represent a risk for people with genetically susceptibility for T1D, since there are various other potential problematic proteins in CM.

Best wishes,

Pedro Bastos, MA, MS, Ph.D. candidate in Medical Sciences at Lund University, Sweden;

Pedro Bastos | About The Paleo Diet TeamPedro Bastos provides consultations, research, and advice to The Paleo Diet community. He is a member of the New York Academy of Sciences, the International Society for the Study of Fatty Acids and Lipids, and the Nutrition Society. Pedro is a certified personal trainer and strength and conditioning instructor, and he holds post-graduate diplomas in exercise and health (from School of Sport Science of Rio Maior, Portugal) and in biochemistry and orthomolecular medicine (from Fernando Pessoa University, Portugal). He received his master’s degree in human nutrition and food quality through Universitat de les Illes Balears (Spain). His research interests are dairy products and human health, nutrition and chronic inflammatory/auto-immune diseases, role of micronutrients in human health, prevention of osteoporosis and sarcopenia, nutrition and liver adenomas, and the role of nutrition in sports injury prevention.

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REFERENCES

1. Chandan RC. Milk composition, physical and processing characteristics. In Hui YH, Chandan RC, Clark S, et al. Handbook of Food Products Manufacturing – Health, Meat, Milk, Poultry, Seafood, and Vegetables. John Wiley & Sons; 2007: 347-377

2. Park YW, Haenlein GFW. Handbook of milk of non-bovine mammals. Blackwell Publishing; 2006

3. Kamiński S, Cieslińska A, Kostyra E. Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet. 2007;48(3):189-98.

4. Woodford K. Devil in the Milk: Illness, health and politics of A1 and A2 milk. Craig Potton Publishing; 2007.

5. Merriman TR. Type 1 diabetes, the A1 milk hypothesis and vitamin D deficiency. Diab Res Clin Pract. 2008:1–8.

6. Lindeberg. Food And Western Disease: Health and Nutrition from an Evolutionary Perspective. Wiley-Blackwell; 2010.

7. Truswell AS. The A2 milk case: a critical review. Eur J Clin Nutr. 2005; 59: 623–631.

8. Clemens RA. Milk A1 and A2 peptides and diabetes. Nestle Nutr Workshop Ser Pediatr Program. 2011;67:187–195.

9. Goldfarb MF. Relation of time of introduction of cow milk protein to an infant and risk of type-1 diabetes mellitus. J Proteome Res. 2008 May;7(5):2165-7

10. Vaarala O. Is it dietary insulin? Ann N Y Acad Sci. 2006 Oct;1079:350-9.

11. Karjalainen J, et al. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med. 1992 Jul 30;327(5):302-7.

12. Pérez-Bravo F, et al. Duration of breast feeding and bovine serum albumin antibody levels in type 1 diabetes: a case-control study. Pediatr Diabetes. 2003 Dec;4(4):157-61.

13. Banwell B, et al. Abnormal T-cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes. Ann Neurol. 2008 Jan;63(1):98-111.

14. Mäkelä M, et al. Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin. J Autoimmun. 2006 Aug;27(1):54-61.

 15. Vaarala O, et al. Removal of Bovine Insulin From Cow’s Milk Formula and Early Initiation of Beta-Cell Autoimmunity in the FINDIA Pilot Study. Arch Pediatr Adolesc Med. 2012 Jul 1;166(7):608-14.

 16. Knip M, et al. Dietary intervention in infancy and later signs of beta-cell autoimmunity. N Engl J Med. 2010 Nov 11;363(20):1900-8.

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8 Comments on "Milk Allergies and The Paleo Diet"

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  1. William Neville says:

    I would like to add some additional points on A1 milk, A2 milk and how BCM-7 is harmful.

    Originally all milk contained only A2 beta-casein. A point mutation occurred in some European cows about eight thousand years ago. This introduced a new “A1” variant of the beta-casein gene, which was then expressed in the milk of these cows. Beta-casein is a 209 amino acid chain. A1 beta-casein has a histidine at position 67. A2 beta-casein has a proline at position 67. On digestion A1 beta-casein breaks at positions 60 and 66 producing the peptide beta-casomophin-7 (BCM-7). BCM-7 has nothing to do with milk allergy. If a person is allergic to A1 milk, they are just as allergic to A2 milk.

    Other bioactive peptides from the digestion of A1 beta-casein cause increased intestinal permeability otherwise known as leaky gut. Peptides, including BCM-7, pass into the bloodstream through a leaky gut. These peptides produce an immune response which leads to autoimmunity. Hence A1 is associated with Inflammatory Bowel Disease, Multiple Sclerosis and Parkinson’s Disease.

    The presence of three proline molecules in BCM-7 make it resistant to further digestion. GLUC-2 receptors on pancreatic beta-cells share a four amino acid sequence with BCM-7. Antibodies produced against BCM-7 would have the potential to destroy the pancreatic beta-cells leading to Type I diabetes. Cows in France and Iceland produce more A2 milk so there is a lower incidence of Type I diabetes in these countries.

    The incidence of coronary heart disease in different countries is directly proportional to the amount of A1 milk consumed. BCM-7 is responsible for oxidation of LDL particles in arterial walls. This leads to atheroma formation and heart attacks. Malav Trivedi [4] has showen how this effect is brought about by increased DNA methylation, reduced gene expression, a low glutathione level and consequent oxidative stress. A1 milk is produced by most cows in Europe, America, and Australia. Milk containing only the original A2 type of beta casein is produced by cows in Africa and Asia. The Masai and Samburu people of Kenya drink a lot milk, which is all A2, but do not develop heart disease. Americans drink a lot of A1 milk and have heart disease as a result. The quantity of A1 milk consumed is the overriding cause for different heart disease rates between counties. For example Mediterranean people do not drink much milk and what they do consume has a high proportion of A2 beta-casein. This is the reason for their low incidence of heart disease. It is nothing to do with any other aspect of the Mediterranean Diet [2].

    Farmers can convert their herds of cows to A2 producers in 2 generations. If they did many diseases could be prevented.

    References:
    1. Interview with Keith Woodford (http://undergroundwellness.com/podcasts/devil-in-the-milk)
    2. The Devil in the Milk by Keith Woodford
    3. Don’t Drink A1 Milk by Brent Bateman (only available on Kindle)
    4. Role of a Redox-Based Methylation Switch in mRNA Life Cycle (Pre- and Post-Transcriptional Maturation) and Protein Turnover: Implications in Neurological Disorders, Malav S. Trivedi, Richard C. Deth ,Front Neurosci. 2012; 6: 92. Published online 2012 June 26. doi: 10.3389/fnins.2012.00092
    5. Lecture by Malav S. Trivedi, http://www.youtube.com/watch?v=E-tCM-F_Irs

  2. charles grashow says:

    What about raw goat milk or raw Jersey cow milk?

    • William Neville says:

      Goat milk is A2 so it is OK raw or pasteurised. Jersey cows are more often A2 than other European breeds but without testing you cannot be sure.

  3. Andy says:

    Pedro,

    I think there could be something to this A1/A2 idea.

    I am one that seems to fall into the pattern of being allergic to A1 casein. When I eat some cows milk dairy products, I get congested and have trouble breathing. In contrast when I eat goat or sheep dairy products, I have never had a problem.

    • B-Jay says:

      I didnt know that goats milk or sheep dairy products were different. Thankyou for mentioneing it, i am going to give it a try and thankyou to the Paleo diet team for this really helpful and insightful information. Knowledge truly is power. Xx =)

    • William Neville says:

      Nasal congestion after consuming A1 milk is not due to an allergy. BCM7 exerts many of its effects because it is an opioid. It has the potential to cause bloating, abdominal pain, nausea, diarrhoea and constipation. BCM7 stimulates goblet cells to produce mucous. Excessive nasal and throat secretions are the result.

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