BCM7 and Sudden Infant Death Syndrome

BCM7 and Sudden Infant Death Syndrome

Posted on April 10, 2011 by Keith Woodford

Sudden infant death syndrome (SIDS) is every parent’s worst nightmare. In developed countries it is the biggest cause of death in apparently healthy babies. There are many strategies to reduce the incidence, including putting babies to sleep on their backs rather than on their tummies, not sleepingin their parents’ bed, and being in a non-smoking household. Also, it has long been widely accepted that SIDS is less common with breast-fed babies. But none of these address the fundamental biological cause as to what makes some babies susceptible to a sudden cessation of breathing, followed rapidly by death unless a parent or caregiver is immediately ‘on hand’.

Bovine BCM7 (beta-casomorphin7), which I call the ‘milk devil’, has long been suspected as a villain. This ‘milk devil’, which is an opioid derived from casein (and hence the name ‘caso’ from casein and ‘morphin’ from morphine), is only produced from digestion of A1 beta-casein (1, 2), which itself is only produced by some cows of European breeds. This A1 beta-casein is the consequence of a chance mutation in an ancestor some thousands of years ago (3). Unfortunately this mutated gene is now found in a considerable proportion of European cows.

Scientific evidence has linked bovine BCM7 to many health conditions such as Type 1 diabetes and heart disease (4, 5), child development and symptoms of autism (6, 7). On the PUBMED database there are now more than 250 peer reviewed medical and scientific papers on casomorphins. However, the evidence that BCM7 might be a major villain for SIDS has, until now, been somewhat indirect.

Back in the 1990s, beta-casomorphins were found in the brainstems of SIDS babies (8). But comparing this with the brainstems of healthy children was obviously not possible. Also, in young rabbits and rats (9) it had been shown that injecting BCM7 into the blood leads to apnoea (depressed and irregular breathing). But obviously these sorts of trials cannot be done with humans. Also, it is only recently that detection kits have become readily available for testing BCM7 in blood. A further complication has been that in all likelihood some babies are more susceptible than others, but there has been no way to identify the genetic aspect of risk. In my book ‘Devil in the Milk’ (p152), first published in 2007(10), I introduced the latest evidence relating to SIDS (11), but at that time there was nothing conclusive.

However, recent work in Poland led by Dr Elzbieta Kostyra, and published by leading scientific and medical publisher Elsevier in the April 2011 issue of the journal Neuropeptides, has provided answers to the major questions (12). There can now be little doubt that BCM7 is arisk factor for SIDS. Also, it is now clear that the babies most at risk are those who have low levels in their blood of an enzyme called DPP4 (dipeptidyl peptidase 4). This is the only enzyme in humans that can break down BCM7 (13-15).

The Polish work is based on studying babies who have had life threatening events from apnoea, but whom the parents and/ or doctors managed to save. Blood samples from these babies were then compared to healthy babies. Key findings were that the ‘at-risk’ babies had three times the level of bovine BCM7 in their blood as the healthy babies. Also, these at-risk babies had 42% less DPP4 than the healthy babies. Both of these results were statistically significant at p< 0.001. In other words, the chance of getting a result like this due to random factors, rather than being causatively linked either to each other or a common third factor, is less than one in one thousand.

Analysis of the healthy babies showed that variation of BCM7 within this group was positively associated with more DPP4 activity. In other words, in healthy children the body naturally increases DPP4 activity when BCM7 is high. But in the at-risk babies the DPP4 level was actually much lower rather than higher. This demonstrates that the at-risk babies are deficient in their ability to quickly respond to high BCM7 by producing sufficient quantities of the only enzyme that can break it down.

The babies were fed on three types of diet, determined by their mothers. Not surprisingly, those fed milk formula that was high in casein had much higher BCM levels than those fed infant formula that was predominantly (but not exclusively) whey. This was to be expected given that BCM7 can only come from casein and not from whey. However, somewhat intriguingly, babies aged 1-4 months who were apparently being exclusively breastfed also had bovine BCM7 in their blood. How did this get there? The Polish researchers and other scientists have been investigating for quite some time how protein fragments, such as but not only bovine BCM, can get from the mother’s stomach into breast milk. It could be that the BCM7 is being transferred through the blood (16, 17), but it is looking increasingly likely that it might also be via other mechanisms, perhaps including the lymph system. Regardless of how is it is occurring, there seems little doubt that bovine BCM7 can get into human breast milk, and that it can cause life threatening events in babies. So the evidence indicates that it is not only the babies, but also the lactating mothers, who need to be on cows’ milk that is free of A1 beta-casein.

The Polish work led by Dr Kostyra dovetails very nicely with work by Russian scientists that was published in another international journal, Peptides, in late 2009 (6) . That work showed that babies fed infant formula not only had high levels of bovine BCM7in their blood, but that a proportion of these babies were much slower than other babies to metabolise and eliminate the BCM7. These slow eliminators were at high risk of delayed psychomotor development. The Russian scientists did not investigate the reason why some babies were slow BCM7 eliminators, but an obvious hypothesis would be that they had low DPP4 in the blood. This latest Polish work now provides strong confirmatory evidence for this hypothesis.

The implications of this work would seem obvious. If infants are to be fed milk formula then it needs to be free of A1 beta-casein. In other words, it needs to come from cows that are what we call ‘A2 cows’ and which produce ‘A2 milk’. Also, lactating mothers would be well advised to not drink milk containing A1 beta-casein.

My assumption is that the mainstream dairy industry will try and denigrate this research. For example, Dairy Australia has a standard response to any new research on A1 beta-casein along the lines that ‘all milk is the same’. Of course all milk is not the same and such a statement is scientific nonsense. So how will they denigrate this research? Detractors might say that it is ‘just one study’. This was a typical response to the Russian work (6) published in 2009. They might also refer to the European Food Safety Authority (EFSA) report of January 2009 (1), which claimed there was no proof that BCM7 was getting through from the digestive system to the blood. Back in 2009 that statement might have been defensible, in that arguably there was strong evidence (which EFSA failed to acknowledge) but not final proof. But now in 2011 that position is no longer tenable. They may also argue – as was said with the Russian research, which like this Polish research came out of leading scientific institutions – that we do not know enough about their research standards. Well, in that case it is time they went and found out. These are leading scientific institutions. In any case, both the Russian and Polishwork is published in highly ranked international journals following international peer review.

Major elements of the mainstream dairy industry, at least in Australia and New Zealand, have known about BCM7 and the apparent links to a range of health conditions for more than a decade. They hoped that those apparent links might disappear. And for a while it seemed that this might happen. Now, there is no chance that this will happen.

So what can the industry do about it? Well, one thing they could do is breed A2 cows. This is easy to do, using semen that carries the A2 variant of the beta-casein gene. Most New Zealand and Australian bulls already have their A1/A2 status known and recorded. In ten years time the national herds could be close to pure A2, with only inconsequential levels of A1 beta-casein remaining. Then we would have all of our dairy herds the way nature originally intended! The irony is that we could already be in that position if we had only acted when evidence first emerged.But because only a minority of farmers have been converting their herds, the industry will now have to work out how to sell ‘A1 milk’ for the next 10 years. That might be a challenge, and hence there will be a continuing industry fightback (‘we must not say anything negative about milk’, or ‘nothing is proven’). There will still be plenty of people who will drink the ‘ordinary milk’ despite the risks, and indeed many of those people may not be susceptible to the BCM7. So ordinary milk will still sell while the change is being made.

However, for parents of young children in particular, the time has come for them to be made aware of the emerging evidence: BCM7, and hence milk that contains A1 beta-casein, is an evidence-basedrisk factor for a range of childhood health conditions. SIDS has now moved up that list of conditions. There are options to reduce those risks.

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UPDATE: (14 April 2011)

It has been suggested to me that this is all a bit scary. Perhaps it is even scaremongering. The first (i.e. it is scary) I disagree with, and the second (scaremongering) I refute even more strongly. It is SIDS and not this story that is scary. This is a story of hope and moving forwards with solutions. But I do agree that perhaps a little more guidance might be helpful. Some time in the future, and hopefully the near future,it will be possible to purchase infant formula made from the milk of A2 cows. In the meantime the ‘no-cost’ or ‘low-cost’ options to reduce risk are:
1) breast-milk
2) whey-based infant formula (although most of these formulas will still contain some casein).
It seems that mothers who are breast-feeding can further reduce their risk by themselves drinking A2 milk; i.e.milk that is free of A1 beta-casein . And once the babies are weaned from the breast or from infant formula, then the milkthey drink can also be from A2 cows, at least in countries like Australia and New Zealand where A2 milk is commercially available.
Of course for specific advice parents should consult a professional dietitian.

Update: This version was updated 25 April 2011.

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Note: the full reference for the SIDS paper is:

Wasilewska J, Sienkiewicz-Szlapka E, Kuzbida E, Jarmolowska B, Kaczmarski M, Kostyra E. The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE). Neuropeptides. 2011 DOI: 10.1016/j.npep.2011.01.005 ( This is a corrected proof, peer reviewed, and able to be cited, available online to subscribers to the journal, with hard copy and page numbers still to be assigned.)

Other References

1. Scientific Report of EFSA prepared by a DATEX Working Group on the potential health impact of β-casomorphins and related peptides. EFSA Scientific Report (2009) 231, 1-107.

2 De Noni I, Release of b-casomorphins 5 and 7 during simulated gastro-intestinal digestion of bovine b-casein variants and milk-based infant formulas. Food Chemistry 2008; 110:897-903

3. Ng-Kwai-Hang KF, Grosclaude F. Genetic polymorphism of milk proteins. In: Fox PFaM, P.L.H editor. Advanced Dairy Chemistry: Volume 1: Proteins, Parts A&B. New York: Kluwer Academic/Plenum Publishers; 2002. p. 739-816.

4. Elliott RB, Harris DP, Hill JP, Bibby NJ, Wasmuth HE. Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption. Diabetologia. 1999 Mar;42(3):292-6.

5. Laugesen M, Elliott R. Ischaemic heart disease, Type 1 diabetes, and cow milk A1 beta-casein. N Z Med J. 2003 Jan 24;116(1168):U295.

6. Kost NV, Sokolov OY, Kurasova OB, Dmitriev AD, Tarakanova JN, Gabaeva MV, et al. Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Peptides. 2009 Oct;30(10):1854-60.

7. Cade JR, Privette MR, Fregly M, Rowland N, Sun Z, Zele V, et al. Autism and Schizophrenia: Intestinal Disorders. Nutr Neurosci. 2000;3:57-72.

8. Pasi A, Mahler H, Lansel N, Bernasconi C, Messiha FS. beta-Casomorphin-immunoreactivity in the brain stem of the human infant. Res Commun Chem Pathol Pharmacol. 1993 Jun;80(3):305-22.

9. Hedner J, Hedner T. beta-Casomorphins induce apnea and irregular breathing in adult rats and newborn rabbits. Life Sci. 1987 Nov 16;41(20):2303-12.

10 Woodford, K. ‘Devil in the Milk. Craig Potton Publishing 2007. (Updated Edition 2010, American Edition published by Chelsea Green 2009)

11 Sun, Z., Zhang, Z., Wang, X., Cade, R., Elmer, Z., Fregly, M., Relation of betacasomorphin to apnea in sudden infant death syndrome. Peptides. 2003; 24,:937–943

12. Wasilewska J, Sienkiewicz-Szlapka E, Kuzbida E, Jarmolowska B, Kaczmarski M, Kostyra E. The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE). Neuropeptides. 2011.

13. Nausch I, Mentlein R, Heymann E. The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV from human placenta. Biol Chem Hoppe Seyler. 1990 Nov;371(11):1113-8.

14. Kreil G, Umbach M, Brantl V, Teschemacher H. Studies on the enzymatic degradation of beta-casomorphins. Life Sci. 1983;33 Suppl 1:137-40.

15. Tiruppathi C, Miyamoto Y, Ganapathy V, Roesel RA, Whitford GM, Leibach FH. Hydrolysis and transport of proline-containing peptides in renal brush-border membrane vesicles from dipeptidyl peptidase IV-positive and dipeptidyl peptidase IV-negative rat strains. J Biol Chem. 1990 Jan 25;265(3):1476-83.

16. Iwan M, Jarmolowska B, Bielikowicz K, Kostyra E, Kostyra H, Kaczmarski M. Transport of micro-opioid receptor agonists and antagonist peptides across Caco-2 monolayer. Peptides. 2008 Jun;29(6):1042-7.

17. Shimizu M, Tsunogai M, Arai S. Transepithelial transport of oligopeptides in the human intestinal cell, Caco-2. Peptides. 1997;18(5):681-7.