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BANT Featured Article
Why A2
Milk in
the UK?
Sue McGarrigle is Technical Advisor for Bionutri and provides training and
seminar programmes for CAM practitioners of all disciplines. She lectures
to a variety of groups at national conferences, BANT groups and College
and University students. Sue writes extensively, is a published author and
has contributed to several healthcare publications.
Sue McGarrigle - ND, DipION, NTCC, CNHC Registered, MBANT
It is unusual that I am writing an article about
the use of cows’ milk, particularly as many of
us agree in essence that it should not be part
of the adult diet; genetically speaking, the
human body was not designed to drink milk
after the weaning period.
The first milk users are not thought to have been milk drinkers;
(National Geographic August 6 2008) the utilisation of milk came
from natural fermentation processes used to preserve food which
led to the development of butter, cheese and yogurt about the
time early man moved away from a hunter-gatherer society into
an agricultural and community based society. Fermentation
became popular at the dawn of civilization not only because it
preserved food, but also because it provided a variety of tastes
and food forms with unique nutrient complexes, the abundant
microorganisms in the fermentation process producing vitamins,
enzymes, antioxidants, beta-glucans and phytonutrients.(1)
Fermented foods are now for many people a vital missing link in
today’s diet and with the advent of refrigeration this has negated
our need to ferment milk so it can be utilised as an important
nutritional and anti-microbial food. Here in the UK abundant
supplies of pasteurised, homogenised bovine milk and other dairy
products are a staple of our daily diet at all ages and we are the
only species drinking another species’ fresh milk.
For many people in the UK population, milk, particularly A1 betacasein dominant milk mainly from British Friesian cows, is now so
entrenched into our daily nutritional intake that when problematic,
trying to eliminate it or find suitable quality alternatives has been
difficult in many past cases, along with good compliance.
Adults frequently mistake gastrointestinal symptoms as a sign that
they may have lactose intolerance or are unable to digest dairy
products at all without knowing why. But there are aspects to milk
digestion that I have found many practitioners and members of the
public are not aware of including A1 milk protein intolerance so a
solution may be not to impose restrictions on dairy, but to consume
milk containing only A2 beta-casein and this article will focus on
the potential health benefits of A2 rather than A1 milk inclusion in
the diet.
Lactose Intolerance
Kefir an example
of a fermented milk
product
Before we get into the growing body of research behind A2 Milk I am
first going to talk about lactose intolerance as this is a common food
intolerance associated with drinking milk that needs to be set apart.
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Nature has evolved for most babies to have the natural ability to
digest their primary food i.e. breast or formula milk and produce
adequate levels of lactase an enzyme that catalyzes hydrolysis
of lactose into glucose and galactose in their digestive system
with some exceptions; an example being premature babies who
may have transient lactase deficiency which lasts temporarily
and may lead to colicky type symptoms in the first few weeks of
life. Infants of every racial and ethnic group worldwide produce
lactase, however, sometime after weaning, in the majority of the
world’s children, there is a genetically programmed decrease in
lactase (lactase nonpersisters).(2)Today in most cultures the world
over, adults do not drink milk and regardless they do not need the
lactase enzyme.
In some human populations lactase persistence has evolved as
an adaptation to the consumption of non-human milk and dairy
products beyond infancy. (3) The ability to digest lactose into
adulthood (lactase persistence) would have only been useful
to humans after the invention of animal husbandry and the
domestication of animal species that could provide a consistent
source of milk. Hunter-gatherer populations before the Neolithic
revolution were overwhelmingly lactose intolerant, as are modern
hunter-gatherers. (4, 5) Genetic studies suggest that the oldest
mutations associated with lactase persistence only reached
appreciable levels in human populations in the last ten thousand
years. (6, 7) Therefore lactase persistence is often cited as an
example of both recent human evolution (8, 9) and, as lactase
persistence is a genetic trait but animal husbandry a cultural trait,
gene-culture coevolution in the mutual human-animal symbiosis
initiated with the advent of agriculture. (10)
It has been determined that this continued genetic expression of
lactase enzyme, (lactase persistence), is dependent on ancestry
and racial background. Lactase persistence through natural
selection is found at moderate to high frequencies in Europeans
and some African, Middle Eastern and Southern Asian populations
(11) and this was a strong evolutionary advantage for people able
to consume milk and its nutrients without digestive discomfort, in
order to survive and, when the alternative was contaminated water.
The majorities of people around the world remain lactase nonpersistent (12) and consequently are affected by varying degrees
of lactose intolerance as adults – though not all genetically lactase
non-persistent individuals are noticeably lactose intolerant and not
all lactose intolerant individuals have the lactase non-persistence
allele. In the UK, around five in 100 people have lactose
intolerance. (BUPA 2013)
Lactose intolerance (which is not a milk allergy- the definition
being an immune reaction to one or more proteins in milk) has
been defined as symptoms developing after ingestion of lactose
which do not develop after placebo challenge in a person with
lactose maldigestion. Lactose intolerance has been reported to
cause uncomfortable reactions in the digestive tract and apart
from having a genetically determined characteristic may have
a secondary cause, such as gastro-enteritis or chemotherapy.
The lactose-rich diet in Western countries can cause symptoms
in individuals with the lactase non-persistence phenotype. If
diagnosed correctly symptoms are caused by the undigested
lactose in the gut after ingestion of lactose containing foods
and may include abdominal bloating and cramps, flatulence,
diarrhoea, nausea, borborygmi (rumbling stomach), or vomiting
after consuming significant amounts of lactose. (13) Lactose
malabsorption refers to inefficient digestion of lactose due to
reduced expression or impaired activity of the enzyme lactase.
Studies have shown however that even diagnosed ‘lactose
malabsorbers’ are capable of consuming moderate amounts
of dairy, tolerating an average 12 grams of lactose when
administered in a single dose (the lactose content found in 1
cup of milk) with little to no symptoms. (14) Additionally, many
adults who believe they have lactose intolerance are actually
suffering from other gastrointestinal disorders such as SIBO, yeast
overgrowth, coeliac disease, or Irritable Bowel Syndrome, and do
not see significant benefit from eliminating dairy. In addition, not all
foods with milk in them will cause problems. For example, lactose
is broken down by fermentation processes and is not found in
hard cheese such as cheddar or emmenthal. (15)
For individuals who wish to improve their digestive health the use
of probiotic bacteria found in fermented foods such as cottage
cheese and yogurt, which can metabolise lactose for energy, can
have significant benefits. Examples of popular lactic acid bacteria
such as L.kefir, L.acidophilus, L.bulgaricus, L.casei, B.longum
and B.lactis can improve symptoms of/and lactose digestion and
tolerance. (16, 17)
More significantly a proportion of adults who report milk
intolerance symptoms, lactose intolerance may not be the cause,
as cases of perceived lactose intolerance are more common than
its prevalence in adults. In a group of 406 randomly recruited men
and women 20.2% reported abdominal discomfort following dairy
intake, but only 6.4% of those had lactose intolerance diagnosed
by a physician. (18) Studies show about 20 per cent of British
consumers do not drink milk, but only 5-6 per cent are clinically
proven to be lactose intolerant. In these cases, A2 milk, free from
A1 protein, could potentially enable them to drink milk again. (19)
Difference between bovine and human milk
As the primary source of food we are raised on and beyond,
milk’s chemical and physical structure varies considerably
between species. There are considerable insights to be gained
by comparing bovine milk to human milk. As a starting point, it
is a fairly safe assumption that if there are problems associated
with bovine milk then they will be because of components that are
present in bovine milk but absent from human milk or, alternatively,
because the balance between components is substantially
different between the two. Bovine and human milk solids differ,
casein being much higher in cows’ milk (80:20 ratio), but the
liquid whey is more dominant in human milk (90:10 in colostrum,
60:40 in mature milk and 50:50 in late milk), human milk is higher
in lactose, similar in fat but much lower in protein. It is also
considerably lower in minerals so it can be iso-osmotic with blood
in the mammary gland. (19) The major proteins in human milk are
whey whereas the higher protein content in cows is mainly casein.
Bovine caseins are confirmed as alphas1, alphas2, beta, and
kappa-casein.(20) It is the beta-caseins that are the main focus of
attention for human health.
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Beta-casein content and potential BCM-7 release per 250mL of milk.
Although beta casein is the most important of the human casein
proteins, it is different to the beta casein produced by cows having
a shorter protein chain.
There are two primary forms of beta-casein contained in cow’s
milk, A1 beta-casein and A2 beta-casein, in human milk all beta
casein is of the A2 type. (19)
A1 beta casein is a string of 209 amino acids that comprises 30%
of the protein contained in cows’ milk and very closely resembles
the other milk protein A2 beta casein.
A2 beta-casein is the beta-casein form cows have produced
since before they were first domesticated, over 10,000 years ago.
It is considered safe and nutritious and has no known negative
effects on human health. Sheep and goats also produce A2 milk.
Sometime in the past few thousand years, a natural mutation
occurred in some European dairy herds that changed the betacasein they produced. The gene encoding beta-casein was
changed such that the 67th amino acid in the 209 amino acid
chain that is the beta-casein protein was switched from proline to
histidine. (A2 Corporation)
A1 and A2 beta-casein proteins showing the amino acid difference
at position 67. This difference can be detected easily by a noninvasive DNA test that indicates accurately which beta-casein
genes a cow carries.
This new kind of beta-casein that was created is known as A1
beta-casein, and is generally more common in many of the big
black-and-white cow breeds of European descent such as the
Holstein and Friesian. It is likely that the A1 allele became common
not through selection due to any specific advantage but more
due to what animal breeding specialists call the founder effect.
The founder effect is about the very large impact of the genetic
profile of the individual animal from which the breed was founded.
Due to their size, milk production,
and demeanour, Holstein/Friesian
breeds of cow are used to produce
the vast majority of Northern Europe
and America’s milk, some 75% of
the world’s 300 million strong dairy
herds produce milk that contains
the protein beta casein A1.
(World Guernsey Cattle Federation,19)
Photo courtesy
www.lismulligan-friesians.co.uk
British Friesian breeds originate in Western Europe, in particular
Holland and North Germany. The British Friesian became
established in the UK during the Nineteenth Century, particularly
in the eastern and home counties and southern Scotland. The
first Herd Book was founded in 1909. The Holstein, as we know
today, was first established in North America starting with an
imported bull and four heifers from Holland into the United States
in the 1850s. The breed first appeared in the UK in the years
immediately after the Second World War, during which time around
2000 in-calf heifers, plus a few bulls and cows, were imported
from Canada in conjunction with shiploads of store cattle.
(Holstein UK)
Cows in the well-known dairy breeds, including the Guernsey,
can produce either or both of the bovine beta casein proteins.
They can be A1/A1, A1/A2, or A2/A2. Research has shown that
about 96% of Guernsey cows produce only beta casein A2 (World
Guernsey Cattle Federation), which is interesting because I have
been following the rise in popularity of A2 milk, and this all started
when my interest was certainly piqued several years ago when
it came to my attention that a very small, private trial had been
initiated in a school on the east coast of England. 50 children on
the autistic spectrum had been offered A2 milk and yogurt from
Guernsey cow’s with some surprising and very positive results i.e.
not the usual reactions that you would expect when compared
to ingestion of A1 milk. Since then I have been tracking the
research surrounding A2 bovine milk that has been published and
discovered some very interesting facts.
Proteins are a very diverse family of large organic compounds
involved in many important biological processes. Following their
enzymatic hydrolysis during food processing or digestion, proteins
may release fragments from their primary amino acid sequence.
These fragments are called peptides, and many of them are
page 3
known to be physiologically active. The possible beneficial effects
of bioactive peptides have attracted increasing interest in recent
years. On the other hand, there are also reports suggesting
that some food-derived peptides might adversely affect human
health. Opioid peptides play a role in various biological processes
including respiration, analgesia, constipation and behaviour. (21)
However, as noted by Maklakova et al. (1993), “Depending on the
type of peptide, the mode of its administration into the organism,
the species of experimental animal, and the peptide dose, it is
possible to register an entire spectrum of effects, ranging from
significant motor excitation to a complete inhibition of locomotor
activity and catotonia”
There is a somewhat controversial claim, backed by several years
of research, that a component of beta-casein in A1 milk, which is
drunk by most people in the western world, could be a cause of
diabetes, heart disease, autism and schizophrenia in people with
immune deficiencies. It is also claimed that A2 milk is benign in
this respect. However, the argument most strongly advanced by
the proponents of the benefits of A2 Milk is not that A1 Milk causes
these illnesses but rather that A1 milk is digested in a different way
to A2 resulting in the release of a peptide or protein fragment from
the milk protein beta-casein called Beta-Casomorphin-7(BCM-7),
which if it gets through the gut and into the blood of genetically
susceptible people can have a detrimental effect by exacerbating
underlying problems.(19)Bovine BCM-7 is not the only opioid that
can be produced in milk. BCM-7 and even more so BCM-5 that
in some situations can be formed from it, are by far the strongest.
Internal differences mean bovine BCM-7 is 10 xs more potent than
the theoretical human equivalent. (22, 23)There are also opioid
antagonists in milk that can to a larger extent negate the effect of
the weaker opioids. (World Guernsey Cattle Federation, 19, 24)
How is Beta-Casomorphin-7 (BCM-7) formed
The difference between the A1 and A2 beta caseins of just a
single amino acid sounds like a minor difference, but is quite
significant because the bond between histidine and its adjacent
amino acid in A1 beta casein is much weaker and much more
easily broken than the bonding of proline in A2 beta casein. (19)
Detailing this cause for concern with milk containing A1 betacasein is that the 67th amino acid switch from proline to histidine
readily allows a digestive enzyme to cut out a 7 amino acid
segment of the protein immediately adjacent to that histidine.
When proline is present in that location (as it is in A2 beta-casein),
that same segment is either not separated at all or the separation
occurs at a very low rate. The 7 amino acid segment that is
separated from A1 beta casein is BCM-7, is an exogenous opioid
that can bind opioid receptors expressed in digestive, immune
and neural tissue. (25)
Comparison between A1, A2 and human beta-casein structures
BCM-7 has Potential to Affect a Range of Tissues-Dr A J Clarke
Dr S Kukuljan
What about ingestion of other dairy products? There is a variety
of heat methods used in pasteurisation and dependent on this
they have the potential to break down and denature proteins. It is
unclear as the protein structure breaks down which peptides are
released and more BCM-7 may be released upon subsequent
digestion than occurs when using intermediate temperature
methods. When making ice cream A1 milk may be heated to
high temperature to help mixing with other ingredients and has
been known to cause reactions. Small amounts of BCM-7 may be
found in cheese but this varies from cheese to cheese and may
be negligible. It is unclear how much BCM-7 may be released
during digestion as beta-casein in two of Britain’s most popular
cheeses is still intact at 63% for cheddar and 69% for mozzarella.
Regarding intolerance the issue is further clouded by people who
can’t drink A1 milk but can tolerate A2 milk and can also tolerate
small amounts of cheese but this may be due to the low amount of
lactose contained in cheese. The cheese making process might
render BCM-7 inactive but if there were very small quantities
of BCM-7 this may not affect healthy individuals but may affect
individuals with leaky gut. (19)
Absorption of BCM-7
In healthy adults it should be difficult for BCM-7 as a large
molecule to get through the gut wall and into the bloodstream,
there is no simple answer as to the outcome because it does
depend on the age, health and genetic make-up of the individual.
Cleavage of BCM-7
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With people who do suffer from leaky gut syndrome, BCM-7 and
other peptides may pass easily into the bloodstream and BCM-7
may be detected in the urine.
New-born babies may be susceptible as they need to be able to
pass large molecules through the gut wall i.e. to absorb colostrum
from their mother’s milk. Other groups of individuals who may be
susceptible are undiagnosed coeliac sufferers and individuals on
the autistic spectrum.
Evidence has been published that once BCM-7 has entered the
bloodstream it crosses the blood brain barrier and attaches there
to opioid receptors. (19, 26, 27, 28) Rodent studies have shown
that intracarotid injection with BCMs results in their accumulation
in blood-brain barrier-free and blood-brain barrier-protected areas.
(29)
I am going to summarise some of the main findings for various
conditions (see below) but there is a great deal of research and
evidence for the various pathologies and complex interactions
involving BCM-7. If you want to explore this in far more depth I
would recommend reading Devil in the Milk by Professor Keith
Woodford who looks at the illness, health and politics of A1 and
A2 milk. I would also recommend the website betacasein.org as a
good source of the research that has been carried out.
A Short Summary of Research
Digestive system
Bovine BCM-7 when released in the gut can affect the digestive
system and like other opioids can reduce the rate of passage
through the gut, causing constipation. (30, 31, 32, 33)
BCMs are mu-type opioid agonists and mu-receptor activation
is known to produce constipation. Zogbhi et al. (2006) examined
the in vitro effects of BCM-7 on human colon goblet-like cells
(HT29-MTX cells) and found that BCM-7 increased mRNA levels
of the mucin MUC5AC (219% after 24 hours of stimulation) and
the secretion of this mucin (169% of controls), dependent on muopioid receptor activation. Notably, mucous owes its hydrophilic
and viscoelastic properties to secretory mucins and MUC5AC is
also one of the two main mucins produced in the respiratory tract.
However, more research is needed to confirm BCM-mediated
intestinal motility effects in humans. (34-42) This might explain why
babies fed on formula milk rather than human milk are susceptible
to constipation. BCM-7 may also increase problems of lactose
intolerance as transit is slow with more fermentation occurring.
BCM-7 has been shown to increase inflammatory activity of
colonic immune cells and mucous production and thickening in
the rat small intestine. (43)
Researchers are now looking at the potential role BCM-7 may
have in Ulcerative Colitis, Crohns disease and other autoimmune
conditions and neurodegenerative conditions such as Multiple
Sclerosis and Parkinsons Disease. (19)
Infants
Human BCM-7 has been identified in human breast milk and
other human beta-casomorphins have been found in the blood
of pregnant and lactating women but not in men or non-pregnant
women, leading researchers to suggest that BCM-type mammary
products have physiological significance during pregnancy or
after parturition. (44, 45)
Elevated circulating human BCM-7 has been correlated with
beneficial developmental outcomes in breast fed infants, while
the opposite has been observed in their bovine milk containing
formula-fed counterparts with similarly elevated levels of bovine
BCM-7.(46) In addition, Jarmolowska et al. (2007) have further
shown that human BCM-7 concentration in colostrum (produced in
the first days of lactation) is 7 times higher than in human milk at 2
months of age, which suggests that a human infant’s requirement
for human BCM-7 is significantly lower at 2 months compared
with the first few days of life and that exposure to the more potent
bovine BCM-7 at around 2 months of age may be undesirable.
This work is consistent with earlier animal studies that have shown
that BCM-7 induces apnoea and irregular breathing in new-born
rabbits and adult rats that is analogous to sudden infant death
syndrome (SIDS) in humans. (47). But evidence has shown that
there are possibly many factors that can contribute to SIDS.
The latest research by a Polish research group further confirms the
presence of BCM-7 in the blood of babies, and that BCM-7 may be
a risk factor for apnoea (expressed as “apparent life threatening
events”), compared to a group of healthy infants. In the at-risk
apnoea infants, blood BCM-7 levels were on average three times
higher compared with the normal infants. (48)
Recent Polish research also identifies that at-risk infants have
low blood levels of DPP-IV, the enzyme that metabolises BCM7. In the at-risk babies, DPP-IV levels were 58% of those found
in healthy babies. Furthermore, in the normal children, BCM-7
was positively associated with DPP-IV levels. This relationship is
absent in the at-risk babies. The statistics associated with these
findings are strong (i.e. p<0.001 in each case). Not surprisingly,
the Polish researchers also found that BCM-7 levels were higher in
babies fed formula which was high in casein, compared to those
fed formula that was low in casein. However, it could be regarded
as surprising that bovine BCM-7 was also found in the blood of
1-4 month babies who were breast fed. The suggestion by the
researchers is that bovine BCM-7 from milk ingested by lactating
mothers can be transferred directly to the mothers’ milk. (49)
Heart Disease
Evidence regarding the connection between A1 and Heart
Disease includes Epidemiology, animal studies and infant
observational studies.
Professor Eliot’s work on the relationship between A1 milk and
Type I diabetes (88) (see Diabetes section) was reviewed by
Corann McLachlan, who then identified similar relationships
across countries between intake of A1 milk and incidence of heart
disease. Countries such as Iceland, where the milk is mainly A2
have much lower heart disease levels than countries of similar
ethnicity such as Finland where there are high intakes of A1 milk.
In some countries such as Germany where there are considerable
breed differences between regions (and hence different levels of
A1 beta casein) there are corresponding regional differences in
heart disease. In Japan, where A1 consumption is very low, heart
disease is also very low despite Japanese being heavy smokers.
(Smoking is usually considered a big risk factor). The Masai in
Kenya drink very high levels of milk but have very low levels of
heart disease; all of their milk is A2. (19)
Major differences in CHD incidence between countries of the
developed world show strong correlations between A1 betacasein intake and the incidence of heart disease. The reported
correlation coefficient (r) for the relationship between A1 betacasein consumption and heart disease is 0.76 or higher which
page 5
is significant. Neither total milk protein nor A2 beta-casein intake
have been linked to heart disease incidence. (50, 51)
A1 versus A2 beta-casein intake in participant background diets.
Oxidation of ‘LDL’ cholesterol is fundamental to the process
whereby fatty plaques are laid down in artery walls, leading to
heart disease. The effects of BCM-7 on heart disease may not
just be from the oxidant activity but also from an opioid-related
mechanism related to immune function. (19)
Even though strong and significant relationships have been shown
linking A1 beta-casein with heart disease; currently there is no
proof that the statistical correlations prove ‘causation’ with absolute
certainty, there have been no definitive human trials which could
be difficult as heart disease takes so long to develop and it is not
known whether there may be involvement of other factors.
It is interesting though that the incidence of heart disease in
Guernsey where Guernsey cows yield A2 milk is lower than the
UK. Coincidence?
Autism and Schizophrenia
1990 A1 beta-casein supply (A1/capita) and 1995 ischemic heart
disease, 20 countries (r=0.76, 95% CI: 0.48-0.90). Dotted lines are
the 95% confidence limits of the regression line (51)
Other research in human infants conducted by a Czechoslovakia
research group supports the idea that bovine BCM-7 may be an
early contributor to heart disease later in life. Steinerova et al.
(2004) have shown that formula fed infants (beta-casein containing
formula) have elevated serum levels of antibodies to oxLDL
relative to breast fed babies. Given that BCM-7 has been shown
to oxidise LDL in vitro, it is possible that the differences in oxidised
LDL between the formula and breast fed babies are mediated via
A1 beta-casein derived BCM-7. (52, 53)
Professor Julie Campbell from the University of Queensland is a
specialist in vascular heart disease. Her research team fed A1
milk and A2 milk to rabbits. The rabbits fed A1 milk had higher
cholesterol levels than the rabbits fed A2 milk. Much more
importantly, the A1 rabbits developed lesions and thickening on
the artery walls. Professor Campbell’s work was published in 2003
in the international medical journal ‘Atherosclerosis’ (Tailford et al.
2003). The conclusions were that A1 milk is ‘atherogenic’ (causes
heart disease) and that A2 milk may have a protective effect.
Particularly important (and worrying) is that the lesions in the
arteries of rabbits fed A1 milk were very similar to what is known
as ‘juvenile fatty streaks’ in humans. This arterial damage was
paralleled by a shift in the LDL: HDL ratio. (54)
Trials in adult humans have investigated the differential effects of
A1 versus A2 beta-casein consumption on parameters of heart
disease (55, 56). Both trials were unable to detect any differential
effects in serum cholesterol levels and clinical markers of heart
disease risk over 6 to 12 weeks. However, this is not unexpected
given the investigated parameters are not linked directly to known
BCM-7 activities, namely the oxidation of LDL. In addition, these
trials had small participant numbers, and while the incidence of
systemic exposure to bovine BCM-7 remains unknown, it is likely to
be low and low incidence conditions require large study numbers
to detect differences between two treatments. Furthermore, neither
of these trials confirmed the production and absorption of BCM-7
in the serum of volunteers, neither included washout periods prior
to the intervention arms and both failed to control adequately for
‘The Opioid Excess Theory’ describes the hypothesis that
exogenous opioids from the incomplete digestion of gluten and
casein proteins can be absorbed across the gut into circulation
and become biologically active through opioid receptor binding
and thereafter aggravate symptoms in those with neurological
conditions. (56, 57, 58) Alternatively, exogenous opioids may
affect the serotoninergic system and play a pathogenic role
in the development of autism (59, 60) resulting from adverse
gastrointestinal pathology and abnormalities in exorphin peptide
chemistry and metabolism. To this end, gastrointestinal symptoms
are reportedly common in children with autism (61-65) and in
adults with other psychiatric conditions such as schizophrenia.
(66, 67) Recent research in human infants highlights that there
are indeed differences in the rate of exorphin peptide clearance
between babies. (68, 69) Currently, the cause or causes of autism
spectrum disorders remain unknown, although genetic factors play
a key role. (70, 71,)
However, new evidence from a study of 192 pairs of monozygotic
and dizygotic twin’s highlights that environmental triggers may also
play a causative role in susceptible individuals. More specifically,
Hallmayer et al. (2011) found that shared environmental factors
accounted for 58% of ASD cases, whereas genetic factors could
explain only 38%. (72) Early exposure to environmental modifiers
may also contribute to variable expression of autism-related traits
in some individuals.
Bovine BCM-7 has been detected in the blood of human infants by
two different research groups using immunoassay methods, and
bovine BCM-7 has also been detected in the urine of children with
autism spectrum disorders using mass spectrometry analysis. (59)
Note: BCM-7 enters many areas of the brain linked to autism
whereas similar peptides from gluten cannot access most of these
areas. (19)
Gluten & Casein Free (GFCF) diets have been reported to improve
the symptoms of autism. (73) Effectiveness of the diet is avoidance
of exposure to food derived opioids (e.g.: BCM-7). Investigations
by teams led by Cade, Reichelt and Shattock in three different
countries confirm this.
Systemic oxidative stress and brain neuro-inflammation have been
described in autistic subjects, in association with significantly
lower plasma levels of the antioxidant glutathione (GSH). Trivedi
et al (2012) focused on studying the effects of opioid and food
page 6
derived opioid peptides with implications in autism spectrum
disorders (ASD) and drug addiction, investigating the epigenetic
changes and consequent gene expression changes under the
influence of redox status of neurons. They tested the hypothesis
that casein and gluten-derived peptides modulate cysteine uptake
by EAAT in cultured human neuronal and intestinal epithelial cells
via their effect on opiate receptors, and this action alters cysteine
availability for GSH production. The levels of glutathione regulate
the levels of S-adenosyl methionine (SAM) via the activity of
methionine synthase enzyme. SAM is a methyl donor for more than
200 methylation reactions including DNA and Histone methylation.
DNA methylation analysis indicated global epigenetic changes
induced by these peptides. The findings provided mechanistic
support for the association of GI inflammation with coeliac disease
and autism spectrum disorders and provided a plausible rationale
for a GFCF dietary intervention in treating these diseases.
The current study also provides a rationale for the preferential use
of human breast milk over bovine milk/milk formula for infants.
Their acute inhibition of cysteine uptake was similar to the effect
of morphine, but less extensive, and was completely blocked
by the opiate antagonist naltrexone, confirming opiate receptor
involvement. The bovine form of BCM-7 was more potent as
compared to the human form in inhibiting cysteine uptake and
altering thiol metabolite levels.
High levels of antibodies to beta-casein were found in >90%
children with autism and schizophrenia. Within 3 months, GlutenCasein free diets resulted in improvements in most categories of
the ‘behaviours’ in 81% of autistic children. (74, 75)
Bovine BCMs were about 10-fold more potent than human BCMs
and that 10-fold the dose of naloxone (an opioid antagonist)
was needed to inhibit the effect of bovine BCMs compared with
morphine. (76)
In experimental rats that were given an intranigral injection
with bovine BCM-7 and other BCMs they exhibited behavioural
tendencies similar to those of autism and schizophrenia which
were reversed with administration of a morphine antagonist. The
contralateral rotational behaviour increased in a dose-dependent
manner (intensity and duration), depending on the location of the
injection. (76, 77, 78, 79)
What needs to be established is whether opioids from beta casein
cause the syndromes of autism and schizophrenia or whether they
are causing or exacerbating the symptoms.
Diabetes
The initial link between A1 milk and Type 1 (childhood) diabetes
was made by Professor Bob Elliot at Auckland University, who
noted that Samoan children living in Samoa did not get diabetes
but that Samoan children in New Zealand did. Subsequently he and
colleagues demonstrated very strong between-country correlations
between intake of A1 milk and level of Type 1 diabetes.
Although genetic factors play a key role in development of Type 1
diabetes mellitus (DM-1), environmental and nutritional factors are
believed to be modifiers, as only ~5% or fewer subjects with genetic
susceptibility to DM-1 develop the clinical disease. (80-82)
A recent double-blind, randomised trial of the first nutritional
primary prevention study for DM-1 (TRIGR-Trial to Reduce IDDI in
Genetically at Risk-) has found that autoantibody development can
be delayed by giving hydrolysed formula (rather than regular cow’s-
milk formula) during the first 6–8 months in ‘at-risk’ infants. (83)
Several studies report that breast feeding is protective. (84-88)
A range of studies in developed countries have found that most of
the between-country differences in the incidence of DM-1 can be
explained by intake levels of the specific milk protein variant A1
beta-casein, and that this is a much stronger explanatory factor
than total milk protein consumption per se. (51, 89, 90, 91)
Correlation of A1 beta-casein per capita (excluding cheese) in
grams/day and new cases of DM-1 in 0 to 14-year olds between
1990-94 (r=0.92, 95% CI: 0.72-0.97) (p<0.0001). Dotted lines are
the 95% confidence limits of the regression line [adapted from
reference. All are higher-income countries with European type
lifestyles (51)
There is also evidence from Finland that amongst genetically
susceptible children (i.e. those who have an older sibling with Type
1 diabetes) there is a relationship between the amount of cow’s
milk that is drunk and the chance of getting diabetes. (19)
It is hypothesised that BCM-7’s opioid characteristics might
contribute to the impairment of the development of gut-associated
immune tolerance in ‘at risk’ individuals and as such “it might
act as an adjuvant in the autoimmune reaction involved in the
destruction of beta-cells in prediabetic subjects”. (24, 92, 93, 94)
This is supported by the attenuation of A1 beta-casein’s
apparent diabetogenicity following the administration of the
opioid antagonist naloxone. (95) Secondly the potential antigenic
determination characteristic of beta-casein may lead to the
autoimmune destruction of pancreatic beta-cells. (96, 97) There
may be molecular mimicry between a sequence of the beta-casein
protein and an epitope of the GLUT 2 transporter which may give
rise to autoantibodies capable of targeting pancreatic beta-cells. (98)
What has been established is the following:
Digestion of A1 but not A2 beta casein yields BCM-7
BCM-7 has the potential to bind opioid receptors expressed
in cells throughout the body, including digestive, immune and
neurological
BCM-7 has been observed to be produced, absorbed and
circulated in some humans, particularly infants
Emerging evidence links BCM-7 to adverse effects on infant
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development and health, and intolerance type reactions in adults
The proportion and type of individuals susceptible to BCM-7
exposure needs to be determined
A1 has been linked by numerous epidemiological studies and
animal trials with an increased risk in the incidence of heart
disease and type 1 diabetes
Infants have a range of abilities to break down BCM-7 (and
thereby prevent negative BCM-7 effects)
Consumption of milk containing only the A2 type of beta casein at
the exclusion of A1 avoids exposure and risk of adverse reaction
associated with the A1 or derived fragment BCM-7
Important note: You may have noticed the use of Casein Tryptic
Hydrolysate (CTH) by some supplement companies. To avoid
confusion-CTH is as1-casein (alphas1-casein) hydrolysed with
trypsin which yields a-casozepine, a decapeptide, a polypeptide
that consists of a chain of ten amino acids which acts as an
anticonvulsant and anxiolytic molecule with benzodiazepine-like
activity. When peptides isolated from CTH were examined for
their affinity for the -amino-butyric acid (GABA) type A receptor,
only one peptide, named a-casozepine, corresponding to the
91–100 fragment from bovine as1-casein, expressed affinity for
GABAA receptor. The GABAA receptor complex plays a major
role in the pharmacology, neurochemistry and physiopathology of
stress and anxiety. The physicochemical characteristics and the
pharmacological action of a-casozepine leads to the hypothesis
Summary
Science relating to beta-casein variants has been the focus
of two regulatory body reviews: by the New Zealand Food
Safety Authority (NZFSA) in 2004 (100), which focused
primarily on epidemiological analyses and feeding trials and
by the European Food Safety Authority (EFSA) in 2009 (51),
which examined potential links between BCM-7 and noncommunicable diseases. The EFSA report acknowledged that
BCM-7 is an opioid that could affect a range of cells and tissue,
including the digestive and immune systems, but that further
research is needed to determine a causal link between A1
beta-casein consumption and disease. However, subsequent
to the EFSA report two independent research groups have
detected bovine BCM-7 in the circulation of formula-fed infants
(containing A1 beta-casein) (68, 69), evidence that was not
considered by EFSA.
The reality is that the consumption of milk is a ‘way of life’ for
British households and there is no doubt that it is very nutritious
even though there are a loss of certain enzymes and beneficial
bacteria during pasteurisation, there has been much debate
about the pro’s and con’s for pasteurisation versus raw milk but
there have been some interesting benefits shown regarding
ingestion of dairy which is another story. We also live in northern
climes; many diets lack a wide variety and particularly leafy
green vegetables and dairy foods are a cheap source of food
for those on low incomes. Dairy from grass fed cows is also
the primary source of the natural trans-fat conjugated linoleic
acid (CLA), which may have anti-cancer and other beneficial
properties. Yes there are issues affecting over-consumption of
milk with the inclusion of growth factor, saturated fat and protein,
for the huge percentage of people who are lactase persistent in
the UK my thoughts are that the emerging evidence regarding
that this peptide might play a role, as an external ligand, in the
regulation of the nervous system of the mammalian new-born and
might be involved in the traditional calming properties attributed
to milk. CTH has not been shown to be problematic in lactose
intolerance or milk allergy sufferers. (99)
From the Dairy Council
Farmers do not fill their cows with growth hormones (this is
illegal), and only use antibiotics to treat cows suffering from
mastitis. The milk from cows treated in this way is not collected
for public consumption. Regular testing of all milk supplies by
the government, confirms that no antibiotic residues are present
in retail milk. Interestingly raw milk doesn’t have the same testing
stipulations for antibiotics as pasteurised milk. Not all raw milk is
tested.
India
After an international study highlighted the link between a protein
in the milk produced by western breed of cows and a range of
serious illnesses, the Indian Council of Medical Research is now
conducting a systematic study on this aspect. Entire world dairy
authorities have taken cognizance of the research first made
public by New Zealand researchers in 2006. (The New Indian
Express April 2013)
BCM-7 in A1 milk cannot be ignored and that where we, as
nutritional therapists, advise clients on elimination, reduction
or use of alternative sources of milk for our clients that the
alternative of A2 milk is another important consideration.
Notably, Professor Boyd Swinburn stated in his Report to the
New Zealand Food Safety Authority entitled ‘Beta casein A1
and A2 in milk and human health’ (2004) that:
“……The appropriate government agencies have several
important responsibilities in this matter: to support further
research in the area (especially clinical research); to clearly
communicate the state of knowledge and judged risks to the
public, and; to take specific actions to promote and protect the
health of the public, where appropriate”. and
“As a matter of individual choice, people may wish to reduce or
remove A1 beta-casein from their diet (or their children’s diet)
as a precautionary measure. This may be particularly relevant
for those individuals who have or are at risk of the diseases
mentioned (type 1 diabetes, coronary heart disease, autism
and schizophrenia). However, they should do so knowing that
there is substantial uncertainty about the benefits of such an
approach”.
In conclusion, while further research is needed to establish a
cause-effect relationship between exposure to BCM-7 and the
non-communicable conditions, there is evidence to suggest that
BCM-7 is linked to various unwanted physiological effects in
susceptible individuals.
References
http://www.bant.org.uk/bant/pdf/BANTnews/articles/WHY_A2_MILK_HAS_ENTERED_BRITAIN_
REFERENCES_BANT_NEWS_JUL2013_ISSUE_50.pdf
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