Journal of Nutritional & Environmental Medicine (2002) 12(3), 187–196
A Multi-country Ecological Study of Dietary Risk and
Risk-reduction Factors for Prostate Cancer
WILLIAM B. GRANT PHD
12 Sir Francis Wyatt Place, Newport News, VA 23606–3660, USA
Purpose: To investigate dietary factors for prostate cancer mortality (PrCM).
Design: An ecological analysis was performed using age-strati ed multi-country PrCM
rates and dietary supply data.
Materials and Methods: The PrCM rate data were obtained from the World Health
Organization. The dietary supply data were obtained from the Food and Agriculture
Organization of the United Nations. Multivariate regression analyses were performed with
groupings of countries based on geopolitical associations. A time lag between diet and
mortality of up to 19 years was used.
Results: The consumption of vegetable protein was found to be an important risk-reduction
factor for PrCM as one factor in a multivariate regression analysis. In addition, a high
consumption of vegetable products as a fraction of total energy was inversely correlated
with PrCM. In contrast, a high consumption of animal products as a fraction of total
energy, animal fat, the non-fat portion of milk, and added sugar, was found to be a risk
factor for PrCM.
Conclusions: This study supports previous ndings for milk and calcium, animal fat,
animal products, vegetables and vegetable products, and extends the literature with the
nding that added sugar is an important risk factor. The high inverse correlation between
PrCM and the consumption of vegetable protein is probably due to the high iso avonoids
and lignan content in foods such as pulses (beans) and whole grains. Animal products,
which induce the expression of insulin-like growth factor-1, and dietary sweeteners, which
also increase insulin production, may enhance prostate cancer development and subsequent
mortality. It is hoped that these results will be tested in case-control and cohort studies.
Keywords: animal products , calcium, diet, IGF-1, insul
Journal of Nutritional & Environmental Medicine (2002) 12(3), 145–151
Is Milk Best for Infants and Toddlers?
R. J. HARRIS MD FRCP FRCPCH DCH
Academic Department of Child Health, Queen Mary School of Medicine and
Dentistry, The Royal London Hospital, London E1 1BB, UK
Tower Hamlets is a deprived inner city area with a high level of ethnic minority groups,
and has many nutritional problems. Iron de ciency and rickets are among the commonest
seen. One of the main causes remains late or inappropriate weaning, as indicated in
research carried out 15 years ago in Tower Hamlets and, as a result, an undue reliance
on unmodi ed cow’s milk, usually given in a bottle, for the rst 2–3 years of life. Late
weaning results in dif culties with chewing and swallowing, and as a direct consequence
speech and language therapy is often needed to help overcome the problem. The danger of
drinking excessive amounts of unmodi ed cow’s milk is discussed, together with the
controversies surrounding the possible long-term consequences of iron de ciency. Rickets
continues to occur, and much of this stems from ignorance on the part of both parents and
health professionals about current Department of Health guidelines for vitamin supplementation,
and a prolonged exposure to unmodi ed cow’s milk. Measures to combat the
problems are discussed.
Keywords: excess milk drinking, late weaning, iron de ciency, rickets.
Polymorphism of bovine beta-casein and its potential
effect on human health
Stanis³aw Kamiñski1, Anna Cieoeliñska1, El¿bieta Kostyra2
1Department of Animal Genetics, University of Warmia and Mazury, Olsztyn, Poland
2Department of Biochemistry, University of Warmia and Mazury, Olsztyn, Poland
Abstract. Proteins in bovine milk are a common source of bioactive peptides. The peptides are released by the digestion of caseins and whey proteins. In vitro the bioactive peptide beta-casomorphin 7 (BCM-7) is yielded by the
successive gastrointestinal proteolytic digestion of bovine beta-casein variants A1 and B, but this was not seen in
variant A2. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk.
Variants A1 and A2 of beta-casein are common among many dairy cattle breeds. A1 is the most frequent in Holstein-
Friesian (0.310–0.660), Ayrshire (0.432–0.720) and Red (0.710) cattle. In contrast, a high frequency of A2
is observed in Guernsey (0.880–0.970) and Jersey (0.490–0.721) cattle. BCM-7 may play a role in the aetiology
of human diseases. Epidemiological evidence from New Zealand claims that consumption of beta-casein A1 is
associated with higher national mortality rates from ischaemic heart disease. It seems that the populations that
consume milk containing high levels of beta-casein A2 have a lower incidence of cardiovascular disease and type
1 diabetes. BCM-7 has also been suggested as a possible cause of sudden infant death syndrome. In addition, neurological
disorders, such as autism and schizophrenia, seem to be associated with milk consumption and a higher
level of BCM-7. Therefore, careful attention should be paid to that protein polymorphism, and deeper research is
needed to verify the range and nature of its interactions with the human gastrointestinal tract and whole organism.
Heart Disease, Diabetes, Gut Immune Suppression and
C. N. S. McLACHLAN and A. J. CLARKE
A2 Corporation, 58 College Hill, Ponsonby, Auckland, New Zealand
The consumption of cow’s milk containing the b -casein variant A1 has been linked with type
1 diabetes (insulin-dependent diabetes mellitus; IDDM) in both NOD mice and BB rats.
Supporting this, epidemiological studies that include both inter- and intra-country data
yield a strong association of this protein’s presence in milk with the incidence of IDDM.
A stronger association can be observed when correlating b -casein A1 consumption with
ischaemic heart disease (IHD) mortality, with a signi cant regression correlation
coef cient (r2 5 0.86). This suggests that the rate of b -casein A1 consumption, excluding
that contained in cheese, is a more accurate predictor of heart disease between and within
countries than that reported for traditional risk factors. It is often assumed that the
response rates of illness to dietary inputs are dose speci c. Should this not be the case, as
animal studies of both IHD and IDDM indicate, then positive, null or negative outcomes
will be achieved depending on the approach of the sample to a genetically at-risk group,
or to the general population. In diseases such as those noted above where immune
dysfunction or gut immune suppression appear to play a major role, failure to compare
immune response may skew the data analysis and hide causality. Thus, the failure to detect
strong associations between consumption of speci c dietary components and diseases in
studies of individuals, as is the case with both IHD and IDDM in the population at large,
may re ect a non-linear relationship between dietary components and disease.
Keywords: casein, casomorphin , IDDM, IHD, diabetes , heart disease, epidemiology , immune.
β-casein A1, ischaemic heart disease
mortality, and other illnesses
C. N. S. McLachlan
A2 Corporation Ltd, Devonport, Auckland, New Zealand
Summary The risk factors identified with cardiovascular disease studied in the WHO MONICA project have been
shown to have a limited relationship with the coronary heart disease mortality rates between centres, and in mirroring
the historical rise and decline in deaths from the disease. Here we show that correlation of the calculated consumption
of the milk protein, β-casein A1 (excluding milk protein in cheese) against ischaemic heart disease (IHD) mortality has
a r2 = 0.86. In the states of the former West Germany, where the breed composition of regional cattle herds has
remained virtually constant since the 1950s, IHD mortality by state correlates with the estimated consumption of β-
casein A1. Information on other recognized dietary risk factors does not indicate any significant regional difference.
Similarly, the populations of Toulouse in France and Belfast in Northern Ireland have almost identical collective
‘traditional’ risk factors for heart disease, yet the respective mortality rates vary more than threefold. People from
Northern Ireland are estimated to consume 3.23 times more β-casein A1, excluding cheese, than the French. The
remarkable agreement between mortality and the consumption of this allele suggests that this factor is worthy of serious consideration as a potential source of cardiovascular disease when taken in conjunction with regional variations in the traditional risk factors. β-casein A1 consumption also correlates strongly with type 1 diabetes incidence in 0–14-year-olds, suggesting that IHD and diabetes may share at least one causative risk factor. © 2001 Harcourt
Health Implications of Milk Containing
β-Casein with the A2 Genetic Variant
Stacey J. Bell, D.Sc., R.D.
Research and Development, Ideasphere, Inc., 56 Amherst Road, Belmont, MA 02478
Gregory T. Grochoski
Chief Science Officer, Ideasphere, Inc., 3133 Orchard Vista Drive, SE, Grand Rapids, MI 49546
Andrew J. Clarke
Chief Executive, A2 Corporation Limited, 58 College Hill, Ponsonby, Auckland 1001, New Zealand
Milk from dairy cows has long provided a high quality source of protein and selected micronutrients such as calcium to most populations. Recently, a relationship between disease risk and consumption of a specific bovine β-casein fraction either A1 or A2 genetic variants has been identified. Populations, which consume milk containing high levels of β-casein A2 variant,
have a lower incidence of cardiovascular disease and type 1 diabetes. Furthermore, consumption of milk with the A2 variant
may be associated with less severe symptoms of autism and schizophrenia. The mechanism of action focuses on β-casein
A1 and related forms preferentially that are able to produce a bioactive opioid peptide, β-casomorphin-7 (β-CM-7) during
digestion. Infants may absorb β-CM-7 due to an immature gastrointestinal tract. Adults, on the other hand, appear to reap
the biological activity locally on the intestinal brush boarder. β-CM-7 can potentially affect numerous opioid receptors in the
nervous, endocrine, and immune systems. Whether there is a definite health benefit to milk containing the A2 genetic variant
is unknown and requires further investigation.
Keywords bovine milk, β-casein, β-casomorphin