Raw Milk Pros: Peer Review by Food Poisoning Attorney 6-6-08

I thought it might be helpful to bring a bit of rationality to the "raw milk debate."  Here is a summary of the findings of a review of peer-reviewed literature on the topic of the consumption of raw milk at least the pros:

•    There is substantial epidemiological evidence from studies in Europe that consumption of raw milk products in childhood has a “protective” effect for some allergic conditions (e.g., asthma, hay fever, eczema); other factors associated with living on a farm such as contact with animals and barns showed a similar effect in these studies.  Plausible explanations for these observations exist including the “hygiene hypothesis” and modulation of the immune system early in life.  At the same time, no author recommends raw milk as a preventive measure for allergies at this time because of the potential hazards due to foodborne pathogens such as EHEC and Salmonella  known to occur in raw milk.  The body of literature suggests that further studies are needed to identify the specific factors in raw milk (and other farm exposures) that lead to a protective effect for allergic conditions.

•    No articles could be found substantiating an increased risk of autism due to pasteurized milk or a protective effect from raw milk consumption, respectively.

•    Probiotics are increasingly recognized in the literature as an effective approach for managing some gastrointestinal and allergic conditions.  Specific criteria that define “probiotics” have been published and raw milk does not fit this definition.  No articles suggested that raw milk should be used as a probiotic.

•    Raw milk and cheeses may contain microflora (“beneficial bacteria”) that produce metabolites and other antibacterial compounds that may be toxic to foodborne pathogens.   The presence and quantity of these specific compounds, the bacterial species involved, and the log reduction for different foodborne pathogens from these bacteria/compounds has not been defined in raw milk; therefore, these properties cannot be considered a substitution for a “kill step.”

•    Although studies have shown modest reductions in some vitamins and other nutrients after pasteurization of milk, these changes are insignificant according to a review by Potter et al (1984), human nutrition studies have shown no advantage of raw over pasteurized milk.  A review of more recent literature did not reveal any changes in this position.

•    No references could be found to support some benefits reported by raw milk advocates such as promotion of tooth development/reduction of dental caries; enhanced fertility; or existence of an undefined substance to protect against arthritis (“anti-stiffness” factor)

Detailed Literature Review of the “Pros” of Raw Milk Consumption:

I.     Protection against allergic conditions (e.g., asthma, hay fever, eczema)

a.    Raw milk advocates frequently cite recent epidemiological studies that have demonstrated a statistically significant inverse relationship between “farm” or “unpasteurized” milk and allergic conditions in children.  A number of studies, mostly among children in various European countries, provide convincing evidence that a protective effect is associated with unpasteurized milk consumption during childhood.  However, the underlying mechanism for this observation remains unclear and the overwhelming consensus among authors of these papers is that because of the potential health hazards from foodborne pathogens (EHEC, Salmonella, etc.)  consumption of raw farm milk cannot be recommended as a preventive measure  for allergic conditions.

i.    Historical perspective:  The “Hygiene Hypothesis”

1.    The “hygiene hypothesis” is an accepted phenomenon that states children without (or with reduced) exposure to infectious agents (especially parasites) and other microorganisms are more susceptible to developing allergic disease.
2.    In the last decade, researchers documented an association between children from “farming environments” and protection against the development of allergies.  A couple papers as examples:

Kilpelainen, M., E. O. Terho, H. Helenius, and M. Koskenvuo. 2000. Farm environment in childhood prevents the development of allergies. Clin Exp Allergy 30:201-8.

Riedler, J., W. Eder, G. Oberfeld, and M. Schreuer. 2000. Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin Exp Allergy 30:194-200.

ii.    The next step in understanding the statistically significant association between children living in farm environments and reduced allergies involved dissecting out the specific factors that might be involved using epidemiological studies (conducted mostly in Europe).  During these studies, raw milk was repeatedly identified as an independent “protective” factor for various allergic conditions.  Raw milk was not the only independent factor found to be significant for rural children– others included “barn exposure” and “animal contact,” for example.  Some of the studies are contradictory (see below) and there were inconsistencies regarding which type of allergic conditions were influenced by raw milk exposure (e.g., asthma, atopy, excema).  Below are some of the articles most frequently cited by advocates of raw milk consumption as “evidence” to support using raw milk as a “treatment” or “preventive measure” for allergies in children.  Highlights from the abstracts and text are in bullets.

Perkin, M. R. 2007. Unpasteurized milk: health or hazard? Clin Exp Allergy 37:627-30.

•    This is an editorial in the same issue with the Waser article below
•    Reviews epidemiological evidence of the protective effect of raw milk for allergic disorders in children
•    He concludes that the Waser paper “adds to the weight of evidence that a protective effect is associated with unpasteurized milk consumption….The key issue now is to determine what underlies this protective effect and whether it is possible to separate the protective effect from the hazardous [pathogens] substances.”

Waser, M., K. B. Michels, C. Bieli, H. Floistrup, G. Pershagen, E. von Mutius, M. Ege, J. Riedler, D. Schram-Bijkerk, B. Brunekreef, M. van Hage, R. Lauener, and C. Braun-Fahrlander. 2007. Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Clin Exp Allergy 37:661-70.

•    NOTE:  a major limitation of this study – raw milk was not distinguished from boiled “farm milk”
•    Study enrolled 14,893 children aged 5-13 from 5 European countries
•    “A strong and consistent inverse association was observed for the prevalence of asthma, wheeze, rhino conjunctivitis, and pollen, in children who consumed farm milk since their first year of life.”  [Odds ratios/CIs are in the paper].
•    No association with eczema (versus other studies showing an association)
•    “At present, we can only speculate about the components of farm milk responsible for the observed protective effect.”
•    “The underlying mechanism of the farm milk effect is not known.”
•    “In conclusion…Dietary interventions are an attractive means for primary prevention.  However, raw milk may contain pathogens such as salmonella or EHEC, and its consumption may therefore imply serious health risks.  A deepened understanding of the relevant “protective” components of farm milk and a better insight into the biological mechanisms underlying the reported epidemiological observation are warranted as a basis for the development of a safe product for prevention.  At this stage, consumption of raw farm milk cannot be recommended as a preventive measure.”

Perkin, M. R., and D. P. Strachan. 2006. Which aspects of the farming lifestyle explain the inverse association with childhood allergy? J Allergy Clin Immunol 117:1374-81.

•    Cross sectional survey of 879 children in rural England
•    Raw milk was the exposure mediating the protective effect on skin prick test positivity (a measure of allergic disease)
•    Like others, they speculate that the “diverse milieu” of bacteria in raw milk may explain the association (“hygiene hypothesis), but say these associations do not confirm a causal relationship
•    They conclude with “However, it is important to mention that unpasteurized milk consumption is not hazard free, and milk-related outbreaks of Cryptosporidium species and Campylobacter species and E. coli O157 have all been described.  It is thus premature to recommend unpasteurized milk as a putative protective agent for allergic disease.

Riedler, J., C. Braun-Fahrlander, W. Eder, M. Schreuer, M. Waser, S. Maisch, D. Carr, R. Schierl, D. Nowak, and E. von Mutius. 2001. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129-33.

•    Cross sectional survey involving 2,618 parent of 6-13 yo children in rural areas of 3 European countries
•    Overall findings:  “long term and early life exposure to stables and farm milk induces a strong protective effect against development of asthma, hay fever, and atopic sensitization.
•    Speculate that farm milk contains more gram negative bacteria and lipopolysaccharide (LPS, endotoxin) than pasteurized milk, which may be a factor in the allergic effect
•    The authors do not comment on the pros or cons of raw milk consumption, per se

Wickens, K., J. M. Lane, P. Fitzharris, R. Siebers, G. Riley, J. Douwes, T. Smith, and J. Crane. 2002. Farm residence and exposures and the risk of allergic diseases in New Zealand children. Allergy 57:1171-9

•    Smaller epidemiological study (293 children) from New Zealand
•    Consumption of raw milk as part of the infant diet was associated with less allergic disease, especially eczema and allergic rhinitis; exposure to animals also significant
•    Speculate that exposure to bacteria in raw milk in early life may stimulate an immune response that protects against allergies
•    Supports the hygiene hypothesis
•    No recommendation to promote raw milk (pro or con)

Other articles

Barnes, M., P. Cullinan, P. Athanasaki, S. MacNeill, A. M. Hole, J. Harris, S. Kalogeraki, M. Chatzinikolaou, N. Drakonakis, V. Bibaki-Liakou, A. J. Newman Taylor, and I. Bibakis. 2001. Crete: does farming explain urban and rural differences in atopy? Clin Exp Allergy 31:1822-8.

•    They hypothesize that rates of atopy would be lower among the rural children compared with urban children because of contact with farm animals (“or perhaps raw milk”) in early childhood. The “hygiene hypothesis”
•    Regression analysis showed independent protective effects from raw milk consumption on atopy for children under 5 years
•    They also found a significant association with animal contact (independent of raw milk consumption)
•    The differences between rural/urban were not clear
•    No statement regarding raw milk consumption (pro or con)

Bieli, C., W. Eder, R. Frei, C. Braun-Fahrlander, W. Klimecki, M. Waser, J. Riedler, E. von Mutius, A. Scheynius, G. Pershagen, G. Doekes, R. Lauener, and F. D. Martinez. 2007. A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. J Allergy Clin Immunol 120:1308-15.

•    These authors explore the genetic mechanism that might explain the protective effect of raw milk consumption and asthma in children
•    They find a change in a specific gene (CD14)

Debarry, J., H. Garn, A. Hanuszkiewicz, N. Dickgreber, N. Blumer, E. von Mutius, A. Bufe, S. Gatermann, H. Renz, O. Holst, and H. Heine. 2007. Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties. J Allergy Clin Immunol 119:1514-21.

•    The authors show that 2 bacterial species from cowsheds were able to reduce allergic reactions in mice through alterations in the innate immune system.
•    They conclude that their findings “strongly support the hygiene hypothesis, which states that an environment rich in microbiologic structures, such as a farming environment, might protect against the development of allergies.

Ege, M. J., R. Frei, C. Bieli, D. Schram-Bijkerk, M. Waser, M. R. Benz, G. Weiss, F. Nyberg, M. van Hage, G. Pershagen, B. Brunekreef, J. Riedler, R. Lauener, C. Braun-Fahrlander, and E. von Mutius. 2007. Not all farming environments protect against the development of asthma and wheeze in children. J Allergy Clin Immunol 119:1140-7.

•    Epidemiological study involving 8,263 school age children from rural areas in 5 European countries
•    Statistically significant protective effect against asthma by several farm factors (odds ratios and CIs are in the text):  farm milk consumption; pig keeping; animal sheds

Hebeisen, D. F., F. Hoeflin, H. P. Reusch, E. Junker, and B. H. Lauterburg. 1993. Increased concentrations of omega-3 fatty acids in milk and platelet rich plasma of grass-fed cows. Int J Vitam Nutr Res 63:229-33.

•    They find higher omega 3 fatty acids in milk grass fed cattle
•    Black-Sharpe Dietary Fat Hypothesis suggests that omega 3 fatty acids may have a beneficial effect on allergies
•    They conclude, “milk from grass fed cows may be nutritionally superior to milk from cows eating conserved grass with regard to omega 3 FAs
•    Not stated here, but pasteurization should have no significant effect on FA composition (in other words, do not need to use ‘raw milk” for this possible benefit, but whole—full fat—milk may be a factor)

Radon, K., D. Windstetter, J. Eckart, H. Dressel, L. Leitritz, J. Reichert, M. Schmid, G. Praml, M. Schosser, E. von Mutius, and D. Nowak. 2004. Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects. Clin Exp Allergy 34:1178-83

•    Survey of 321 young adults from rural environments in Germany
•    No independent effect of raw milk and atopy
•    Combined protective effect of raw milk + barn animal exposure before age 7
•    No comment on use of raw milk (pro or con)

Remes, S. T., K. Iivanainen, H. Koskela, and J. Pekkanen. 2003. Which factors explain the lower prevalence of atopy amongst farmers' children? Clin Exp Allergy 33:427-34.

•    Finish study of 366 farmers and non farmers children
•    No association with raw milk and allergic disease
•    Less atrophy among fresh vegetable eaters
•    This study conflicts with other studies

Von Ehrenstein, O. S., E. Von Mutius, S. Illi, L. Baumann, O. Bohm, and R. von Kries. 2000. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 30:187-93

•    Study purpose:  to test the hypothesis that children living on a farm have lower prevalences of allergic disease
•    Cross sectional survey of children aged 10,163 (5-7 years)
•    Farmer’s children had significantly lower prevalences of hay fever, asthma, and wheeze than children not living in an agricultural environment; increasing exposure to livestock was significant
•    Consumption of whole but not skim milk was associated with decreased hay fever and asthma
o    Speculate that protective effect might be from foods rich in fatty acids
o    Suggest that raw milk may have a higher microbial load (especially Lactobacillus) than industrially processed skim milk

II.    Raw milk is protective against autism

Nothing in the literature was found to support this in the literature.  WAPF cites this article, which seems irrelevant.

Meisel, H. 2005. Biochemical properties of peptides encrypted in bovine milk proteins. Curr Med Chem 12:1905-19

III.    Raw milk is a probiotic

An entire issue of Clinical Infectious Diseases was dedicated to probiotics in 2008, but no mention of raw milk as a recommended source of probiotics could be found.  The article below is by one of the experts in the field and defines probiotics; raw milk does not meet this definition.

Clinical Infectious Disease Journal, February 2008
http://www.journals.uchicago.edu/toc/cid/2008/46/3

Sanders, M. E. 2008. Probiotics: definition, sources, selection, and uses. Clin Infect Dis 46 Suppl 2:S58-61; discussion S144-51.

•    The term "probiotic" should be used only for products that meet the scientific criteria for this term-namely, products that contain an adequate dose of live microbes that have been documented in target-host studies to confer a health benefit.
•    Probiotics must be identified to the level of strain, must be characterized for the specific health target, and must be formulated into products using strains and doses shown to be efficacious.
•    NOTE:  raw milk does not meet this definition

Another recent article concerning probiotics and milk

Ivory, K., S. J. Chambers, C. Pin, E. Prieto, J. L. Arques, and C. Nicoletti. 2008. Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis. Clin Exp Allergy.

•    Lactic acid bacteria are among the most important probiotic organisms
•    Probiotics are believed to reduce allergic symptoms by modulating the immune system
•    The authors provide a rationale for probiotic use by demonstrating 2 lactic acid bacterial species that modified the allergic response, specifically indicators of seasonal allergic rhinitis (SAR)
•    They suggest that “probiotics hold much promise as a functional food,” but nowhere is it suggested that “raw milk” would be a recommended food for this purpose
•    NOTE:  the experiment was carried out by inoculating the specific bacterial species into a milk drink (not explicitly stated, but no indication it was raw milk:  “all dairy milk drinks were supplied by…with HACCP certification for the safety…”

IV.    Raw milk contains “beneficial” bacteria.

There is evidence that there may be metabolites toxic to foodborne pathogens and antibacterial compounds that are produced by other bacterial species in raw milk.   These compounds may help the bacteria that produce them to survive and compete in the food environment.  Some of these properties are exploited by the food industry, but often to promote food quality, not foodborne pathogen control per se (at least not as the only method to control pathogens).  The presence of these compounds in raw milk has not been defined and thus should not be relied upon as a “kill step” for dangerous foodborne pathogens that may also be present in raw milk.

Representative examples from the literature

Doyle, M. P., and D. J. Roman. 1982. Prevalence and survival of Campylobacter jejuni in unpasteurized milk. Appl Environ Microbiol 44:1154-8.

•    This study compared the survival of 8 C. jejuni strains in sterile and raw milk
•    The survival time (number of days) of C. jejuni strains varied depending on the specific strain
•    Campylobacter survived longer in sterile milk than raw milk at refrigeration temperatures
o    The authors speculated that other microflora in raw milk may have produced toxic metabolites that inactivated the C. jejuni (for example, lactoperoxidase)
o    Although Campylobacter levels dropped off sooner in raw milk over the study period, there could still be enough surviving bacteria to represent an “infectious dose” (see Figure 2)
•    The authors conclude:  “our results indicate the presence and possible persistence of C. jejuni in raw grade A milk and reaffirm the need for pasteurization.”

V.    Raw milk has a higher nutritive value

a.    Historical perspective

i.    Raw milk advocates frequently cite older articles about pasteurization with nutritional claims that were never substantiated by later research/nutrition studies.  For example:

Hess AF.  Infantile scurvy:  its influence on growth.  The American Journal of Diseases of Children.  1916; 152-165.

Bell RW.  The effect of heat on the solubility of the calcium and phosphorus compounds in milk.  The Journal of Biological Chemistry.  1925;64(2):391-400.

Pottenger FM.  Effect of heat-processed foods and metabolized vitamin D milk on dentofacial structures of experimental animals.  Am J Orthod 1946;32:467-485.

•    In Pottenger article, raw milk advocates erroneously cited this article as having reported that disease occurred in cats fed pasteurized milk (see Potter et al, below).

b.    Current literature

i.    Potter et al wrote a review discussing the hazards and purported benefits of raw milk consumption for JAMA in 1984.  

Potter, M. E., A. F. Kaufmann, P. A. Blake, and R. A. Feldman. 1984. Unpasteurized milk. The hazards of a health fetish. Jama 252:2048-52.

In table 1, they summarize the argument against the purported nutritive benefits as follows:

Pasteurization causes insignificant decreases in thiamine, vitamin B12, and vitamin C content; no effect has ever been demonstrated on the bioavailability of other raw milk constituents with known nutritive value; human nutrition studies have shown no advantage of raw over pasteurized milk.

No current peer-reviewed literature directly supporting “a higher nutritive value” for raw milk was found.  One example of a questionable article that the raw milk advocates cite:

Rajakumar, K. 2001. Infantile scurvy: a historical perspective. Pediatrics 108:E76.

•    This article is confusing/misleading when compared with other descriptions of the emergence of scurvy (vitamin C) deficiency in infants at the end of the 19th century
•    The author repeatedly refers to “”the increased incidence of infantile scurvy during that period was attributed to the usage of heated milk and proprietary foods.”
•    From other readings, these “ready to eat” formulas became popular and replaced other vitamin C sources in the infant’s diet during this time period.  Since milk (raw or pasteurized) is not an important source of vitamin C, the most likely explanation for the epidemic was the removal of fruit and vegetable juices from the infant’s diet; adding these foods back into the diet resolved the problem.
•    This is not a “current day” issue with our diverse food including fruit and vegetable sources for infants.

VI.  Some older purported benefits that are not used as frequently by raw milk advocates, and do not have references (mostly anecdotal)

•    Promotes proper development of teeth and reduces incidence of caries
•    Enhances fertility
o    Potter et al:  this concept is based on misrepresentation of animal feeding studies that involved deficient diets
•    Contains undefined substance to protect against arthritis (“anti-stiffness” factor)

LIST OF ALL REFERENCES

1.    Barnes, M., P. Cullinan, P. Athanasaki, S. MacNeill, A. M. Hole, J. Harris, S. Kalogeraki, M. Chatzinikolaou, N. Drakonakis, V. Bibaki-Liakou, A. J. Newman Taylor, and I. Bibakis. 2001. Crete: does farming explain urban and rural differences in atopy? Clin Exp Allergy 31:1822-8.
2.      Bell RW.  The effect of heat on the solubility of the calcium and phosphorus compounds in milk.  The Journal of Biological Chemistry.  1925;64(2):391-400.
3.      Bieli, C., W. Eder, R. Frei, C. Braun-Fahrlander, W. Klimecki, M. Waser, J. Riedler, E. von Mutius, A. Scheynius, G. Pershagen, G. Doekes, R. Lauener, and F. D. Martinez. 2007. A polymorphism in CD14 modifies the effect of farm milk consumption on allergic diseases and CD14 gene expression. J Allergy Clin Immunol 120:1308-15.
4.    Debarry, J., H. Garn, A. Hanuszkiewicz, N. Dickgreber, N. Blumer, E. von Mutius, A. Bufe, S. Gatermann, H. Renz, O. Holst, and H. Heine. 2007. Acinetobacter lwoffii and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties. J Allergy Clin Immunol 119:1514-21.
5.    Doyle, M. P., and D. J. Roman. 1982. Prevalence and survival of Campylobacter jejuni in unpasteurized milk. Appl Environ Microbiol 44:1154-8.
6.    Ege, M. J., R. Frei, C. Bieli, D. Schram-Bijkerk, M. Waser, M. R. Benz, G. Weiss, F. Nyberg, M. van Hage, G. Pershagen, B. Brunekreef, J. Riedler, R. Lauener, C. Braun-Fahrlander, and E. von Mutius. 2007. Not all farming environments protect against the development of asthma and wheeze in children. J Allergy Clin Immunol 119:1140-7.
7.    Hebeisen, D. F., F. Hoeflin, H. P. Reusch, E. Junker, and B. H. Lauterburg. 1993. Increased concentrations of omega-3 fatty acids in milk and platelet rich plasma of grass-fed cows. Int J Vitam Nutr Res 63:229-33.
8.    Hess AF.  Infantile scurvy:  its influence on growth.  The American Journal of Diseases of Children.  1916; 152-165.
9.    Ivory, K., S. J. Chambers, C. Pin, E. Prieto, J. L. Arques, and C. Nicoletti. 2008. Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis. Clin Exp Allergy.
10.    Kilpelainen, M., E. O. Terho, H. Helenius, and M. Koskenvuo. 2000. Farm environment in childhood prevents the development of allergies. Clin Exp Allergy 30:201-8.
11.    Meisel, H. 2005. Biochemical properties of peptides encrypted in bovine milk proteins. Curr Med Chem 12:1905-19.
12.    Perkin, M. R. 2007. Unpasteurized milk: health or hazard? Clin Exp Allergy 37:627-30.
13.    Perkin, M. R., and D. P. Strachan. 2006. Which aspects of the farming lifestyle explain the inverse association with childhood allergy? J Allergy Clin Immunol 117:1374-81.
14.    Pottenger FM.  Effect of heat-processed foods and metabolized vitamin D milk on dentofacial structures of experimental animals.  Am J Orthod 1946;32:467-485.
15.    Potter, M. E., A. F. Kaufmann, P. A. Blake, and R. A. Feldman. 1984. Unpasteurized milk. The hazards of a health fetish. Jama 252:2048-52.
16.    Radon, K., D. Windstetter, J. Eckart, H. Dressel, L. Leitritz, J. Reichert, M. Schmid, G. Praml, M. Schosser, E. von Mutius, and D. Nowak. 2004. Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects. Clin Exp Allergy 34:1178-83.
17.    Rajakumar, K. 2001. Infantile scurvy: a historical perspective. Pediatrics 108:E76.
18.    Remes, S. T., K. Iivanainen, H. Koskela, and J. Pekkanen. 2003. Which factors explain the lower prevalence of atopy amongst farmers' children? Clin Exp Allergy 33:427-34.
19.    Riedler, J., C. Braun-Fahrlander, W. Eder, M. Schreuer, M. Waser, S. Maisch, D. Carr, R. Schierl, D. Nowak, and E. von Mutius. 2001. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129-33.
20.    Riedler, J., W. Eder, G. Oberfeld, and M. Schreuer. 2000. Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Clin Exp Allergy 30:194-200.
18.    Sanders, M. E. 2008. Probiotics: definition, sources, selection, and uses. Clin Infect Dis 46 Suppl 2:S58-61; discussion S144-51.
19.    Von Ehrenstein, O. S., E. Von Mutius, S. Illi, L. Baumann, O. Bohm, and R. von Kries. 2000. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy 30:187-93.
20.    Waser, M., K. B. Michels, C. Bieli, H. Floistrup, G. Pershagen, E. von Mutius, M. Ege, J. Riedler, D. Schram-Bijkerk, B. Brunekreef, M. van Hage, R. Lauener, and C. Braun-Fahrlander. 2007. Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Clin Exp Allergy 37:661-70.
21.    Wickens, K., J. M. Lane, P. Fitzharris, R. Siebers, G. Riley, J. Douwes, T. Smith, and J. Crane. 2002. Farm residence and exposures and the risk of allergic diseases in New Zealand children. Allergy 57:1171-9.