The present invention relates generally to products, processes and methods for reducing, eliminating or preventing in a patient the gastrointestinal inflammatory symptoms caused by ingesting bovine food products and particularly to a method of reducing, eliminating or preventing the clinical symptoms of infants suffering from colic.
Colic is a disorder of early infancy which is typically characterized by paroxysms of crying, apparent abdominal pain and irritability. Although intestinal pain or distress are related to this problem, the causes and the specific mechanisms of infant colic are generally considered to be unknown. This frustration is clearly evident in the related literature because colic etiology and pathogenesis are poorly understood. See, for example, A Clinical Manual of Emergency Pediatrics, E. F. Crain and J. C. Gershel eds., pg. 182, Appleton-Century-Crofts, Norwalk, Conn. (1986).
The direct cause of recurrent colic attacks is usually not apparent, though it has been suggested that the attacks may be associated with hunger and with swallowed air which has passed into the intestine. Other suggested causes include overfeeding, certain types of foods, especially those of high carbohydrate content, individual infant temperament and emotional upset, even parental anxiety. No single factor consistently accounts for colic, nor does any treatment consistently provide satisfactory relief. See, for example, Nelson Textbook of Pediatrics, 13th edition, R. E. Behrman and V. C. Vaughan, eds., Section 3.13, W. B. Saunders Co., Phila., Pa. (1987).
Not unexpectedly, there are numerous unproven theories about the association of different foods and formulas with the symptoms of colic. Allergies to cow milk, immaturity of an infant's gastrointestinal tract or central nervous system, or poor feeding technique have all been considered. Even though diet has been implicated as a possible cause, the relationship between diet and colic is still disputed. Some cases of colic may represent intolerance to cow milk (cow milk allergy or congenital lactose intolerance) but these probably constitute only a small minority of cases. Some consider empirical changes of formula need not be considered routine therapy for colic, Manual of Clinical Problems in Pediatrics, K. B. Roberts ed., p. 79, Little, Brown, & Co., Boston, Mass. (1990). No one theory or concomitant therapy has of yet gained uniform acceptance.
For the most part colic is a diagnosis which is made after other reasons or causes of similar symptoms, such as infections, have been eliminated. The most typical symptom of colic is unexplained or excessive crying. Excessive crying episodes may be more quantitatively defined to include episodes crying at full force many times a day at least four days a week for at least one week or more. Each episode may last from thirty minutes to two hours and total crying may be more than three hours a day. See, for example, the description of the clinical symptoms set out in the Merck Manual of Diagnosis and Therapy, 15th Edition, p. 1833 (1987) and by Lothe and Lindberg, Pediatrics 83:262-266 (1989). Although excess crying is a principal symptom, one or more of the following symptoms may also be present in an affected infant including abdominal guarding, legs pulled up, or disturbed sleep.
Both nursing and formula fed infants develop colic at a similar rate and a number of causes and associated remedies have been used to try and reduce or eliminate the distress associated with colic. In some mild cases, an infant may respond to being held, rocked or gently patted. Use of pacifiers is another well known remedy to soothe infants that have a strong sucking urge even after feeding. Other infants may respond by being tightly swaddled. Dietary changes and in some cases the judicious use of a sedative may be recommended to provide relief.
Recently, evidence has become available that points to diet as being a principal cause of infant colic. Specifically, a double blind study of Lothe and Lindberg, Pediatrics, 83:262-266 (1989) reports that cow milk whey proteins elicit symptoms of infant colic in colicky formula fed infants. In this study, Lothe and Lindberg found that a majority of infants whose colic had subsided on a casein hydrolyzate (whey-free) formula reacted with colicky symptoms when given formula spiked with powdered whey protein. These authors also suggested that .beta.-lactoglobulin may be particularly suspect as a cause of the symptoms, and noted that this bovine protein has also been found to be transferred to human breast milk. However, the level of .beta.-lactoglobulin that is found in breast milk (.mu.g levels) is significantly lower than the levels of .beta.-lactoglobulin in formula (mg levels) which is inconsistent with the observation that both nursing and formula fed infants suffer from colic at equivalent rates and with apparently equivalent serverity. Other studies, however, do not unambiguously show either a direct or indirect relationship between bovine proteins and infant colic. See, for example, the report of Evans, et al., Lancet, 1:1340-1342 (1981).
Recent reports suggest that another bovine protein is associated with colic. For example, Clyne and Kulczycki, Ped. Res., 25:160A (1989), initially reported that milk samples from a number of nursing mothers contained substantial amounts of bovine immunoglobulin G (IgG), and that high levels of bovine IgG were found in the diets of colicky infants. Later, the same authors, Pediatrics, 87:439-444 (1991), compared the levels of bovine IgG in bovine milk-based formulas and breast milk. Their results suggest that substantial quantities of bovine IgG are present in human breast milk and indicate that significantly higher levels of IgG are present in the milk of mothers of colicky infants. The study also shows that mothers without high levels of bovine IgG in their milk do not appear to have colicky infants.
There is clearly a long sought need of a method of reducing or eliminating the symptoms of colic in infants which is met by the present invention.
Furthermore, the present invention also provides a method of reducing the gastrointestinal symptoms associated with the ingestion of bovine products, especially milk based products, in older children and adults. In particular, patients suffering from some gastrointestinal disorders such as ulcerative colitis, eosinophilic gastroenteritis, or Crohn's disease may have symptoms that are initiated or exacerbated by ingesting food products containing bovine IgG. These unwanted symptoms may be reduced or eliminated by providing food products having a reduced bovine IgG content to these patients.