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Intestinal alkaline phosphatase (IAP) is an enzyme manufactured in the small intestine, which has the primary function of splitting cholesterol and long chain fatty acids.

Intestinal alkaline phosphatase is seen normally in the serum of subjects who have B or O blood types, especially after a fatty meal. Pathologically the band may be present in perforation of the bowel, ulcerative disease of the intestine and faintly in liver cirrhosis. Acute infarction of the intestine will cause a release of IAP from the mucosa.

Large erosive or ulcerative lesions of the stomach, duodenum or other small intestinal areas, or colon may result in an elevation of the serum alkaline phosphotase (ALP) level. The small intestinal lesions associated with malabsorption are associated with an elevation of the serum intestinal ALP level only if there is an erosive or ulcerative mucosal lesion.


The activity of intestinal alkaline phosphatase and serum alkaline phosphatase is strongly correlated with ABH secretor phenotypes. Independent of ABO blood group, ABH non-secretors have lower alkaline phosphatase activity than ABH secretors. It has been estimated that the serum alkaline phosphatase activity of non-secretors is only about 20% of the activity in the secretor groups.

The intestinal component of alkaline phosphatase is involved with both the breakdown of dietary cholesterol and the absorption of calcium. The differences in intestinal alkaline phosphatase are almost exclusively related to one fraction of the intestinal alkaline phosphatase. Normal molecular mass intestinal alkaline phosphatase (NIAP) is present in the serum of both secretors and non-secretors regardless of ABO blood group. However, the high molecular mass intestinal alkaline phosphatase only appears in serum of Lewis (a-b+) blood group secretors.

It should be mentioned that in addition to ABH secretor status, ABO polymorphism is also linked to the levels and persistence of intestinal alkaline phosphatase. Numerous studies have associated group O individuals with the highest alkaline phosphatase activity and group A the least.

These findings suggest that the link between group O individuals and adaptation to cholesterol-containing foods in the diet (such as meats) reaches its greatest accommodation in group O secretors. Conversely, group A non-secretors would have the lowest levels of intestinal alkaline phosphatase and the greatest difficulties in handling dietary fat. In addition, one study has implied that the group A antigen itself may inactivate IAP.

Association of the ABO and secretor phenotypes with a polymorphism of serum alkaline phosphatases

Human serum alkaline phosphatases can be separated into two major zones by electrophoresis in starch gel. The rapidly migrating component is present in all serums and is thought to originate in liver, and possibly bone, whereas the enzyme with slower mobility originates in the small intestine. The intestinal enzyme call be differentiated from other serum alkaline phosphatases by several criteria in addition to electrophoretic mobility. It is inhibited by L-phenylalanine and resistant to treatment With neuraminidase and differs antigenically from the other enzymes. Arfors, Beckman and Lundin first pointed out that the slower phosphatase band occurs almost exclusively in the serum of Group B and O secretors, and is almost never found in those of Group A secretors or in nonsecretors of any type. They also presented data implicating at least one of her independent locus in regulating the appearance of the intestinal phosphatase in serum. These findings have been extended and confirmed by several groups in studies of populations in many parts of the world.

With more sensitive techniques for demonstrating alkaline phosphatase activity, it was found that small amounts of this enzyme are present in the serums of 10 to 15 per cent of group A secretors, and a smaller number of nonsecretors. The serums of approximately 70 to 80 per cent of Group O and B secretors contain this enzyme, in much larger quantities than in the Group A secretors or nonsecretors. Group AB persons are intermediate in percentage of positive persons and in quantities of phosphatase in serum.

The concentration of the intestinal phosphatase is lowest in the serum during fasting and rises after ingestion of fat, reaching a peak at about seven to eight hours. This increase is most marked in Group O and B secretors, but it is detectable in most people. The concentration of intestinal alkaline phosphatase in human thoracic-duct lymph rises after a fatty meal, and presumably most of the intestinal phosphatase enters the blood by way of the lymphatic system. Schreffier and Langnall et al measured the alkaline phosphatase concentration in the mucosa of the human small intestine. The former found no correlation between alkaline phosphatase levels and ABO groups or secretor type, but the latter observed that Group O and B secretors had the highest mean concentration of alkaline phosphatase, Group A secretors had the next highest concentration, and nonsecretors had the lowest amount; in that study, however, there was a marked overlap between the three groups in the range of enzyme activity, and the differences observed were much smaller than those found in se­rum. In view of these data it seems likely that the ABO and secretor genes influence the rate at which the intestinal phosphatase enters the blood, or its catabolism, rather than its synthesis in the intestine.

Cattle and sheep erythrocytes contain antigens similar to human A and H determinants. An analogous association has been found between serum alkaline phosphatase and blood­group polymorphisms in these species.

The association of ABO and secretor types with this serum enzyme polymorphism is of particular interest because of the association of the same traits with certain diseases of the gastrointestinal tract. Elucidation of the mechanism by which the blood­group genes participate in producing the alkaline phosphatase polymorphism may provide a lead to their role in the physiology and pathology of the gastrointestinal tract.

Beckman and Zoschkel have recently reported an association between blood Group A and a polymorphism of human serum acid phosphatases. Two major bands of acid phosphatase activity call be re­solved by starch-gel electrophoresis, and the concentration of the enzyme with the greater anodal mobility was higher in persons of blood Group A or AB than in those of B or O.

Source: Nollevaux et al., BMC Cell Biology 2006, 7:20

In vitro reproduction of the features of the human small intestinal epithelium showing varying levels of intestinal alkaline phosphatase activity (red) using the intestinal cell lineage Caco-2.


The ABO blood groups-dependent reference intervals for serum alkaline phosphatase isozymes and total activity in individuals 20-39 years of age

Rinsho Byori 1995 May;43(5):508-512 Nakata N, Tozawa T Department of Clinical Laboratories, Hyogo College of Medicine, Nishinomiya.

  • Reference intervals of the activity of serum alkaline phosphatase isozymes (AP-IZ: high molecular-, liver-, bone- and intestinal-types) were determined according to the ABO (blood type) system in 200 healthy subjects aged 20-39 years. AP activity was determined according to the JSCC method. AP-IZ was stained by the formazan method after isolation by TITANIII-Lipo plate electrophoresis. For the electrophoresis, treated serum with neuraminidase and untreated one were concomitantly used for detecting liver AP and bone AP respectively. As a result of comparison of mean AP-IZ activity among the groups divided according to the ABO system, total AP, intestinal AP and liver AP activities in the type B and O persons were significantly higher than in the type A and AB persons. It is well known that the activities of total AP and intestinal AP in type B and O persons are higher than in type A and AB persons, but there have been no reports showing that the activity of liver AP in type B and O persons is higher than in type A and AB persons. Furthermore, in the type B and O persons there was a low correlation (r = 0.195, p < 0.05) between the activities of liver AP and intestinal AP.
Isoenzymes of alkaline phosphatase - reference values in young people and effects of protein diet

Stepan J, Graubaum HJ, Meurer W, Wagenknecht C Experientia 1976;32(7):832-834

  • In 260 normal students, 20-25 years old, the variation in the activities of serum alkaline phosphatase and its isoenzymes with sex, ABO blood groups, and protein intake were studied. The values are on the whole higher in males than in females. The activity of the intestinal isoenzyme was higher in subjects taking protein-rich diet than in those taking protein poor diet.
Intestinal alkaline phosphatase and the ABO blood group system--a new aspect

Clin Chim Acta 1980 Nov 20;108(1):81-87 Bayer PM, Hotschek H, Knoth E

The influence of erythrocytes of different blood groups on the intestinal isoenzyme of alkaline phosphatase (EC was investigated. Binding of the enzyme to erythrocyte membranes was demonstrated by sedimentation experiments, by enzyme electrophoresis, by gel chromatography and immunologically using a modified Coombs technique. We found that red cells of blood group A bind almost all intestinal alkaline phosphatase; erythrocytes of blood group B or O to a much lesser degree. This is in accordance with the fact that intestinal alkaline phosphatase is found more frequently in the serum of individuals of blood group O or B than in serum of persons of blood group A. We conclude that underlying the described blood group dependent differences in synthesis of intestinal alkaline phosphatase lies a mechanism involved in the regulation of the activity of intestinal alkaline phosphatase in human serum.

Total serum alkaline phosphatase (SAP) and serum cholesterol in relation to secretor status and blood groups in myocardial infarction patients

Indian Heart J 1989 Mar;41(2):82-85 Mehta NJ, Rege DV, Kulkarni MB

The relation of total serum alkaline phosphatase and serum cholesterol in convalescing patients of myocardial infarction with secretor status and blood groups have been studied. Serum cholesterol and alkaline phosphatase levels showed significant difference in secretors (98) and nonsecretors (56) in myocardial groups. Total cholesterol and total serum alkaline phosphatase levels showed significant difference in secretors when blood groups A and O are compared. While in nonsecretors, significant values obtained in A/O, A/B for cholesterol and A/B, A/AB for alkaline phosphatase levels.

Serum levels of human alkaline phosphatase isozymes in relation to blood groups.

Domar U, Hirano K, Stigbrand T Clin Chim Acta 1991 Dec 16;203(2-3):305-313 Department of Medical Chemistry and Biophysics, University of Umea, Sweden.

By use of sensitive immunocatalytic assays, based on isozyme specific monoclonal antibodies, the activities of the three main human alkaline phosphatases were determined in serum. The activities were related to ABO blood groups and secretor phenotypes. The activity of intestinal alkaline phosphatase was found to be strongly correlated with ABO blood groups and secretor phenotypes, while neither the placenta alkaline phosphatase activity nor the tissue unspecific alkaline phosphatase activity demonstrated any dependence on blood groups or secretor phenotypes. Non-secretors, independent of ABO blood groups, demonstrated low activities of intestinal alkaline phosphatase in serum, amounting to approximately 20% of the activities in the secretor groups. Within the secretor group, the lowest activities were observed for blood group A (2.8 +/- 1.1 IU/l; mean +/- SEM) and the highest for blood groups B and O (14.1 +/- 1.1 IU/l and 19.0 +/- 2.5 IU/l, respectively). These results confirm that the activities of intestinal alkaline phosphatase in serum have to be related both to ABO blood groups and to secretor phenotypes in order to be informative in clinical contexts.