Scientific Basis of the Blood Group Diet

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FINALLY MOVING BEYOND POLEMICS

STUDY: Scientific basis of the blood group diet.

JOURNAL: Tidsskr Nor Laegeforen. 2001 Jun 10;121(15):1838-9. Norwegian.

AUTHORS: Poleszynski DV. [PubMed - indexed for MEDLINE]

ABSTRACT: Eat Right 4 Your Type by J. D’Adamo describes a strategy

of adapting lifestyle and nutrition to each individual’s physiology and

biochemistry. The author’s theory is based on research within, amongst

others, physical anthropology, neurology, biochemistry, nutrition,

lectinology, epidemiology, psychology, immunology and genetics. Going

through the literature shows that Doctor D’Adamo can be mistaken on

certain points, and is vague on others. Nonetheless, his general theory

seems to be based on scientific studies, and reports show that it

works. “Helsevesenet” - the Public Norwegian Health Institutions -

should start using the parts of the theory that are based in fact, and

the medicinal circles should do more testing and align the theory with

basic medicinal science and clinical research.

35,000 examples of Eat Right 4 Your Type have been printed in Norway.

[btw: the country only has a population of 4 million] The book has been

complimented by laypersons and ‘natural therapists’ and is rejected by

others (2).

The theory is based on five elements:

- an evolutionary perspective of the human being, including a theory on

how the blood types evolved, based on the ABO-system.

- Proved relationships between blood types and physical and

psychological diseases, used to explain the blood types’ geographical

distribution, degrees of risk factor, and strategies for reducing risk.

- Lectins in food can influence [ones] state of health. They can have

positive and negative biological effects, i.e. some can be the source of

illness, while others can be used therapeutically.

- Existing relationships between genes, like blood type and/or type of

tissue, combined with secretor status ( a/b) and other

physiological and biochemical variables make it possible to identify an

individual’s genetic “fingerprint”.

- Genotyping can, among other things, be used to predict what foods one

tolerates and how one handles stress.

Eat Right 4 Your Type has been criticized for being categorical (2). The

Literature list is sparing (1). An article of 1980 explains the

background (3), an other from 1990 gives documentation on lectin

activity (4), and in January 2001 a new, better documented, book came

out (5).

Evolution and Blood Types: The fact that primates have the same A- and

O- blood type antigens is taken to mean that we have inherited them from

common ancestors (2). This can seem logical, since our earliest

ancestors were vegetarian, and the hominids on a higher level of

evolution were the first to become meat eaters. However, research on the

genetic sequences of primates and humans tend to corroborate that ABO

genetic polymorphism in primates is a result of convergent evolution,

i.e. unrelated mutations, and are not the result of a common genetic

origin (6).

Historically, populaces have eaten food that is perceived as adverse for

their blood type, e.g. Inuits who are blood type A (meat and fat) and

American Indians, blood type O (corn and potatoes). Native populations

on “civilized food” usually develop a range of new chronic disorders

(7). We do not know what role the blood type can play in differences in

peoples state of health.

Blood Type and Illness: Links between blood type and illness have been

known for over 80 years, is well documented (8), and is discussed in

manuals in genetics (9). Among significant relationships show the odds

ratios (OR) for cancer, shows an [over frequency???] in Type A compared

to Type O of 1,11 (colon and rectum), to 1,64 (salivary gland). A large

study of stomach cancer (N=55,434) shows an OR for type A = 1,22

compared to type O. Contrariwise, in Type O there is a higher rate of

cancer of the small intestine (OR 1,35), ulcers (OR 1,53), or bleeding

ulcers (OR 1,46) compared to type A, while type A has more eosinophilia

(OR 2,38) and tromboemboli (OR 1,61). Differences in the propensity for

infection (8) can explain geographical differences in the ratios of

blood types. H. Pylori gives a high frequency of ulcers in Type O, who

also have a high frequency of disbiosis caused by Candida Albicans (1,8)

Lectins in Illness and in Health: Lectins, in groups (glyco)proteins,

bind irreversibly to carbohydrates and are used by plants as defence

against being eaten by animals, and as intercellular communication

signal substances. After this group of substances were characterised in

1888 (10) over 1,000 foods have been found to contain lectins with

biological impact. [The various biological effects] depend on, amongst

other factors, the number of binders - those with only one [binder], for

example, cannot agglutinate cells. Biological effects from experiments

carried out on humans and 14 different types of animals are known (12).

Lectins in barley, wheat, potato, rice, rye, tomatoes, and a number of

legumes can agglutinate erythrocytes in humans of all blood types.

Lectins can have effects resembling those of insulin on fat cells,

hinder growth of cancer cells, induce clotting of blood plates and

increase the secretion of histamine.

Blood type influences biological variables: Certain people produce more

digestive acids than others and are more susceptible to ulcers and

heartburn. People of type O seem to produce more digestive acids than

those of blood type A, and a variety of enzyme activity in the blood and

the intestines vary depending on blood type (5). This is valid for

alkaline phosphatase, monoaminoxidase and dopamine-beta- hydroxsylase. A

probable reason for this is that the genes that code for proteins and

are located near the blood type gene on chromosome 9Q34 is influenced by

this.

Blood type and personality: A range of sources link blood type to

personality, and the extent of risk for mental disorders (5). It has

been substantiated that there is a high degree of polymorphism between

receptors and transporters of dopamine and serotonin and a relationship

between blood type and stress. One study shows that those of blood type

O secrete less cortisone after donating blood than do those of type A

(5). Since hard physical effort releases stress hormones, it is quite

likely that individuals of type O can tolerate [intense, physical]

exercise better than type A’s (1,5).

Conclusion: The ABO-system, secretor status and other systems (MN, Rh)

sheds light on the disposition for illness. Lectins in food affect our

health, and the blood type gene influences near by genes. Interactions

between blood type and environment can probably explain why some get

sick while others remain healthy through a long life.

Literature

1. D'Adamo PJ, Whitney C. Blodtypedietten. Spis riktig for din blodtype.

Oslo: Wem 3 A/S, 1999.

2. Moen T. " Blodtypedietten " - vitenskap eller fantasi? Tidsskr Nor

Lægeforen 2001; 121: 355 - 8.

3. D'Adamo PJ. Diet, disease and the ABO bloodgroups: a review of the

literature. Seattle, WA: Bastyr College of Naturopathic Medicine,

1981. www.dadamo.com/literature/lrc.htm (3.2.1999).

4. D'Adamo PJ. Gut ecosystem dynamics III. Lectins and mitogens.

Townsend Letter for Doctors & Patients 1990; 85 - 6: 528.

5. D'Adamo PJ, Whitney C. Live right for your type. New York: G. P.

Putnam's Son, 2001.

6. Kermarrec N, Roubinet F, Apoil PA, Blancher A. Comparison of allele 0

sequences of the human and non-human primate ABO system. Immunogenetics

1999; 49: 517 - 26.

7. Price WP. Nutrition and physical degeneration. 10. utg. Pasadena, CA:

The Price-Pottenger Nutrition Foundation, 1979.

8. Mourant AE, Kopec AC, Domaniewska-Sobozak K. Blood groups and

diseases. A study of associations of diseases with blood groups and

other polymorphisms. Oxford: Oxford University Press, 1978.

9. Vogel F, Motulsky AG. Human genetics. Problems and approaches. 3.

utg. Berlin: Springer-Verlag, 1997.

10. Pusztai A, Bardocz S, ed. Lectins. Biomedical perspectives. London:

& Francis, 1995.

11. Liener IE, Sharon N, Goldstein IJ, red. The Lectins: properties,

functions, and applications. Orlando, FL: Academic Press, 1986.

12. Van Damme EJM, Peumans WJ, Pusztai A, Bardocz S. Handbook of plant

lectins: properties and biomedical applications. Chicester: Wiley &

Sons, 1998.

COMMENTARY: I wish to thank Katrina (a particpant on the Bulletin Board)

for this translation from the original article which appeared in

Norwegian.

Perhaps my only problem with the article is that it holds the simplicity

of my first book, Eat Right 4 Your Type, somewhat against me, even

though the author references far more technical scientific articles that

I've written that actually precede its publication. One cannot do two

things simultaneously: You can write simplified books for the general

public or technical works for scholarly journals. They must be evaluated

differently, as they have widely different aims.

Nonetheless, I am gratified that the blood group diet theory is becoming

the subject of a more serious scholarly interest, although perhaps

despite its success in the mass-market, rather than because of it.

Metabolic and Immunologic Consequences of ABH Secretor and Subtype

Status

J. D'Adamo, ND, and S. , ND

Abstract

Determining ABH secretor phenotype and/or (Le) blood group status

can be useful to the metabolically-oriented clinician. For example,

differences in ABH secretor status drastically alter the carbohydrates

present in body fluids and secretions; this can have profound influence

on microbial attachment and persistence. typing is one genetic

marker which might help identify subpopulations of individuals

genetically prone to insulin resistance, autoimmunity, and heart

disease. Understanding the clinical significance of ABH secretor status

and the blood groups can provide insight into seemingly unrelated

aspects of physiology, including variations in intestinal alkaline

phosphatase activity, propensities toward blood clotting, reliability of

some tumor markers, the composition of breast milk, and several

generalized aspects of the immune function. Since the relevance of ABH

blood group antigens as tumor markers and parasitic/bacterial/viral

receptors and their association with immunologically important proteins

is now well established, the prime biologic role for ABH blood group

antigens may well be independent and unrelated to the erythrocyte.

(Altern Med Rev 2001;6(4):390-405)

Functional and Genetic Factors Involved in ABH Secretion

The term " ABH secretor, " as used in blood banking, refers to secretion

of ABO blood group antigens in fluids such as saliva, sweat, tears,

semen, and serum. A person who is an ABH secretor will secrete antigens

according to their blood group; for example, a group O individual will

secrete H antigen, a group A individual will secrete A and H antigens,

etc. Soluble (secreted) antigens are called substances. To test for

secretor status, an inhibition or neutralization test is done using

saliva. The principle of the test is that if ABH antigens are present in

a soluble form in a fluid (e.g., saliva) the antigens will neutralize

their corresponding antibodies, and the antibodies will no longer be

able to agglutinate red cells possessing the same antigens.

One of the primary differences in physiology between secretors and

non-secretors involves qualitative and quantitative differences in

components of their saliva, mucus, and other bodily secretions. ABH

secretion is controlled by two alleles, Se and se. Se is dominant and se

is recessive (or amorphic). Approximately 80 percent of people are

secretors (SeSe or Sese).

In the most rudimentary sense, it is the secretor gene (FUT2 at 19q13.3)

that codes for the activity of the glycosyltransferases needed to

assemble aspects of both the ABO and (Le) blood groups. This is

accomplished in concert with the gene for group O, or H (FUT1) and the

gene for the pheno-type. These enzymes are then active in places

like goblet and mucous gland cells, resulting in the presence of the

corresponding antigens in bodily fluids.1

The H antigens are indirect gene products expressed as fucose-containing

glycan units, residing on glycoproteins or glycolipids of erythrocyte

membranes or on mucin glycoproteins in secretions. They serve as the

fucosylated-glycan substrates for glycosyltransferases that give rise to

the epitopes for the A, B, and blood group antigens. The major

difference between the two genes is in their pattern of expression. The

FUT1 (H) gene is expressed predominantly in erythroid tissues giving

rise to FUT1 (H enzyme) whose products reside on erythrocytes, whereas

the FUT2 (Secretor) gene is expressed predominantly in secretory tissues

giving rise to FUT2 (Secretor enzyme) and to products that reside on

mucins in secretions.2

When alleles of both genes fail to express active enzymes, individuals

bearing them in homozygous state lack the substrates for the A or B

glycosyltransferases and do not express the A and B epitopes.

Relationship of ABH Secretor Status and System

Two broad categories of blood type exist. These are the

positive (either Le (a+b-) or Le (a-b+)) and negative (Le (a-b-))

phenotypes. Since FUT1 provides the glycans necessary for

glycosyltransferase conversion into the antigen in addition to

ABH, the blood group determinants are structurally related to

determinants of the ABO and the H/h blood group systems and the outcome

of typing can be used for the de facto determination of ABH

secretor status among positive individuals (Table 1). In the

presence of FUT2 alleles that express type 1 H determinants, the

phenotype will be Le (a-b+), but individuals in whom the FUT2 gene is

not expressed will be Le(a+b-).

Among positive individuals, ABH secretors are always Le (a-b+)

since they convert all their (a) antigen into (. Conversely,

among positives, ABH non-secretors are always Le (a+b-) since they

lack the FUT2 dependent glycosyltransferase to accomplish this. A small

segment (1-8 percent of the population, dependent on race) will be

negative and typing cannot be used to determine ABH secretor

status. In these individuals determination via saliva is necessary to

determine ABH secretor status. It can be quite useful to determine both

ABH secretor status and blood group phenotype, since secretor

status provides some degree of generalized information regarding disease

states but negative individuals also appear to have unique

interactions with certain disease states.

Although ABH secretor status is often thought of as an all-or-none

situation, this is generally not the case. In some ABH non-secretors

(known as partial or weak secretors) there will often be some form of

active A or B blood group substance in the saliva; however, the quantity

and quality of these substances is greatly reduced, predisposing them to

similar functional problems as other non-secretors.3,4

Antigenic Structures in Fluid Secretions

There are several advantages to having large quantities of blood type

antigens (both ABO and ) secreted into saliva. First, salivary

carbohydrate structures found in mucins can aggregate some oral bacteria

and constituents of pellicle and plaque. Since saliva of secretors

contains substantially more diversity and total carbohydrate than

non-secretor mucins, this places secretors at a slight advantage.

Second, these same blood type carbohydrate structures, due to the known

" sweet tooth " (carbohydrate avidity) of many dietary lectins, may place

secretors at an advantage with respect to the binding of blood type

specific dietary lectins prior to any disruptive interaction of lectins

with cell surface glycoproteins.

In the gastric mucosa of healthy individuals the normal mucosa of

secretors is characterized by a uniform distribution of blood type

antigens in the pits. Healthy mucosa of non-secretors shows little

staining for these blood type antigens, but instead, demonstrates

significant quantities of the I(Ma) antigen. This tendency to express

the I(Ma) antigen will subsequently have an impact on antibody

capabilities, as will be evidenced when immunity is discussed.5

Physiological Manifestations

Brush-Border Hydrolases

ABO blood group determines much of the enzyme activity in the tissue

(brush-border) of the intestine. At least six intestinal hydrolases have

ABO blood group antigenic determinants directly related to ABO blood

group. Basically, the intestinal glycoproteins of blood group A and B

individuals express A or B antigens, while blood group O subjects

express the H determinant. The expression of these ABH antigens is under

the control of the secretor gene; so these ABH antigens are not detected

in the hydrolases of non-secretor subjects.6 ABH secretors have greater

quantities of free ABH antigens in the makeup of their intestinal

secretions, which has significant effects on bacterial and lectin

adherence to the gut microvilli.

Intestinal Alkaline Phosphatase Activity

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

percent of the activity in the secretor groups.7-10

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 this enzyme. 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

Le (a-b+) blood group secretors.11

In addition to ABH secretor status, ABO polymorphism is also linked to

the levels and persistence of intestinal alkaline phosphatase.12

Numerous studies have associated group O individuals with the highest

alkaline phosphatase activity, and group A the least.13

These findings suggest 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 the group A antigen itself may

inactivate NIAP.14

Bacterial Flora

The role of the ABO blood group in determining the bacteria making up a

healthy gastrointestinal ecosystem is particularly strong in ABH

secretors. Since ABH secretor status and ABO blood group dictate the

presence and specificity of A, B, and H blood group antigens in human

gut mucin glycoproteins, this can influence the populations of bacteria

capable of taking up local residence. This occurs because some of the

bacteria in the digestive tract are actually capable of producing

enzymes that allow them to degrade the terminal sugar of the ABH blood

type antigens for a constant food supply.15

For example, bacteria capable of degrading blood group B antigen produce

enzymes that allow them to detach the terminal alpha-D-galactose and use

this sugar for food. Blood group A degrading bacteria would have similar

capabilities with respect to N-acetylgalactosamine. Group B secretors

produce greater levels of B-degrading than A- or H-degrading activity,

and A secretors produce greater levels of A-degrading than B- or

H-degrading activity. Because of this capability, the bacteria that use

ABH antigens for food have a competitive advantage and can thrive in the

environment created by the preconditioning of ABH secretions.16

Although comparatively small populations of bacteria produce blood

group-degrading enzymes (estimated populations are 108 per g), the

quantity of these bacteria are several orders of magnitude greater in

different blood types and are much more stable residents. For example,

B-degrading bacteria have a population density about 50,000-fold greater

in blood group B secretors than in other subjects. Similar bacterial

specificity and enzyme activity is found among other blood types.15,16

Breast Milk Components

Significant variations in the carbohydrate residues in human breast milk

are found depending on the mother's ABO, , and Secretor blood types

(Table 2). During the first week of lactation the ability to produce

neuraminyloligosaccharides is linked to the ABH secretor groups. And the

ability to produce oligosaccharides with Le(a) or Le( characteristics

is linked to and Secretor systems. The consequences of this are

that secretors will produce higher levels of N-acetylneuraminic acid and

lower levels of galactose in their breast milk than non-secretors. In

the ABH secretor groups, blood type A and O secretors also have higher

N-acetylglucosamine contents than B and AB secretors (p < 0.001), while

the A and B secretors have higher galactose levels. The secretor

groups are also distinguished by a significantly higher level of fucose.

The ABH (+), Le (a-b-) group had higher lactose contents than the other

groups.17

Blood Clotting

ABO blood group impacts the clotting ability to a significant degree. In

fact, it has been estimated that a significant fraction (30%) of the

genetically determined variance in plasma concentration of the von

Willebrand factor antigen (vWf) is directly related to ABH determinants.

As a rule, it is blood group O individuals who have the lowest amount of

this clotting factor.18

ABH non-secretors are reported to have shorter bleeding times and a

tendency toward higher factor VIII and vWf. This relationship appears to

be another example of blood type synergy between ABO and

Secretor/Non-secretor phenotypes. In fact, secretor genetics appear to

interact with ABO genetics to influence as much as 60 percent of the

variance of the plasma concentration of vWf, with secretors (Le(a-b+))

having the lowest vWf concentrations.19,20

Among persons belonging to blood group O (the blood type most likely to

have problems with clotting), the lowest concentrations of vWf:Ag and

VIII:Ag are found in the group O secretors. On the other hand, blood

group O non-secretors will have higher concentrations of both vWf:Ag and

factor VIII antigen (VIII:Ag), providing them with a better capability

for clotting.18

Among blood groups A, B, and AB, also having the Le (a-b-) phenotype is

associated with the highest degree of clotting factors (Table 3). In

white men with these blood types, the Le (a-b-) phenotype implies

significantly higher levels of factor VIII and von Willebrand factor.

Among black men with blood type A, B, or AB, and phenotype Le (a-b-), a

similar trend is found with these individuals having the highest values

for factor VIII and von Willebrand factor. In women with blood type A,

B, or AB, and phenotype Le (a-b-) a correlation exists for higher levels

of factor VIII.18

Researchers have suggested the Le (a-b-) phenotype (and blood groups A,

B, and AB especially), by virtue of their association with raised levels

of factor VIII and von Willebrand factor, might be at a higher risk for

future thrombotic and heart disease.21

Dental Cavities

In all blood groups the average number of cavities is lower for ABH

secretors than for non-secretors. This difference is most significant

for smooth surface areas of the teeth. Also, secretors of blood group A

have been shown to have the lowest numbers of cavities.22

Diabetes, Heart Disease, and Syndrome X

Diabetes

negative individuals are at a greater risk of developing diabetes

(especially type 2 diabetes) and they might be at a greater risk of

developing complications from diabetes. Findings also suggest a greater

proportion of non-secretors are found among patients with diabetes,

particularly of the type 1, or insulin-dependent type.23-24

The Le(a-b-) red blood cell phenotype appears to confer the greatest

risk of developing diabetes. This blood type is observed greater than

three times more frequently (29%) in diabetics irrespective of their

clinical type. Non-diabetics categorized as low insulin responders to

glucose are also significantly more likely to be negative.25 Among

individuals with type 1 diabetes, the prevalence of severe retinopathy

as a complication of diabetes is lower in ABH secretors than in the ABH

non-secretor group.26

Heart Disease

Data suggests that ABH non-secretor phenotype might be a risk factor for

ischemic heart disease (IHD) while ABH secretor status might confer a

degree of genetic resistance. Evidence also suggests that the

negative phenotype might be an even more important genetic marker for

increased risk of heart disease among males. This finding was reported

in the Copenhagen Male study and replicated in the NHLBI Family Heart

Study.

Eight percent of men with the Le (a-b-) phenotype had a history of

nonfatal myocardial infarction (among -positive men the frequency

was only 4%). Even more serious is research showing that men with Le

(a-b-) had an increased risk of death from heart IHD (IHD case fatality

rate (RR = 2.8 (1.5-5.2), p = 0.01)) compared with others. Adjusted for

age, relative risk climbed even higher to 4.4 ((1.9-10.3), p < 0.001),

and for all causes of mortality RR = 1.6 ((1.0-2.6), p < 0.05).27

Results from the NHLBI Family Heart Study also showed a higher risk of

coronary heart disease (odds ratio was 2.0 (95% confidence interval =

1.2 to 3.1)) for Le (a-b-) versus other groups. Triglycerides were

significantly higher in the Le (a-b-) subjects. Among women, there was

also a trend towards increased risk of IHD among -negative

phenotypes; however, the trend was dramatically weaker than among male

subjects.28

Additional research has also duplicated these results, supporting and

adding to the weight of evidence linking Le (a-b-) with high risk for

the development of ischemic heart disease. Even excluding the

-negative phenotype, the secretor phenotype Le (a-b+) was found to

be a genetic marker of resistance against the development of IHD, while

ABH non-secretor status is a risk factor predisposing individuals

towards heart disease.29,30

Effects of Alcohol

In men, Le (a-b-), a group genetically at high risk of IHD, alcohol

consumption seems to be especially protective. In the Copenhagen study,

researchers found that drinking alcohol was the only risk factor that

had an interaction with -negative blood type and that alcohol could

strongly modify risk in an inverse (hence positive) manner. There was a

significant inverse dose-effect relationship between alcohol consumption

and decreasing risk.31

Paradoxical with the cardiovascular benefits of alcohol in

-negative individuals, several large studies have associated

alcoholism with ABH non-secretor status and the -negative

phenotype.32,33

Metabolic Syndrome X

Data suggest that Le (a-b-) men exhibit features of insulin resistance

syndrome or syndrome X, including a tendency to prothrombic metabolism,

higher body mass index levels, elevated triglycerides, fasting levels of

serum insulin and plasma glucose. These same relationships do not appear

to hold true for Le (a-b-) women.

A group of metabolic problems comprised of insulin resistance, elevated

plasma glucose, lipid regulation problems (elevated triglycerides,

increased small low-density lipoproteins, and decreased high-density

lipoproteins), high blood pressure, a prothrombic state, and obesity

(especially central obesity or a predisposition to gaining weight in the

abdomen) combine to form " metabolic syndrome X " (MSX). This cluster of

metabolic disorders seems to promote the development of type 2 diabetes,

atherosclerosis, and cardiovascular disease. And while insulin

resistance might lie at the heart of the problem, all of these metabolic

disorders appear to contribute to health problems.

Because of the associations with non-secretor status and both diabetes

and heart disease, many different researchers have explored the

connection between MSX and and non-secretor blood types. Similar

to diabetes and heart disease, individuals with Le (a-b-) phenotype are

most predisposed to MSX. It has even been hypothesized that Le (a-b-)

men and syndrome X share a close genetic relationship on chromosome 19

and that the Le (a-b-) phenotype is a genetic marker of insulin

resistance syndrome.34

As was discussed in the prior section on clotting, non-secretors and

especially -negative individuals, are particularly prone to

prothrombic metabolism (a tendency to form clots more readily and to

have slower bleeding times). The tendency to higher tri-glycerides was

mentioned in the discussion on heart disease.35

Researchers have also investigated blood types as part of the

Copenhagen Study and have found very supportive evidence of trends

toward metabolic differences. Compared to all other men, the Le (a-b-)

men had a significantly higher systolic blood pressure (6 mm Hg; p =

0.0024). They also had higher values of body mass index (8%; p = 0.016),

total body fat mass (25%; p = 0.015), fasting values of serum insulin

(32%; p = 0.006), serum C-peptide (20%; p = 0.029), and plasma glucose

(8%; p = 0.003). These trends, while consistent for men, did not hold

true for women.36,37

Immunological Consequences

Basic Functions

Evidence suggests that ABH non-secretors have lower levels of IgG.38,39

Tests of 202 Caucasian researchers found IgA concentrations to be

significantly lower in non-secretors than in secretors.40,41 This seems

to imply that the ABH non-secretor state is associated with a " Defense

In Depth " strategy (i.e., let the invader in and attempt to destroy it

internally) versus the ABH secretor state, which implies a " Preclusive

Strategy " (i.e., wall out the invader and don't allow entrance in the

first place). For example, the free ABH antigen on the mucosa barriers

of ABH secretors acts as an effective anti-adhesive mechanism against

ABH specific bacterial fimbriae lectins.

On the other hand, the ability to secrete relatively different

concentration of the components of the blood group substances as

determined by secretors/non-secretor genetics seems to affect phagocytic

activity of the leukocytes in a manner that actually places

non-secretors at somewhat of an advantage. In general, leukocytes of

non-secretors have substantially greater ingestion power as compared to

secretors. Although this ability appears to be across the board for all

non-secretors, blood group O and B non-secretors have the greatest

advantage and highest phagocytic activity.42 Perhaps this is a

compensatory mechanism for their more limited antigenic barrier in their

body fluids and secretions.

Pathologic cold agglutinins are produced either in response to infection

or by paraneoplastic or neoplastic growth of a single immunocyte clone.

In either case, they generally share the same immunochemical

characteristics and polysaccharide specificities. Cold agglutinins

regularly occur in the course of Mycoplasma pneumoniae (primary atypical

pneumonia) where they are usually specific for the I antigen. Data are

suggestive that the level of the anti-I cold agglutinin in the serum of

normal individuals may be affected by the donor's ABO group, secretor

status, and gender. For individuals with blood group O, B and AB,

secretors have higher levels of an antibody presumed to be auto-anti-I

(cold hemagglutinin). The level of this antibody is usually even higher

among non-A female secretors than for males.43

Diabetic non-secretors appear to have lower levels of some complement

fractions when compared to diabetic secretors. Researchers have found

that in individuals with type 1 diabetes mellitus, the mean level of

complement fraction C3c for non-secretors is significantly lower than

that found for secretors. The level of fraction C4 among ABH

non-secretors was also significantly lower than that of ABH secretors.44

Helicobacter pylori

The genetics of the ABH secretor/non-secretor system interact to alter

an individual's risk for ulcers. In several studies, non-secretors of

ABH substances have been found to have a significantly higher rate of

duodenal and peptic ulcers.45,46

The Copenhagen study found the lifetime prevalence of peptic ulcer in

men who were ABH non-secretors was 15 percent (statistically 15 percent

of ABH non-secretors will have an ulcer at some point in their lives).

And, the attributable risk of peptic ulcer in men who were Le (a + b-)

or ABH non-secretors, with blood group O or A phenotypes was 37

percent.47

Overall, the relative risk of gastroduodenal disease for non-secretors

compared with secretors is 1.9 (95% confidence interval). Duodenal ulcer

patients are more likely to be non-secretors, and being a non-secretor

acts as a multiplicative risk factor with the gene for

hyperpepsinogenemia I to impact the risk of duodenal ulcer.48,49

Because of the increased prevalence of ulcers among non-secretors,

researchers have suggested that secretor status might influence

bacterial colonization density or the ability of H. pylori to attach to

gastroduodenal cells. Regarding the overall interaction with H. pylori

infection, non-secretor status is generally considered to be a separate

independent risk factor for gastroduodenal disease in addition to H.

pylori infection; however, there is more to this story involving some

interesting interactions between secretor status, genetics, and H.

pylori.48

Because non-secretors are limited in their ability to secrete the Le(

blood group antigen into the mucus secretions of their digestive tract,

it has been proposed that they are at a competitive disadvantage from

preventing H. pylori attachment. In fact, the Le( antigens have been

found to act as somewhat of a preferential target for H. pylori

attachment. Thus, lack of Le( in mucosal fluids of ABH non-secretors

might indirectly contribute to colonization by H. pylori.50-52

In a simplified sense, when the Le( antigen is free floating in the

mucus, it probably acts to bind up some of the H. pylori before it can

contact and attach to host tissue. In essence, being an ABH secretor

provides an ability to put some biological decoys or metabolic chaff out

into the gastric secretions that is very specific for H. pylori. Also,

in ABH non-secretors the immune response against H. pylori appears to be

lower and H. pylori appears to attach with higher aggressiveness and

cause more inflammation.53

Individuals with Le (a+b-) ABH non-secretor phenotype also show a

significantly higher proportion of the H. pylori-seronegative subjects

and a lower IgG (H. pylori immunoglobulin G (IgG) antibody) immune

response to H. pylori antigens as compared with the individuals of Le

(a-b+)/secretor phenotype.

Evidence also indicates that 100 percent of non-secretors with duodenal

ulcers culture positive for H. pylori infection. However, among

non-secretors with gastric ulcer, H. pylori is found in only about 12.5

percent of the cases. This is not observed among secretors, who are

nearly equally likely to have H. pylori infection in either gastric or

duodenal ulcer.54

Bacterial Urinary Tract Infections

ABH non-secretors are at a greater risk for recurrent urinary tract

infections (UTI) and are much more likely to develop renal scars. This

susceptibility is even greater among the negative subset. The ABH

secretor phenotype conveys a measure of protection; cutting the risk of

recurrent UTI by greater than 50 percent and dramatically decreasing the

likelihood that renal scars will develop.

ABH non-secretors appear to be at extra risk for recurrent urinary tract

infections. In one study of women with recurrent UTI, 29 percent of the

women were the Le (a+ b-) non-secretor phenotype, while another 26

percent of the women were Le (a- b-) recessive phenotype. When the women

with ABH non-secretor and recessive phenotypes were combined and

considered collectively, the odds ratio (an estimate of relative risk of

recurrent urinary tract infection) for those without the secretor

phenotype Le (a-b+) was 3.4.55-58

A form of synergy also appears to exist between UTI risk, secretor

status, and the lack of ability to create anti-B isohemagglutinin.

Essentially, blood groups B and AB and the non-secretor phenotype seem

to work together to increase the relative risk of recurrent UTI among

these women.59 Evidence also indicates that women and children with

renal scarring subsequent to recurrent UTI and pyelonephritis are more

likely to be ABH non-secretors.56,60,61 As many as 55-60 percent of all

ABH non-secretors have been found to develop renal scars, even with the

regular use of antibiotic treatment for UTI, whereas, as few as 16

percent of ABH secretors will develop similar renal scarring.62

This tendency to scarring does not seem to be dictated as much by the

aggressiveness of the bacterial infection as by the more aggressive

inflammatory response created by ABH non-secretors against the bacterial

infection. The levels of C-reactive protein, erythrocyte sedimentation

rate, and body temperature are significantly higher in non-secretors

than in secretors (p < 0.04) with recurrent UTI. As a consequence, in

non-secretors the renal scarring seems to be secondary to their acute

phase inflammatory response.63

Neisseria sp.

The genetically determined inability to secrete the water-soluble

glycoprotein form of the ABO blood group antigens into saliva and other

body fluids is a recognized risk factor for Neisseria meningococcal

disease. ABH non-secretors are consistently over represented among

individuals contracting this infection. This overrepresentation is even

greater among individuals who are carriers of the infection.64 Secretory

immune capabilities and other factors appear to contribute to the

relative protection against colonization by meningococci enjoyed by ABH

secretors. ABH non-secretors typically have lower levels of

anti-meningococcal salivary IgM. And, to add insult to injury, both the

IgA and IgM antibodies produced by ABH secretors are more effective at

providing protection against this microorganism.65

Candida sp.

ABH non-secretors are much more likely to be carriers of Candida sp. and

to have problems with persistent Candida infections. Blood group O

non-secretors are the most affected of the non-secretor blood types. One

of the innate defenses against superficial infections by Candida species

appears to be the ability of an individual to secrete the water-soluble

form of his ABO blood group antigens into body fluids. The protective

effect afforded by the secretor gene might be due to the ability of

glycocompounds in the body fluids of secretors to inhibit adhesins

(attachment lectins) on the surface of the yeast. In attachment studies,

preincubation of blastospores with boiled secretor saliva significantly

reduced their ability to bind to epithelial cells. ABH non-secretor

saliva did not reduce the binding and often enhanced the numbers of

attached yeast colonies.66-67 In one study, among individuals with type

2 diabetes, 44 percent of ABH non-secretors were oral carriers of this

yeast.68

Although non-secretors make up only about 26 percent of the population,

they are significantly over represented among individuals with either

oral or vaginal Candida infections, making up almost 50 percent of

affected individuals.66 The inability to secrete blood group antigens in

saliva also appears to be a risk factor in the development or

persistence of chronic hyperplastic candidosis. In one study, the

proportion of non-secretors of blood group antigens among patients with

chronic hyperplastic candidosis was 68 percent.69

Women with recurrent idiopathic vulvovaginal Candidiasis are much more

likely to be ABH non-secretors. Combining both ABH non-secretor

phenotype and absence of the gene Le (a- b-), the relative risk of

chronic recurring vulvovaginal Candidiasis is 2.41-4.39, depending on

the analysis technique and control group.70

Oral carriage of Candida is also significantly associated with blood

group O (p < 0.001) and, independently, with non-secretion of blood

group antigens (p < 0.001), with the trend toward carriage being

greatest in group O non-secretors.71

Autoimmune Disease

ABH non-secretors appear to have an increase in the prevalence of a

variety of auto-immune diseases including ankylosing spondylitis,

reactive arthritis, psoriatic arthro-pathy, Sjogren's syndrome, multiple

sclerosis, and Grave's disease. This susceptibility toward autoimmune

problems appears to be most pronounced among Le (a-b-) phenotypes. Among

individuals with spondylo-arthropathies, non-secretors are reported to

make up 47 percent of the patient population. In the subgroup of these

patients suffering from ankylosing spondylitis, ABH non-secretors

account for 49 percent of patients. Since the control population has a

prevalence of non-secretors of 27 percent (consistent with the expected

percent in the general population), it appears that in

spondyloarthropathies in general, and ankylosing spondylitis

specifically, non-secretors are dramatically over represented,39,72

although this association has not gone uncontested.73

Among individuals with primary Sjogren's syndrome, blood group

frequency differs from that of the general population, due mainly to an

increased Le (a-b-) frequency.74

The inability to secrete the water-soluble glycoprotein form of the ABO

blood group antigens into saliva is significantly more common in

patients with Graves' disease than control subjects (40% versus 27%: p <

0.025), but not among those with Hashimoto's thyroiditis or spontaneous

primary atrophic hypo-thyroidism.75

ABH non-secretors with Grave's disease were found to produce higher

levels of antitubulin antibodies, while levels of other antibodies were

similar to secretors.75

Celiac Disease

ABH non-secretors are at an increased risk for development of celiac

disease. One study found 48 percent of patients with celiac disease were

reported to be ABH non-secretors.76 This appears to be especially true

for the recessive Le (a-b-) phenotype. Evidence suggests an increased

prevalence of complications and celiac-associated abnormalities in the

non-secreting and -negative celiac patients.77

Pulmonary Considerations

ABH secretors are significantly over represented among patients with

influenza viruses A and B (55/64, 86%; p < 0.025), rhinoviruses (63/72,

88%; p < 0.01), respiratory syncytial virus (97/109, 89%; p < 0.0005),

and echoviruses (44/44, p < 0.0005). Why this increased risk appears in

secretors has not been clearly established.78

Among coal miners, asthma has been related significantly to non-secretor

phenotype. In this population, significantly lower lung function and

higher likelihood of wheezing is found among -negative or

non-secretor subjects with blood group O.79 Independent findings suggest

that the ability to secrete ABH antigens might decrease the risk of

COPD. Non-secretors have been found to have significantly greater

impairment of forced expiration. ABH non-secretors have lower mean

values of forced expiratory volume in one second as a percentage of

forced vital capacity (FEV1/FVC%) and a significantly larger proportion

of them had aberrant values, defined as FEV1/FVC% less than 68.80 ABH

non-secretor status also offers a slight increase risk for habitual

snoring.81

Neoplasia and Malignancy

Secretor and Phenotypes and Tumor

Markers Accurately predicting the relevance of some tumor markers for

diagnosis of cancer appears to be dependent on both secretor status and

blood group. As an example, some researchers have suggested that

taking into account aspects of and/or secretor status in order to

establish reference ranges might actually be a way to increase the

clinical utility of the CA 19-9 tumor marker (Table 4).82

There is a substantial difference in levels of this tumor marker under

the control of secretor and genetics. Individuals having

homozygous inactive Se alleles (sese) and homozygous active Le alleles

(LeLe), exhibited the highest mean CA19-9 value. All of the

-negative individuals consisting of an lele genotype had completely

negative CA19-9 values, irrespective of the Se genotype.

On the other hand, -negative individuals showed a higher mean

DU-PAN-2 value than did the -positive individuals. Among patients

with colorectal cancer, the -negative patients (lele) with

colorectal cancer showed undetectable CA19-9 values (i.e., less than 1.0

unit/mL), but many of them exhibited highly positive DU-PAN-2 values. In

contrast, many of the -positive patients (LeLe or Lele) had

positive CA19-9 values; whereas, very few of them exhibited positive

DU-PAN-2 values.83

The implication is that the CA19-9 measurement is not a useful tumor

marker for -negative individuals, although DU-PAN-9 appears to be.

-negative individuals do not express any kinds of type 1 chain

antigens (Le (a), Le (, and secretory (a)) in their

digestive organs. It is, therefore, not useful to measure the CA19-9

titer of the -negative cancer patient.84

Preneoplastic Changes and Cancer

As a general rule, a higher intensity of oral disease is found among ABH

non-secretors. So it is not surprising that when it comes to

precancerous or cancerous changes to tissue of the mouth and esophagus,

ABH non-secretors seem to fair worse than ABH secretors. This oral

disease susceptibility is reflected in the occurrence of epithelial

dysplasia, for example, which is found almost exclusively in the

non-secretor group.85

Barrett's esophagus, a condition often preceding the development of

esophageal cancer, and esophageal cancer also show a positive

association with Le (a+b-) non-secretor phenotypes.86

Conclusion

Determining ABH secretor phenotype and/or blood group status may

be useful as risk factor determinates for a number of conditions

including heart disease, diabetes, insulin resistance, certan types of

cancer, Candida, H. pylori, autoimmune diseases, celiac disease, chronic

urinary tract infections, and others.

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On Monday, April 22, 2002, at 11:35 AM, Amy ez wrote:

> I was thinking, in my struggles to make the BTD work for me, have their

> been

> any controlled scientific studies as to the validity, effectiveness,

> success

> rate of the BTD? I have convinced myself to believe in it, and that it

> is

> good and right, but more and more I am questioning that....I decided to

> believe in this based on all the testimonials from all the people on

> this

> list and at Dr D's site, and the amazing results they have had. But

> then I

> got to thinking, what if there are just as many people out there that

> have

> tried this and it didn't work for them, and since they are not

> necessarily

> supportive of the whole theory there is no record of them? It just got

> me to

> think that maybe there are some people that this just doesn't work the

> same

> for, like me? I don't me to cause an uproar, just wondering if there is

> any

> real published scientific evidence, other than anecdotal...

> Amy O+ Sec still struggling with all of this...