Do dietary lectins cause disease?

[Guest guest]

BMJ 1999;318:1023-1024 ( 17 April )

Editorials

Do dietary lectins cause disease?

The evidence is suggestiveand raises interesting possibilities for treatment

In 1988 a hospital launched a " healthy eating day " in its staff canteen at

lunchtime. One dish contained red kidney beans, and 31 portions were served. At

3 pm one of the customers, a surgical registrar, vomited in theatre. Over the

next four hours 10 more customers suffered profuse vomiting, some with

diarrhoea. All had recovered by next day. No pathogens were isolated from the

food, but the beans contained an abnormally high concentration of the lectin

phytohaemagglutinin.1 Lectins are carbohydrate binding proteins present in most

plants, especially seeds and tubers like cereals, potatoes, and beans. Until

recently their main use was as histology and blood transfusion reagents, but in

the past two decades we have realised that many lectins are (a) toxic,

inflammatory, or both; ( resistant to cooking and digestive enzymes; and ©

present in much of our food.2 It is thus no surprise that they sometimes cause

" food poisoning. " But the really disturbing finding came with the discovery in

1989 that some food lectins get past the gut wall and deposit themselves in

distant organs. 3 4 So do they cause real life diseases?

This is no academic question because diet is one part of the environment that is

manipulable and because lectins have excellent antidotes, at least in vitro.

Because of their precise carbohydrate specificities, lectins can be blocked by

simple sugars and oligosaccharides. Wheat lectin, for example, is blocked by the

sugar N-acetyl glucosamine and its polymers.5 These natural compounds are

potentially exploitable as drugs should lectin induced diseases be identified.

Wheat gliadin, which causes coeliac disease, contains a lectin like substance

that binds to human intestinal mucosa,6 and this has been debated as the

" coeliac disease toxin " for over 20 years.7 But coeliac disease is already

managed by gluten avoidance, so nothing would change were the lectin hypothesis

proved. On the other hand, wheat lectin also binds to glomerular capillary

walls, mesangial cells, and tubules of human kidney and (in rodents) binds IgA

and induces IgA mesangial deposits. This suggests that in humans IgA nephropathy

might be caused or aggravated by wheat lectin; indeed a trial of gluten

avoidance in children with this disease reported reduced proteinuria and immune

complex levels.8

Of particular interest is the implication for autoimmune diseases. Lectins

stimulate class II HLA antigens on cells that do not normally display them, such

as pancreatic islet and thyroid cells.9 The islet cell determinant to which

cytotoxic autoantibodies bind in insulin dependent diabetes mellitus is the

disaccharide N-acetyl lactosamine,10 which must bind tomato lectin if present

and probably also the lectins of wheat, potato, and peanuts. This would result

in islet cells expressing both class II HLA antigens and foreign antigen

togethera sitting duck for autoimmune attack. Certain foods (wheat, soya) are

indeed diabetogenic in genetically susceptible mice.11 Insulin dependent

diabetes therefore is another potential lectin disease and could possibly be

prevented by prophylactic oligosaccharides.

Another suspect lectin disease is rheumatoid arthritis. The normal human IgG

molecule possesses carbohydrate side chains, which terminate with galactose. In

rheumatoid arthritis much of the galactose is missing, so that the subterminal

sugarN-acetyl glucosamineis exposed instead. These deficient IgG molecules

feature strongly in the circulating immune complexes that cause fever and

symptoms.12 In diet responsive rheumatoid arthritis one of the commonest trigger

foods is wheat, and wheat lectin is specific for N-acetyl glucosaminethe sugar

that is normally hidden but exposed in rheumatoid arthritis. This suggests that

N-acetyl glucosamine oligomers such as chitotetraose (derived from the chitin

that forms crustacean shells) might be an effective treatment for diet

associated rheumatoid arthritis. Interestingly, the health food trade has

already siezed on N-acetyl glucosamine as an antiarthritic supplement.13

Among the effects observed in the small intestine of lectin fed rodents is

stripping away of the mucous coat to expose naked mucosa and overgrowth of the

mucosa by abnormal bacteria and protozoa.14 Lectins also cause discharge of

histamine from gastric mast cells,15 which stimulates acid secretion. So the

three main pathogenic factors for peptic ulceracid stimulation, failure of the

mucous defence layer, and abnormal bacterial proliferation (Helicobacter pylori)

are all theoretically linked to lectins. If true, blocking these effects by

oligosaccharides would represent an attractive and more physiological treatment

for peptic ulcer than suppressing stomach acid. The mucus stripping effect of

lectins16 also offers an explanation for the anecdotal finding of many

allergists that a " stone age diet, " which eliminates most starchy foods and

therefore most lectins, protects against common upper respiratory viral

infections: without lectins in the throat the nasopharyngeal mucus lining would

be more effective as a barrier to viruses.

But if we all eat lectins, why don't we all get insulin dependent diabetes,

rheumatoid arthritis, IgA nephropathy, and peptic ulcers? Partly because of

biological variation in the glycoconjugates that coat our cells and partly

because these are protected behind a fine screen of sialic acid molecules,

attached to the glycoprotein tips.10 We should be safe. But the sialic acid

molecules can be stripped off by the enzyme neuraminidase, present in several

micro-organisms such as influenzaviruses and streptococci. This may explain why

diabetes and rheumatoid arthritis tend to occur as sequelae of infections. This

facilitation of lectins by micro-organisms throws a new light on postinfectious

diseases and makes the folklore cure of fasting during a fever seem sensible.

Alternative medicine popularisers are already publishing articles about dietary

lectins,17 often with more enthusiasm than caution, so patients are starting to

ask about them and doctors need to be armed with facts. The same comment applies

to entrepreneurs at the opposite end of the commercial spectrum. Many lectins

are powerful allergens, and prohevein, the principal allergen of rubber latex,

is one. It has been engineered into transgenic tomatoes for its fungistatic

properties,18 so we can expect an outbreak of tomato allergy in the near future

among latex sensitive individuals. Dr Arpad Pusztai lost his job for publicising

concerns of this type (20 February, p 483).

L J Freed, Allergist.

14 Marston Road, Salford M7 4ER

--------------------------------------------------------------------------------

1.. Gilbert RJ. Healthy eating day. Communicable Disease Report 1988; 33: 3-4.

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

lectins: properties and biomedical applications. London: Wiley, 1998:31-50.

c.. Pusztai A, Greer F, Grant G. Specific uptake of dietary lectins into the

systemic circulation of rats. Biochem Soc Trans 1989; 17: 481-482.

d.. Wang Q, Yu L-G, BJ, Milton J, JM. Identification of intact

peanut lectinin peripheral venous blood. Lancet 1998; 352: 1831-1832[Medline].

5.. Goldstein IJ, Poretz RD. Isolation and chemical properties of lectins. In:

Liener IE, Sharon N, Goldstein IJ, eds. The lectins. Orlando: Academic Press ,

1986.

f.. Kolberg J, Sollid L. Lectin activity of gluten identified as wheat germ

agglutinin. Biochem Biophys Res Comm 1985; 130: 867-872[Medline].

7.. Weiser MM, AP. An alternative mechanism for gluten toxicity in

coeliac disease. Lancet 1976; i: 567.

h.. Coppo R, Amore A, Roccatello D. Dietary antigens and primary IgA

nephropathy. J Am Soc Nephrol 1992; 2(10 suppl): S173-S180[Abstract].

9.. What triggers auto-immunity? Lancet 1985; ii: 78-79.

j.. Uchigata Y, Spitalnik SL, Tachiwaki O, Salata KF, Notkins AL. Pancreatic

islet cell surface glycoproteins containing Gal (1-4)GNAc-R identified by

cytotoxic monoclonal antibodies. J Exp Med 1987; 165: 124-139[Abstract].

11.. FW, Kolb H. Cow's milk and insulin-dependent diabetes mellitus.

Lancet 1996; 348: 613.

l.. Bond A, Kerr MA, Hay FC. Distinct oligosaccharide content of rheumatoid

arthritis derived immune complexes. Arthr Rheum 1995; 38: 744-749[Medline].

13.. Toohey L. Natural substances combat arthritis with " immune power " . Nutri

Notes 1997; 2: 1-6.

n.. Banwell JG, R, Kabir I, Costerton JW. Bacterial overgrowth by

indigenous microflora in the PHA-fed rat. Can J Microbiol 1988; 34:

1009-1013[Medline].

15.. Greer F, Pusztai A. Toxicity of kidney bean (Phaseolus vulgaris) in rats:

changes in intestinal permeability. Digestion 1985; 32: 42-46[Medline].

16.. Freed DLJ, Buckley CH. Mucotractive effect of lectin. Lancet 1978; i:

585-586.

q.. Anonymous, but attributed to D'Adamo P. Blood type: the link with diet and

disease. What Doctors Don't Tell You 1998; 9: 1-4.

r.. Lee HI, Raikhel NV. Prohevein is poorly processed but shows enhanced

resistance to a chitin-binding fungus in transgenic tomato plants. Braz J Med

Biol Res 1995; 28: 743-750[Medline].

--------------------------------------------------------------------------------

©

http://www.bmj.com/cgi/content/full/318/7190/1023

[Guest guest]

I think you may have posted this interesting piece before, a. I didn't

comment previously, but Dr. D'Adamo's popular " Eat Right 4 Your Type "

book describes his theory of how dietary lectins influence our health and

that people of each blood type should consume specific lectins and avoid

others. The osteopathic physician who prescibed minocycline for me

recommended the book and suggested that I try the food guidelines. I've been

on this diet since 1998 and feel much better on it. Right or wrong, it's

fascinating reading.

----- Original Message -----

From: " a " <aA@...>

<egroups>

Sent: Sunday, December 31, 2000 3:44 PM

Subject: [ ] Do dietary lectins cause disease?

BMJ 1999;318:1023-1024 ( 17 April )

Editorials

Do dietary lectins cause disease?

The evidence is suggestiveand raises interesting possibilities for treatment

In 1988 a hospital launched a " healthy eating day " in its staff canteen at

lunchtime. One dish contained red kidney beans, and 31 portions were served.

At 3 pm one of the customers, a surgical registrar, vomited in theatre. Over

the next four hours 10 more customers suffered profuse vomiting, some with

diarrhoea. All had recovered by next day. No pathogens were isolated from

the food, but the beans contained an abnormally high concentration of the

lectin phytohaemagglutinin.1 Lectins are carbohydrate binding proteins

present in most plants, especially seeds and tubers like cereals, potatoes,

and beans. Until recently their main use was as histology and blood

transfusion reagents, but in the past two decades we have realised that many

lectins are (a) toxic, inflammatory, or both; ( resistant to cooking and

digestive enzymes; and © present in much of our food.2 It is thus no

surprise that they sometimes cause " food poisoning. " But the really

disturbing finding came with the discovery in 1989 that some food lectins

get past the gut wall and deposit themselves in distant organs. 3 4 So do

they cause real life diseases?

This is no academic question because diet is one part of the environment

that is manipulable and because lectins have excellent antidotes, at least

in vitro. Because of their precise carbohydrate specificities, lectins can

be blocked by simple sugars and oligosaccharides. Wheat lectin, for example,

is blocked by the sugar N-acetyl glucosamine and its polymers.5 These

natural compounds are potentially exploitable as drugs should lectin induced

diseases be identified.

Wheat gliadin, which causes coeliac disease, contains a lectin like

substance that binds to human intestinal mucosa,6 and this has been debated

as the " coeliac disease toxin " for over 20 years.7 But coeliac disease is

already managed by gluten avoidance, so nothing would change were the lectin

hypothesis proved. On the other hand, wheat lectin also binds to glomerular

capillary walls, mesangial cells, and tubules of human kidney and (in

rodents) binds IgA and induces IgA mesangial deposits. This suggests that in

humans IgA nephropathy might be caused or aggravated by wheat lectin; indeed

a trial of gluten avoidance in children with this disease reported reduced

proteinuria and immune complex levels.8

Of particular interest is the implication for autoimmune diseases. Lectins

stimulate class II HLA antigens on cells that do not normally display them,

such as pancreatic islet and thyroid cells.9 The islet cell determinant to

which cytotoxic autoantibodies bind in insulin dependent diabetes mellitus

is the disaccharide N-acetyl lactosamine,10 which must bind tomato lectin if

present and probably also the lectins of wheat, potato, and peanuts. This

would result in islet cells expressing both class II HLA antigens and

foreign antigen togethera sitting duck for autoimmune attack. Certain foods

(wheat, soya) are indeed diabetogenic in genetically susceptible mice.11

Insulin dependent diabetes therefore is another potential lectin disease and

could possibly be prevented by prophylactic oligosaccharides.

Another suspect lectin disease is rheumatoid arthritis. The normal human IgG

molecule possesses carbohydrate side chains, which terminate with galactose.

In rheumatoid arthritis much of the galactose is missing, so that the

subterminal sugarN-acetyl glucosamineis exposed instead. These deficient IgG

molecules feature strongly in the circulating immune complexes that cause

fever and symptoms.12 In diet responsive rheumatoid arthritis one of the

commonest trigger foods is wheat, and wheat lectin is specific for N-acetyl

glucosaminethe sugar that is normally hidden but exposed in rheumatoid

arthritis. This suggests that N-acetyl glucosamine oligomers such as

chitotetraose (derived from the chitin that forms crustacean shells) might

be an effective treatment for diet associated rheumatoid arthritis.

Interestingly, the health food trade has already siezed on N-acetyl

glucosamine as an antiarthritic supplement.13

Among the effects observed in the small intestine of lectin fed rodents is

stripping away of the mucous coat to expose naked mucosa and overgrowth of

the mucosa by abnormal bacteria and protozoa.14 Lectins also cause discharge

of histamine from gastric mast cells,15 which stimulates acid secretion. So

the three main pathogenic factors for peptic ulceracid stimulation, failure

of the mucous defence layer, and abnormal bacterial proliferation

(Helicobacter pylori) are all theoretically linked to lectins. If true,

blocking these effects by oligosaccharides would represent an attractive and

more physiological treatment for peptic ulcer than suppressing stomach acid.

The mucus stripping effect of lectins16 also offers an explanation for the

anecdotal finding of many allergists that a " stone age diet, " which

eliminates most starchy foods and therefore most lectins, protects against

common upper respiratory viral infections: without lectins in the throat the

nasopharyngeal mucus lining would be more effective as a barrier to viruses.

But if we all eat lectins, why don't we all get insulin dependent diabetes,

rheumatoid arthritis, IgA nephropathy, and peptic ulcers? Partly because of

biological variation in the glycoconjugates that coat our cells and partly

because these are protected behind a fine screen of sialic acid molecules,

attached to the glycoprotein tips.10 We should be safe. But the sialic acid

molecules can be stripped off by the enzyme neuraminidase, present in

several micro-organisms such as influenzaviruses and streptococci. This may

explain why diabetes and rheumatoid arthritis tend to occur as sequelae of

infections. This facilitation of lectins by micro-organisms throws a new

light on postinfectious diseases and makes the folklore cure of fasting

during a fever seem sensible.

Alternative medicine popularisers are already publishing articles about

dietary lectins,17 often with more enthusiasm than caution, so patients are

starting to ask about them and doctors need to be armed with facts. The same

comment applies to entrepreneurs at the opposite end of the commercial

spectrum. Many lectins are powerful allergens, and prohevein, the principal

allergen of rubber latex, is one. It has been engineered into transgenic

tomatoes for its fungistatic properties,18 so we can expect an outbreak of

tomato allergy in the near future among latex sensitive individuals. Dr

Arpad Pusztai lost his job for publicising concerns of this type (20

February, p 483).

L J Freed, Allergist.

14 Marston Road, Salford M7 4ER

----------------------------------------------------------------------------

----

1.. Gilbert RJ. Healthy eating day. Communicable Disease Report 1988; 33:

3-4.

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

lectins: properties and biomedical applications. London: Wiley, 1998:31-50.

c.. Pusztai A, Greer F, Grant G. Specific uptake of dietary lectins into

the systemic circulation of rats. Biochem Soc Trans 1989; 17: 481-482.

d.. Wang Q, Yu L-G, BJ, Milton J, JM. Identification of

intact peanut lectinin peripheral venous blood. Lancet 1998; 352:

1831-1832[Medline].

5.. Goldstein IJ, Poretz RD. Isolation and chemical properties of lectins.

In: Liener IE, Sharon N, Goldstein IJ, eds. The lectins. Orlando: Academic

Press , 1986.

f.. Kolberg J, Sollid L. Lectin activity of gluten identified as wheat

germ agglutinin. Biochem Biophys Res Comm 1985; 130: 867-872[Medline].

7.. Weiser MM, AP. An alternative mechanism for gluten toxicity in

coeliac disease. Lancet 1976; i: 567.

h.. Coppo R, Amore A, Roccatello D. Dietary antigens and primary IgA

nephropathy. J Am Soc Nephrol 1992; 2(10 suppl): S173-S180[Abstract].

9.. What triggers auto-immunity? Lancet 1985; ii: 78-79.

j.. Uchigata Y, Spitalnik SL, Tachiwaki O, Salata KF, Notkins AL.

Pancreatic islet cell surface glycoproteins containing Gal (1-4)GNAc-R

identified by cytotoxic monoclonal antibodies. J Exp Med 1987; 165:

124-139[Abstract].

11.. FW, Kolb H. Cow's milk and insulin-dependent diabetes mellitus.

Lancet 1996; 348: 613.

l.. Bond A, Kerr MA, Hay FC. Distinct oligosaccharide content of

rheumatoid arthritis derived immune complexes. Arthr Rheum 1995; 38:

744-749[Medline].

13.. Toohey L. Natural substances combat arthritis with " immune power " .

Nutri Notes 1997; 2: 1-6.

n.. Banwell JG, R, Kabir I, Costerton JW. Bacterial overgrowth by

indigenous microflora in the PHA-fed rat. Can J Microbiol 1988; 34:

1009-1013[Medline].

15.. Greer F, Pusztai A. Toxicity of kidney bean (Phaseolus vulgaris) in

rats: changes in intestinal permeability. Digestion 1985; 32:

42-46[Medline].

16.. Freed DLJ, Buckley CH. Mucotractive effect of lectin. Lancet 1978; i:

585-586.

q.. Anonymous, but attributed to D'Adamo P. Blood type: the link with diet

and disease. What Doctors Don't Tell You 1998; 9: 1-4.

r.. Lee HI, Raikhel NV. Prohevein is poorly processed but shows enhanced

resistance to a chitin-binding fungus in transgenic tomato plants. Braz J

Med Biol Res 1995; 28: 743-750[Medline].