Lectins, anyone heard of them?

[Guest guest]

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

Gilbert RJ.

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33:

3-4.

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Bardocz S.

Handbook of plant lectins: properties and biomedical

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Pusztai A, Greer F, Grant G.

Specific uptake of dietary lectins into the systemic circulation of

rats. Biochem Soc Trans 1989;

17:

481-482.

Wang Q, Yu L-G, BJ, Milton J,

JM.

Identification of intact peanut lectinin peripheral venous blood. Lancet

1998;

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FW, Kolb H.

Cow's milk and insulin-dependent diabetes mellitus. Lancet

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Bond A, Kerr MA, Hay FC.

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38:

744-749[Medline].

Toohey L.

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Banwell JG, R, Kabir I, Costerton

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Bacterial overgrowth by indigenous microflora in the PHA-fed rat. Can

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Anonymous, but attributed to D'Adamo P.

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