Amyloid, a term for a misfolded form of an otherwise normal protein, is most often associated with amyloid-beta, the waxy protein that builds up in the brains of people with Alzheimer's disease. But at least 20 other kinds of amyloid, each derived from a different protein, can crop up in various parts of the body. What such malformed proteins have in common is their hairlike shape and tendency to compromise the function of the organ in which they reside.
At least one food—the fatty delicacy known as foie gras—can be naturally rich in amyloids. A new study in rodents shows that consumption of foie gras, which is the primary ingredient of high-quality liver pâté, can trigger amyloid disease in mice.
Over the years, researchers had shown that when some tissues experience excessive inflammation, they can inappropriately develop amyloid forms of various proteins. Among such tissues are fatty livers. Foie gras is made by force-feeding geese or ducks until their livers become grossly enlarged. The flavor of the fattened organ, which is typically pureed and served with toast or crackers, is buttery and delicate.
Now, researchers have analyzed commercially prepared foie gras and confirmed the presence of amyloid proteins within it. An amyloid-laden extract of this foie gras, when fed or injected into mice, triggered the animals to produce the same form of amyloid sometimes seen in people with chronic inflammatory diseases, such as rheumatoid arthritis.
Excessive amyloid buildup—known as amyloidosis—damages the function of an organ.
The findings confirm that amyloid diseases are transmissible, says study leader Alan Solomon of the University of Tennessee Graduate School of Medicine. (He points out that another kind of amyloid—the prions that cause mad cow disease—are similarly transmissible.) What seems to be happening, he explains, is that once the foie gras' amyloid proteins enter the mice, the molecules trigger some of the animals' native proteins to misfold, amplifying concentrations of the amyloid.
There is no need to panic, Solomon cautions. His team chose animals for its tests that were especially vulnerable to amyloid disease. All the mice had been genetically engineered to develop amyloid protein A amyloidosis—known as AA—an occasional complication of rheumatoid arthritis and certain other inflammatory diseases.
Healthy animals—or people—might consume the same foie gras–derived amyloid that the test animals did and suffer no ill effect.
How toxic could foie gras possibly be? The amyloid accumulation in foie gras–treated animals led to tissue damage that started in the spleen and eventually spread into the liver, heart, tongue, and gastrointestinal tract. Within 2 months, most of the mice were at death's door, Solomon's team reports in the June 26 Proceedings of the National Academy of Sciences.
What's so foul about this fowl product?
Making foie gras usually entails force-feeding geese or ducks. Starting several weeks prior to slaughter, a farmer inserts a tube down a bird's throat and then gorges the animal with corn gruel several times a day.
Solomon suspects that the stress the procedure puts on an animal, especially on its liver, contributes to the formation of amyloids.
Through a series of chemical tests, his group confirmed the presence of amyloids in commercially marketed duck and goose foie gras. The researchers then injected extracts of the products into the tails of 2-month-old, genetically-engineered mice that are prone to amyloidosis. Other such mice received just injections of saline.
The animals that received the foie gras extract developed lethal amyloid disease throughout their spleens, livers, and reproductive tracts within 2 months. Because of their genetic susceptibility, the mice getting saline also progressed to that stage of disease—but it took about 8 months. These results confirm an "amyloid enhancing" effect of the injected extract, Solomon and his colleagues report.
In a second trial, they injected an inflammatory agent into healthy, genetically normal mice. The inflammation, which continued for weeks, was designed to simulate the state of a chronic inflammatory disease. One group of 10 mice was also injected with a foie gras extract. Within 3 weeks, eight of the rodents experienced liver and spleen amyloidosis. Those organs remained clean of amyloid in a group of 10 mice that received only a saline injection following the inflammatory stimulus.
That finding indicates that foie gras is not solely a threat to genetically prone animals.
In a final experiment, the researchers forced a new group of genetically engineered mice to consume either saline or an extract of foie gras for 5 straight days. Two months later, five of eight extract-treated animals developed "amyloid deposits in virtually all organs examined"—but especially in their livers and spleens. Saline-only animals remained amyloidfree.
Risks are low
Solomon points out that the dose of foie gras administered in his experiments was high. For comparison, he says, "an equivalent dose for a human would be about 3.5 to 3.8 pounds." Also, people obviously never inject foie gras into their tails. The exaggerated dose and simplified method of administration was used merely to test quickly whether amyloid intake might initiate or promote amyloidosis. The fact that it did now suggests, he says, that follow-up tests with lower doses are warranted to see whether there's a threshold to the ingested amyloid's toxicity.
Clearly, this is not a major public health risk, Solomon says, since there's no evidence that AA disease is epidemic in regions of the world—such as France—where foie gras consumption is relatively high.
Nevertheless, Solomon counsels that people at high risk of AA, which includes those with rheumatoid arthritis and tuberculosis, might want to eschew foie gras—just to play it safe.
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