Tetrodotoxin: the poison of puffer fish

By Cristiano Antonino On Dec 12, 2022

Tetrodotoxin (TTX) is a neurotoxin known to be contained in pufferfish. The pufferfish family is not the only one in which we can find tetrodotoxin, also found in some octopuses and newts

The effects of this poison are deadly, with gradual paralysis and cardiorespiratory blockage.

Despite this, fugu that contains a small dose of it is still cooked in Japan.

In nature, numerous animals have tetrodotoxin

The pufferfish family (the Tetraodontidae, from the Greek for “four teeth”), is certainly the best known, as well as the one from which it takes its name.

Other organisms in which it is found, especially of marine environment, include some octopuses, cuttlefish, starfish, crabs, toads and newts.

What is special about all these species is that they contain similar bacterial families that are believed to be responsible for producing the poison.

In fact, the toxin would be a product of bacterial metabolism by Vibrionaceae and Pseudomonas spp.

Through natural selection, these animals would have evolved to become immune to tetrodotoxin and be able to live in symbiosis with the bacterial species.

The concentration of toxin within pufferfish varies in different compartments.

The most contaminated areas are mainly internal organs such as the liver, ovaries and intestines.

There is also a fair amount of TTX in the skin, while it is hardly present in the flesh.

Tetrodotoxin between history and legend

The use of pufferfish for food purposes dates back to antiquity.

In fact, the earliest evidence of consumption in Japanese cuisine dates back to the Jōmon period, more than 2,000 years ago.

Fugu has remained a typical dish throughout Japanese history, with some periods of hiatus.

In fact, the consumption of puffer fish was banned both under the Tokugawa family and during the Meiji period, roughly from 1600 until the early 1900s.

Even today, it is also forbidden by law for the emperor to consume fugu for his own safety.

According to legend, it is not only the Japanese who use pufferfish venom.

In fact, it appears that tetrodotoxin is present in numerous recipes used by Haitian bokors.

The bokor is a voodoo sorcerer devoted to black magic, particularly important in the process of zombification.

The myth became known mostly as a result of Edmund Wade Davis’ accounts of the events of Clairvius Narcisse, a Haitian farmer who was declared dead on May 2, 1962, and reappeared on the same island in 1980.

The farmer claimed to have been turned into a zombie by a bokor, only to be forced to serve him in the following years.

Davis tried to explain the process of apparent death by the effects of tetrodotoxin, speculating that, in low doses, it causes the same symptoms reported by Clairvius.

However, this idea will be refuted by the scientific community of the time, as the effects of poison are different from those described.

Effects and risks of the poison

The average lethal dose (LD50) of tetrodotoxin in mice is 334 μg per kg.

It has been estimated that in humans it takes only 1 to 4 mg of venom to meet certain death.

For comparison, cyanide has an LD50 value of 8.5 mg per kg, hundreds of times as much.

To date, there is still no effective antidote.

The only possible treatment is gastric lavage, to be performed immediately, with administration of activated charcoal, which binds the toxic molecules.

In addition, since it is a thermostable molecule, even cooking would not diminish the effect of the toxin on humans.

The effect of tetrodotoxin is through its binding to sodium channels located on cell membranes, inactivating them.

Specifically, the venom blocks the neuronal action potential mechanism, preventing the passage of sodium and subsequent depolarization.

The binding between TTX and the channel site is very strong, being able to last as long as 10 seconds

In comparison, sodium remains bound for no more than 1 nanosecond.

The first symptom of tetrodotoxin poisoning is numbness of the tongue and lips, which appears about 20 minutes after consumption.

Then paresthesia of the face and body extremities, shortness of breath and tinnitus (ringing sensations in the ears) set in.

Other symptoms due to poisoning may include nausea, vomiting, and headache.

The onset of paralysis, with cardiorespiratory failure, is the last vital phase, usually within 4-6 hours of ingestion.

Throughout this time, the individual remains conscious.

Methods of preparation

So-called fugu is considered a typically Japanese delicacy.

Tending to be served as sashimi, however, pufferfish can also be brought to the table in the form of nigiri or fried.

Nigiri is one way in which sushi can be served, resting a slice of fish on a compact block of rice.

The fugu sashimi plating is generally made to resemble a chrysanthemum flower.

The flesh of puffer fish is transparent-whitish in color, fairly tough in texture, and, compared to other similar preparations, has a decidedly less pronounced, almost flavorless taste.

Although tetrodotoxin is not naturally present in the dishes served, only licensed chefs are allowed to prepare fugu.

In recent years, however, death statistics have been drastically reduced.

In fact, of the 23 cases reported in Japan from 1993 to 2006, only one was caused by eating fugu in a restaurant.

Despite this, Italy was one of the first countries to ban its import and consumption, back in 1992.

It was quickly followed by other states, until the entirety of the European Union in 2004.

In Japan one can also rarely find some cuts in which there is a minimal amount of poison, so that one can feel a brief tingling sensation on the tongue and lips.