In this blog post, we’ll examine everything from the formation and accumulation of tetrodotoxin—the highly toxic substance found in pufferfish—to how it acts on nerve cells, the symptoms of poisoning, and how to safely consume pufferfish.
In the past, there were frequent incidents where people lost their lives due to improper consumption of pufferfish. One such case was reported as follows: At a sushi restaurant in Masan, two customers eating fugu sashimi began experiencing numbness in their hands and called the chef to complain. The chef responded, “I prepared it properly. There’s absolutely no way that could happen,” and proceeded to eat the sashimi himself. Shortly thereafter, all three people—the customers and the chef—died. While it is difficult to verify the specific details of this particular incident today, pufferfish poisoning is indeed dangerous enough to cause respiratory muscle paralysis and lead to death.
Every living organism has its own “secret weapon.” Driven by a survival instinct to protect itself from the external environment or other organisms, it defends itself in various ways. One such method is poison. The stinger of a honeybee, the venom of a snake, and the toxins in certain mushrooms are prime examples. One of the most common natural toxins to which we may be exposed through food is pufferfish poison. Known to act as a defense mechanism against predators, this toxin’s formal name is “tetrodotoxin.” Tetrodotoxin is a potent neurotoxin found not only in pufferfish but also in some other aquatic animals and amphibians.
In fact, it is unlikely that pufferfish synthesize large amounts of this toxin on their own. Research to date has identified several microorganisms that are presumed to produce tetrodotoxin or be involved in its production; it is believed that pufferfish ingest tetrodotoxin through the food chain and accumulate it in their bodies. In other words, rather than pufferfish being inherently toxic from the start, their toxicity can decrease if they are raised in an environment free of toxic substances, and it can increase if they are fed food containing tetrodotoxin. However, there are still unresolved aspects regarding the exact processes of tetrodotoxin production and accumulation, and the toxicity of pufferfish can vary significantly depending on the species, individual, region, diet, and rearing environment. Therefore, one should not assume that pufferfish raised in freshwater or aquaculture environments are necessarily safe.
Tetrodotoxin is a very potent natural toxin. It causes paralysis primarily by blocking voltage-gated sodium channels, which are essential for transmitting electrical signals in nerves and muscles. In the early stages of poisoning, symptoms such as numbness or sensory abnormalities in the lips and tongue, as well as numbness in the face and limbs, may appear. Subsequently, muscle strength weakens and paralysis progresses, potentially affecting the respiratory muscles. In severe cases, respiratory arrest and cardiovascular failure can lead to death. Symptoms generally appear within a few hours after consuming pufferfish, though this may vary depending on the amount consumed and the individual’s physical condition.
So, how does tetrodotoxin produce these effects? Before explaining the mechanism of action, let’s briefly examine how stimuli are conducted through nerves. On a rainy day, we close all the doors in our house to keep the rain out. But what would happen if, one day, a strong stimulus—like a bolt of lightning—blew the roof and doors away? Rain would pour into the house unchecked. Similarly, the nerve cells in our bodies have a kind of channel that regulates the movement of charged particles in and out. When no stimulus is present, the ion channels in the cell membrane are closed, and the inside of the cell membrane remains relatively negatively charged compared to the outside.
However, when a stimulus is applied to a nerve cell, voltage-gated sodium channels open, allowing positively charged sodium ions to rapidly flow into the cell, thereby altering the cell membrane’s potential. This change in potential leads to an action potential, which transmits an electrical signal along the nerve cell; nerve cells use this process to exchange information with one another.
Tetrodotoxin, the toxin found in pufferfish, blocks this very process of stimulus transmission, paralyzing the nerves and muscles in our bodies. To be more specific, once tetrodotoxin is absorbed into the body, it binds to the outer surface of voltage-gated sodium channels found in nerve cells and skeletal muscle cells, preventing sodium ions from passing through the channels. In other words, it acts like a barricade, blocking the movement of sodium ions. Consequently, even when a stimulus is received, sodium ions cannot enter the cell in sufficient quantities, making it difficult for normal action potentials to be generated or transmitted. As a result, nerve cells cannot transmit normal signals to the muscles, leading to sensory abnormalities, muscle weakness, and paralysis. To put it simply, imagine fans waiting for a celebrity at an airport who, upon seeing the celebrity appear, start running frantically toward them. However, a bodyguard resembling a pufferfish—tetrodotoxin—appears and blocks the fans, preventing them from approaching the celebrity. Just as the fans cannot reach the celebrity, if sodium ions cannot move normally, the transmission of electrical signals in nerve cells is also disrupted.
Because tetrodotoxin blocks the transmission of electrical signals between nerves and muscles, poisoning can cause sensory abnormalities, muscle weakness, and paralysis. In severe cases, paralysis of the respiratory muscles can lead to respiratory arrest, followed by cardiovascular complications, shock, and even death. Since tetrodotoxin is not easily removed through standard cooking methods, it is crucial to precisely remove the toxic parts and handle the fish safely.
We have now explored the dangers of pufferfish poison. However, just as a beautiful rose has thorns, pufferfish—despite their potent venom—have long been highly regarded for their taste and culinary value. Pufferfish have been a popular delicacy in South Korea, Japan, and China since ancient times, and pufferfish cuisine has been an integral part of culinary culture for so long that it is said the Song Dynasty poet Su Dongpo even praised its flavor. While the flesh of some pufferfish species is edible, certain parts—such as the liver and ovaries—may contain high concentrations of tetrodotoxin. Therefore, even with edible pufferfish, the general public should not prepare or consume them on their own; one must always eat pufferfish that has been safely prepared by a qualified professional. Currently, the Enforcement Decree of the Food Sanitation Act of the Republic of Korea stipulates that food service operators who prepare or sell pufferfish requiring the removal of toxins must employ a chef who has obtained a pufferfish preparation certification in accordance with the “National Technical Qualifications Act.” In addition, the Ministry of Food and Drug Safety has recently advised against consuming hybrid pufferfish, which can easily be mistaken for edible pufferfish, and urges the public to consume only pufferfish prepared by experts, as toxic parts may still contain tetrodotoxin even in edible varieties. Particular caution is required, as hybrid pufferfish—which can be easily confused with edible pufferfish—are being discovered due to changes in their habitats and other factors.
The field of study that investigates the nature, causes, and effects on the human body of hazards present in food—such as pufferfish toxin—is called food toxicology. The purpose of food toxicology is to ensure that consumers can eat safer food by identifying various hazards that may be present in food, assessing their risks, and researching methods to reduce or eliminate them. Fugu toxin is also one of the key subjects of study in food toxicology, and understanding the processes of toxin formation and accumulation, detection methods, and the risks of poisoning and prevention measures is crucial for food safety.
