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Q: Are lychees poisonous? Why are children dying after eating them?

Krishna: The reason  for the death of these children of lychee farmers is still being investigated. Several theories are flying around. 

Lychees are tropical fruits with a pleasant fragrance and a sweet flavour. But they can be dangerous when they are unripe. The lychee  plant belong to the soapberry family, or the Sapindaceae, and contain  toxins. In specific circumstances, unripe lychees can cause hypoglycemia (low blood sugar) and a dangerous brain dysfunction that may be deadly.

The lychee or litchi plant is an evergreen flowering tree that is native to China. Its scientific name is Litchi chinensis. The small fruits are round, ovoid, or heart-shaped and are borne in clusters. The fruits have a maximum length of around two inches. Most are smaller than this, however. The outer rind of the fruit is usually red, orange-red, or pink and has a bumpy appearance. There are yellow patches on some lychees. One variety has yellow-green fruits.

The inner flesh of a lychee is white, smooth, and translucent. A brown seed is located in the middle of the flesh. Some fruits have unusually small seeds, which is considered to be a desirable feature by both growers and eaters. The flesh is technically called the aril and is the only part of the fruit that is edible. An aril is a covering that partially or completely surrounds a seed. It's sometimes produced by the seed itself and is frequently fleshy.

Raw lychees are an excellent source of vitamin C and a good source of copper. They also contain a useful amount of vitamin B6 and potassium. Their taste and nutrients make them a great fruit to eat. It's important that they're ripe, however, at least until we have a better understanding of the fruit's potential toxicity. 

Ever since the 1990s, investigators have been seeking an explanation for the puzzling deaths of Indian children after eating lychees. Various theories have appeared. These include poisoning by pesticides, a viral infection due to animal droppings on the fruit, and heavy metal poisoning.

A major analysis that linked the problem to lychee toxins was published in early 2017. The analysis was based on poisonings that occurred in 2014 in an area containing many orchards with lychee trees. The poisonings took place from May to July, which is the lychee season, and were absent during the rest of the year. The affected children visited the orchards and ate lots of lychees.

After eating unripe fruit, the children went to bed without exhibiting any symptoms. During the night, however, some of them woke up crying. This was followed by seizures, coma, and often death, even when the children were taken to a hospital. The children had low blood sugar and encephalopathy, or brain dysfunction. The researchers discovered that many of the affected children—especially those that died—didn't eat evening meals or ate only small ones. The investigators say that most of the children came from poor socioeconomic backgrounds. It's possible that hunger was the reason for the willingness of some children to eat unripe lychees. The researchers found that many of the children ate so many lychees that they didn't want an evening meal even when it was available, however. The combination of eating a large number of lychees without eating an adequate amount of other food produced the most serious symptoms.

Unripe lychees contain two toxins—methylenecyclopropyl glycine or MCPG and hypoglycin A. These are related chemicals with similar but not identical structures. The investigators found metabolites of the toxins in many of the children that ate the unripe fruit. A metabolite is a substance produced in the body from the chemical in question.

Humans eating a satisfactory diet are normally able to regulate their blood sugar level (or blood glucose level) within a narrow range. The sugar is used by cells as an energy source. Excess glucose from the diet is stored in the liver as glycogen. If someone hasn't eaten for a while, glycogen is broken down to produce glucose. A constant blood sugar level is necessary for normal brain function.

According to the researchers, young children have a limited ability to store glycogen in their liver. As a result, when they haven't eaten for a while they need to convert fatty acids to glucose. The lychee toxins interfere with this process. Therefore after eating a sufficient number of unripe lychees children may experience hypoglycemia. In some cases the blood sugar level becomes very low during the night. This harms the brain and is responsible for the dangerous and distressing symptoms of lychee poisoning.

The investigators say that the solution to the lychee problem is for parents to warn their children about eating the fruit and to ensure that the children get a good evening meal. The food should help to prevent the blood sugar from dropping during the night. The number of deaths has decreased significantly since the recommendation was made, but children are still dying. The scientists also recommended that children taken to a hospital after being poisoned receive "rapid glucose correction".

However, other experts suspect the illness is caused by a pathogen that has yet to be discovered, calling the illness acute encephalitis syndrome instead. “Why we’re having so many cases of hypoglycemia needs investigation according to them. They say, the lychee has no relation to it.” Researchers have been looking for a pathogen for decades without success and locals call it “lychee disease,” according to the these people.

Lychee fruits naturally contain the compound methylene cyclopropyl glycine (MCPG), which is found at higher levels in unripe fruit. A 2014 study in Muzaffarpur district, where the outbreaks occur, found that the children in the affected villages would spend time in lychee orchards, eating the fruits throughout the day. Sick children did not have elevated white blood cell counts, suggesting that they were not fighting off infection, according to the study. The authors also found that in the presence of MCPG, “fatty acid metabolism and glucose synthesis is severely impaired,” which can lead to acute encephalopathy syndrome (AES).

Muzaffarpur and its surrounding area grow up to 70 percent of India’s lychees. It remains an unknown why other lychee-producing regions of India are not affected, and why some children who are too young to eat the fruit also die from AES. Some families who spoke with the media do not think lychees are the cause of the illness. In one case, a five-year-old girl went to bed on an empty stomach and had not eaten lychee that day but woke up convulsing and later died, according to the Times.

Other investigators have raised the possibility that it’s not the lychees themselves that are to blame, but pesticides used on the farms. Chemical & Engineering News describes a study from 2017 that found 85 percent of 14 affected kids had been on a lychee farm within three days of their symptoms. “We investigated different things. The signs and symptoms to us did suggest a type of poisoning. So we investigated this angle very directly,” coauthor Emily Gurley, an epidemiologist at Johns Hopkins Bloomberg School of Public Health, tells C&EN. “Pesticides was the simplest explanation based on our investigation.”

Scientists  think  that it is multifactorial, but so far it is a mystery. A mystery yet to be solved. When we do, we will get a firm conclusion. Until then one has to be very careful.

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