讀外刊 | 吃水果和肝的甜蜜負擔

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近幾年很愛吃水果，尤其是藍莓。但藍莓果醬真的讓我誤會了藍莓好多年……

今天讀《經濟學人》(20180210)期science and technology欄目里的Diet and health: Bitter fruits。

Diet and health: Bitter fruits

It is not supposed to leave the small intestine

FRUCTOSE {果糖} is the sweetest of the natural sugars. As its name suggests, it is found mainly in fruits. Its job seems to be to appeal to the sweet tooths {a great liking for sweet-tasting foods} of the vertebrates these fruit have evolved to be eaten by, the better to scatter their seeds far and wide. Fructose is also, however, often added by manufacturers of food and drink, to sweeten their products and make them appeal to one species of vertebrate in particular, namely Homo sapiens. And that may be a problem, because too much fructose in the diet seems to be associated with liver disease and type 2 diabetes.

果糖(是葡萄糖的同分異構體，化學式C6H12O6)是水果和蜂蜜中存在的一種單糖(指分子結構中含有3~6 個碳原子的糖)。植物為了繁衍，會竭盡全力去吸引潛在的傳播者。果糖的存在就是為了吸引喜愛甜食的有脊椎動物去啃咬這些果子，以便達到種子四散的目的。人類的食物和飲料中也常添加果糖。但這些糖的攝入也可能與肝方面的疾病和2型糖尿病有相關性。

（1型糖尿病：一種自身免疫疾病，病因是自身免疫系統殺死了產生胰島素的胰島貝塔細胞，身體失去了合成胰島素的能力。

2型糖尿病：一種代謝疾病，病因是身體因為某種原因(比如肥胖和缺乏運動)對胰島素失去了響應，但其實身體合成和分泌胰島素的能力並沒有受到破壞性干擾。）

The nature of this association has been debated for years. Some argue that the effect is indirect. They suggest that, because sweet tastes suppress the feeling of being full (the reason why desserts, which come at the end of a meal, are sweet), consuming foods rich in fructose encourages overeating and the diseases consequent upon that. Others think the effect is more direct. They suspect that the cause is the way fructose is metabolised. Evidence clearly supporting either hypothesis has, though, been hard to come by.

對於果糖是不是與上述疾病的產生有相關性還是有爭議的。一種觀點認為沒有直接聯繫，只是由於甜的感覺會壓制飽腹感，感覺不到已經吃撐了，最後多吃了的那部分才是發病的可能。另一種觀點認為有直接聯繫，是果糖的代謝方式的問題。還沒有明確的證據能支持這兩種觀點。

This week, however, the metabolic hypothesis has received a boost from a study published in Cell Metabolism by Josh Rabinowitz of Princeton University and his colleagues. Specifically, Dr Rabinowitz』s work suggests that fructose, when consumed in large enough quantities, overwhelms the mechanism in the small intestine that has evolved to handle it. This enables it to get into the bloodstream along with other digested molecules and travel to the liver, where some of it is converted into fat. And that is a process which has the potential to cause long-term damage.

就在前幾天，普林斯頓大學的Josh Rabinowitz和他的同事在Cell Metabolism上發表了一篇文章。大意就是說過量的果糖會讓小腸吸引不堪重負，漏網的果糖就會跟其他物質被分解後的分子一起通過血流運送到肝臟，到那兒之後有一些會轉化為脂肪。這個過程就有可能導致一些長期的損害 (脂肪肝)。

Dr Rabinowitz and his associates came to this conclusion by tracking fructose, and also glucose {葡萄糖}, the most common natural sugar, through the bodies of mice. They did this by making sugar molecules that included a rare but non-radioactive isotope of carbon, 13C. Some animals were fed fructose doped with this isotope. Others were fed glucose doped with it. By looking at where the 13Cwent in each case the researchers could follow the fates of the two sorts of sugar.

這個結論是Rabinowitz博士和他的同伴通過監測實驗鼠體內的果糖和葡萄糖得來的。他們用非放射性的碳同位素(13C)標記了糖分子。一些被餵食含這個同位素的果糖，另一些被餵食含這個同位素的葡萄糖，然後監測這兩種糖的歸宿。

The liver is the prime metabolic processing centre in the body, so they expected to see fructose dealt with there. But the isotopes told a different story. When glucose was the doped sugar molecule,13C was carried rapidly to the liver from the small intestine through the hepatic portal vein {the vein that takes blood containing substances from food directly to your liver}. This is a direct connection between the two organs that exists to make such transfers of digested food molecules. It was then distributed to the rest of the body through the general blood circulation. When fructose was doped, though, and administered in small quantities, the isotope gathered in the small intestine instead of being transported to the liver. It seems that the intestine itself has the job of dealing with fructose, thus making sure that this substance never even reaches the liver.

葡萄糖和果糖走的路線不太一樣。葡萄糖能很快地從小腸通過肝門靜脈到達肝臟。果糖會「滯留」在小腸里。

Having established that the two sorts of sugar are handled differently, Dr Rabinowitz and his colleagues then upped the doses. Their intention was to mimic in their mice the proportionate amount of each sugar that a human being would ingest {to take food or drink into the body} when consuming a small fructose-enhanced soft drink. As they expected, all of the glucose in the dose was transported efficiently to the liver, whence it was released into the wider bloodstream for use in the rest of the body. Also as expected, the fructose remained in the small intestine for processing. But not forever. About 30% of it escaped, and was carried unprocessed to the liver. Here, a part of it was converted into fat.

研究團隊在此基礎上加大了劑量。葡萄糖依然高效地到達了肝臟。果糖依然留在了小腸，但有30%的果糖溜走了，沒有經過處理直接到達了肝臟；在這裡，一些果糖轉化為脂肪。

That is not a problem in the short term. Livers can store a certain amount of fat without fuss. And Dr Rabinowitz』s experiments are only short-term trials. But in the longer term chronic fat production in the liver often leads to disease—and is something to be avoided, if possible.

肝臟里少量的脂肪積存沒關係，過量就不行了。還是要防範量變引起質變。

以下為基於上文的延展閱讀，主要為補充知識。

The Livers Role

肝臟的功能

The liver manages a dizzying array of tasks, including digesting fats, making and storing glucose, and serving as the bodys detox center. Doctors know a lot about how the liver works, but not everything. The liver has myriad functions; some experts think there may be 500.

我們的肝非常努力肯干，承擔了大量的工作。

Glucose Warehouse

The liver is an insulin-guided organ: Its behavior changes depending on the level of the hormone insulin in the body and how sensitive the liver is to that insulin. After eating, blood glucose levels rise, which in people without diabetes triggers the pancreas to release insulin into the blood. Insulin is the signal for the body to absorb glucose from the blood. Most cells just use the glucose to supply them with energy.

But the liver has a special job when it comes to glucose. When levels of glucose (and consequently insulin) are high in the blood, the liver responds to the insulin by absorbing glucose. It packages the sugar into bundles called glycogen {糖原}. These glucose granules {顆粒} fill up liver cells, so the liver is like a warehouse for excess glucose.

肝臟里的葡萄糖是可以被儲存起來的。

When glucose levels drop, insulin production falls, too. The shortage of insulin in the blood is the signal that the liver needs to liquidate its assets, sending its glucose stores back into the blood to keep the body well fed between meals and overnight.

當葡萄糖含量下降，肝臟就要把「存糧」拿出來支援。

The liver doles out stored glucose and has the singular ability to make glucose from scratch. This is a critical function that keeps people alive when food is scarce. In people with diabetes, however, the liver doesnt process and produce glucose normally, adding to the challenge of blood glucose control.

The liver cant directly detect blood glucose levels; it knows only what insulin tells it. So, if there is a shortage of insulin or if the liver doesnt notice the insulin thats there, the liver assumes that the body needs more glucose, even if blood glucose levels are already elevated. That is why people with diabetes can have sky-high blood glucose even if they havent eaten—for example, first thing in the morning. The liver is also responsible for the dangerously high blood glucose levels in people with diabetic ketoacidosis {糖尿病酮症酸中毒}, a condition in which there is such a severe shortage of insulin that the body cant process glucose as energy. Instead, it uses fats. Ketones {酮}, waste products created when the liver breaks down fat, can be toxic in large quantities.

Fat Facts

Processing the bodys fat is a key job for the liver. Once the liver is full of glycogen, it starts turning the glucose it absorbs from the blood into fatty acids, for long-term storage as body fat. The fatty acids and cholesterol are gathered as fatty packages and delivered around the body via the blood. Much of the fat ends up stored in fat tissues.

All of this extra fat produced and stored by the liver can sometimes lead the liver itself to get fat. In a condition known as nonalcoholic fatty liver disease, found in people who arent heavy drinkers (who have their own liver problems), liver cells accumulate excess fat instead of sending it off to fat cells. This disease is common, affecting 20 percent of adults overall and the majority of people with obesity or diabetes, or both. Doctors may test your blood to determine whether you have an ailing liver. In some cases, they may use an imaging technique or a biopsy {活組織檢查 } to detect disease.

For most people, fatty liver doesnt cause any symptoms. But when it does cause problems, theprognosis {a statement about what is likely to happen in a particular situation} can be serious. Severe cases may end in cirrhosis {肝硬化}, which is characterized by scarring and poor liver function. Cirrhosis can be fatal or may require a liver transplant.