華盛頓郵報：美國終止了巨大臨床試驗-酒精研究依然令人迷惑

A huge clinical trial collapses, and research on alcohol remains befuddling

An estimated 88,000 Americans die annually from alcohol-related causes, which include auto-mobile accidents, breast cancer and cirrhosis of the liver. (Goran Kosanovic for The Washington Post)

據估計, 每年有8.8萬美國人死於與酒精有關的原因，包括汽車事故、乳腺癌和肝硬化。(Kosanovic 華盛頓郵報)

By Joel AchenbachAugust 5 at 7:00 AM

《華盛頓郵報》喬爾－阿亨巴赫 發表於2018年8月5日7:00

Research on alcohol consumption is in a pickle. There』s no question that pounding one drink after another is bad for your health. Things get murkier when it comes to 「moderate」 drinking. What does that mean? What』s the limit? Can a health-conscious person serenely order a second round?

研究飲酒的試驗目前陷入困境。毫無疑問，一杯又一杯地喝酒對你的健康有害。而當我們談到「適度」飲酒時，情況變得更加模糊迷惑。什麼意思？到底什麼才是恰當限制？一個健康意識明確的人能心安理得地喝第二輪酒嗎？

The alcohol industry has long embraced the notion that alcohol in moderation not only won』t harm you but is actually good for you. The hypothesis gained traction in the early 1990s when 「60 Minutes」 reported on what is called the French Paradox. The French have low rates of heart disease despite all the butter, cream, foie gras, etc. in the Gallic diet. Some researchers suggested that compounds in red wine, also favored by the French, explain the paradox.

酒精行業長期以來一直認為，適度飲酒不僅不會傷身體，而且還對你有好處。這個假說在二十世紀九十年代初被廣泛引用，當時「60 分鐘」欄目報道了所謂的法國悖論。即：儘管高盧人食物中黃油、奶油、鵝肝等無所不在，法國人卻有較低的心臟病罹患率。一些研究人員表示，法國人青睞的紅酒中的化合物解釋了這種悖論。（Sunni插一句不那麼專業的嘴：看看法國人的身材，再看看法餐的精緻度和小份量，他們怎麼可能是吃無忌憚的人。）

Many studies have shown that people who drink any kind of alcohol in moderation — wine, beer, spirits — have lower rates of heart disease than people who abstain or who drink heavily. But the evidence is stubbornly ambiguous.

許多研究已表明，適度飲用紅酒、啤酒、烈酒等酒類的人患心臟病的幾率比戒酒或酗酒的人還低。但其中採用的證據毫無疑問是含糊不清的。

As reported in the Lancet earlier this year, a survey of the health of nearly 600,000 drinkers in 19 countries found that very moderate drinking — about one drink a day — lowers the rate of certain kinds of heart attacks but raises the risk of other cardiovascular problems. There』s no net benefit in life expectancy, the study found.

正如《柳葉刀》今年早些時候所報道的，在19個國家對近60萬飲酒者的健康狀況進行的一項調查發現，非常適度的飲酒--每天喝一杯--會降低某些類型的心臟病發作率，但會引發其他心血管問題。研究發現，飲酒對於預期壽命沒有凈收益。

Alcohol research is notoriously bedeviled by what are called 「confounding effects.」 The most obvious is that the non-drinking population includes people who can』t drink because of health problems. Meanwhile, healthy people feel free to drink. This can create a misleading impression of cause and effect.

酒精研究眾所周知的深受干擾，人們稱這種混亂叫「混雜效應」。最明顯的是，非飲酒人口中包括了因自身健康問題而不能喝酒的人。同時，身體健康的人總是自我感覺可以隨意飲酒。這會產生一種誤導性的因果印象。

「People who drink moderately are healthier than people who don』t drink. But that doesn』t mean the drinking caused them to be healthier,」 says University of Minnesota social epidemiologist Toben Nelson.

「適度飲酒的人比不喝酒的人健康。但這並不意味著是飲酒導致他們更健康，」明尼蘇達大學社會流行病學家托本－尼爾森說。

This issue was supposed to be clarified by the 10-year, $100 million Moderate Alcohol and Cardiovascular Health (MACH) trial, which started to enroll participants earlier this year. The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, sponsored the trial.

這一問題本應該由耗時10年、耗資1億美元的「適度酒精和心血管健康 (馬赫) 試驗」來澄清，該試驗於今年年初開始廣招試驗參與者的。國家衛生研究院（NIH）附屬的國家酒精濫用和酗酒問題研究所（NIAAA）贊助了這項試驗。

It would have looked at 7,800 people on multiple continents, all older than 50 and at risk for heart disease. Teetotalers and heavy drinkers would have been ineligible to participate. The volunteers would have been randomly assigned into two groups, one that consumed a single alcoholic drink every day for six years and one that abstained from alcohol every day for six years. The goal was to see whether drinking a little bit lowered the rate of heart disease.

該試驗將從多個大洲的年齡超過50歲、有心臟病風險的7800人中獲取調查信息，滴酒不沾者和酗酒者都將沒有資格參加。志願者將被隨機分配到兩組，一組每天飲用一杯酒精飲料持續六年；另一組是六年來每天都要戒酒。目的是看看飲酒是否降低了心臟病的發病率。

But NIH terminated the project on June 15, saying the trial』s results would not be viewed as credible. The majority of the funding for the study was to have come from the alcohol industry, funneled through a nonprofit foundation. This group, the Foundation for the National Institutes of Health, is supposed to be a firewall between industry and researchers, but a March story in the New York Times and a subsequent internal NIH investigation found that researchers had engaged in extensive communication with industry representatives before the government』s approval of the trial.

但國家衛生研究院（NIH）於6月15日終止了該項目，稱該試驗的結果不會被視為可信。這項研究的大部分資金來自酒精行業，通過一個非營利性基金會贊助。作為國家衛生研究院的基金會，該組織本應是工業與研究人員之間的防火牆，但《紐約時報》3月的報道和隨後的內部NIH調查發現，研究人員在政府批准試驗前與酒精業界代表進行了廣泛交流。

The NIH investigation also found flaws with the study design. It didn』t have enough participants, and it didn』t last long enough, said Michael Lauer, a cardiologist and deputy director for extramural research at NIH. Cancer, for example, can take many years to become detectable.

NIH的調查也發現了研究設計本身的缺陷：沒有足夠的參與者、而且持續時間不夠長，邁克爾－勞爾說。他是NIH院外研究的心臟病專家和副主任。比如，癌症可能需要多年才能被檢測到。

The study also did not include women deemed at high risk for getting breast cancer. That』s because research has shown that any alcohol consumption, even a drink a day, increases breast cancer risk. But the decision not to include such women also could have skewed the results of the study.

這項研究也沒有包括入被認為可能患乳腺癌的高危婦女。這是因為研究已表明，任何飲酒：甚至一天喝一杯，都會增加乳腺癌的風險。但試驗者中不包括這些婦女的決定本身也可能會扭曲研究結果。

The NIH report said the trial, as designed, 「could show benefits while missing the harms.」

NIH的報告說，這項試驗的設計，「可以顯示好處的同時也可忽略危害。」

Emails published as part of the NIH report suggest that backers of the trial expected to show that moderate drinking has a health benefit. Researchers are supposed to have what is known as 「equipoise」 going into a trial. That means 「you are approaching a question with a completely neutral attitude,」 Lauer said.

被作為NIH報告的一部分發表的電子郵件顯示，試驗的支持者預計，適度飲酒對健康有好處。研究人員應該有所謂的「平衡能力」進入試驗。這意味著「你正以完全中立的態度接近一個問題，」勞爾說。

「It』s disappointing that these events occurred. It』s disappointing because this is not the high level of stewardship, open competition, that we at NIH are very proud of,」 Lauer said.

「這些事件發生真是令人失望。之所以說它令人失望，是因其不是高水平的研究管理，也不是我們在 NIH非常自豪的公開競爭方式，」勞爾說。

Marion Nestle, a professor emerita of food science at New York University, said, 「This is not open-ended research. This is marketing research.」

紐約大學食品科學女性生殖保健的Marion Nestle教授說，「這並不是無限制結論的開放研究。這是市場調查。」

The trial』s principal investigator, Kenneth Mukamal, an epidemiologist with Harvard』s Beth Israel Deaconess Medical Center, did not respond to an interview request. But he released a statement after NIH』s decision, saying he and his team 「stand fully and forcefully behind the scientific integrity」 of their trial.

該試驗的主要調查員肯尼斯－木卡姆是哈佛大學的貝絲-以色列女執事醫療中心的流行病學家，他沒有回應採訪請求。但他在NIH做出決定後發表了一份聲明, 說他和他的團隊對待此試驗的態度是「充分和有力地支持科學的誠信」。

Cultural factors

文化因素

Alcohol plays such a prominent role in American culture that it』s easy to forget that 98 years ago the prohibition of the sale of alcohol was amended into the Constitution. And teetotaling even today is common: One in 3 American adults does not drink alcohol. One in 2 has not had a drink in the last 30 days.

酒精在美國文化中扮演著如此重要的角色，人們很容易忘記九十八年前禁止銷售酒精的規定曾被修改進入憲法中。滴酒不沾現象甚至在今天也很常見: 1/3 的美國成年人完全不飲酒。1/2的人在過去的30天里沒有喝過酒。

At the other extreme are the millions of Americans who are routinely inebriated. About 1 in 6 adults binge-drink four times a month, with an average of seven drinks per binge, according to the Centers for Disease Control and Prevention.

另一種極端是，成千上萬的美國人經常喝醉。根據疾病控制和預防中心的數據,在6個成年人中大約就有1人每月飲酒四次，平均每次狂飲七杯。

Alcohol can be a killer. The CDC calculates that 88,000 Americans die annually from alcohol-related causes, which include auto-mobile accidents, breast cancer and cirrhosis of the liver.

酒精也可能是奪命殺手。美國疾病控制中心（CDC） 計算結果是，每年有8.8萬美國人死於與酒精有關的原因，包括汽車事故、乳腺癌和肝硬化。

Alcohol is a chemical compound that has multiple and complex effects on many parts of the body, and so it』s impossible to reduce its effects, positive or negative, to a simple metric. A generic description of alcohol is that it is a central nervous system depressant. It impairs perception and slows reaction time. Those effects can increase the risk of accidents or make the intoxicated person more vulnerable to violence and abuse.

酒精是一種化學化合物，對人體的許多部位有多種複雜的影響，因此不可能將其正面或負面效果降低到一個簡單的指標中。對酒精的一般描述是它是中樞神經系統抑製劑。它會損害知覺，減慢反應時間。這些影響可能增加事故的風險，或使醉酒的人更易牽涉暴力和虐待等行為。

「At extreme levels of consumption, alcohol can shut down even the most basic bodily functions, like respiration,」 says Nelson, the Minnesota researcher.

明尼蘇達研究人員納爾遜說：「在極端飲酒水平下，酒精甚至可以關閉掉最基本的身體機能，比如呼吸。」

The body breaks down alcohol into a chemical, acetaldehyde, that can damage cellular DNA and potentially cause cancer. Alcohol is associated with cancers of the mouth and throat, larynx, esophagus, colon and rectum, liver and breast, according to the CDC.

人的身體將酒精分解成一種化學物質－乙醛，它會損傷細胞的DNA，並可能導致癌症。根據CDC的數據，酒精與口腔、咽喉、喉、食管、結腸、直腸、肝臟和乳房等癌症有關。

Alcohol consumption is included in the U.S. dietary guidelines, which say that if you don』t already drink, you shouldn』t start. But they also say that alcohol can be consumed safely in moderation. That』s defined as no more than two drinks a day for a man and one a day for a woman (zero if pregnant, because alcohol disrupts fetal development).

飲酒被列入美國飲食指南中，也即：如果你本身不喝酒，就別開始喝酒。但他們也說，酒精可以在適度的飲用量下保證安全。這個量被定義為一個男人一天不超過兩杯酒，一個女人一天不超過一杯 （如果懷孕就是零杯，因為酒精擾亂胎兒發育)。

Stop the presses: Two-thirds of drinkers fail to drink moderately, says Robert Brewer, head of CDC』s alcohol program.

不要敦促人們喝酒：2/3的飲酒者最終都做不到適度飲酒，疾病控制中心的酒精項目負責人羅伯特－布魯爾說。

「We think of the dietary guidelines on alcohol as aspirational,」 Brewer said. 「Current compliance with the dietary guidelines is poor.」

「我們認為目前對於飲酒的指導準則太充滿鼓舞」，布魯爾說。「目前飲食指南的法規依從性很差。」

Different countries have dramatically different guidelines for moderate drinking. One prominent variant is in Britain, which does not issue distinct standards for men and women. The study published in the Lancet backed this unisex approach: It showed thatlife expectancy begins to drop for both men and women if they drink more than about 100 grams of alcohol a week. That』s equal to about seven 12-ounce beers or five-ounce glasses of wine.

不同國家對適度飲酒有截然不同的指導方針。其中一個突出的不同方針是在英國，英國並不為男性和女性發出不同的標準。《柳葉刀》發表的這項研究支持這種中性的方法 : 如果一周飲酒超過100克以上，男性和女性的預期壽命就會開始下降。這相當於大約七12盎司的啤酒或五盎司的葡萄酒。（1盎司等於 28.35 克－Sunni注。）

The U.S. guidelines take into account the fact that men are larger than women, on average, and have more water as a fraction of their body mass. The average weight of an American adult man is 196 pounds, compared with 169 pounds for the average American woman. Aaron White, chief scientist at NIAAA, said men are, on average, 60 percent water, and women are 50 percent water.

美國的指導方針則考慮到男性比女性更大的事實：平均來說，在身體重量的一小部分中，男性身體有更多的水份。美國成年男子的平均體重是196英鎊，相比於普通美國女性的169英鎊。研究所的首席科學家亞倫－懷特說，平均來說，男性身體60%的水分，而女性是50%的水。

「You』re pouring your drink into more water in the male,」 White said. 「You』ve got more fluid to dilute the alcohol in.」

「對於男性，相當於你把酒倒入更多的水中，」懷特說。「你有更多的液體稀釋酒精。」

By White』s calculation, men should be able to drink about 1.5 times as much as women, on average, to reach the same blood alcohol content. But not twice as much.

根據懷特的計算，平均來說，男性應該能夠喝大約1.5 倍多於女性的酒而達到相同的血液酒精含量，但不是兩倍多。

「People clearly didn』t come up with these moderate drinking guidelines based on math,」 White said.

懷特說：「人們顯然沒有根據數學計算得出這些適度的飲酒指導方針。」

The dietary guidelines do not address alcoholism. That』s a separate, parallel universe of definitions and standards. Alcoholism has evolved as a medical concept, and the DSM-5 — the Diagnostic and Statistical Manual of Mental Disorders — has adopted the term alcohol use disorder, or AUD. That disorder is divided into mild, moderate and severe levels, depending on how many of 11 criteria are met by the drinker.

飲酒指南並沒有解決酗酒問題。這是一個獨立、平行的定義和標準的世界。酗酒已經演變為醫學概念，DSM-5（精神疾病的診斷和統計手冊）則已採用了「酒精飲用紊亂失調」的術語, 或AUD。這種紊亂分為輕度、中度和嚴重程度，取決於飲酒者能滿足11條標準的多少條。

Among the scientists who argue that moderate drinking provides a health benefit is epidemiologist R. Curtis Ellison of the Boston University School of Medicine. He says drinkers should drink a little bit every day, without any days off, because alcohol makes blood platelets less sticky and keeps other clotting factors low.

在那些認為適度飲酒產生健康好處的科學家中，波士頓大學醫學院的流行病學家R. Curtis Ellison說，飲酒者應該每天喝一點點，沒有飲酒休息日，因為酒精使血小板粘性降低，並保持其他凝血因子低指數。

In the opposite camp is Michael Holmes, a University of Oxford epidemiologist who led a 2014 study that found no benefit. Alcohol can cause a rise in blood pressure, coronary-artery calcification and higher body fat, all factors in heart disease, he said. 「The burden of evidence is toward alcohol having a detrimental effect on heart disease, even in small quantities,」 he said.

而處於相反陣營的是牛津大學流行病學家邁克爾－福爾摩斯，他領導研究了一份2014的研究並沒有發現酒精的好處。他說，酒精會導致血壓升高，冠狀動脈鈣化和身體脂肪升高，心臟病的所有因素都是酒精導致的。他說：「證據是酒精對心臟病有傷害性影響，即使是少量的也如此。「

The collapse of the MACH trial left researchers where they』ve been for years, Holmes said: 「We』re at an impasse.」

馬赫試驗的崩潰使得研究者們停滯不前已經多年，霍姆斯說：」我們處於僵局中。「

Looking ahead

展望未來

Where does the field go now?

這一研究領域現在何去何從？

Lauer said that when patients ask him if moderate drinking is good for them, he can only answer, 「I don』t know.」

勞爾說，當病人問他適度飲酒是否對他們有益時，他只能回答：「我不知道。」

He said it would be hard to set up a perfect clinical trial because alcohol has so many different effects. But he said it』s clear that heavy drinking leads to all kinds of negative outcomes, including alcoholism, stomach ulcers, bleeding in the intestinal tract and liver disease.

他說，很難建立一個完美的臨床試驗，因為酒精有這麼多不同的效果。但他說, 很明顯的是，酗酒會導致各種負面結果，包括酗酒、胃潰瘍、腸道出血和肝病。

Lauer continued: 「Lots of different kinds of cancer, including cancer of the oral pharynx and the liver, motor vehicle accidents, poor judgments, ruined marriages.」

勞爾繼續說：「許多不同種類的癌症，包括口腔咽部癌和肝臟癌症，機動車事故，判斷不佳等會導致婚姻破裂。」

The CDC』s Brewer says it』s time to think of new approaches to curbing excessive drinking. Among the possibilities: increasing alcohol taxes, limiting the density of alcohol retailers, limiting the hours alcohol can be sold and creating a public awareness campaign on the dangers of binge drinking.

CDC的布魯爾說，現在是時候考慮新的方法來抑制過量飲酒了。其中的可能辦法包括：提高酒精稅、限制酒精零售商的密度、限制飲酒時間、建立公眾對酗酒危險的宣傳運動。

Given the known dangers and catastrophic consequences of binge drinking, the questions surrounding moderate drinking are arguably esoteric, or at least not an urgent public health issue. Nelson, the Minnesota researcher, said he doesn』t think the drink-a-day riddle is 「a worthwhile scientific question to pursue.」

鑒於酗酒的已知危險和災難性後果，適度飲酒的問題可以說是深奧的，或者至少不是一個緊急的公共衛生問題。明尼蘇達的研究人員尼爾森說，他不認為這個 「每日飲酒度」是「個值得追求的科學問題」。

The endpoint of such research might show a benefit, he said, but society doesn』t have a compelling need to get people who don』t drink to start drinking. It』s more important, he said, to persuade heavy drinkers to moderate.

他說，這類研究的終點可能會帶來好處，但社會並沒有迫切需要讓不喝酒的人開始喝酒。他說，更重要的是說服酗酒者要適度飲酒。

「People like to drink, like to get buzzed, and people like to get drunk, too. But there are major risks associated with heavy drinking,」 he said. His informed message to the public, delivered without any hint of moralizing, is a simple one: 「Drinking is not good for you.」

「人們喜歡喝酒，喜歡微醺感，人們也喜歡喝醉。但是，酗酒也存在重大風險，」他說。他向公眾傳達的信息，不附帶任何說教暗示，而是簡單的：「喝酒對你不好」。

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