碳氢链上含有双键的不饱和脂肪酸（多烯脂肪酸）往往对健康有益已经成为人们的共识，而日常服用含有二十碳五烯酸（EPA）、二十二碳六烯酸（DHA）等ω-3脂肪酸的“深海鱼油”被认为能防止心脏病、老年痴呆症及其他衰老相关疾病。 以往研究表明，DHA能减少阿尔茨海默病 模型 小鼠大脑中 β-淀粉样蛋白形成的沉积斑，但2011年在人体中开展的临床研究却得出DHA不能缓解轻微至中度阿尔茨海默症状的结论。更有甚者，一项为期5年共有4000名平均年龄72岁老年人参与的最新研究披露， ω-3脂肪酸不能逆转老年认知力下降。 作者对这一结果的解释是，可能与服用的时机及服用的方式有关，比如发病之前的预防性服用以及直接食用海产品而不是补充剂，因为已有大量研究发现平常多吃鱼可以降低视网膜黄斑性退化（AMD）、心血管病和老年痴呆症的发病率。 据作者介绍，他们发现服用高剂量抗氧化剂和矿物质，可以减慢AMD进展速度，这为解释 ω-3脂肪酸的矛盾结论提供了一条有趣的线索。假如把 ω-3脂肪酸仅仅当做抗氧化剂，那么在已服用抗氧化剂配方的患者中再补充抗氧化剂当然看不到差异。 事实上， ω-3脂肪酸也许只能起抗氧化剂的作用，而其抗氧化效果则取决于服用的剂量和吸收的效率。若剂量足够而且吸收充分，它们应该能发挥预防恶化及缓解病情的作用。相反，因个体差异导致的吸收障碍必然影响实验结果，从而得出无效的结论。 目前对阿尔茨海默病的发病机理仍不了解，我们假定 β-淀粉样蛋白的沉积是早老性蛋白硝基化导致错误折叠的结果。假如这个假说能获得证实，那么就能合理地解释 ω-3脂肪酸对 阿尔茨海默病有效而对其他老年病低效甚至无效的研究结论。 蛋白质硝基化是由过氧化亚硝酸根负离子（ONOO - ）介导的，而 ONOO - 的形成既需要有一氧化氮（NO），也需要有超氧阴离子（ · O - ），两者在慢性炎症下可以大量产生。若此时加入抗氧化剂，就能淬灭 · O - ，使 ONOO - 无法形成，于是蛋白质硝基化被阻断， 早老性蛋白不会出现错误折叠， β-淀粉样蛋白沉积也就不再发生。 至于其他老年性疾病，并不一定涉及 蛋白质硝基化，如心血管病可能只与慢性炎症直接相关，从而导致血管损伤、粥样硬化、血压异常等症状。因此，不仅服用 ω-3脂肪酸无益，而且补充其他抗氧化剂也可能收效甚微。 由此可以得出初步结论， 此研究因在复方中同时使用了 ω-3脂肪酸和抗氧化剂，故得出 ω-3脂肪酸对于防止老年痴呆症认知力下降无效的结论并不具有说服力，有待今后进一步设计甄别实验加以澄清。 附：几篇相关报道 DHA Improves Memory and Cognitive Function in Older Adults, Study Suggests Boosting Mental Performance With Fish Oil? Omega-3 Fatty Acids Don't Improve Heart's Ability to Relax and Efficiently Refill With Blood No benefit of omega-3 supplements for cognitive decline, study shows Date:August 25, 2015 Source:NIH, National Eye Institute (NEI) Summary: While some research suggests that a diet high in omega-3 fatty acids can protect brain health, a large clinical trial found that omega-3 supplements did not slow cognitive decline in older persons. With 4,000 patients followed over a five-year period, the study is one of the largest and longest of its kind. Share: 0 0 19 10 Total shares: 29 FULL STORY NIH study raises doubt about any benefits omega-3 and dietary supplements like these may have for cognitive decline. Credit: Photo courtesy of NEI While some research suggests that a diet high in omega-3 fatty acids can protect brain health, a large clinical trial by researchers at the National Institutes of Health found that omega-3 supplements did not slow cognitive decline in older persons. With 4,000 patients followed over a five-year period, the study is one of the largest and longest of its kind. It was published today in the Journal of the American Medical Association . Contrary to popular belief, we didn't see any benefit of omega-3 supplements for stopping cognitive decline, said Emily Chew, M.D., deputy director of the Division of Epidemiology and Clinical Applications and deputy clinical director at the National Eye Institute (NEI), part of NIH. Dr. Chew leads the Age-Related Eye Disease Study (AREDS), which was designed to investigate a combination of nutritional supplements for slowing age-related macular degeneration (AMD), a major cause of vision loss among older Americans. That study established that daily high doses of certain antioxidants and minerals -- called the AREDS formulation -- can help slow the progression to advanced AMD. A later study, called AREDS2, tested the addition of omega-3 fatty acids to the AREDS formula. But the omega-3's made no difference. Omega-3 fatty acids are made by marine algae and are concentrated in fish oils; they are believed to be responsible for the health benefits associated with regularly eating fish, such as salmon, tuna, and halibut.* Where studies have surveyed people on their dietary habits and health, they've found that regular consumption of fish is associated with lower rates of AMD, cardiovascular disease, and possibly dementia. We've seen data that eating foods with omega-3 may have a benefit for eye, brain, and heart health, Dr. Chew explained. Omega-3 supplements are available over the counter and often labeled as supporting brain health. A large 2011 study found that omega-3 supplements did not improve the brain health of older patients with preexisting heart disease. With AREDS2, Dr. Chew and her team saw another opportunity to investigate the possible cognitive benefits of omega-3 supplements, she said. All participants had early or intermediate AMD. They were 72 years old on average and 58 percent were female. They were randomly assigned to one of the following groups: 1) Placebo (an inert pill) 2) Omega-3 3) Lutein and zeaxanthin (nutrients found in large amounts in green leafy vegetables) 4) Omega-3 and Lutein/zeaxanthin Because all participants were at risk for worsening of their AMD, they were also offered the original or a modified version of the AREDS formulation (without omega-3 or lutein/zeaxanthin). Participants were given cognitive function tests at the beginning of the study to establish a baseline, then at two and four years later. The tests, all validated and used in previous cognitive function studies, included eight parts designed to test immediate and delayed recall, attention and memory, and processing speed. The cognition scores of each subgroup decreased to a similar extent over time, indicating that no combination of nutritional supplements made a difference. Alzheimer's disease, which is the most common cause of dementia and affects as many as 5.1 million Americans age 65 and older in the U.S., may triple in the next 40 years. Some research has examined the potential benefits of DHA for Alzheimer's. Studies in mice specially bred to have features of the disease found that DHA reduces beta-amyloid plaques, abnormal protein deposits in the brain that are a hallmark of Alzheimer's, although a clinical trial of DHA showed no impact on people with mild to moderate Alzheimer's disease. The AREDS2 data add to our efforts to understand the relationship between dietary components and Alzheimer's disease and cognitive decline, said Lenore Launer, Ph.D. senior investigator in the Laboratory of Epidemiology and Population Science at the National Institute on Aging. It may be, for example, that the timing of nutrients, or consuming them in a certain dietary pattern, has an impact. More research would be needed to see if dietary patterns or taking the supplements earlier in the development of diseases like Alzheimer's would make a difference. * Other omega-3 fatty acids are found in plant foods such as flaxseed, walnuts, soy products, and canola and soybean oils. Specific omega-3 fatty acids from these sources were not studied. The cognitive function component of AREDS2 was supported by the NEI Intramural Research Program and contracts HHS-N-260-2005-00007-C. Additional research funds were provided by the NIH Office of Dietary Supplements; the National Center for Complementary and Integrative Health; the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke. Story Source: The above post is reprinted from materials provided by NIH, National Eye Institute (NEI) . Note: Materials may be edited for content and length. Journal Reference : Age-Related Eye Disease Study 2 (AREDS2) Research Group. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial . JAMA , 2015
本来我只有周末才能抽出时间写科普博客，但看了几篇相关 博文后有些最新感悟今天就想写出来跟各位分享。我这篇博客最早拟出的题目是“氧化与抗氧化：一个被忽视的科学原理”，但觉得这个说法只概括了在专业层面上我想说的话，而没有凝练出我真正想表达的意思，故改为现题。 话题的起因出自本月24日Science上的一篇新闻，文章题目译成中文是“科学家修正了关于饱和脂肪酸争议论文中的若干错误”（见附录）。该文提到的这篇所谓“争议”论文于 本月18日 在线发表于《内科学年报 》（Annals of Internal Medicine）上，文章的题目是“膳食、血液循环、脂肪酸补充剂与心脏风险的关系：系统研究和大数据分析”（ Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk : A Systematic Review and Meta-analysis ） 。 据说该文发表后收到了若干意见，作者根据这些意见已经对文章作了修改，估计我们现在见到的版本应该是更新版。 尽管作者对文章作了一些有针对性的修改，但最后结论仍然不变： 现有证据并不明确支持指南上关于鼓励多食用多价不饱和脂肪酸而少食用全饱和脂质的建议 （Current evidence does not clearly support guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats）。这个结论实际上正是该文被“围攻”的靶子，而修改并未如意“改邪归正”。黄油、肉类、巧克力、奶酪中富含饱和脂肪酸，而鱼类、坚果、植物油中富含不饱和脂肪酸。饱和脂肪酸能增大心血管病风险历来被认为是已成定论的“科学教条”，并被世界卫生组织、美国国家食品药品监督管理局和美、英、加、欧盟膳食协会等权威机构采纳，而这篇文章的结论恰恰挑战了这个定论。 以英国的“指南”为例，它是这样写的：男性每日摄入的饱和脂肪酸不应超过30克，女性每日摄入的饱和脂肪酸不应超过20克。这可视为对不同种类脂肪酸摄取的“清规戒律”，言下之意是过多摄入饱和脂肪酸有害，而适量摄入不饱和脂肪酸有益（或多多益善？）。因此，这篇文章的发表惹来了很多国际权威们的高调反对。哈佛大学公共卫生学院营养学系主任Walter Willett就批评道：“他们（对科学结论）已经造成很大损害”，还说：“我认为可以考虑像快速发表那样立即撤稿”。新西兰Otago大学的Jim Mann也表示：“如果这篇文章让我审稿，我也会建议退稿”。 究竟这篇文章的观点是对还是错呢？我们先看看NCBI就此组织的专题点评给出的结论：尽管存在一些不足，但这是一项令人印象深刻的详细而全面的研究（ Saturated fats and heart disease link unproven ）。以下仅贴出长篇点评中的Conclusion部分，供专业人士参考： In contrast to current recommendations, this systematic review found no evidence that saturated fat increases the risk of coronary disease, or that polyunsaturated fats have a cardioprotective effect. Similarly, there was no significant association between the levels of total omega-3 or omega-6 polyunsaturated fatty acids and coronary disease. This lack of association was seen in both cohort studies, which looked at dietary intake or circulating levels the in blood, and in randomised controlled trials that had looked at the effect of supplementation. There was also no significant association between total saturated fatty acids and coronary risk, both in studies using dietary intake and in those using circulating biomarkers. In addition, there was no significant association between total monounsaturated fatty acids and coronary risk – again, both in studies using dietary intake and those studying fatty acid composition. Dietary trans fatty acid intake was associated with increased coronary disease risk, although circulating levels were not. There are some limitations to this study: For the studies based on dietary intake, it is not clear over how long a period of time their diet was assessed. Dietary questionnaires can be inaccurate due to recall bias and may not be representative of diet over a number of years. The level of fat consumption is unclear – that is, how large the difference in fat consumption per day was between people in the top third compared with people in the bottom third. Some of the studies involved people with a pre-existing health condition, so the results may not be applicable to a healthy population. Despite these limitations, this was an impressively detailed and extensive piece of research, which is likely to prompt further study. Current UK guidelines remained unchanged: The average man should eat no more than 30g of saturated fat a day. The average woman should eat no more than 20g of saturated fat a day. Even if saturated fats don’t directly harm your heart, eating too much can lead to obesity, which in turn can damage it. The key to a healthy diet is “everything in moderation”. The occasional buttered scone or cream cake is not going to hurt you, but you need to be aware of your total calorie intake. Eating a healthy, balanced diet , being physically active and not smoking are the best ways to keep your heart healthy. Analysis by Bazian . Edited by NHS Choices . Follow Behind the Headlines on Twitter . Join the Healthy Evidence forum . 下面就来扼要谈谈我个人的看法： 首先，这涉及到心血管病的发病机理。现有证据表明，心血管病与慢性炎症息息相关，而炎症可以导致活性氧（ROS）与活性氮（RNS）的大量产生。不过，究竟是炎症本身还是ROS和RNS引起心血管病，现在还不清楚。假如是炎症直接导致心血管病，那么无论是饱和脂肪酸还是不饱和脂肪酸都没有抗炎作用，该文关于脂肪酸与心血管病无关的结论就是正确的。如果是 ROS和RNS引起心血管病，那就牵涉到下面要谈的另外一个问题。 其次，涉及到自由基的清除系统。假如过多的 ROS和RNS会导致心血管病，那么具有清除自由基能力的不饱和脂肪酸就能降低心血管病的风险，而饱和脂肪酸却没有这个作用。然而，人体具有完备的抗氧化系统，专门针对体内外环境中出现的氧化剂，小分子的有还原型谷胱甘肽（GSH）等，大分子的有各种抗氧化酶。实际上，外源抗氧化剂的摄入确实能清除自由基，但同时也抑制了内源抗氧化酶的诱导。 在人体中， 抗氧化剂与 抗氧化酶的关系类似于“矛”与“盾”的关系，用“水涨船高”来解释就很容易理解。 从这个意义上来说，不饱和脂肪酸充其量只是部分行使了抗氧化酶的功能，只不过外源抗氧化剂增加了，而内源抗氧化酶就会相应减少 ，这就能解释为什么不饱和脂肪酸与心血管病无关。 再次，还涉及到不饱和脂肪酸的作用。显然，不饱和脂肪酸不仅仅是作为抗氧化剂发挥作用，它们既然被定义为人体的“必需脂肪酸”，那就一定有着不可替代的作用。至于它们是否与心血管病有直接关系，恐怕还要开展更深入的研究。比如，Science文章中提到的一篇 A 2009 review 就这样描述过：用糖类代替饱和脂肪酸不能降低心脏病风险，用不饱和脂肪酸代替饱和脂肪酸就能降低心脏病风险。也就是说，不饱和脂肪酸至少跟心血管病有间接关系，今后的任务是要阐明这种间接关系。 另外，尽管这项研究来自大数据分析，而且以Review的形式发表，但它仍然开展了多人参与的临床研究，研究阵容也很豪华（来自哈佛、剑桥等）。既然能得出不饱和脂肪酸与心血管病无关的结论，那也是不会轻易被人否定的，用作者的话来说就是：结论是Valid的，证据是Hardest的，关键在于我们如何进行正确解读。上述专题评述对此的解读是：虽然饱和脂肪酸不会直接损害心脏，但吃得太多会引起肥胖，而肥胖反过来就能损害心脏。 我认为，心血管病的最大风险来自长期感染（如病原细菌）或非感染（如吸烟、肥胖）导致的经久不愈的慢性炎症，抗氧化剂或不饱和脂肪酸的抗氧化作用都不能消除炎症，因此可能与心血管病没有直接关系。不过，目前不能排除不饱和脂肪酸与心血管病的间接关系，即与发病机制相联系。它们也许可以延缓老年人心血管病的发病进程，因为老龄化会降低对食物中抗氧化剂的吸收及对体内抗氧化酶的诱导，因而削弱本身的抗氧化能力，但这个推测还需经过实验研究证实。 最后，我想说两句题外话：我总感觉在国外发表文章存在“潜规则”，若遇审稿人“看不顺眼”（来自中国？英文表达别扭？）就很难过他们的十指关。同样是中国人，在国外的工作容易发表，而回国后的工作就难以发表。因此，我非常推崇用“发表后评价”制度代替“发表前评审”制度。 附： Scientists Fix Errors in Controversial Paper About Saturated Fats 24 March 2014 3:15 pm 12 Comments Wikimedia Commons/Sage Ross Going nuts. Critics have panned a paper that questions whether unsaturated fats, common in nuts, are healthier than saturated ones. When a paper published on 17 March questioned whether fats from fish or vegetable oils are healthier than those in meat or butter, it quickly made headlines around the world ; after all, the study seemed to debunk a cornerstone of many dietary guidelines. But a new version of the publication had to be posted shortly after it appeared on the website of the Annals of Internal Medicine to correct several errors. And although the study's first author stands by the conclusions, a number of scientists are criticizing the paper and even calling on the authors to retract it. They have done a huge amount of damage, says Walter Willett, chair of the nutrition department at the Harvard School of Public Health in Boston. I think a retraction with similar press promotion should be considered. Health officials have long argued that so-called saturated fatty acids, which are found in butter, meat, chocolate, and cheese, increase the risk of heart disease, and that people should instead eat more unsaturated fatty acids, the type that dominates in fish, nuts, or vegetable oils. In the new study, a meta-analysis, scientists from Europe and the United States pooled 72 individual studies to gauge how different fats influence the risk of a heart attack or other cardiac events, such as angina. These included trials in which participants were randomly assigned to different diets, as well as observational studies in which participants' intake of fatty acids was determined by asking them about their diet or by measuring the fatty acids circulating in the bloodstream. When the researchers compared people with the highest and the lowest intake of saturated fats, they found no clear difference between the risk of heart disease or other cardiac events. Similarly, they found no significant difference between those consuming high or low amounts of the supposedly healthy unsaturated fats. Current evidence does not clearly support guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats, the authors concluded . But even before the paper was published, other scientists began pointing out errors, says first author Rajiv Chowdhury, an epidemiologist at the University of Cambridge in the United Kingdom. For instance, the authors took one study on omega-3 fats, one type of unsaturated fats, to show a slightly negative effect while, in fact, it had shown a strong positive effect. The correction means that the meta-analysis now says people who report eating lots of this particular fat have significantly less heart disease; previously, it said there was no significant effect. Critics also pointed out two important studies on omega-6 fatty acids that the authors had missed. The errors demonstrate shoddy research and make one wonder whether there are more that haven't been detected, writes Jim Mann, a researcher at the University of Otago, Dunedin, in New Zealand, writes in an e-mail. If I had been the referee I would have recommended rejection. Mann and others say the paper has other problems, too. For instance, it does not address what people who reduced their intake of saturated fats consumed instead. A 2009 review concluded that replacing saturated fats with carbohydrates had no benefit, while replacing them with polyunsaturated fats reduced the risk of heart disease. Several scientists say that should have been mentioned in the new paper. Chowdhury says the paper's conclusions are valid, however, even after the corrections. Randomized clinical trials are the hardest kind of evidence, he says, and they don't show a significant effect of saturated or unsaturated fats. But even one of the paper's authors, Dariush Mozaffarian, of the Harvard School of Public Health, admits that he is not happy with the key conclusion that the evidence does not support a benefit from polyunsaturated fats. Personally, I think the results suggest that fish and vegetable oils should be encouraged, he says. But the paper was written by a group of authors, he points out. And science isn't a dictatorship. Another study author, Emanuele Di Angelantonio of the University of Cambridge, says the main problem is that the paper was wrongly interpreted by the media. We are not saying the guidelines are wrong and people can eat as much saturated fat as they want. We are saying that there is no strong support for the guidelines and we need more good trials. Willett says correcting the paper isn't enough. It is good that they fixed it for the record, but it has caused massive confusion and the public hasn't heard about the correction. The paper should be withdrawn, he argues. The controversy should serve as a warning about meta-analyses, Willett adds. Such studies compile the data from many individual studies to get a clearer result. It looks like a sweeping summary of all the data, so it gets a lot of attention, Willett says. But these days meta-analyses are often done by people who are not familiar with a field, who don't have the primary data or don't make the effort to get it. And while drug trials are often very similar in design, making it easy to combine their results, nutritional studies vary widely in the way they are set up. Often the strengths and weaknesses of individual studies get lost, Willett says. It's dangerous.
标签: 不饱和脂肪酸
