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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。
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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.
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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 [specifically docosahexaenoic acid (DHA, 350 mg) and eicosapentaenoic acid (650 mg)] 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
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