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Zero-calorie sweetener linked to heart attack and stroke
A sugar replacement called erythritol – used to add bulk or sweeten stevia, monkfruit and keto reduced-sugar products – has been linked to blood clotting, stroke, heart attack and death, according to a new study.
“The degree of risk was not modest,” said lead study author Dr. Stanley Hazen, director of the Center for Cardiovascular Diagnostics and Prevention at the Cleveland Clinic Lerner Research Institute. People with existing risk factors for heart disease, such as diabetes, were twice as likely to experience a heart attack or stroke if they had the highest levels of erythritol in their blood, according to the study, published Monday in the journal Nature Medicine.
“If your blood level of erythritol was in the top 25% compared to the bottom 25%, there was about a two-fold higher risk for heart attack and stroke. It’s on par with the strongest of cardiac risk factors, like diabetes,” Hazen said.
Additional lab and animal research presented in the paper revealed that erythritol appeared to be causing blood platelets to clot more readily. Clots can break off and travel to the heart, triggering a heart attack, or to the brain, triggering a stroke.
“This certainly sounds an alarm,” said Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health, a hospital in Denver, who was not involved in the research. “There appears to be a clotting risk from using erythritol,” Freeman said. “Obviously, more research is needed, but in an abundance of caution, it might make sense to limit erythritol in your diet for now.”
In response to the study, the Calorie Control Council, an industry association, told CNN that “the results of this study are contrary to decades of scientific research showing reduced-calorie sweeteners like erythritol are safe, as evidenced by global regulatory permissions for their use in foods and beverages,” said Robert Rankin, the council’s executive director, in an email.
The results “should not be extrapolated to the general population, as the participants in the intervention were already at increased risk for cardiovascular events,” Rankin said. The European Association of Polyol Producers declined to comment, saying it had not reviewed the study.
What is erythritol?
Like sorbitol and xylitol, erythritol is a sugar alcohol, a carb found naturally in many fruits and vegetables. It has about 70% of the sweetness of sugar and is considered zero-calorie, according to experts.
Artificially manufactured in massive quantities, erythritol has no lingering aftertaste, doesn’t spike blood sugar and has less of a laxative effect than some other sugar alcohols. “Erythritol looks like sugar, it tastes like sugar, and you can bake with it,” said Hazen, who also directs the Cleveland Clinic’s Center for Microbiome and Human Health. “It’s become the sweetheart of the food industry, an extremely popular additive to keto and other low-carb products and foods marketed to people with diabetes,” he added. “Some of the diabetes-labeled foods we looked at had more erythritol than any other item by weight.”
Erythritol is also the largest ingredient by weight in many “natural” stevia and monkfruit products, Hazen said. Because stevia and monkfruit are about 200 to 400 times sweeter than sugar, just a small amount is needed in any product. The bulk of the product is erythritol, which adds the sugar-like crystalline appearance and texture consumers expect.
An unexpected discovery
The discovery of the connection between erythritol and cardiovascular issues was purely accidental, Hazen said: “We never expected this. We weren’t even looking for it.”
Hazen’s research had a simple goal: find unknown chemicals or compounds in a person’s blood that might predict their risk for a heart attack, stroke or death in the next three years. To do so, the team began analyzing 1,157 blood samples in people at risk for heart disease collected between 2004 and 2011.
“We found this substance that seemed to play a big role, but we didn’t know what it was,” Hazen said. “Then we discovered it was erythritol, a sweetener.” The human body naturally creates erythritol but in very low amounts that would not account for the levels they measured, he said.
To confirm the findings, Hazen’s team tested another batch of blood samples from over 2,100 people in the United States and an additional 833 samples gathered by colleagues in Europe through 2018. About three-quarters of the participants in all three populations had coronary disease or high blood pressure, and about a fifth had diabetes, Hazen said. Over half were male and in their 60s and 70s.
In all three populations, researchers found that higher levels of erythritol were connected to a greater risk of heart attack, stroke or death within three years.
But why? To find out, researchers did further animal and lab tests and discovered that erythritol was “provoking enhanced thrombosis,” or clotting in the blood, Hazen said. Clotting is necessary in the human body, or we would bleed to death from cuts and injuries. The same process is constantly happening internally, as well. “Our blood vessels are always under pressure, and we spring leaks, and blood platelets are constantly plugging these holes all the time,” Hazen said.
However, the size of the clot made by platelets depends on the size of the trigger that stimulates the cells, he explained. For example, if the trigger is only 10%, then you only get 10% of a clot.
“But what we’re seeing with erythritol is the platelets become super responsive: A mere 10% stimulant produces 90% to 100% of a clot formation,” Hazen said. “For people who are at risk for clotting, heart attack and stroke – like people with existing cardiac disease or people with diabetes – I think that there’s sufficient data here to say stay away from erythritol until more studies are done,” Hazen said.
Oliver Jones, a professor of chemistry at RMIT University in Victoria, Australia, noted that the study had revealed only a correlation, not causation. “As the authors themselves note, they found an association between erythritol and clotting risk, not definitive proof such a link exists,” Jones, who was not involved in the research, said in a statement. “Any possible (and, as yet unproven) risks of excess erythritol would also need to be balanced against the very real health risks of excess glucose consumption,” Jones said.
Healthy volunteers
In a final part of the study, eight healthy volunteers drank a beverage that contained 30 grams of erythritol, the amount many people in the US consume, Hazen said, according to the National Health and Nutrition Examination Survey, which examines American nutrition each year. Blood tests over the next three days tracked erythritol levels and clotting risk.
“Thirty grams was enough to make blood levels of erythritol go up a thousandfold,” Hazen said. “It remained elevated above the threshold necessary to trigger and heighten clotting risk for the following two to three days.” Just how much is 30 grams of erythritol? The equivalent of eating a pint of keto ice cream, Hazen said.
“If you look at nutrition labels on many keto ice creams, you’ll see ‘reducing sugar’ or ‘sugar alcohol,’ which are terms for erythritol. You’ll find a typical pint has somewhere between 26 and 45 grams in it,” he said. “My co-author and I have been going to grocery stores and looking at labels,” Hazen said. “He found a ‘confectionery’ marketed to people with diabetes that had about 75 grams of erythritol.”
There is no firm “accepted daily intake,” or ADI, set by the European Food Safety Authority or the US Food and Drug Administration, which considers erythritol generally recognized as safe (GRAS).
“Science needs to take a deeper dive into erythritol and in a hurry, because this substance is widely available right now. If it’s harmful, we should know about it,” National Jewish Health’s Freeman said.
Hazen agreed: “I normally don’t get up on a pedestal and sound the alarm,” he said. “But this is something that I think we need to be looking at carefully.”
注释：
Erythritol: n
表示“赤藓糖醇, 赤丁四醇 ”，如：All EU Member States will allow the use of erythritol by February 2008. 所有欧盟会员国将于2008年2月允许使用赤藓糖醇。
Stevia: n
表示“甜菊 ”，means "any plant of the genus Piqueria or the closely related genus Stevia “，如：Unlike sugar, Stevia, Equal, Sweet ON Low and other ordinary sweeteners, Luo Han Guo extract does not stimulate fat storage, elevate insulin levels or raise cholesterol. 跟糖，甜菊，低糖物质以及普通糖类不同，罗汉果的提取物既不会贮存脂肪，也不会提高胰岛素水平或者使你的胆固醇升高。
keto: n
表示“ 氧化 ”，keto- 表示“酮”之义..，ketonic 表示“ 酮的”，如："The keto form predominates in many aldehydes and ketones, the enol form in ph enol s. 在许多醛和酮中酮基都是最主要的组分。
Cardiovascular: adj
表示“ 心脏血管的 ”，means "of or pertaining to or involving the heart and blood vessels “，如：Cardiovascular disease is the leading cause of death among Americans. 心脏血管的疾病是美国人死亡的首要原因。
cardiac； adj
表示“ 心脏的；心脏病的”，means " of or relating to the heart“，如：Death is caused by cardiac failure. 心脏衰竭引起死亡。
platelet: n
表示“血小板 ”，means "essential for blood clotting “，如：Platelets have a major role in hemostasis. 血小板在止血中起主要作用。
clot: v；n
动词表示“ 凝结 ”，means "change from a liquid to a thickened or solid state; “，如：A haemophiliac's blood will not clot properly. 血友病患者的血液凝固不良。
名词表示“ 凝块 ”，means " “，如：The pipe under the bathroom sink was jammed by a huge clot of hair. 浴室洗手台下的水管被一大团头发堵塞了。
extrapolate： v
表示“推知 ”，means "draw from specific cases for more general cases “，如：It is best if you can extrapolate this data. 最好是能够外推此数据。
Sorbitol :n
表示“山梨糖醇 ”，如：Sorbitol has one very odd property. 山梨醇有一非常奇怪的性质。
xylitol: n
表示“ 木糖醇”，如：The fermentation of corncob hydrolysate to xylitol was studied. 对用玉米芯水解液发酵木糖醇进行了研究。
laxative: n
表示“ 泻药 ”，means "a mild cathartic “，如：I’m constipated. I need some laxative. 我便秘了。给我点泻药。
crystalline: adj
表示“水晶做的,结晶的 ”，means "consisting of or containing or of the nature of crystals “，如：A metal has a crystalline structure. 金属具有晶体结构。
coronary： n
表示“ 冠状动脉或静脉的 ”，means " obstruction of blood flow in a coronary artery by a blood clot (thrombus)“，如：The coronary ostia are involved in the dissection.
解剖时要牵动冠状动脉口
thrombosis: n
表示“ 血栓症”，如：Thrombosis may occur as early as the first day after cannulation. 血栓形成可早在置管后第一天发生。
responsive: adj
表示“应答的 ”，means "containing or using responses; alternating “，如：The disease isn't proving responsive to treatment. 该病对治疗没有反应.
thousandfold: adj
表示“ 千倍的 ”，如：A small investment brings a ten thousandfold profit. 一本万利
pint: n
表示“ 品脱（容量单位，主要在英国、美国及爱尔兰使用 ”，means " “，如：Draw off another pint of beer, please.请再量出一品脱啤酒。
confectionery: n
1. 表示“ 糖果”，means " candy and other sweets considered collectively“，如：The business decided to concentrate on confectionery and soft drinks. 公司决定把其主要业务集中在糖果和软饮料上。
2. 表示“ 甜食店 ”，means "a confectioner's shop “，如：I'm looking for a confectionery to buy a cake. 我找一家到糕点店，买一个圆形大蛋糕。
Pedestal：n
1. 表示“底座 ”，means " a support or foundation“，如：The workers put the statue on its pedestal. 工人们把雕像放到基座上。
2. 表示“受人尊敬的地位 ”，means " a position of great esteem (and supposed superiority);“，如：He put his wife on a pedestal and so was all the more hurt when he found she was capable of deceiving him.他把妻子当作偶像崇拜，因此当他知道她是在欺骗他时，他受到的打击实在太大了
中文简要说明：
打脸数十年研究？这款代糖恐增中风4风险 专家要2类人避开
数十年来，许多研究显示，食用部分低卡甜味剂是安全的，不过国际学术期刊《自然医学杂志》（Nature Medicine）昨（27）日刊登的美国研究指出，一种称为「赤藻糖醇」（erythritol）的代糖，与血栓形成、中风、心脏病发、死亡等风险上升有关，研究人员呼吁有心脏疾病或糖尿病的患者暂时避免食用。
美国有线电视新闻网（CNN）报导，《自然医学杂志》昨日刊登俄亥俄州克里夫兰医院（Cleveland Clinic）勒纳研究所（Lerner Research Institute）等美国、德国学者研究，主导这项研究的心血管诊断与预防中心主任赫森（Stanley Hazen）表示，团队原本的目标是，从血液样本中找出能预测未来3年心脏病发、中风、死亡风险的未知化学物质或化合物，因此团队分析了2004至2011年间1157名有心脏病风险人士的血液样本，结果意外发现赤藻糖醇扮演了重要角色。
为了确认研究成果，团队另外在美国及欧洲分析2100、833件血液样本，三组受试者都患有冠状动脉血栓或高血压，当中1／5有糖尿病，超过半数为60至70岁男性。
研究发现，体内含有更高含量「赤藻糖醇」的受试者，与未来三年心脏病发、中风、死亡风险上升有关。研究显示，原本患有糖尿病等心脏疾病风险的患者，如果血液内赤藻糖醇的含量处于最高水平，心脏病发或中风的机率将会上升2倍。
为何赤藻糖醇会增加心脏病发等风险？
研究人员进行动物实验发现，原来赤藻糖醇会诱发血栓形成。形成血栓是人体必要过程，赫森表示，人体血管处在压力下，当有伤口时，血液会渗出，血小板的作用就是塞住这些伤口。他说血小板形成血栓的规模取决于刺激大小，假设刺激仅10%，仅会形成10%血栓。
不过他说，研究发现血小板对赤藻糖醇非常有反应，光是10%的刺激就能形成90-100%的血栓，他建议，有血栓、心脏病发、中风风险的人，例如有心脏疾病或糖尿病的患者，在有更多研究出现之前，暂时避免食用赤藻糖醇。
未参与这项研究的美国国家犹太医学中心（National Jewish Health）心血管疾病专家弗利曼（Andrew Freeman）表示，这项研究确实令人担忧，食用赤藻糖醇似乎会有血栓风险，但他强调仍需要更多研究佐证，但出于安全，开始限制使用赤藻糖醇是合理的。
过去数十年科学研究显示，赤藻糖醇等低卡甜味剂是安全的
针对研究，美国赤藻糖醇产业组织「卡路里控制协会」（Calorie Control Council）执行长蓝金（Robert Rankin）表示，研究结果与过去数十年来认为赤藻糖醇等低卡甜味剂是安全的科学研究相反，他认为研究成果不该自动适用全体大众，因为研究中的受试者本来就有心血管疾病风险。
墨尔本皇家理工大学（RMIT University）化学系教授琼斯（Oliver Jones）指出，这项研究仅显示赤藻糖醇与血栓风险有关联，但还不是因果关系。
什么是赤藻糖醇？
赤藻糖醇是一种糖醇，存在于许多蔬果中，甜度仅为蔗糖的70%，而且几乎没有热量，食用时不会导致血糖明显上升。赫森表示，赤藻糖醇味道和蔗糖相似，也能烘烤，因此在食品产业中相当受欢迎，尤其业者特别喜欢推荐给糖尿病患者，他说，部分标示适用糖尿病患者的食品中，赤藻糖醇的含量较高。
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