果糖甜味剂可引起代谢失调

纽约——加州大学戴维斯分校的Kimber L. Stanhope博士在美国糖尿病学会(ADA)研究生课程班上指出，加工食品中添加的不同种类的糖对人体的影响也是不同的，这或许可以部分解释为何2型糖尿病发病率居高不下。

多数甜食并不含纯果糖或纯葡萄糖，但针对二者效果差异的动物和人类研究显示，膳食中的宏量营养素可能会与过多的体重和脂肪共同导致代谢性疾病。“与葡萄糖相比，果糖会加剧肥胖和脂代谢失调，同时降低胰岛素敏感性。”

流行病学数据和近期实验证据均提示，如果每日摄入的能量中有25%来自以高果糖谷物糖浆(HFCS)为甜味剂的软饮料，或者12.5%的能量来自以葡萄糖为甜味剂的软饮料，只需2~3周时间即可使年轻成人的心血管疾病(CVD)危险因素增多。其他证据提示，在超重或肥胖的中年人中，假如能量摄入中约有20%来自以果糖为甜味剂的饮料，则6个月内肝脏和内脏的脂肪水平会上升，CVD危险因素也会增加。

糖不同则结果不同

Stanhope博士及其他研究者之所以关注果糖和葡萄糖，是因为二者已被证明可导致代谢失调，而且会促进代谢性疾病的发生、发展。为了梳理这些潜在病因，有必要研究它们的不同作用机制。为此，她们在2009年开展了一项研究，对年龄40~72岁的男、女性给予以葡萄糖或果糖为甜味剂的软饮料作为能量平衡膳食的一部分，受试者的能量需求有25%来自糖，连续干预10周时间。受试者处于超重至中度肥胖的范围，体重指数(BMI)介于25~35 kg/m²。

研究者猜测，果糖可比葡萄糖带来更明显的体重增加，原因是果糖并不刺激饱腹感激素瘦素的产生，但这一假说并未得到验证。两组受试者的平均体重均增加了约1.5 kg，根据双能X线吸收测定(DEXA)扫描评定的体脂量也完全相同。“不过，令人意外的是：摄入果糖的受试者倾向于将新增的脂肪储存在内脏，而葡萄糖组受试者则更多地将新增的脂肪储存于皮下。”

这种分布差异的机制可能涉及脂蛋白脂酶(LPL)——从血液循环中清除甘油三酯并将其转化为脂肪以便储存或转运至肌肉用于供能的限速酶。这种酶由胰岛素激活，并且皮下脂肪相关性LPL已被证明比内脏脂肪相关性LPL对胰岛素活化敏感得多。

与葡萄糖相比，摄入果糖与餐后血糖峰值更低、餐后胰岛素峰值更低以及皮下脂肪LPL活化更少等相关，从而使得更多脂肪被留在血液循环中并被内脏脂肪组织摄取。Stanhope博士表示，这一模式还只是猜想，有待进一步研究证实。

在被问及天然果糖是否与添加到加工食品中的果糖具有相似效应时，Stanhope博士表示，新鲜水果实际上仅含有少量果糖，同时含有诸如抗氧化性化合物等健康成分，其益处远远超过了果糖对代谢的不良影响。

上述发现还提示，现行USDA指南(建议能量摄入中来自添加糖的部分不要超过25%)需要修订，以降低糖摄入量的上限值。“然而，要想获得连制糖行业都无法反驳的有绝对说服力的证据，就必须在临床研究中控制受试者摄入的所有食物，以确保在膳食方面没有任何混杂因素，从而提高研究结论的说服力。”但是，就算研究资金充足，在未来6~7年内恐怕也难有决定性结果出现。“我们真的要一直等待决定性结果吗？还是应该在此之前就着手调整我们的膳食指南呢？”研究者将这一问题留给了我们。

Stanhope博士报告称无相关利益冲突。

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By: NEIL OSTERWEIL, Clinical Endocrinology News Digital Network

NEW YORK – All sugars are not created equal, and the difference in the effects on the body between different types of sugar added to processed foods may explain at least some of the spike in type 2 diabetes incidence, an investigator said at the annual advanced postgraduate course held by the American Diabetes Association.

Most sweetened foods do not contain either pure fructose or pure glucose, but animal and human studies of their differential effects show that macronutrient components of diet can conspire with increased body weight and fat to cause metabolic disease, said Kimber L. Stanhope, Ph.D., associate research nutritional biologist in the department of molecular bioscience at the University of California, Davis, School of Veterinary Medicine.

"Fructose compared to glucose increases visceral adiposity [and] lipid dysregulation and decreases insulin sensitivity," she said.

Both epidemiologic data and recent experimental evidence suggest that consumption of 25% of daily energy as beverages sweetened with high-fructose corn syrup (HFCS), or 12.5% of energy as sucrose-sweetened beverages can increase cardiovascular disease (CVD) risk factors in young adults in as little as 2-3 weeks, she said.

Other evidence suggests that, among middle-aged overweight or obese adults, consumption of sucrose-sweetened drinks at about 20% of energy intakes increases levels of fat in the liver and viscera and increases CVD risk factors over 6 months.

The findings also suggest that current USDA guidelines, which recommend no more than 25% of energy intake from added sugars, need to be revised to lower the acceptable upper limit for sugar, Dr. Stanhope said.

"However, obtaining absolutely definitive evidence that even the sugar industry cannot criticize will require clinical studies in which we provide every gram of food to our subjects, and that will ensure there are absolutely no confounders among the diets of the various groups that could undermine our conclusions," she said.

But even assuming that study funding is available, definitive results may not be available for another 6 or 7 years.

"Do we really want to wait that long before we do something about our dietary guidelines, or before we really start educating the public?" she added.

Different sugars, different results

Dr. Stanhope and other researchers look at fructose and glucose because both have been shown to cause metabolic dysregulation and have been implicated as contributors to metabolic disease. To tease out the possible causes, it is necessary to study their separate mechanistic effects, she said.

She and colleagues conducted a study in 2009 in which men and women aged 40-72 years were given either glucose- or fructose-sweetened beverages as part of energy-balance meals, with the sugars comprising 25% of energy requirements for 10 weeks. The subjects were in the overweight to moderately obese range, with body mass indices (BMIs) ranging from 25 to 35 kg/m2.

The investigators hypothesized that fructose would lead to greater weight gain than glucose because fructose dose not stimulate production of the satiety hormone leptin, but the hypothesis was not borne out. Patients in each group gained a mean of about 1.5 kg, and an identical amount of body fat as measured by dual-energy x-ray absorptiometry (DEXA) scan.

"However, there was a surprise: the subjects consuming fructose tended to deposit the new fat that they gained in the visceral adipose, whereas the subjects consuming glucose deposited more of their new fat in the subcutaneous adipose," Dr. Stanhope said.

The mechanism for the different fat distribution may involve lipoprotein lipase (LPL), the rate-limiting enzyme that clears triglycerides from circulation and deposits them into adipose for storage or to muscle for energy use. The enzyme is activated by insulin, and LPL associated with subcutaneous fat has been shown to be much more sensitive to insulin activation than LPL associated with visceral fat.

Compared with glucose, consumption of fructose is associated with lower postmeal glucose peaks, lower postmeal insulin peaks, and lesser activation of LPL in subcutaneous fats, which therefore leaves more fat in circulation for uptake by visceral adipose tissue, Dr. Stanhope explained, noting that this model is hypothetical and needs to be confirmed with further studies.

Asked in an interview whether naturally occurring fructose was associated with similar effects to that of fructose added to processed foods, Dr. Stanhope said that fresh fruits actually contain only small amounts of fructose and have healthy components such as antioxidant compounds that far outweigh any negligible metabolic effects of fructose.

Dr. Stanhope reported having no financial disclosures.