祖孙三代乳糖不耐受发生率及膳食改善措施研究
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摘要
乳糖不耐受(lactose intolerance，LI)是因肠道乳糖酶减少或活性低下(乳糖酶缺乏，lactose deficiency，LD)，使奶及奶制品中的乳糖不能在小肠内分解而直接进入结肠产生腹胀、腹鸣、排气增多、腹痛、腹泻、等一系列不耐受症状。因此，一些乳糖不耐受者自动避免饮用奶及奶制品，即使继续饮用者也不能充分吸收和利用奶中的营养成分。乳糖不耐受最突出的影响是钙摄取量降低，最终引起一系列与缺钙相关的亚临床症状和疾病，如婴幼儿佝偻病、中老年骨质疏松、骨质软化症等，还可能与心血管疾病、癌症的发生有关。
我国人群乳糖不耐受高发，健康成人乳糖不耐受发生率为65．5-67％。儿童的乳糖不耐受也在28．2-32％，中国人低奶消费量很大程度与乳糖不耐受有关。因此解决我国人群乳糖不耐受问题，提高中国人奶及奶制品的摄入量，改善人群钙营养状况是我国营养学界面临的一项重要任务。
尽管不少流行病学调查提示长期不饮奶与乳糖不耐受可能有关，但中国人长期以来没有饮奶习惯或饮奶很少是否是乳糖酶活性下降的原因?仍没有定论。本课题组研究表明乳糖不耐受者尽管肠道乳糖酶活性降低，但仍然存在一定活性可以消化一定量的乳糖。乳糖不耐受者可以喝奶吗?可以喝多少奶?迄今为止，缺乏研究。本课题组研究还表明乳糖不耐受症状的发生除了与小肠乳糖酶活性下降有关，还受胃排空、肠转运时间和结肠菌群的构成等胃肠因素的影响。探讨与牛奶同食时能延缓胃排空的食物种类和饮奶的方式，也是提高乳糖不耐受者饮奶量的有效途径之一。
本研究以国内外学者对乳糖不耐受的研究为基础，在我课题组前期研究的基础上调查分析祖孙三代饮奶、饮奶相关因素对乳糖不耐受发生率的影响，结合我国居民用膳方式在人体实验和人群调查的基础上提出我国健康人成人可接受牛奶摄入量、改善乳糖不耐受症状切实可行的膳食措施。对指导中国人正确饮奶，增加奶及奶制品的消费量，推进全民饮奶，改善人群钙营养状况有重要的实用价值。
全文从以下三个部分进行研究：
一．祖孙三代乳糖不耐受发生率及其影响因素分析
目的：了解祖孙三代饮奶现况及相关因素对健康的影响，分析祖孙三代乳糖不耐受发生情况及其饮奶相关因素，探讨长期、多代饮奶行为对乳糖酶活性的影响。
方法：在成都市区及其郊县某城镇共3个幼儿园中采用随机整群抽样的方法选取55名3-6岁儿童及其父母、祖父母303名总共358人用儿童问卷、成人问卷进行调查，对获取的资料根据饮奶频率、一次饮奶量等计算出每份问卷的年平均累计饮奶量(AMIy)。243人进行了氢呼气试验(HBT)并结合粪便乳糖(醋酸铅法)诊断出乳糖不耐受的患者。用SPSS11．0作χ~2检验、相关、等级相关、Binary Logistic回归等统计分析。
结果：1．儿童饮奶率为74．6％，最主要的原因是家长让喝(56．1％)、喜欢喝(41．5％)；父母代饮奶率为48．1％，祖父母代的饮奶率为32．0％。成人喝奶的原因以有营养为主(97．36％)，不喝牛奶的原因以不习惯和不喜欢为主(66．14％)；儿童和成人饮奶种类以鲜牛奶为主(70．7％、74．6％)，饮酸奶的人数分别为2．4％、7．9％；饮奶儿童身高、体重高于不饮奶儿童，差异有统计学意义(P＜0．05)，儿童AMIy与儿童的身高、体重呈正相关，r分别为0．353、0．380(P＜0．05)。成人饮奶者中，经常腿抽筋、腰酸背痛的发生率为14．2％、19．9％，明显低于不饮奶者(85．8％、80．2％)，差异有统计学意义(P均＜0．005)：经常腿抽筋、腰酸背痛的成人AMIy均明显低于腿不抽筋、不腰酸背痛的人(P=0．000)；儿童AMIy与其母亲、祖代AMIy呈正相关(r分别为0．614、0．447，P＜0．05)；成人AMIy与其文化程度有一定关系，高中、大学学历的人AMIy明显高于初中及以下文化程度的人，差异有统计学意义(P＜0．05)。
2．醋酸铅法与氢呼气试验判定乳糖酶缺乏(LD)的一致性：Kappa值为0．421(P＜0．01)，灵敏度为83．3％，特异度60．7％。
3．用醋酸铅法与氢呼气试验结合诊断幼儿、父母、祖父母的乳糖不耐受发生率分别为51．0％、68．8％、67．6％；成人不饮奶者乳糖不耐受发生率(74．54％)高于每天饮奶者(26．67％)，差异有统计学意义(χ~2=21．452，P＜0．05)；祖父母、父母两代均不饮奶的家庭中儿童乳糖不耐受发生率(88．3％)高于两代均饮奶(45．5％，P＜0．05)和两代部分饮奶家庭中儿童乳糖不耐受发生率(32．1％，P＜0．01)，差异有统计学意义。
4．年平均累计饮奶量(AMIy)与乳糖不耐受严重程度呈负相关(r=-0．353，P＜0．05)，差异有统计学意义。用Binary Logistic回归模型分析结果为：饮奶年限、饮奶频率、一次饮奶量对乳糖不耐受发生的危险性有影响，差异有统计学意义(p＜0．05)，饮奶年限和饮奶频率与乳糖不耐受发生的危险性呈负相关，OR分别为0．317、0．465；一次饮奶量与乳糖乳糖不耐受发的危险性呈正相关，OR为6．337。
结论：
1．儿童饮奶率为74．6％，父母代为48．1％，祖父母代为32．0％；饮奶能促进儿童生长发育；成人腿抽筋、腰酸背痛等症状与年平均累计饮奶量有关；儿童饮奶受母亲影响较大；成人的文化程度对自身饮牛奶的行为有影响。
2．饮奶与乳糖乳糖不耐受有关：饮奶频率、饮奶年数与乳糖乳糖不耐受症状发生的危险性呈负相关，一次饮奶量与乳糖乳糖不耐受症状发生的危险性呈正相关。长期低剂量饮奶，可改善乳糖乳糖不耐受症状。
3．祖代、父母代不饮牛奶与儿童乳糖不耐受有关。
4．平均年累计饮奶量(AMIy)是一个估算长期饮奶量的较好指标。
5．醋酸铅法(半定量检测粪便乳糖的方法)，简便、安全、经济，适宜于规模大的现场调查。
二．严重乳糖乳糖不耐受者可接受牛奶摄入量的实验研究
目的：找出严重乳糖不耐受者可接受牛奶摄入量，观察此量后在健康成人的耐受情况。
方法：采用氢呼气试验从38名受试者中筛选出8名有水样状腹泻的乳糖不耐受者，分成低、高剂量组(分别为A、B组)参加饮奶试验。两组的症状评分之和大致相等，据文献报道及单因素优选法(黄金分割法)确定两组对象分别饮用25g和38．2g奶粉(分别含6．25g和9．55g乳糖)和水冲调成的200ml牛奶，分析受试者△HBT值、症状评分、粪便乳糖含量(醋酸铅法)。采用随机整群抽样方法选取健康的100名青年、80名中年、100名老年人，观察摄入25g奶粉(含乳糖6．25g)后出现的乳糖不耐受症状。
结果：两组受试者在饮奶试验中无一例腹泻发生，仅有不同程度的轻微症状(打嗝、胀气)；高剂量组(B组)对象饮奶后，其△HBT值、症状评分、粪便乳糖均高于低剂量组(A组)。健康成人饮用25g奶粉(含乳糖6．25g)冲调的牛奶后，80．3％的对象未产生任何乳糖不耐受症状。
结论：曾有严重腹泻的乳糖不耐受者在食用25g奶粉后，仅表现轻微乳糖不耐受症状，无腹痛、稀便和水样腹泻；健康成人即使为乳糖不耐受者也能饮用适量牛奶，大多数健康成人摄入25g奶粉(含乳糖6．25g)后不会出现任何乳糖不耐受症状，结合我国的实际情况建议20g奶粉(含乳糖5g，配成160ml牛奶)作为我国健康成年人可接受牛奶摄入量。
三．改善乳糖不耐受症状的膳食措施研究
目的：结合我国居民用膳方式，寻找饮牛奶时改善乳糖不耐受症状的膳食措施。
方法：采用氢呼气试验从38名受试者中筛选出8名有水样状腹泻的乳糖不耐受者，参加用正交实验设计的不同食物与25g奶粉(含乳糖6．25g)搭配的饮奶试验；采用随机整群抽样方法选取100名健康大学生参加以不同方式摄入25g奶粉(含乳糖6．25g)的饮奶试验，观察饮奶试验后出现的乳糖不耐受症状。
结果：受试者饮牛奶，同时摄入鸡蛋、馒头、锅魁、面包后△HBT值比单独饮用牛奶均有降低(均小于1．786 mg╱m~3)；正交直观分析、方差分析均表明：鸡蛋与牛奶混食者粪便乳糖和症状评分比馒头与牛奶混食者低，差异有统计学意义(P＜0．05)，全麦面包与牛奶混食者症状评分最高；不同饮奶方式引起乳糖不耐受症状的发生率不同，早餐空腹饮牛奶者乳糖不耐受发生率27．6％(27／98)高于午餐或晚餐饮牛奶者13．7％(13／98)，χ~2=6．16，P＜0．05，差异有统计学意义。
结论：食物种类和不同饮奶方式对乳糖不耐受症状有明显影响，建议不要空腹饮奶，而在正餐饮牛奶，并注意与高蛋白膳食、固体(干)的食物搭配，避免与含膳食纤维高的食品(如全麦面包)一起食用。
总之，乳糖不耐受者也能饮用适量牛奶，乳糖不耐受者应当解除不能饮奶的“枷锁”，只要坚持长期一次饮或食用含乳糖不超过5g的奶及奶制品，不要空腹饮奶，而在正餐饮牛奶，并注意与高蛋白膳食、固体(干)的食物搭配，避免与含膳食纤维高的食品(如全麦面包)一起食用，可以改善乳糖不耐受症状，还能增加饮奶量，维护乳糖不耐受人群健康。祖父母代、父母代不饮牛奶与儿童乳糖不耐受有关，此结论为明确长期是否饮奶的膳食模式与乳糖酶持续活性与无持续活性的基因多态性差异的关系提供了有力证据。但要阐明长期不饮奶与乳糖不耐受发生的关系，还需要类似的扩大样本量和不同种族人群的研究证据。
Lactose intolerance (LI)exists in the subjects with lactase deficiency(LD),which have gastrointestinal symptoms including abdominal distension,cramps,flatulence,and watery stools after consuming lactose and its foods. For this reason, milk and dairy products are eliminated from the diet of many LI subjects, which could lead to the nutrition-related diseases, especially disease related to calcium-deficiency,such as rickets, osteoporosis and asteomalacia etc. In China, the prevalence of LI is 65.5-67% in adults and 28.2-32% in children. Therefore, increasing calcium intake via ameliorating LI symptoms is one of important issue in nutrition.
Despite the results from a lot of epidemiological studies indicate LI maybe relate with long-term non-milk drinking, but whether is the decline of lactase activity in adult of Chinese caused by less milk drinking or non-milk drinking habit is not clear yet. Results from our research group suggested that subjects with LI had low lactase activity but still had residual lactase activity that can absorb some amount of lactose. Can LI subjects drink milk? How much milk could they accept? These questions should be answered. Studies by our research group also demonstrations that the serious symptoms after milk ingestion in LI subjects may vary widely, depending upon not only the degree of intestinal lactase deficit but also gastric emptying time ,orocecal transit time and colonic micro flora in subjects. It is a good way to increasing intake of cow's milk in LI subjects by exploring various foods and milk drinking manner to delaying gastric emptying.
The aim in present study is to investigate milk consumption in three generations, including children, their parents and grandparents, and to analyze the effects of drinking cow's milk on prevalence of LI based on many studies including our program. The acceptable intake of cow's milk for healthy adults and measures of alleviating symptoms of LI were put forward in the present study. When people drank the milk, combining eating habits of our residents by epidemiology survey and human trail. Therefore the results of the present study will play an important role in the practice in pushing civil milk drinking program, improving calcium level of Chinese people.
The present study includes three parts as follows:
1. Study on prevalence and influencing factors of lactose intolerance in three generations include children, parents and grandparents
Objective: To investigate milk consumption and effect on health of three generations include children, parents and grandparents, and to analyze the prevalence and influencing factors of LI among them, and to explore the effect of long-term and generations's milk drinking behavior to lactase.
Methods: 55 children aged 3-6 include their parents and grandparents 358, which selected from 3 three kindergartens in Chengdu and its suburb by clustered random sampling, were investigated by questionnaire, accumulative Cow's Milk Intake per year(AMIy) by frequencies,years,amounts of milk that they drank in their lifetime..LI were diagnosed by Hydrogen Breath Test (HBT) and stool lactose (by the way of lead acetate with aqueous ammonia) in 243 persons among those three generations. Statistical analysis is carried out by SPSS11.0.
Results 1.The rate of milk drinking in children, parents and grandparents was 74.6%,48.1% and 32.0% respectively; 66.1% of parents and grandparents take a dislike to milk and are unaccustomed to it .The height and weight of children with milk drinking habit were more higher and heavier than those with non-milk drinking habit(P＜0.05, respectively) .There were positive correlations between AMIy of children and their height、weight (r is 0.353、0.380 ,P=0.000 ,respectively) .The rate of milk drinking and AMIy in adults with leg cramp and waist ache were significant in comparing with that of those with non-symptoms (P＜0.005、P=0.000,respectively) .There were positive correlations between AMIy of children and that of mother, grandparents (r is 0.614、0.447, P＜0.01 respectively) .There were correlation between AMIy of adults and their cultural standard. AMIy of person graduated from senior high school and college is significant in comparing with that of which graduated from junior high school or below (P＜0.05) .
2. Concordance of diagnose LD by HBT and the way of lead acetate with aqueous ammonia: Kappa value was 0.421 (P＜0.01) ,sensitivity was 83.3%, specificity was 60.7%.
3. The prevalence of LI in children ,parents and grandparents was 50.9%、68.8%、67.6% respectively. The prevalence of LI in adults those with un-milk drinking habit was significant in comparing with those with milk drinking per day (x~2=21.452 P＜0.05). The prevalence of LI in child whose parents and grandparents with un-milk drinking habit was significant in comparing with those milk drinking habit (x~2=4.57 P＜0.01) .
4.There were negative correlations between AMIy and severity degree of LI symptom (r=-0.353, P＜0.05)。Binary Logistic regression showed that: years, frequency, and amount of milk per time that they drank in their lifetime were with statistical significance (P＜0.05) There were negative correlations between years , frequency of milk drinking and LI ,OR were 0.317、0.465, respectively. There were positive correlations between amount milk of per time and LI, OR was 6.337
Conclusion: 1.The rate of milk drinking in children, parents and grandparents was 74.6%,48.1% and 32.0% respectively. Drinking milk can improve children's growth and development. Leg cramp and waist ache of adults are related with accumulative Cow's Milk Intake per year (AMIy).Children's milk drinking habits were significantly influenced by mother. Cultural standard of adults can affect their milk drinking habits
2. LI is related to milk drinking. There were negative correlations between years , frequency of milk drinking and LI symptoms. There were positive correlations between amount of milk per time and LI symptoms.Drinking moderate amount milk for years per day might alleviate the symptoms of intolerance
3. LI of the child is related to un-milk drinking of his parents and grandparents.
4. A MIy is preferable index to rough estimate milk intake.
5. stool lactose eaxamined by the way of lead acetate with aqueous can be used for screening LD.
2. Study on the acceptable intake of cow's milk for severe LI
Objective: To find out the acceptable intake of cow's milk in subjects with severe LI and then observe intolerance symptoms in healthy adults after they drank thus allowance.
Methods: Eight LI subjects with watery diarrhea who were selected from 38 subjects by HBT were divided into group A, group B to go on drinking cow's milk test. The subjects in group A ingested 25g milk powder, the subjects in group B ingested 38.2g milk powder(contain 6.25g,9.55g lactose and make 200 ml of milk solution respectively) according to literature and single factor optimization method(0.618 golden mean) to analyze their△hydrogen excretion(mg/m~3) ,symptom score and stool lactose. The 100 younger, the 80 middle-age and the 100 elder subjects were selected by clustered random sampling to observe symptoms after they ingested 25g milk powder.
Results: No case with diarrhea occurred in these two group but mild symptoms (burp, break wind). hydrogen excretion(mg/m~3) and symptom score in the high dose group (group B)are a little higher than those in low dose group (group A) . Most of healthy adults (80.3%) have no intolerance symptoms after they ingested 25g milk powder (make 200 ml of milk solution).
Conclusion: There was only mild symptoms after LI with diarrhea ingested 25g cow's milk powder ,no bellyache ,loose and water stool occurre.The study demonstrates that most of adults, even with LI, can tolerance 25g cow's milk powder(6.25g lactose). According to the condition of our country. It is suggested 20g cow's milk powder(5g lactose, make 160 ml of milk solution) is the acceptable intake of healthy adults in China.
3. Study on measures of ameliorating symptoms of LI during drinking milk
Objective: To find out measurements of alleviating symptoms of LI when people drank the milk, combining diet habits of our residents.
Methods: Eight LI subjects with watery diarrhea who were selected from 38 subjects by HBT were divided into 4 groups to go on drinking cow's milk test with various foods by orthogonal trail. The 100 healthy college students were selected by clustered random sampling to observe symptoms after they ingested 25g milk powder by different manners.
Results:△hydrogen excretion of groups which ingested milk with various food is lower than those ingested milk only(all less than 1.786 mg/m~3). Egg is better than Manitou in alleviating symptoms. (F value of stool lactose and symptom score are 7.5、9.0 ,respectively＜0.05) .Whole wheat bread can aggravate flatus. The prevalence of the symptom in 100 college students by drinking milk in fast state (27/98) was significantly comparing with that by drinking milk with regular meal (13/98), (x~2=6.16, P＜0.05) .
Conclusion: The study demonstrates that various foods, various milk drinking manner can affect the intolerance symptom .We suggested:Don't drink milk in fast state, milk with egg and staple food such as steamed bread, bread or gomuti is best selection for breakfast. Drinking milk with regular manner can alleviate symptom of intolerance. For lactose intolerance, don't take whole wheat bread.
In general, LI of the child is related to un-milk drinking of his parents and grandparents .It is provided powerful evidence to demonstrate that lactase gene polymorphism (lactase persistence and nonpersistence)is related with long-term drinking and non drinking milk.LI subject should release from incapable of drinking milk .It is not only alleviating symptoms of LI but also improving intake of cow's milk when LI subjects keep on drinking milk or eat other dairy products which contain less 5g lactose per time for long term.
我国人群乳糖不耐受高发，健康成人乳糖不耐受发生率为65．5-67％。儿童的乳糖不耐受也在28．2-32％，中国人低奶消费量很大程度与乳糖不耐受有关。因此解决我国人群乳糖不耐受问题，提高中国人奶及奶制品的摄入量，改善人群钙营养状况是我国营养学界面临的一项重要任务。
尽管不少流行病学调查提示长期不饮奶与乳糖不耐受可能有关，但中国人长期以来没有饮奶习惯或饮奶很少是否是乳糖酶活性下降的原因?仍没有定论。本课题组研究表明乳糖不耐受者尽管肠道乳糖酶活性降低，但仍然存在一定活性可以消化一定量的乳糖。乳糖不耐受者可以喝奶吗?可以喝多少奶?迄今为止，缺乏研究。本课题组研究还表明乳糖不耐受症状的发生除了与小肠乳糖酶活性下降有关，还受胃排空、肠转运时间和结肠菌群的构成等胃肠因素的影响。探讨与牛奶同食时能延缓胃排空的食物种类和饮奶的方式，也是提高乳糖不耐受者饮奶量的有效途径之一。
本研究以国内外学者对乳糖不耐受的研究为基础，在我课题组前期研究的基础上调查分析祖孙三代饮奶、饮奶相关因素对乳糖不耐受发生率的影响，结合我国居民用膳方式在人体实验和人群调查的基础上提出我国健康人成人可接受牛奶摄入量、改善乳糖不耐受症状切实可行的膳食措施。对指导中国人正确饮奶，增加奶及奶制品的消费量，推进全民饮奶，改善人群钙营养状况有重要的实用价值。
全文从以下三个部分进行研究：
一．祖孙三代乳糖不耐受发生率及其影响因素分析
目的：了解祖孙三代饮奶现况及相关因素对健康的影响，分析祖孙三代乳糖不耐受发生情况及其饮奶相关因素，探讨长期、多代饮奶行为对乳糖酶活性的影响。
方法：在成都市区及其郊县某城镇共3个幼儿园中采用随机整群抽样的方法选取55名3-6岁儿童及其父母、祖父母303名总共358人用儿童问卷、成人问卷进行调查，对获取的资料根据饮奶频率、一次饮奶量等计算出每份问卷的年平均累计饮奶量(AMIy)。243人进行了氢呼气试验(HBT)并结合粪便乳糖(醋酸铅法)诊断出乳糖不耐受的患者。用SPSS11．0作χ~2检验、相关、等级相关、Binary Logistic回归等统计分析。
结果：1．儿童饮奶率为74．6％，最主要的原因是家长让喝(56．1％)、喜欢喝(41．5％)；父母代饮奶率为48．1％，祖父母代的饮奶率为32．0％。成人喝奶的原因以有营养为主(97．36％)，不喝牛奶的原因以不习惯和不喜欢为主(66．14％)；儿童和成人饮奶种类以鲜牛奶为主(70．7％、74．6％)，饮酸奶的人数分别为2．4％、7．9％；饮奶儿童身高、体重高于不饮奶儿童，差异有统计学意义(P＜0．05)，儿童AMIy与儿童的身高、体重呈正相关，r分别为0．353、0．380(P＜0．05)。成人饮奶者中，经常腿抽筋、腰酸背痛的发生率为14．2％、19．9％，明显低于不饮奶者(85．8％、80．2％)，差异有统计学意义(P均＜0．005)：经常腿抽筋、腰酸背痛的成人AMIy均明显低于腿不抽筋、不腰酸背痛的人(P=0．000)；儿童AMIy与其母亲、祖代AMIy呈正相关(r分别为0．614、0．447，P＜0．05)；成人AMIy与其文化程度有一定关系，高中、大学学历的人AMIy明显高于初中及以下文化程度的人，差异有统计学意义(P＜0．05)。
2．醋酸铅法与氢呼气试验判定乳糖酶缺乏(LD)的一致性：Kappa值为0．421(P＜0．01)，灵敏度为83．3％，特异度60．7％。
3．用醋酸铅法与氢呼气试验结合诊断幼儿、父母、祖父母的乳糖不耐受发生率分别为51．0％、68．8％、67．6％；成人不饮奶者乳糖不耐受发生率(74．54％)高于每天饮奶者(26．67％)，差异有统计学意义(χ~2=21．452，P＜0．05)；祖父母、父母两代均不饮奶的家庭中儿童乳糖不耐受发生率(88．3％)高于两代均饮奶(45．5％，P＜0．05)和两代部分饮奶家庭中儿童乳糖不耐受发生率(32．1％，P＜0．01)，差异有统计学意义。
4．年平均累计饮奶量(AMIy)与乳糖不耐受严重程度呈负相关(r=-0．353，P＜0．05)，差异有统计学意义。用Binary Logistic回归模型分析结果为：饮奶年限、饮奶频率、一次饮奶量对乳糖不耐受发生的危险性有影响，差异有统计学意义(p＜0．05)，饮奶年限和饮奶频率与乳糖不耐受发生的危险性呈负相关，OR分别为0．317、0．465；一次饮奶量与乳糖乳糖不耐受发的危险性呈正相关，OR为6．337。
结论：
1．儿童饮奶率为74．6％，父母代为48．1％，祖父母代为32．0％；饮奶能促进儿童生长发育；成人腿抽筋、腰酸背痛等症状与年平均累计饮奶量有关；儿童饮奶受母亲影响较大；成人的文化程度对自身饮牛奶的行为有影响。
2．饮奶与乳糖乳糖不耐受有关：饮奶频率、饮奶年数与乳糖乳糖不耐受症状发生的危险性呈负相关，一次饮奶量与乳糖乳糖不耐受症状发生的危险性呈正相关。长期低剂量饮奶，可改善乳糖乳糖不耐受症状。
3．祖代、父母代不饮牛奶与儿童乳糖不耐受有关。
4．平均年累计饮奶量(AMIy)是一个估算长期饮奶量的较好指标。
5．醋酸铅法(半定量检测粪便乳糖的方法)，简便、安全、经济，适宜于规模大的现场调查。
二．严重乳糖乳糖不耐受者可接受牛奶摄入量的实验研究
目的：找出严重乳糖不耐受者可接受牛奶摄入量，观察此量后在健康成人的耐受情况。
方法：采用氢呼气试验从38名受试者中筛选出8名有水样状腹泻的乳糖不耐受者，分成低、高剂量组(分别为A、B组)参加饮奶试验。两组的症状评分之和大致相等，据文献报道及单因素优选法(黄金分割法)确定两组对象分别饮用25g和38．2g奶粉(分别含6．25g和9．55g乳糖)和水冲调成的200ml牛奶，分析受试者△HBT值、症状评分、粪便乳糖含量(醋酸铅法)。采用随机整群抽样方法选取健康的100名青年、80名中年、100名老年人，观察摄入25g奶粉(含乳糖6．25g)后出现的乳糖不耐受症状。
结果：两组受试者在饮奶试验中无一例腹泻发生，仅有不同程度的轻微症状(打嗝、胀气)；高剂量组(B组)对象饮奶后，其△HBT值、症状评分、粪便乳糖均高于低剂量组(A组)。健康成人饮用25g奶粉(含乳糖6．25g)冲调的牛奶后，80．3％的对象未产生任何乳糖不耐受症状。
结论：曾有严重腹泻的乳糖不耐受者在食用25g奶粉后，仅表现轻微乳糖不耐受症状，无腹痛、稀便和水样腹泻；健康成人即使为乳糖不耐受者也能饮用适量牛奶，大多数健康成人摄入25g奶粉(含乳糖6．25g)后不会出现任何乳糖不耐受症状，结合我国的实际情况建议20g奶粉(含乳糖5g，配成160ml牛奶)作为我国健康成年人可接受牛奶摄入量。
三．改善乳糖不耐受症状的膳食措施研究
目的：结合我国居民用膳方式，寻找饮牛奶时改善乳糖不耐受症状的膳食措施。
方法：采用氢呼气试验从38名受试者中筛选出8名有水样状腹泻的乳糖不耐受者，参加用正交实验设计的不同食物与25g奶粉(含乳糖6．25g)搭配的饮奶试验；采用随机整群抽样方法选取100名健康大学生参加以不同方式摄入25g奶粉(含乳糖6．25g)的饮奶试验，观察饮奶试验后出现的乳糖不耐受症状。
结果：受试者饮牛奶，同时摄入鸡蛋、馒头、锅魁、面包后△HBT值比单独饮用牛奶均有降低(均小于1．786 mg╱m~3)；正交直观分析、方差分析均表明：鸡蛋与牛奶混食者粪便乳糖和症状评分比馒头与牛奶混食者低，差异有统计学意义(P＜0．05)，全麦面包与牛奶混食者症状评分最高；不同饮奶方式引起乳糖不耐受症状的发生率不同，早餐空腹饮牛奶者乳糖不耐受发生率27．6％(27／98)高于午餐或晚餐饮牛奶者13．7％(13／98)，χ~2=6．16，P＜0．05，差异有统计学意义。
结论：食物种类和不同饮奶方式对乳糖不耐受症状有明显影响，建议不要空腹饮奶，而在正餐饮牛奶，并注意与高蛋白膳食、固体(干)的食物搭配，避免与含膳食纤维高的食品(如全麦面包)一起食用。
总之，乳糖不耐受者也能饮用适量牛奶，乳糖不耐受者应当解除不能饮奶的“枷锁”，只要坚持长期一次饮或食用含乳糖不超过5g的奶及奶制品，不要空腹饮奶，而在正餐饮牛奶，并注意与高蛋白膳食、固体(干)的食物搭配，避免与含膳食纤维高的食品(如全麦面包)一起食用，可以改善乳糖不耐受症状，还能增加饮奶量，维护乳糖不耐受人群健康。祖父母代、父母代不饮牛奶与儿童乳糖不耐受有关，此结论为明确长期是否饮奶的膳食模式与乳糖酶持续活性与无持续活性的基因多态性差异的关系提供了有力证据。但要阐明长期不饮奶与乳糖不耐受发生的关系，还需要类似的扩大样本量和不同种族人群的研究证据。
Lactose intolerance (LI)exists in the subjects with lactase deficiency(LD),which have gastrointestinal symptoms including abdominal distension,cramps,flatulence,and watery stools after consuming lactose and its foods. For this reason, milk and dairy products are eliminated from the diet of many LI subjects, which could lead to the nutrition-related diseases, especially disease related to calcium-deficiency,such as rickets, osteoporosis and asteomalacia etc. In China, the prevalence of LI is 65.5-67% in adults and 28.2-32% in children. Therefore, increasing calcium intake via ameliorating LI symptoms is one of important issue in nutrition.
Despite the results from a lot of epidemiological studies indicate LI maybe relate with long-term non-milk drinking, but whether is the decline of lactase activity in adult of Chinese caused by less milk drinking or non-milk drinking habit is not clear yet. Results from our research group suggested that subjects with LI had low lactase activity but still had residual lactase activity that can absorb some amount of lactose. Can LI subjects drink milk? How much milk could they accept? These questions should be answered. Studies by our research group also demonstrations that the serious symptoms after milk ingestion in LI subjects may vary widely, depending upon not only the degree of intestinal lactase deficit but also gastric emptying time ,orocecal transit time and colonic micro flora in subjects. It is a good way to increasing intake of cow's milk in LI subjects by exploring various foods and milk drinking manner to delaying gastric emptying.
The aim in present study is to investigate milk consumption in three generations, including children, their parents and grandparents, and to analyze the effects of drinking cow's milk on prevalence of LI based on many studies including our program. The acceptable intake of cow's milk for healthy adults and measures of alleviating symptoms of LI were put forward in the present study. When people drank the milk, combining eating habits of our residents by epidemiology survey and human trail. Therefore the results of the present study will play an important role in the practice in pushing civil milk drinking program, improving calcium level of Chinese people.
The present study includes three parts as follows:
1. Study on prevalence and influencing factors of lactose intolerance in three generations include children, parents and grandparents
Objective: To investigate milk consumption and effect on health of three generations include children, parents and grandparents, and to analyze the prevalence and influencing factors of LI among them, and to explore the effect of long-term and generations's milk drinking behavior to lactase.
Methods: 55 children aged 3-6 include their parents and grandparents 358, which selected from 3 three kindergartens in Chengdu and its suburb by clustered random sampling, were investigated by questionnaire, accumulative Cow's Milk Intake per year(AMIy) by frequencies,years,amounts of milk that they drank in their lifetime..LI were diagnosed by Hydrogen Breath Test (HBT) and stool lactose (by the way of lead acetate with aqueous ammonia) in 243 persons among those three generations. Statistical analysis is carried out by SPSS11.0.
Results 1.The rate of milk drinking in children, parents and grandparents was 74.6%,48.1% and 32.0% respectively; 66.1% of parents and grandparents take a dislike to milk and are unaccustomed to it .The height and weight of children with milk drinking habit were more higher and heavier than those with non-milk drinking habit(P＜0.05, respectively) .There were positive correlations between AMIy of children and their height、weight (r is 0.353、0.380 ,P=0.000 ,respectively) .The rate of milk drinking and AMIy in adults with leg cramp and waist ache were significant in comparing with that of those with non-symptoms (P＜0.005、P=0.000,respectively) .There were positive correlations between AMIy of children and that of mother, grandparents (r is 0.614、0.447, P＜0.01 respectively) .There were correlation between AMIy of adults and their cultural standard. AMIy of person graduated from senior high school and college is significant in comparing with that of which graduated from junior high school or below (P＜0.05) .
2. Concordance of diagnose LD by HBT and the way of lead acetate with aqueous ammonia: Kappa value was 0.421 (P＜0.01) ,sensitivity was 83.3%, specificity was 60.7%.
3. The prevalence of LI in children ,parents and grandparents was 50.9%、68.8%、67.6% respectively. The prevalence of LI in adults those with un-milk drinking habit was significant in comparing with those with milk drinking per day (x~2=21.452 P＜0.05). The prevalence of LI in child whose parents and grandparents with un-milk drinking habit was significant in comparing with those milk drinking habit (x~2=4.57 P＜0.01) .
4.There were negative correlations between AMIy and severity degree of LI symptom (r=-0.353, P＜0.05)。Binary Logistic regression showed that: years, frequency, and amount of milk per time that they drank in their lifetime were with statistical significance (P＜0.05) There were negative correlations between years , frequency of milk drinking and LI ,OR were 0.317、0.465, respectively. There were positive correlations between amount milk of per time and LI, OR was 6.337
Conclusion: 1.The rate of milk drinking in children, parents and grandparents was 74.6%,48.1% and 32.0% respectively. Drinking milk can improve children's growth and development. Leg cramp and waist ache of adults are related with accumulative Cow's Milk Intake per year (AMIy).Children's milk drinking habits were significantly influenced by mother. Cultural standard of adults can affect their milk drinking habits
2. LI is related to milk drinking. There were negative correlations between years , frequency of milk drinking and LI symptoms. There were positive correlations between amount of milk per time and LI symptoms.Drinking moderate amount milk for years per day might alleviate the symptoms of intolerance
3. LI of the child is related to un-milk drinking of his parents and grandparents.
4. A MIy is preferable index to rough estimate milk intake.
5. stool lactose eaxamined by the way of lead acetate with aqueous can be used for screening LD.
2. Study on the acceptable intake of cow's milk for severe LI
Objective: To find out the acceptable intake of cow's milk in subjects with severe LI and then observe intolerance symptoms in healthy adults after they drank thus allowance.
Methods: Eight LI subjects with watery diarrhea who were selected from 38 subjects by HBT were divided into group A, group B to go on drinking cow's milk test. The subjects in group A ingested 25g milk powder, the subjects in group B ingested 38.2g milk powder(contain 6.25g,9.55g lactose and make 200 ml of milk solution respectively) according to literature and single factor optimization method(0.618 golden mean) to analyze their△hydrogen excretion(mg/m~3) ,symptom score and stool lactose. The 100 younger, the 80 middle-age and the 100 elder subjects were selected by clustered random sampling to observe symptoms after they ingested 25g milk powder.
Results: No case with diarrhea occurred in these two group but mild symptoms (burp, break wind). hydrogen excretion(mg/m~3) and symptom score in the high dose group (group B)are a little higher than those in low dose group (group A) . Most of healthy adults (80.3%) have no intolerance symptoms after they ingested 25g milk powder (make 200 ml of milk solution).
Conclusion: There was only mild symptoms after LI with diarrhea ingested 25g cow's milk powder ,no bellyache ,loose and water stool occurre.The study demonstrates that most of adults, even with LI, can tolerance 25g cow's milk powder(6.25g lactose). According to the condition of our country. It is suggested 20g cow's milk powder(5g lactose, make 160 ml of milk solution) is the acceptable intake of healthy adults in China.
3. Study on measures of ameliorating symptoms of LI during drinking milk
Objective: To find out measurements of alleviating symptoms of LI when people drank the milk, combining diet habits of our residents.
Methods: Eight LI subjects with watery diarrhea who were selected from 38 subjects by HBT were divided into 4 groups to go on drinking cow's milk test with various foods by orthogonal trail. The 100 healthy college students were selected by clustered random sampling to observe symptoms after they ingested 25g milk powder by different manners.
Results:△hydrogen excretion of groups which ingested milk with various food is lower than those ingested milk only(all less than 1.786 mg/m~3). Egg is better than Manitou in alleviating symptoms. (F value of stool lactose and symptom score are 7.5、9.0 ,respectively＜0.05) .Whole wheat bread can aggravate flatus. The prevalence of the symptom in 100 college students by drinking milk in fast state (27/98) was significantly comparing with that by drinking milk with regular meal (13/98), (x~2=6.16, P＜0.05) .
Conclusion: The study demonstrates that various foods, various milk drinking manner can affect the intolerance symptom .We suggested:Don't drink milk in fast state, milk with egg and staple food such as steamed bread, bread or gomuti is best selection for breakfast. Drinking milk with regular manner can alleviate symptom of intolerance. For lactose intolerance, don't take whole wheat bread.
In general, LI of the child is related to un-milk drinking of his parents and grandparents .It is provided powerful evidence to demonstrate that lactase gene polymorphism (lactase persistence and nonpersistence)is related with long-term drinking and non drinking milk.LI subject should release from incapable of drinking milk .It is not only alleviating symptoms of LI but also improving intake of cow's milk when LI subjects keep on drinking milk or eat other dairy products which contain less 5g lactose per time for long term.
引文
1. Matthews SB, Waud JP, Roberts AG. Systemic lactose intolerance :A new perspective on an old problem. Postgrand Med J 2005; 81:167-173
2. Swagerty D.L. Jr, Walling A.D., Klein R.M. Lactose intolerance. Am. Fam. Physician. 2002; 65(9): 1855-1856.
3. Jarvis JK, Miller GD. Overcoming the barrier of lactose intolerance to reduce health disparities. J Natl Med Assoc 2002; 94(2): 55-66.
4. Russo F, De Carne M, Buonsante A, et al. Hypolactasia and metabolic changes in post-menopausal women. Maturitas. 1997; 26:: 193-202.
5. Jackson KA & Savaiano DA. Lactose maldigestion, calcium intake and osteoporosis in African-, Asian-, and Hispanic-Americans. J Am Coll Nutr.2001; 20(2 suppl): 198s-207s.
6. Campbell AK, Wann KT, Matthews SB. Lactose cause heart arrhythmia in the flea. Comparat Biochem Physi. 2004; Part B 139: 225-234.
7．余清．有关乳糖不耐受的研究进展．卫生研究．2006；35(3)：360-362．
8. Von TC, Kohn C, Steinkamp M, et al. Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis. J. Clin. Gastroenterol. 2002; 34(1): 49-53.
9. John WS, John B, Zulfiqar B, et al.Choronic Diarrhea and Malabsorption(Including Short Gut Syndrome):Working Group Report of the First World Congress of pediatric Gastroenterology, Hepatology, and Nutrition.J Pediatr Gastroenterol Nutr 2002; 35: 98s-105s.
10．吴坤，主编．营养与食品卫生学．第5版．北京：人民卫生出版 社，2005，110-112
11．梅方权．中国的牛奶与营养改善的发展分析．中国乳业，2002(1)：12-15．
12．王陇德，主编．中国居民营养与健康状况调查报告之一---2002综合报告．北京：人民卫生出版社，2005，20-22
13．杨月欣，何梅，崔红梅等．中国儿童乳糖不耐受发生率的调查研究卫生研究．1999；28：44-4
14．郑家驹，薛连生 乳糖吸收不良症种族及年龄差异性的初步研究．中华内科杂志．1987；26(3)：135-137
15．钟燕．乳糖不耐受基础研究进展．国外医学卫生学分册．2000；27(3)：168—171
16. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. 1 Review of the medical research. Am J Dig Dis. 1969; 14: 819-836.
17. Shaw AD.Davies GJ. Lactose intolerance:problem in diagnosis and treatment .J Clin. Gastroenterology.1999; 28(3): 208-216
18. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. 2A culture historical hypothesis. Am J Dig Dis. 1970; 15: 695-710.
19. Flatz G, Rotthauwe HW. Evidence against nutritional adaption of tolerance to lactose. Humangenetik. 1971; 13: 118-125.
20. Hollox EJ.Evolutionary Genetics: Genetics of lactase persistence-fresh lessons in the history of milk drinking.Euro J Hum Genet.2005; 13(3): 267-9
21．钟燕，黄承钰，阴文娅，Vonk RJ．用双标稳定同位素技术分析乳糖酶缺乏者小肠黏膜乳糖酶活性 卫生研究 2005；34(3)：312-316
22. Vonk RJ,Priebe MG,Koetse HA,Stellaard F,Lenoir-Wijnkoop I,Antoine JM,Zhong Y Huang CY.Lactose intolerance :analysis of underlying factors.Eur J Clin Invest 2003; 33: 70-75
23. Hertzler SR, Huynh BC Savaiano DA. How much lactose is low lactose J Am Diet Assoc.1996; 96(3): 243-246
24. Hertzler SR,Savaiano DA. Colonic adaptation to daily lactose feeding in lactose maldigesters reduce lactose intolerance Am J Clin Nutr.1996; 64(2): 232-236
25．黄辉德 王明春 等．应用氢呼气试验对乳糖酶缺乏症的研究．中国药学杂志，1998；33(5)：308-310
26. Priebe MG, Wachters-Hagedoorn RE, Stellaard F, et al.Oro-ceoal transit time:influence of a subsequent meal. Eur J Clin Invest 2004; 34: 417-421.
27. Pribila BA, Hertzler SR, Martin BR, Weaver CM, Savaiano DA.Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet.J Am Diet Assoc 2000; 100: 524-528.
28．钟燕 黄承钰 阴文娅 胃肠因素对成人乳糖不耐受的作用世界华人消化杂志 2005；13(13)：1618-1620
29. Suarez FL, Savaiano DA,Levitt MD:Review article:the treatment of lactose intolerance.Alim Parmacol Ther.1995; 9:589-597
30. Lee SY,Madan A, Furuta GT, Colgan SP,Sibley6 E.Lactase gene transcription is activated in response to hypoxia in intestinal epithelial cells.Mol Genet Metab 2002; 75:65-69
31. Martini MC,Savaiano DA.Reduced intolerance symptoms from lactose consumed during a meal Am J Clin Nutr.1988; 47: 57-60
32. Stefan L, Christi. Production, Metabolism, and Excretion of hydrogen in the large intestine. Gastroenterology. 1992; 102: 1269-1277
33. Bowonder B,Dasgupta B,Gupta S,Prasad S.Impact of dairy development Programmes.Food Nutr Bull 1986; 8: 48-58
34. Seva PA, Silva Rd.Lactose malabsorption dignosis with H_2 breath test.Arq Gastroenterol.1999; 36(1): 18-26
35．姚福宝 王建奎 史文生．粪便乳糖检测法诊断乳糖吸收不良与不耐受．实用儿科杂志，1991；6(3)：123
36．金汉珍．乳糖不耐受症．临床儿科杂志．1997；15(4)：246-247
37．曾果．健康成人牛奶不耐受症的研究．中国公共卫生．1998；14(1)：28
38．何梅．乳糖酶缺乏和乳糖不耐受．国外医学卫生学分册．1999；26(6)：339
39. Scrimshaw NS et al,Prevalence of lactose maldigestion.Am J Clin Nutr,1988(48): 1086-1098.
40．钟燕．用H~2／~(13)CO_2呼吸试验检测乳糖不耐受者呼气成分的研究．卫生研究 2002；31(3)：180-183
41．刘桂芬，主编．卫生统计学．北京：中国协和医科大学出版社．2003；170
42．倪宗瓒，主编．．医学统计学．．北京：人民卫生出版社 1990；255-256
43．钱宇平，主编 流行病学 第二版 北京：人民卫生出版社，1988：．69-71
44. Jorge L Rosado,SM.Milk consumption,symptom response,and lactose digestion in milk intolerance. Am J Clin Nutr 1987; 45: 1457-60.
45. Stephenson LS.Lactose intolerance and milk consumption:the relation of tolerance to symptoms. Am J Clin Nutr 1974; 27: 296-303.
46. Huang Cheng Yu. A survey of social nutrition status of the elderly in the urban area of chengdu,Sichuan Province.Biomedical and Environmental Science 1998; 11:286-296
47．倪宗瓒，主编．医学统计学．北京：人民卫生出版社．1990；18
48．张文彤，主编．SPSS统计分析基础教程．北京：高等教育出版社．2004；23-27
49．马斌荣．SPSS for Windows Ver．11．5在医学统计中的应用．第三版 北京：科学出版社。2004；87-203
50．王艳华，李传威，等．中国乳品消费研究．工业技术经济．2003；129(5)：95-98
51. Kanis JA, Johansson H,Oden A. A meta-analysis of milk intake and fracture risk:low utility for ase finding.Osteoporos Int.2005; 16:799-804
52. Weinsier RL, Carlos LK.Dairy foods and bone health:examimation of the evidence.Am J Clin Nutr.2000; 72: 681-689
53．吕斌，何伟等．多代饮奶对小鼠骨钙代谢的影响．河南医学研究．2005；14(4)：295-297
54．江汉．母亲文化程度对儿童饮食习惯的影响．武汉大学学报 2002；23(3)：282
55．于文涛，赵丽云，李杰等．儿童饮奶行为干预．中国学校卫生．1999；20(4)：245-246
56．唐咏梅，关维俊，宁鸿珍等．营养改善学龄儿童饮奶行为的效果观察．2003；24(6)：577-578
57．王爱华 张延东 黄宝润等．小儿乳糖不耐受临床探讨 临床儿科 杂．2000；18(3)：154-156
58．赵聪敏 张雨平 温思懿等 儿童乳糖酶缺乏的临床评价．第三军医大学学报 2000；22(6)：594-596
59．何伟．长期多代饮奶对鼠乳糖酶活性及mRNA水平的影响研究．四川大学博士学位论文．2005．87-88
60. Obermayer-Pietch BM,Bonell CM,Walter DE, et al.Genetic predisposition for adult lactose intolerance and relation to diet,bone density, and bone fractures.J bone miners Res.2004; 19(10): 1746-1747
61. Siley E.Genetic Variantion and lactose intolerance:dection methods and clinical implication.Am J Pharm,2004; 49 (4): 239-245
62. Stefan L, Christi. Production, Metabolism, and Excretion of hydrogen in the large intestine. Gastroenterology. 1992; 102:1269-1277
63. Jarvela IE Molecular genetics of adult-type hypolactasia. Annals of Medicine. 2005; 37(3): 179-85
64．张文彤，主编．世界优秀统计工具SPSS11．0统计分析教程(高级篇)．北京希望电子出版社．北京：2002；92-109
65. Vesa TH, Korpela RA, Sahi T. Tolerance to small amounts of lactose in lactose maldigester Am J Clin Nutr 1996 Aug,64(2): 197-201
66. Labayen I,Forga L, Gonzalez A,et al. Relationship between lactose digestion,gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption.Aliment Parmcaol Ther,2001; 15: 543-549
67. Zhong Y, Priebe MG, Vonk RJ,et al.The role of microbiota in lactose intolerance J Dig Dis,2004; 49:78-83
68. Pettetier X, Laure-Boussge S, Donazzolo Y.Hydrogen excertion upon ingestion male subjects:importance of the live flora. Eur J Clin Nutr.2001; 55: 509-512.
69．钟燕，黄承钰，阴文娅等．益生菌和酸奶对乳糖不耐受者的作用．营养学报．2005；27(5)：401-405
70．Willett W著 郝玲 李竹主译 营养流行病学 北京：人民卫生出版社，2005．69-95
71. Suarez FL, Savaiano DA, Levitt MD.A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance.N Engl J Med 1995; 333:1-4
72. Suarez FL, Savaiano DA, Levitt MD.Review article:the treatment of lactose intolerance.Alim Pharmacol Ther,1995; 9:589-597
73．宁正祥 主编 食品成分分析手册 第1版 北京：中国轻工业出版社，1997．1-4
74．卢险峰 编著 最优化方法应用基础 第1版 上海：同济大学出版社，2003．68-72
75. Suarez FL, Savaiano DA, Arbisi P, et al Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance Am J Clin Nutr.1997; 65(5): 1502-1506
76．赵秋莲，张明立 我国乳品市场需求分析及其营销策略 中国乳品工业 2003；31(4)：41-44
77．吴坤 主编 营养与食品卫生学 第5版 北京：人民卫生出版社．2003．210-220
78. Lois D, Bean MC, Gregory D, et al. Allaying fears and fallacies about lactose intolerance. J Am Diet Assoc.1998; 98(6): 672-676
79．杨功焕，马杰民，刘娜等．中国人群2002年饮食、体力活动和体重指数的现状调查．中华流行病学杂志．2005；26(4)：246-251
80．洪忠新，武力，张力红等．中老年人饮食营养状况调查与分析．中国全科医学．2006；23(9)：1994-1996．
81．李军，刘小燕，郭辉等．大学生营养知识、态度与膳食行为的调查．中国临床康复．2004；8(5)：1028-1029．
82．晏梁如，邹小晖．小学生早餐行为及影响因素分析．现代预防医学2006；33(11)：2128-2131
83．倪宗瓒，主编．．医学统计学．北京：人民卫生出版社．1990；76-93
84. Savvedra JM, Perman JA. Current concepts Ⅰ lactose malabsorption and intolerance. Annu Rev Nutr. 1989; 9: 475-502
85．斯莫特A．J．P．M，阿克曼L．M．A著 柯美云等译胃肠动力病学 北京：科学出版社．1996；72-76
1 Scrimshaw NS et al. Prevalence of lactose maldigestion. Am J Clin Nutr,。1988; 48: 1083s-1098s
2. Suarez-F Levitt M. Lactose malabsorption and diarrhea. Nutrition 1997; 13(1): 53-54
3. Poulter M, Hollox E, Harvey CB, et al. The causal element for the lactase persistence/non-persistence polymorphism is located in a 1Mb region of linkage disequilibrium in Europeans. Ann Human Gen, 2003; 67(pt 4): 298-311
4．杨月欣，何梅，崔红梅等．中国儿童乳糖不耐受发生率的调查研究卫生研究．1999；28：44-46
5. Swallow DM. Genetics of lactase persistence and lactose intolerance. Annu Rev Genet. 2003; 37: 197-219
6. Gupta SK, Chong SK, Fitzgerald JF. Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes.. J Pediatr Gastroenterol Nutr. 1999; 28(3) 246-251
7．姜天安，叶瑞云，孙晓明等．对腹泻患儿的小肠黏膜形态、乳糖酶及乳糖水解率的研究．中华医学杂志1987；67(9)：409-502
8. Ushijima H. Rotavirus infection in Asia. J Pediatrics International, 2000; 42(4): 392-394
9 Jarvela, IE. Mutations in the Translated Region of the Lactase Gene(LCT) Underlie Congenital Lactase Deficiency. Am J Hum Genet. 2006; 78(2): 339-344
10. Jarvela, IE. Molecular genetivs of adult-type hypolactasia Ann Med 2005; 37(3): 179-185
11. Olds LC, Sibley E. Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum Mol Genet. 2003; 12(18): 2333-2340.
12. Matthews SB, Waud JP, Roberts AG. Systemic lactose intolerance: A new perspective on an old problem. Postgrand Med J 2005; 81: 167-173
13. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. 1 Review of the medical research. Am J Dig Dis. 1969; 14: 819-836.
14. Hollox EJ. Evolutionary Genetics: Genetics of lactase persistence-fresh lessons in the history of milk drinking. European Journal of Human Genetics 2005; 13(3): 267-9
15. Lee WS, Boey CC et al. Chronic diarrhoes in infants and young children: causes, Chinical features and outcome. J Paediatr Child Health. 1999; 35(3):; 260-3
16．王爱华 张延东 黄宝润等．小儿乳糖不耐受临床探讨 临床儿科杂．2000；18(3)：154-156
17．萧树东．主编 胃肠病学(胃肠道菌群和菌群失调)．上海，上海科学技术出版社．2001；115-116．
18. Erika Isolauri et al Probiotics: effect on immunity Am J Clin Nutr 2001; 73: 444s-450s
19. Elmer GW. Probiotivs: living drugs" Am J Health Syst Pham. 2001; 58(12): 1101-1109.
20 Bevilacqua L, Ovidi M, Di Mattia E, et al. Screening of Bifidobacterium strains isolated from human faeces for antagonistic activities against potentially bacterial pathogens. Microbiol Res, 2003; 158(2): 179-185
21．姚希贤主编 临床消化学1999 34-46
22. Nizami SQ, Bhutta ZA, Molla AM Efficacy of traditional rice-lentil-yogurt diet, lactose free milk protein-based formula and soy protein formula in management of secondary lactose intolerance with acute childhood diahrroea. J trop pediatr 1996; 42(3): 133-137
23 Heynan MB. Lactose intolerance in infants, children, and adolescents. Pediatrics. 2006; 118(3): 1279-1286
24 中国腹泻病诊断治疗方案 中国实用儿科杂志1998；13(6)：381-384
25. Sullivan PB. Nutitional mangment of acute diarrhoea. Nutrition 1998; 14(10): 758-762
26. Lin MY, Dipalma JA, Martini MC, et al. Comparative effects of exogenous lactase(beta-galactosidase) proparations on in vivo lactose digestion. Dig Dis Sci. 1993; 38(11): 2022-2027
27. Saavedra JM Clinical applications of probiotic agents Am J Clin Nutr 2001; 73(6): 1147S-51S.
28. During MJ et al. Peroal gene therapy of lactose intolerance using adeno-associated virus vector. Nat Med. 1998; 4(10): 1131-1135
2. Swagerty D.L. Jr, Walling A.D., Klein R.M. Lactose intolerance. Am. Fam. Physician. 2002; 65(9): 1855-1856.
3. Jarvis JK, Miller GD. Overcoming the barrier of lactose intolerance to reduce health disparities. J Natl Med Assoc 2002; 94(2): 55-66.
4. Russo F, De Carne M, Buonsante A, et al. Hypolactasia and metabolic changes in post-menopausal women. Maturitas. 1997; 26:: 193-202.
5. Jackson KA & Savaiano DA. Lactose maldigestion, calcium intake and osteoporosis in African-, Asian-, and Hispanic-Americans. J Am Coll Nutr.2001; 20(2 suppl): 198s-207s.
6. Campbell AK, Wann KT, Matthews SB. Lactose cause heart arrhythmia in the flea. Comparat Biochem Physi. 2004; Part B 139: 225-234.
7．余清．有关乳糖不耐受的研究进展．卫生研究．2006；35(3)：360-362．
8. Von TC, Kohn C, Steinkamp M, et al. Lactose intolerance in active Crohn's disease: clinical value of duodenal lactase analysis. J. Clin. Gastroenterol. 2002; 34(1): 49-53.
9. John WS, John B, Zulfiqar B, et al.Choronic Diarrhea and Malabsorption(Including Short Gut Syndrome):Working Group Report of the First World Congress of pediatric Gastroenterology, Hepatology, and Nutrition.J Pediatr Gastroenterol Nutr 2002; 35: 98s-105s.
10．吴坤，主编．营养与食品卫生学．第5版．北京：人民卫生出版 社，2005，110-112
11．梅方权．中国的牛奶与营养改善的发展分析．中国乳业，2002(1)：12-15．
12．王陇德，主编．中国居民营养与健康状况调查报告之一---2002综合报告．北京：人民卫生出版社，2005，20-22
13．杨月欣，何梅，崔红梅等．中国儿童乳糖不耐受发生率的调查研究卫生研究．1999；28：44-4
14．郑家驹，薛连生 乳糖吸收不良症种族及年龄差异性的初步研究．中华内科杂志．1987；26(3)：135-137
15．钟燕．乳糖不耐受基础研究进展．国外医学卫生学分册．2000；27(3)：168—171
16. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. 1 Review of the medical research. Am J Dig Dis. 1969; 14: 819-836.
17. Shaw AD.Davies GJ. Lactose intolerance:problem in diagnosis and treatment .J Clin. Gastroenterology.1999; 28(3): 208-216
18. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. 2A culture historical hypothesis. Am J Dig Dis. 1970; 15: 695-710.
19. Flatz G, Rotthauwe HW. Evidence against nutritional adaption of tolerance to lactose. Humangenetik. 1971; 13: 118-125.
20. Hollox EJ.Evolutionary Genetics: Genetics of lactase persistence-fresh lessons in the history of milk drinking.Euro J Hum Genet.2005; 13(3): 267-9
21．钟燕，黄承钰，阴文娅，Vonk RJ．用双标稳定同位素技术分析乳糖酶缺乏者小肠黏膜乳糖酶活性 卫生研究 2005；34(3)：312-316
22. Vonk RJ,Priebe MG,Koetse HA,Stellaard F,Lenoir-Wijnkoop I,Antoine JM,Zhong Y Huang CY.Lactose intolerance :analysis of underlying factors.Eur J Clin Invest 2003; 33: 70-75
23. Hertzler SR, Huynh BC Savaiano DA. How much lactose is low lactose J Am Diet Assoc.1996; 96(3): 243-246
24. Hertzler SR,Savaiano DA. Colonic adaptation to daily lactose feeding in lactose maldigesters reduce lactose intolerance Am J Clin Nutr.1996; 64(2): 232-236
25．黄辉德 王明春 等．应用氢呼气试验对乳糖酶缺乏症的研究．中国药学杂志，1998；33(5)：308-310
26. Priebe MG, Wachters-Hagedoorn RE, Stellaard F, et al.Oro-ceoal transit time:influence of a subsequent meal. Eur J Clin Invest 2004; 34: 417-421.
27. Pribila BA, Hertzler SR, Martin BR, Weaver CM, Savaiano DA.Improved lactose digestion and intolerance among African-American adolescent girls fed a dairy-rich diet.J Am Diet Assoc 2000; 100: 524-528.
28．钟燕 黄承钰 阴文娅 胃肠因素对成人乳糖不耐受的作用世界华人消化杂志 2005；13(13)：1618-1620
29. Suarez FL, Savaiano DA,Levitt MD:Review article:the treatment of lactose intolerance.Alim Parmacol Ther.1995; 9:589-597
30. Lee SY,Madan A, Furuta GT, Colgan SP,Sibley6 E.Lactase gene transcription is activated in response to hypoxia in intestinal epithelial cells.Mol Genet Metab 2002; 75:65-69
31. Martini MC,Savaiano DA.Reduced intolerance symptoms from lactose consumed during a meal Am J Clin Nutr.1988; 47: 57-60
32. Stefan L, Christi. Production, Metabolism, and Excretion of hydrogen in the large intestine. Gastroenterology. 1992; 102: 1269-1277
33. Bowonder B,Dasgupta B,Gupta S,Prasad S.Impact of dairy development Programmes.Food Nutr Bull 1986; 8: 48-58
34. Seva PA, Silva Rd.Lactose malabsorption dignosis with H_2 breath test.Arq Gastroenterol.1999; 36(1): 18-26
35．姚福宝 王建奎 史文生．粪便乳糖检测法诊断乳糖吸收不良与不耐受．实用儿科杂志，1991；6(3)：123
36．金汉珍．乳糖不耐受症．临床儿科杂志．1997；15(4)：246-247
37．曾果．健康成人牛奶不耐受症的研究．中国公共卫生．1998；14(1)：28
38．何梅．乳糖酶缺乏和乳糖不耐受．国外医学卫生学分册．1999；26(6)：339
39. Scrimshaw NS et al,Prevalence of lactose maldigestion.Am J Clin Nutr,1988(48): 1086-1098.
40．钟燕．用H~2／~(13)CO_2呼吸试验检测乳糖不耐受者呼气成分的研究．卫生研究 2002；31(3)：180-183
41．刘桂芬，主编．卫生统计学．北京：中国协和医科大学出版社．2003；170
42．倪宗瓒，主编．．医学统计学．．北京：人民卫生出版社 1990；255-256
43．钱宇平，主编 流行病学 第二版 北京：人民卫生出版社，1988：．69-71
44. Jorge L Rosado,SM.Milk consumption,symptom response,and lactose digestion in milk intolerance. Am J Clin Nutr 1987; 45: 1457-60.
45. Stephenson LS.Lactose intolerance and milk consumption:the relation of tolerance to symptoms. Am J Clin Nutr 1974; 27: 296-303.
46. Huang Cheng Yu. A survey of social nutrition status of the elderly in the urban area of chengdu,Sichuan Province.Biomedical and Environmental Science 1998; 11:286-296
47．倪宗瓒，主编．医学统计学．北京：人民卫生出版社．1990；18
48．张文彤，主编．SPSS统计分析基础教程．北京：高等教育出版社．2004；23-27
49．马斌荣．SPSS for Windows Ver．11．5在医学统计中的应用．第三版 北京：科学出版社。2004；87-203
50．王艳华，李传威，等．中国乳品消费研究．工业技术经济．2003；129(5)：95-98
51. Kanis JA, Johansson H,Oden A. A meta-analysis of milk intake and fracture risk:low utility for ase finding.Osteoporos Int.2005; 16:799-804
52. Weinsier RL, Carlos LK.Dairy foods and bone health:examimation of the evidence.Am J Clin Nutr.2000; 72: 681-689
53．吕斌，何伟等．多代饮奶对小鼠骨钙代谢的影响．河南医学研究．2005；14(4)：295-297
54．江汉．母亲文化程度对儿童饮食习惯的影响．武汉大学学报 2002；23(3)：282
55．于文涛，赵丽云，李杰等．儿童饮奶行为干预．中国学校卫生．1999；20(4)：245-246
56．唐咏梅，关维俊，宁鸿珍等．营养改善学龄儿童饮奶行为的效果观察．2003；24(6)：577-578
57．王爱华 张延东 黄宝润等．小儿乳糖不耐受临床探讨 临床儿科 杂．2000；18(3)：154-156
58．赵聪敏 张雨平 温思懿等 儿童乳糖酶缺乏的临床评价．第三军医大学学报 2000；22(6)：594-596
59．何伟．长期多代饮奶对鼠乳糖酶活性及mRNA水平的影响研究．四川大学博士学位论文．2005．87-88
60. Obermayer-Pietch BM,Bonell CM,Walter DE, et al.Genetic predisposition for adult lactose intolerance and relation to diet,bone density, and bone fractures.J bone miners Res.2004; 19(10): 1746-1747
61. Siley E.Genetic Variantion and lactose intolerance:dection methods and clinical implication.Am J Pharm,2004; 49 (4): 239-245
62. Stefan L, Christi. Production, Metabolism, and Excretion of hydrogen in the large intestine. Gastroenterology. 1992; 102:1269-1277
63. Jarvela IE Molecular genetics of adult-type hypolactasia. Annals of Medicine. 2005; 37(3): 179-85
64．张文彤，主编．世界优秀统计工具SPSS11．0统计分析教程(高级篇)．北京希望电子出版社．北京：2002；92-109
65. Vesa TH, Korpela RA, Sahi T. Tolerance to small amounts of lactose in lactose maldigester Am J Clin Nutr 1996 Aug,64(2): 197-201
66. Labayen I,Forga L, Gonzalez A,et al. Relationship between lactose digestion,gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption.Aliment Parmcaol Ther,2001; 15: 543-549
67. Zhong Y, Priebe MG, Vonk RJ,et al.The role of microbiota in lactose intolerance J Dig Dis,2004; 49:78-83
68. Pettetier X, Laure-Boussge S, Donazzolo Y.Hydrogen excertion upon ingestion male subjects:importance of the live flora. Eur J Clin Nutr.2001; 55: 509-512.
69．钟燕，黄承钰，阴文娅等．益生菌和酸奶对乳糖不耐受者的作用．营养学报．2005；27(5)：401-405
70．Willett W著 郝玲 李竹主译 营养流行病学 北京：人民卫生出版社，2005．69-95
71. Suarez FL, Savaiano DA, Levitt MD.A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance.N Engl J Med 1995; 333:1-4
72. Suarez FL, Savaiano DA, Levitt MD.Review article:the treatment of lactose intolerance.Alim Pharmacol Ther,1995; 9:589-597
73．宁正祥 主编 食品成分分析手册 第1版 北京：中国轻工业出版社，1997．1-4
74．卢险峰 编著 最优化方法应用基础 第1版 上海：同济大学出版社，2003．68-72
75. Suarez FL, Savaiano DA, Arbisi P, et al Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance Am J Clin Nutr.1997; 65(5): 1502-1506
76．赵秋莲，张明立 我国乳品市场需求分析及其营销策略 中国乳品工业 2003；31(4)：41-44
77．吴坤 主编 营养与食品卫生学 第5版 北京：人民卫生出版社．2003．210-220
78. Lois D, Bean MC, Gregory D, et al. Allaying fears and fallacies about lactose intolerance. J Am Diet Assoc.1998; 98(6): 672-676
79．杨功焕，马杰民，刘娜等．中国人群2002年饮食、体力活动和体重指数的现状调查．中华流行病学杂志．2005；26(4)：246-251
80．洪忠新，武力，张力红等．中老年人饮食营养状况调查与分析．中国全科医学．2006；23(9)：1994-1996．
81．李军，刘小燕，郭辉等．大学生营养知识、态度与膳食行为的调查．中国临床康复．2004；8(5)：1028-1029．
82．晏梁如，邹小晖．小学生早餐行为及影响因素分析．现代预防医学2006；33(11)：2128-2131
83．倪宗瓒，主编．．医学统计学．北京：人民卫生出版社．1990；76-93
84. Savvedra JM, Perman JA. Current concepts Ⅰ lactose malabsorption and intolerance. Annu Rev Nutr. 1989; 9: 475-502
85．斯莫特A．J．P．M，阿克曼L．M．A著 柯美云等译胃肠动力病学 北京：科学出版社．1996；72-76
1 Scrimshaw NS et al. Prevalence of lactose maldigestion. Am J Clin Nutr,。1988; 48: 1083s-1098s
2. Suarez-F Levitt M. Lactose malabsorption and diarrhea. Nutrition 1997; 13(1): 53-54
3. Poulter M, Hollox E, Harvey CB, et al. The causal element for the lactase persistence/non-persistence polymorphism is located in a 1Mb region of linkage disequilibrium in Europeans. Ann Human Gen, 2003; 67(pt 4): 298-311
4．杨月欣，何梅，崔红梅等．中国儿童乳糖不耐受发生率的调查研究卫生研究．1999；28：44-46
5. Swallow DM. Genetics of lactase persistence and lactose intolerance. Annu Rev Genet. 2003; 37: 197-219
6. Gupta SK, Chong SK, Fitzgerald JF. Disaccharidase activities in children: normal values and comparison based on symptoms and histologic changes.. J Pediatr Gastroenterol Nutr. 1999; 28(3) 246-251
7．姜天安，叶瑞云，孙晓明等．对腹泻患儿的小肠黏膜形态、乳糖酶及乳糖水解率的研究．中华医学杂志1987；67(9)：409-502
8. Ushijima H. Rotavirus infection in Asia. J Pediatrics International, 2000; 42(4): 392-394
9 Jarvela, IE. Mutations in the Translated Region of the Lactase Gene(LCT) Underlie Congenital Lactase Deficiency. Am J Hum Genet. 2006; 78(2): 339-344
10. Jarvela, IE. Molecular genetivs of adult-type hypolactasia Ann Med 2005; 37(3): 179-185
11. Olds LC, Sibley E. Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum Mol Genet. 2003; 12(18): 2333-2340.
12. Matthews SB, Waud JP, Roberts AG. Systemic lactose intolerance: A new perspective on an old problem. Postgrand Med J 2005; 81: 167-173
13. Simoons FJ. Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. 1 Review of the medical research. Am J Dig Dis. 1969; 14: 819-836.
14. Hollox EJ. Evolutionary Genetics: Genetics of lactase persistence-fresh lessons in the history of milk drinking. European Journal of Human Genetics 2005; 13(3): 267-9
15. Lee WS, Boey CC et al. Chronic diarrhoes in infants and young children: causes, Chinical features and outcome. J Paediatr Child Health. 1999; 35(3):; 260-3
16．王爱华 张延东 黄宝润等．小儿乳糖不耐受临床探讨 临床儿科杂．2000；18(3)：154-156
17．萧树东．主编 胃肠病学(胃肠道菌群和菌群失调)．上海，上海科学技术出版社．2001；115-116．
18. Erika Isolauri et al Probiotics: effect on immunity Am J Clin Nutr 2001; 73: 444s-450s
19. Elmer GW. Probiotivs: living drugs" Am J Health Syst Pham. 2001; 58(12): 1101-1109.
20 Bevilacqua L, Ovidi M, Di Mattia E, et al. Screening of Bifidobacterium strains isolated from human faeces for antagonistic activities against potentially bacterial pathogens. Microbiol Res, 2003; 158(2): 179-185
21．姚希贤主编 临床消化学1999 34-46
22. Nizami SQ, Bhutta ZA, Molla AM Efficacy of traditional rice-lentil-yogurt diet, lactose free milk protein-based formula and soy protein formula in management of secondary lactose intolerance with acute childhood diahrroea. J trop pediatr 1996; 42(3): 133-137
23 Heynan MB. Lactose intolerance in infants, children, and adolescents. Pediatrics. 2006; 118(3): 1279-1286
24 中国腹泻病诊断治疗方案 中国实用儿科杂志1998；13(6)：381-384
25. Sullivan PB. Nutitional mangment of acute diarrhoea. Nutrition 1998; 14(10): 758-762
26. Lin MY, Dipalma JA, Martini MC, et al. Comparative effects of exogenous lactase(beta-galactosidase) proparations on in vivo lactose digestion. Dig Dis Sci. 1993; 38(11): 2022-2027
27. Saavedra JM Clinical applications of probiotic agents Am J Clin Nutr 2001; 73(6): 1147S-51S.
28. During MJ et al. Peroal gene therapy of lactose intolerance using adeno-associated virus vector. Nat Med. 1998; 4(10): 1131-1135