不同鈣來源與其配方對鈣質生物利用率影響之臨床試驗

A comparison on calcium bioavailability of various calcium sources and their formula

洪宗譽(Tsung-Yu Hung)

指導教授 ： 蔡敬民

中原大學/工學院/生物科技研究所/碩士(2014年)

https://doi.org/10.6840/cycu201400144

摘要

本實驗目的欲比較鈣的生物利用率是否會受到不同鈣來源與其配方而有明顯的影響？實驗方法採用衛生署公告之「健康食品之骨質保健功效評估方法」中之「鈣質生物利用率測定」。本試驗包括擬訴求可作為「鈣」補充來源之5種市售產品(檸檬酸鈣-奶粉、檸檬酸鈣-順暢奶粉、檸檬酸鈣、牛奶鈣-牛乳、牛奶鈣-發酵乳)，實驗以最普遍作為鈣添加物或補充劑之碳酸鈣（CaCO3）作為對照樣品。本試驗採用人體試驗，且同一受試者進行交叉測試「對照樣品」與各項「受試樣品」，以抵銷個人的生理誤差。本計畫招募20歲以上健康之成年男性或女性共40人，排除平時消化吸收、已有骨質疏鬆、排便狀況不良或空腹一次喝500 mL之鮮乳會有不適現象者，如為女性受試者則必須為非懷孕、非授乳者。
實驗前對受試者先進行解說相關注意事項，並指導實驗前與實驗期間試驗者必須維持其原飲食習慣之穩定，且盡量避免攝取含高量鈣、維生素D或草酸（Oxalate）、植酸（Phytate）等會顯著影響鈣吸收之食品。實驗方法為將受試者隨機分成6組，每組6或7人，試驗前隔夜空腹至少12小時，但可飲水。試驗開始時，先收集受試者之血液與尿液各約5 mL，並同時每組給予等量不同鈣質來源之試驗樣品或碳酸鈣，攝取後於2、4、6小時分別取同量的血液與尿液樣本。於此試驗期間，每位受試者補充不含鈣離子等礦物質的純水，擔心因空腹過久會造成血糖過低者得補充純糖。完成一梯次試驗後相隔≧ 7天，再輪替進行下一梯次試驗，即各組除所攝取的鈣樣品不同外，其餘均與第一次攝食試驗完全相同，如此輪替試驗共6次，使每位受試者都有機會攝取到6種不同樣品（含作為對照之碳酸鈣），而每項樣品有40位受試者。收集的第0、2、4、6小時之血清與尿液分別測定其Ca濃度和尿液的Ca/Creatinine比率，以及第 0 和 4 小時之血清副甲狀腺激素（Parathyroid hormone, PTH）濃度。
試驗結果顯示試驗組的血鈣值在補充後2小時顯著上升，且攝取各不同試驗樣品時之上升幅度皆明顯高於攝取碳酸鈣樣品（p< 0.05），其中以檸檬酸鈣-奶粉與檸檬酸鈣-順暢奶粉的上升幅度最大；而於補充後4小時其血清鈣質濃度會逐漸下降，但其血清鈣濃度能維持高於碳酸鈣組（p< 0.05）；補充後6小時其血清鈣質濃度大多回到接近基礎值，但其增高量仍高於碳酸鈣組（p< 0.05）。此結果顯示本實驗所採用的5種產品，其所含的鈣質之生物利用率均明顯高於碳酸鈣。
攝取含鈣樣品後副甲狀腺激素受影響程度的探討，試驗結果顯示5個試驗組PTH濃度下降改變量在攝取樣品後4小時均顯著大於碳酸鈣組（p< 0.05），其中以檸檬酸鈣與檸檬酸鈣-順暢奶粉組的濃度下降最大，其次是檸檬酸鈣-奶粉。此現象大致反應檸檬酸鈣-奶粉與檸檬酸鈣-順暢奶粉組的血清鈣上升幅度最大，而其PTH的分泌也相對被抑制最大，然而檸檬酸鈣組的血清鈣上升幅度並非最大，但其PTH平均降幅卻是最大。本試驗的2個牛奶鈣組之血清鈣上升幅度高於碳酸鈣組，但仍明顯低於檸檬酸鈣-奶粉與檸檬酸鈣-順暢奶粉組，而其PTH的降幅也是大於碳酸鈣組，小於檸檬酸鈣-奶粉與檸檬酸鈣-順暢奶粉組，呈現相當一致性的改變幅度。
5個試驗組的尿鈣/肌酸酐比值於補充後2小時也都顯著高於碳酸鈣組（p< 0.05），這顯示試驗組中的鈣質被吸收進入體內的量確實顯著高於碳酸鈣，而因血鈣必須維持恆定，以致過多的血鈣很快地必須經由尿液排出體外。然而雖然牛奶鈣-牛乳與牛奶鈣-發酵乳組的血鈣增幅在5樣品組中並非最高，但無論是尿鈣排出量、排出增加量或增加率在攝取後2小時卻均呈現牛奶鈣-牛乳與牛奶鈣-發酵乳組為最高，明顯較大於3組檸檬酸組的排出量（p< 0.05）。但在第4小時後，「檸檬酸鈣-奶粉」及「檸檬酸鈣-順暢奶」的尿鈣排出增加率就比「牛奶鈣-牛乳」及「牛奶鈣-發酵乳」較高（p< 0.05）。
積分攝取樣品後0-6小時之血鈣濃度增加變化曲線下之面積顯示：本實驗所使用的3大類鈣來源中以檸檬酸鈣的生物利用率（Bioavailability）最佳，其次為牛乳鈣，而碳酸鈣為最差。綜合各項指標結果顯示，當檸檬酸鈣添加在乳粉中的生物利用率又比單純攝取檸檬酸鈣較高；而在牛乳或發酵乳中的牛乳鈣之生物利用率則無明顯的差異。

關鍵字

骨質疏鬆症 ； 鈣質生物利用率 ； 血鈣 ； 尿鈣 ； 副甲狀腺激素

並列摘要

The aim of this study was to assess the absorption rate of various calcium supplements by comparing its calcium bioavailability with calcium carbonate. The experiment was designed to follow the evaluation method of calcium bioavailability announced by Department of Health, Taiwan. The experiment included demands "calcium" supplement sources of five kinds of commercial products, experiment with the most common additives or supplements of calcium as calcium carbonate (CaCO3) as a control sample. Each subject must be single-blind crossover study "control sample" and the "test sample" to offset the individual's physiological errors. Forty volunteers healthy adult males and females voluntarily participated in the study. Male or female subjects, who had osteoporosis after usual digestion and absorption and who felt discomfort after fasting drinking 500 ml milk, and female subjects, who were pregnant or lactating, were both excluded from the study.
Before the experiment was conducted, the experimental details and precaution were explained to all the subjects. The subjects were guided in such that they should maintain a steady original diet before and during the experiment. In addition, they were told to avoid the intake of food with high levels of calcium, vitamin D or oxalic acid (Oxalate), and phytic acid (Phytate), which may significantly affect calcium absorption from food. The subjects divided in to six groups with six or seven persons in each group were fasted for at least 12 hours or overnight before the experiment, but drinking water was allowed during fasting. Each volunteer received either the test products or CaCO3 (the control product) during the period of experiment. Five ml of fasting serum and that of urine specimen were collected before the experiment. Subjects were allowed a single intake of the test sample or the control, which contained the amount of calcium equivalent to that in CaCO3, and then subjected to calcium absorption test. Serum and urine specimen were collected 2, 4, and 6 hours after the intake of the products. During this experiment, each subject supplement without calcium and other minerals in the water, worry about fasting blood sugar is too low for too long will cause those who would add pure sugar. During the wash out period (> = 1 week) subjects will maintain a normal diet. And then proceed to the next echelon rotation test, except that each group a different calcium intake samples, the rest are identical with the first feeding trial, a total of six times so rotation test, so that each participant has the opportunity to take in to six different samples (including as a control of calcium carbonate), and each sample had 40 subjects. The first collection of 0,2,4,6 hours were measured in serum and urine concentrations of Ca and urine Ca / Creatinine ratio, and 0 and 4 hours of serum parathyroid hormone (PTH) concentration.
Experimental results show that two hours after intake of five calcium supplements and calcium carbonate, the serum calcium concentrations significantly increased and serum calcium concentrations after intake of five calcium supplements were significantly higher than after intake of calcium carbonate(p<0.05). Among them, "calcium citrate - milk" and "calcium citrate - smooth milk," the largest increase. Four hours after intake all sample, serum calcium concentration decreased, but the serum calcium concentration can be maintained higher than the calcium carbonate group (p<0.05). Six hours after intake of the five calcium supplements, serum calcium concentrations reverted back to the original fasting serum calcium concentrations, but they continued to be significantly higher than after intake calcium carbonate(p<0.05). Taken together, the calcium absorption rate of the five calcium supplements is significantly higher than that of calcium carbonate, hence higher calcium bioavailability.
After ingestion of calcium investigate the effect of sample PTH levels by the test results show that five test groups PTH concentration decreased the amount of change in the four hours after ingestion of calcium carbonate samples were significantly greater than the group (p <0.05), which "calcium citrate "and" calcium citrate - smooth milk, "the concentration decreased the most, followed by" calcium citrate - milk. "This phenomenon is roughly response "calcium citrate - milk" and "calcium citrate - smooth milk," the largest increase in serum calcium, and PTH secretion is relatively suppressed the biggest, but "calcium citrate" is not the rise of serum calcium the biggest, but it is the largest average decline PTH. The test 2 "milk calcium" rise above the serum calcium carbonate, but still significantly below the "calcium citrate - milk" and "calcium citrate - smooth milk", and its decline is also greater than the calcium carbonate PTH group , less than "calcium citrate - milk " and "calcium citrate - smooth milk", presents a considerable change in the consistency of the amplitude.
Five test groups urinary calcium / creatinine ratio in the two hours after calcium supplements are also significantly higher than the group (p <0.05), indicating that the test group of calcium is absorbed into the body is indeed significantly higher than the amount of calcium carbonate , but because of the need to maintain a constant blood calcium, resulting in too much calcium to be excreted quickly in the urine. However, although the "milk of calcium - milk 'and' milk calcium - fermented milk," the calcium increase in five sample set is not the highest, but it is in urinary calcium excretion, but the rate of increase or increase the amount of discharge are presented in two hours after ingestion "Milk calcium - milk" and "Milk calcium - fermented milk" is the highest, significantly larger in the discharge amount of 3 citric acid (p <0.05). But in the first four hours later, "calcium citrate - Milk" and "calcium citrate - smooth milk" in urinary calcium excretion higher than the rate of increase of "Milk calcium - milk" and "Milk calcium - fermented milk."
Integral calcium concentration after 0-6 hours of ingestion of the sample increase the area under the curve display: This study used three categories of sources of calcium to calcium citrate bioavailability the best, followed by milk calcium , and calcium carbonate as the worst. Comprehensive indicators showed that, when added to milk in calcium citrate bioavailability off than simply a higher intake of calcium citrate; while no significant difference in the milk or milk fermented milk calcium bioavailability.

並列關鍵字

osteoporosis ； parathyroid hormone ； calcium bioavailability ； serum calcium and urinary calcium

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