- 學位論文
維生素K及益生菌補充與骨質健康和代謝危險因子之關聯性
Study on the effects of vitamin K or probiotics supplementation on bone health and metabolic risk factors
摘要
代謝症候群是指數種心血管疾病危險因子群集的現象，導致罹患心血管疾病、第二型糖尿病、中風及死亡的風險增加；有研究也發現心血管疾病與骨質疏鬆有所關聯。先前研究顯示維生素K可以改善代謝危險因子（高空腹血糖、三酸甘油酯、血壓、較大的腰圍以及高密度脂蛋白膽固醇（high density lipoprotein cholesterol, HDL-C）偏低），並作為羧化骨骼相關蛋白之輔因子使其活化。過去研究表明補充益生菌能降低發炎因子（如：腫瘤壞死因子（tumer necrosis factor-α）等）而降低蝕骨細胞活性，又因代謝危險因子也與發炎反應有所關聯，故給予益生菌可能因改善身體發炎狀態而同時保護心血管和骨骼健康。 本研究以50歲以上且具有一到二項代謝危險因子的人為受試者，以140mg維生素K及100mg葉黃素（有效維生素K2劑量0.1%，含量為140μg；有效葉黃素劑量10%，含量為10mg）或益生菌（含有L. rhamnosus+L. reuteri+B. bifidum）分別為實驗組一和二，照組則給予240mg葉黃素（有效葉黃素劑量10%，含量為24mg）。所有受試者於基線和介入三個月後皆須參與各項人體測量、體組成檢測、飲食頻率及生活型態等問卷資料收集並提供禁食八小時之靜脈血液樣本；骨質密度掃描僅於基線進行一次。血液分析項目包括空腹血糖（fasting glucose, FG）、三酸甘油酯（triglyceride, TG）、總膽固醇（total cholesterol）、HDL-C、低密度膽固醇（low density lipoprotein cholesterol, LDL-C）、糖化血色素（glycated hemoglobin, HbA1c）、胰島素、凝血酶原時間（prothrombin time, PT）、骨膠原蛋白碳末端肽鏈（C-telopeptide of type I collagen, CTX-1）、骨鈣蛋白（osteocalcin, OC）、未羧化骨鈣蛋白（uncarboxylated osteocalcin, ucOC）、羧化基質Gla蛋白（carboxylated matrix Gla protein, MGP）及未羧化基質Gla蛋白（uncarboxylated matrix Gla protein, ucMGP）。 結果顯示與基線資料相比，以維生素K介入後骨骼相關生化指標有改善的趨勢，尤其在CTX-1（Δ=-1.89±0.75, p=0.041）和MGP（Δ=27.85±10.76, p=0.034）有顯著差異，在代謝危險因子部份也有改但與基線之差異未達統計顯著性；益生菌補充組在介入後代謝危險因子與基線相較有改善但沒有統計顯著差異，而CTX-1與基線相比有顯著下降趨勢（Δ=-1.51±0.3, p=0.033）；對照組與兩個實驗組相比，在骨骼相關生化指標方面改善成效較小，甚至是反向增加未羧化蛋白水平（ΔucMGP=253.49±120.77）。 本研究顯示維生素K或是益生菌的介入或許可以改善代謝危險因子狀況以及提高體內骨骼相關蛋白羧化程度而促進其活化，但介入效果是否能夠持續；或是否可能隨介入時間延長而提高改善幅度則有待未來進一步研究。
並列摘要
Metabolic syndrome refers to the cluster of several metabolic disorders that would increase the risk of developing heart disease, stroke, diabetes and even death. In addition, it has been reported that there seems to be some connection between cardiovascular disease and osteoporosis. Previous studies have shown that vitamin K may improve metabolic risk factors (high levels of fasting blood glucose and/or triglycerides, high blood pressure, larger waist circumference, and low level of high-density lipoprotein (HDL) cholesterol) and act as a cofactor for the carboxylation of bone-related proteins, which is critical to the activation of these proteins in the bone matrix. On the other hand, it has also been demonstrated that probiotics decrease the level of inflammatory markers, such as tumor necrosis factor which could stimulate the activity of osteoclasts. Moreover, metabolic risk factors are also related to inflammation, thus probiotics may protect both cardiovascular system and both health by improving inflammatory status. In the current study, subjects with one or two metabolic risk factors were recruited and were randomly assigned to one of the two experimental groups or the placebo control group. Daily dose of the vitamin K experimental group was 140mg vitamin K plus 100mg lutein (containing 140μg effective vitamin K2 and 10mg effective lutein). The probiotics experimental group was supplemented with capsules containing L. rhamnosus+ L. reuteri+ B. bifidum, whereas subjects in the placebo control group were provided with a daily dose of 240mg lutein (containing 10% effective lutein dose). The duration of intervention was 3 months. Data on anthropometric measurements, dietary intake and lifestyle questionnaire as well as venous blood samples were collected at baseline and the end of the 3rd month except that bone health status scanned by dual-exergy X-ray absorptiometry was performed only at blaseline. Blood levels of fasting glucose, triglyceride, total and high as well as low density lipoprotein cholesterols, HbA1c (glycated hemoglobin), insulin, and markers of bone turnover including CTX-1 (C-telopeptide of type I collagen), total and uncarboxylated osteocalcin, total and uncarboxylated MGP (matrix Gla protein) and prothrombin time were analyzed. The results showed that compared to the level at baseline, the bone-related proteins tended to improve after supplementation with vitamin K, especially in CTX-1 (Δ=-1.89±0.75, p=0.041) and MGP (Δ=27.85±10.76, p=0.034), and there were also improvements in metabolic risk factors though the difference did not reach statistically significance. In the subjects of the probiotics experimental group the changes in the metabolic risk factors were not statistically significant after 3 months of supplementation, yet the level of CTX-1 significantly decreased compared to that of baseline. In contrast, the levels of bone related markers of subjects in the placebo group had less improvement, and the levels of uncarboxylated proteins appeared to slightly increased(ΔucMGP=253.49±120.77). In summary, the results of the current study showed that supplementation of vitamin K or probiotics may improve the status of metabolic risk factors and/or the carboxylation and activation of bone-related proteins including both osteocalcin and MGP. Further studies may be required to examine whether the effects would sustain or whether longer duration of supplementation would result in more benefits.
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