第四節 血壓相關飲食介入臨床試驗
4.1 Dietary Approaches to Stop Hypertension (DASH) trial15
美國國家衛生研究院心肺血液研究中心於 1997 年對 459 位受試者進行多中心 的預防高血壓飲食計畫。研究當中使用平行試驗比較美國一般飲食、蔬果含量較 多的飲食以及DASH 飲食介入八週後對血壓正常者與偏高者的影響，研究期間維 持受試者的體重。DASH 飲食強調多攝取「全穀、蔬果、低脂乳製品、白肉和堅 果」；減少「脂肪總量、飽和脂肪」攝取，是一種富含鉀、鎂、鈣、纖維與較少飽 和脂肪酸、較少膽固醇的飲食(營養素請參考 table 3-24 USA DASH)。結果發現 DASH 飲食對收縮壓與舒張壓有顯著下降效果，並且較一般飲食或蔬果含量較多 的飲食的效果好。
4.2 Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart)13 美國國家衛生研究院心肺血液研究中心於 2005 年對 164 位受試者進行多中心 的預防心血管疾病飲食計劃，研究當中使用交叉試驗比較DASH 飲食、增加蛋白 質比例的DASH 飲食、增加單元不飽和脂肪酸的 DASH 飲食介入六週後對血壓偏 高者的血壓與血脂影響，研究期間維持受試者的體重(營養素請參考 table 3-24 OmniHeart DASH、OmniHeart protein diet、OmniHeart MUFA diet)。結果發現增加 蛋白質比例的DASH 飲食對血壓、LDL-C 和三酸甘油酯都有顯著下降效果，並且 較DASH 飲食的效果好。增加單元不飽和脂肪酸比例的 DASH 飲食對血壓、和三 酸甘油酯都有顯著下降效果，對HDL-C 有上升的效果，並且較 DASH 飲食的效果 好。以蛋白質或單元不飽和脂肪酸取代部分醣類在此試驗能更有效下降血壓，減 少心血管疾病的風險。
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Table 1-2 Epidemiology study on the relation between blood pressure and protein.
Study Study design Subjects Nutrient
(association direction) Analysis and findings
8He J et al.,1995 cross-sectional
study 827 Chinese adults total protein (-)
After adjusting for age, BMI, alcohol use, urinary excretion of sodium and total energy intake, a 1 SD higher intake of dietary total protein (39 g) was associated with lower systolic (-3.55 mmHg), and diastolic (-2.16
mmHg) blood pressures.
10Stamler J et al.,1996 (INTER-SALT)
cross-sectional study
10020 adults from 32 countries worldwide
(aged 20–59 y)
24-hour urinary total nitrogen
(-)
Total nitrogen and urea as indexes of total protein intake. Significant independent inverse relationships were found between BP (systolic and diastolic) and both 24-hour urinary total nitrogen and urea nitrogen, with adjustment for age, sex, alcohol intake, body mass, and 24-hour urinary sodium, potassium, calcium, and magnesium.
111Stamler J et al.,2002
prospective study
1714 men
(aged 40–55 y) plant protein (-) Vegetable protein and antioxidant index were inversely related to change in SBP and DBP.
After adjustment for potential confounders and several dietary factors, participants in the highest quintile of vegetable protein intake had a lower risk of incident HT compared with those in the lowest quintile [hazard ratio (HR) = 0.5, 95% confidence interval (CI) 0.2-0.9, p for trend
= 0.06].
total protein (N) Total or animal protein and total fiber as well as fiber from other sources different from cereal were not associated with the risk of HT.
(-): Negative association; (+): Positive association; (N): No association
9
Table1-2 Epidemiology study on the relation between blood pressure and protein (continued).
Study Study design Subjects Nutrient
(association direction) Analysis and findings
11Elliott P et al.,2006 (INTER-MAP)
cross-sectional study
4680 respondents from China, Japan,
UK and USA (aged40–59 y)
plant protein (-) There was a significant inverse relationship between vegetable protein intake and blood pressure.
animal protein (N) For animal protein intake, significant positive blood pressure differences did not persist after adjusting for height and weight.
total protein (N)
For total protein intake (which had a significant interaction with sex), there was no significant association with blood pressure in women, nor in men after adjusting for dietary confounders.
112Wang YF et al.,2008 (PRE-MIER)
cross-sectional study
810 untreated pre or mild htpertensives (aged 25-79 y)
plant protein (-) Dietary plant protein was inversely associated with both SBP and DBP in cross-sectional analyses at the 6-month follow-up
9Umesawa M
et al.,2009 (CIRCS) cross-sectional study
7585 Japanese men and women (aged 40-69 y)
total protein (-)
After adjustment for cardiovascular disease risk factors, a 25.5-g/d increment in total protein intake was associated with a decrease in SBP of 1.14 mm Hg (P < 0.001) and in DBP of 0.65 mm Hg (P < 0.001)
plant protein (-) A 13.1-g/d increment in plant proteinintake was associated with a decrease in DBP of 0.57 mm Hg (P < 0.001).
(-): Negative association; (+): Positive association; (N): No association
10
Table 1-3 Clinical trial on the relation between blood pressure and protein.
Study Study design Subjects Type of the diet Analysis and findings
13Appel LJ et al.,2005 (OmniHeart)
cross-over trial
164 US participants (mean age 64y)
Protein rich diet vs.
CHO rich diet
Compared with the carbohydrate diet, the protein diet further decreased mean SBP by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension
113Papakonstantinou
E et al.,2010 cross-over trial
17 obese, newly diagnosed type 2 diabetes patients (aged 30–65 y)
High protein low fat diet vs. low protein high
fat diet
High protein low fat diet improved significantly both SBP and DBP when compared with the low protein high fat diet (P<0.001 and P<0.001, respectively).
114Delbridge EA
et al.,2009 parallel trial
141 obese men and women (aged 18–75 y)
High protein diet vs.
high CHO diet
By the end of the study, reductions in systolic blood pressure were 14.3 +/- 2.4 mm Hg for the HP group and 7.7 +/- 2.2 mm Hg for the HC group (P < 0.045).
11
Table 1-4 Epidemiology study on the relation between blood pressure and fatty acid.
Study Study design Subjects Nutrient
(association direction) Analysis and findings
18Ascherio A
No significant associations with hypertension were observed for sodium, total fat, or saturated, trans-unsaturated, and polyunsaturated fatty acids.
21Psaltopoulou T et al.2004 (EPIC)
prospective
study 20,343 olive oil (-) Intakes of olive oil, vegetables, and fruit were significantly inversely associated with both SBP and DBP. Olive oil has the dominant beneficial effect on arterial blood pressure in this population.
22Trevisan M et al.,1990
cross-sectional study
4903 Italian men and women (aged 20-59
y) olive oil (-) In both sexes consumption of olive oil and vegetable oil was inversely associated with serum cholesterol and glucose levels and SBP.
12Alonso A
et al.,2004(SUN) prospective
study 6,863 participants olive oil (-) In a Mediterranean population, we found olive oil consumption to be associated with a reduced risk of hypertension only among men.
(-): Negative association; (+): Positive association; (N): No association
12
Table 1-5 Clinical trial on the relation between blood pressure and fatty acid.
Study Study design Subjects Type of the diet Analysis and findings
24Ferrara LA
Resting BP was significantly lower at the end of the MUFA diet compared with the PUFA diet.
13Appel LJ et al.2005
(OmniHeart) cross-over
trial 164 US participants
( mean age 54y) MUFA rich diet vs.
CHO rich diet
Compared with the carbohydrate diet, the MUFA diet decreased SBP by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02) Increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02).
25Perona JS et al.2004 cross-over trial
31 medically treated HT elderly patients and
31 normotensive (NT) elderly volunteers
Olive oil vs.
sunflower oil
No significant differences were found for DBP.
SBP was normalized in HT by dietary VOO but not by SO.
19Rasmussen BM
et al., 2006 parallel trial 162 healthy subjects MUFA diet vs.
SFA diet
SBP and DBP decreased with the MUFA die but did not change with the SFA diet. The MUFA diet caused a significantly lower DBP than did the SFA diet (P = 0.0475).
The favorable effects of MUFA on DBP disappeared at a total fat intake above the median (>37% of energy).
13
Table 1-5 Clinical trial on the relation between blood pressure and fatty acid (continued).
Study Study design Subjects Type of the diet Analysis and findings
26Morris MC
et al.,1993 Meta-analysis 31 placebo-controlled trials on 1356 subjects
omega-3 fatty acids in fish oil
The mean reduction in blood pressure caused by fish oil for the 31 studies was -3.0/-1.5 mm Hg
Both eicosapentaenoic acid and docosahexaenoic acid were significantly related to blood pressure response.
There was a significant effect of -3.4/-2.0 mm Hg in the group of hypertensive studies
There is a dose-response effect of fish oil on blood pressure of -0.66/-0.35 mm Hg/g omega-3 fatty acids.
27Geleijnse JM
et al., 2002 Meta-analysis A total of 36 trials were included, 22 of which had
a double-blind design
omega-3 fatty acids in fish oil
BP effects tended to be larger in populations that were older (> 45 years) and in hypertensive populations (BP >or= 140/90 mmHg).
98Meena S
et al.,2007 Meta-analysis
Study diets had to be isoenergetic, and the subjects’ body weight had
to remain stable.
high carbohydrate and high-cis-monoun
saturated fat diets
When the meta-analysis was limited to randomized crossover studies, both systolic and diastolic blood pressure were higher with a high-carbohydrate than with a high cis-monounsaturated fat diet, but the differences were not significant.
27Hartweg J
et al.,2007 Meta-analysis
Randomised controlled trials comparing dietary or
non-dietary intake ofn-3 PUFA with placebo
in type 2 diabetes
n-3 PUFA Reducing the level of diastolic blood pressure (five trials, 248 subjects) by a mean of 1.8 mm Hg (95% CI 0.0-3.6, p = 0.05)
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第五節 糖尿病之定義與台灣現況
糖尿病是一種由於體內胰島素供應不足或是因為身體細胞對於胰島素敏 感度下降(或稱胰島素抗性)的代謝疾病。正常情況下，胰島素是由胰臟內的一 種內分泌細胞，稱作貝他細胞（Beta cell）所分泌的。胰島素是體內調控血中 葡萄糖濃度最重要的荷爾蒙，而糖尿病患者由於胰島素供應不足或利用能力 降低，因此造成血糖高於正常人。除此之外，胰島素也和身體內其他重要營 養素的代謝及利用有很大的關係，例如促進脂肪細胞將脂肪酸酯合成為脂肪。
因此糖尿病除了會影響血糖濃度之外，同時也會增加血脂異常和其他心血管 疾病的風險。
目前美國糖尿病學會56 (American Diabetes Association)依據病因的不同，
將糖尿病區分為四類，包括第一型糖尿病、第二型糖尿病、妊娠型糖尿病和 其他特異型糖尿病，大多數是第二型糖尿病。在發展成第二型糖尿病的過程 中，起初會出現葡萄糖耐受度異常，以糖化血色素5.7-6.4%或空腹血漿血糖值 在100-125mg/dl 或口服葡萄糖耐受度測驗(Oral Glucose Tolerance Test )的兩小 時後血糖值為140-199 mg/dl 來判定。若糖化血色素≧6.5%或空腹血糖值超過 126mg/dL 或口服葡萄糖耐受度測驗的兩小時後血糖值大於 200mg/dL 或任一 時間的血糖值大於200mg/dL 則被視為糖尿病發生。
台灣在2005~2008 年的營養健康調查顯示 19～44 歲的糖尿病盛行率低於 5％，但是到了 45～64 歲女性超過 10％，男性更是超過 18％，老年人（＞65 歲）男女性的盛行率更分別達到27.7％ 與 24％57。若是與1993~1996 的國民 營養調查相比，台灣19 歲以上男性的糖尿病盛行率從 3.2%上升至
10.9%，而女性則從 5.5%上升至 7.2%58。近年來糖尿病盛行率上升，生活型態 扮演很重要的角色。過重和肥胖以及營養素攝取不均衡都與糖尿病有關係。
以下針對與血糖相關的營養素進行探討。
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第六節 血糖與飲食因子：回顧觀察性研究與臨床試驗結果 6.1 脂肪酸
飲食當中脂肪的種類與血糖的調控有關，以下針對不同脂肪酸的臨床 試驗來探討脂肪酸與糖尿病控制的關係。
6.1.1 飽和脂肪酸(SFA)
流行病學研究發現攝取較高的飽和脂肪酸會增加第二型糖尿病的風險
59,60，另外也有研究指出較低的多元不飽和脂肪酸和飽和脂肪酸比例 (P:S)
會增加第二型糖尿病人心血管疾病的風險61。在胰島素敏感度方面，部分的 流行病學研究62-64和臨床試驗65顯示飽和脂肪酸會顯著下降胰島素敏感度，
也有部分的研究沒有發現顯著的影響66,67。
6.1.2 單元不飽和脂肪酸(MUFA)
臨床試驗顯示若是將飲食中部份的飽和脂肪酸用單元不飽和脂肪酸取 代，能夠下降血糖，並且增加胰島素敏感度68,69，但也有研究顯示增加單元 不飽和脂肪酸不會增加胰島素敏感度63,65。到底是油裡面的某些成份影響胰 島素抗性，還是身體組成改變後影響胰島素敏感度是值得關注的。
6.1.3 n-3多元不飽和脂肪酸( n-3 PUFA)
統合分析顯示，n-3多元不飽和脂肪酸對於胰島素敏感度、血糖和糖化 血色素沒有顯著影響69,70。一項臨床試驗觀察不同n-6:n-3的比值與胰島素的 關係，研究發現降低n-6:n-3的比值不會顯著影響胰島素敏感度71。
6.2 鎂
鎂是葡萄糖代謝中酵素的輔助因子72。在一些前瞻性研究中發現，鎂攝取 量與糖尿病的發生風險呈現負相關73-75，但也有研究顯示糖尿病的風險與血清 鎂濃度相關，而與鎂攝取量沒有顯著相關性76。另外在橫斷性研究中發現鎂攝 取量與空腹胰島素濃度呈現顯著負相關77。在臨床試驗中發現，鎂補充劑能夠 改善胰島素敏感度78，並且改善空腹血糖值和糖化血色素79。
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6.3 膳食纖維
在前瞻性研究中發現，膳食纖維攝取量與胰島素濃度呈現負相關80，並且 能降低糖尿病風險81。美國糖尿病學會(American Diabetes Association)建議糖尿 病者或葡萄糖不耐者攝取膳食纖維來幫助改善血糖及血脂82。
6.4 升糖指數及升糖負荷
升糖指數(Glycimic index; GI)是指用含 50 克醣類食物比起食用標準食物 (葡萄糖或白麵包)之血糖反應區線面積的百分比。升糖負荷(glycimic load;GL) 除了考慮升糖指數，還考慮每一份食物所含醣類克數(重新定義)，其公式如下：
GL=(GI x 一份食物所含醣類克數)/100。
在過去的研究中發現，低升糖指數飲食能降低糖化血色素83,84，增加 HDL-C85，並且減少糖尿病的發生率86,87和心血管疾病88。在針對近年觀察性 研究的統合分析指出，升糖指數與升糖負荷都與第二型糖尿病風險呈現顯著正 相關89。
6.5 維生素 C
研究顯示糖尿病患者血中vitamin C 濃度較正常人低，這可能跟體內的氧 化壓力增加有關90,91。補充劑臨床試驗中發現，高劑量的ascorbic acid (2 g/day)
研究顯示糖尿病患者血中vitamin C 濃度較正常人低，這可能跟體內的氧 化壓力增加有關90,91。補充劑臨床試驗中發現，高劑量的ascorbic acid (2 g/day)