Endothelial dysfunction in hypercholesterolemia is reversed by a nutritional product designed to enhance nitric oxide activity

被引:41
作者
Maxwell, AJ
Anderson, B
Zapien, MP
Cooke, JP
机构
[1] Cooke Pharma Inc, Belmont, MA USA
[2] Stanford Univ, Div Cardiovasc Med, Palo Alto, CA 94304 USA
关键词
L-arginine; hypercholesterolemia; atherosclerosis; blood flow; nitric oxide; vasoconstriction; dilation; endothelial function;
D O I
10.1023/A:1007886725480
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The objective of this study was to investigate the vascular and biochemical effects of a formulated product in the form of a bar enriched with a combination of nutrients known to enhance the synthesis or activity of endothelium-derived nitric oxide (EDNO). Individuals with hypercholesterolemia manifest impaired flow-mediated vasodilation, which is largely due to a reduction in EDNO activity. Oral supplementation with large amounts (6-21 g/day) of L-arginine, the precursor of EDNO, have been shown to improve endothelium-mediated vasodilation in hypercholesterolemia. Such large doses are effective but may be impractical to take in capsule form. Accordingly, we have developed a nutrient bar enriched with L-arginine as well as other ingredients that additively enhance EDNO activity. A pilot study in 41 hypercholesterolemic individuals indicated that the bar was well tolerated, had no adverse effects on serum chemistries or lipid profile, and normalized endothelial vasodilator function. To definitively determine if the nutrient bar normalizes endothelial function, a double-blind, placebo-controlled study was performed. Flow-mediated endothelium-dependent vasodilation was assessed by high-resolution ultrasonography before and after 1 week of bar use (2 bars/day) in an additional group of 43 volunteer subjects (57 +/- 10 years old; 22 men, 21 women) with hypercholesterolemia. Subjects manifested an impaired flow-mediated vasodilation before the intervention. Vasodilator function in the active bar group improved to within a normal range (6.5 +/- 3% before to 10 +/- 5% after, P = 0.02; normal, 12 +/- 3%) and was significantly better (P < 0.01) than in the placebo bar group (7.1 +/- 3% before to 6.7 +/- 4% after). These findings reveal that use of a nutrient bar designed to enhance EDNO activity improves flow-mediated endothelium-dependent vasodilation in hypercholesterolemic individuals.
引用
收藏
页码:309 / 316
页数:8
相关论文
共 49 条
  • [1] Aji W, 1997, CIRCULATION, V95, P430
  • [2] Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys
    Anthony, MS
    Clarkson, TB
    Hughes, CL
    Morgan, TM
    Burke, GL
    [J]. JOURNAL OF NUTRITION, 1996, 126 (01) : 43 - 50
  • [3] Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits
    BodeBoger, SM
    Boger, RH
    Kienke, S
    Junker, W
    Frolich, JC
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 219 (02) : 598 - 603
  • [4] L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia - A randomized, controlled study
    BodeBoger, SM
    Boger, RH
    Alfke, H
    Heinzel, D
    Tsikas, D
    Creutzig, A
    Alexander, K
    Frolich, JC
    [J]. CIRCULATION, 1996, 93 (01) : 85 - 90
  • [5] BODEBOGER SM, 1997, CIRCULATION S1, V96, P1419
  • [6] Asymmetric dimethylarginine (ADMA):: A novel risk factor for endothelial dysfunction -: Its role in hypercholesterolemia
    Böger, RH
    Bode-Böger, SM
    Szuba, A
    Tsao, PS
    Chan, JR
    Tangphao, O
    Blaschke, TF
    Cooke, JP
    [J]. CIRCULATION, 1998, 98 (18) : 1842 - 1847
  • [7] Boger RH, 1997, VASA-J VASCULAR DIS, V26, P180
  • [8] Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits - Comparison with lovastatin
    Boger, RH
    BodeBoger, SM
    Brandes, RP
    Phivthongngam, L
    Bohme, M
    Nafe, R
    Mugge, A
    Frolich, JC
    [J]. CIRCULATION, 1997, 96 (04) : 1282 - 1290
  • [9] Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease
    Böger, RH
    Bode-Böger, SM
    Thiele, W
    Creutzig, A
    Alexander, K
    Fröhlich, JC
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1998, 32 (05) : 1336 - 1344
  • [10] FOLIC-ACID - AN INNOCUOUS MEANS TO REDUCE PLASMA HOMOCYSTEINE
    BRATTSTROM, LE
    ISRAELSSON, B
    JEPPSSON, JO
    HULTBERG, BL
    [J]. SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION, 1988, 48 (03) : 215 - 221