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Endothelial Dysfunction in Hypercholesterolemia is Reversed by a Nutritional Product Designed to Enhance Nitric Oxide Activity

Cardiovascular Drugs and Therapy volume 14, pages 309–316 (2000)Cite this article

Abstract

The objective of this study was to investigate the vascular andbiochemical effects of a formulated product in the form of a bar enrichedwith a combination of nutrients known to enhance the synthesis oractivity of endothelium-derived nitric oxide (EDNO). Individuals withhypercholesterolemia manifest impaired flow-mediated vasodilation, which islargely due to a reduction in EDNO activity. Oral supplementation withlarge amounts (6–21 g/day) of L-arginine, the precursor of EDNO,have been shown to improve endothelium-mediated vasodilation inhypercholesterolemia. Such large doses are effective but may be impracticalto take in capsule form. Accordingly, we have developed a nutrient barenriched with L-arginine as well as other ingredients that additivelyenhance EDNO activity. A pilot study in 41 hypercholesterolemic individualsindicated that the bar was well tolerated, had no adverse effects on serumchemistries or lipid profile, and normalized endothelial vasodilatorfunction. To definitively determine if the nutrient bar normalizesendothelial function, a double-blind, placebo-controlled study wasperformed. Flow-mediated endothelium-dependent vasodilation was assessedby 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. Subjectsmanifested an impaired flow-mediated vasodilation before theintervention. Vasodilator function in the active bar group improved towithin a normal range (6.5 ± 3% before to10 ± 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 to6.7 ± 4% after). These findings reveal that use of a nutrientbar designed to enhance EDNO activity improves flow-mediatedendothelium-dependent vasodilation in hypercholesterolemicindividuals.

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Authors and Affiliations

  1. Cooke Pharma, Inc., Belmont, California

    Andrew J. Maxwell, Barbara Anderson & Michael P. Zapien

  2. Division of Cardiovascular Medicine, Stanford University, Palo Alto, California, USA

    John P. Cooke

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  1. Andrew J. Maxwell
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  2. Barbara Anderson
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  3. Michael P. Zapien
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  4. John P. Cooke
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Maxwell, A.J., Anderson, B., Zapien, M.P. et al. Endothelial Dysfunction in Hypercholesterolemia is Reversed by a Nutritional Product Designed to Enhance Nitric Oxide Activity. Cardiovasc Drugs Ther 14, 309–316 (2000). https://doi.org/10.1023/A:1007886725480

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  • DOI: https://doi.org/10.1023/A:1007886725480

  • L-arginine
  • hypercholesterolemia
  • atherosclerosis
  • blood flow
  • nitric oxide
  • vasoconstriction/dilation
  • endothelial function