The effect of dietary nitrate and vitamin C on endothelial function, oxidative stress and blood lipids in untreated hypercholesterolemic subjects: A randomized double-blind crossover study
Basaqr R, Skleres M, Jayswal R, Thomas DT
Clinical nutrition (Edinburgh, Scotland) · 24 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
- Intake measured by
- Not stated
Who paid for it
- Funding
- Independent funding
- University or hospital
- University of Kentucky
- Government
- National Institutes of Health
- Government
- National Center for Research Resources
- Government
- National Center for Advancing Translational Sciences
- Government
- NCATS NIH HHS
- Grants
- National Center for Advancing Translational Sciences (UL1TR 000117); National Institutes of Health (UL1‐TR‐000117)
Based on 5 listed funder(s).
Publication
- Published
- 2020-10-13 · Clin Nutr · vol. 40 · issue 4 · pp. 1851–1860
- Publisher
- Elsevier BV
- Cited
- 31 citations · more than 80% of similar papers · 1.4× the field average
- References
- 72 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Vitamin C and Antioxidants Research · Antioxidant Activity and Oxidative Stress · Nitric Oxide and Endothelin Effects
- Keywords
- Medicine, Crossover study, Vitamin C, Oxidative stress, Double blind, Endothelial dysfunction, Internal medicine, Vitamin E, Vitamin, Blood lipids, Cholesterol, Endocrinology, Antioxidant, Biochemistry, Pathology
- MeSH
- endothelium, humans, hypercholesterolemia, nitrates, ascorbic acid, lipids, vitamins, cross-over studies, double-blind method, oxidative stress, aged, middle aged, female, male
4 authors
From US
- Reem Basaqr · correspondingUniversity of Kentucky
- Michealia Skleres · correspondingUniversity of Kentucky
- Rani D. Jayswal · correspondingUniversity of Kentucky
- David Travis Thomas · correspondingUniversity of Kentucky
Abstract
Background
Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO3) to nitrite (NO2) to NO. The combined effect of vitamin C and NO3 supplementation is relatively unexplored in untreated hypercholesterolemia.
Aims
We aimed to examine whether co-administration of vitamin C and nitrate for 4-weeks would improve endothelial function (primary outcome), plasma NO metabolites, oxidative stress, and blood lipids (secondary outcomes).
Methods
Subjects 50-70 years of age with low density lipoprotein (LDL) > 130 mg/dL and RHI ≤2 were enrolled in this randomized double-blind crossover study. Subjects were assigned to two 4-week supplementation treatments starting with 70 ml of concentrated beetroot juice (CBJ) with 1000 mg of vitamin C (NC) or CBJ with matched placebo (N), then switched to alternate treatment following 2-week washout. The change in reactive hyperemia index (RHI), sum of plasma NO metabolites (NO2 + NO3 (NOx)), oxidized LDL (oxLDL), and serum lipids were assessed at baseline and at 4-weeks of each treatment period.
Results
Eighteen subjects (11M:7F) completed all study visits. No significant treatment differences were observed in RHI change (N: 0.21 ± 0.12; NC: 0.20 ± 0.17; p = 0.99). Secondary analysis revealed that a subgroup of NC subjects who started with a baseline RHI of 1.67 (1.23 ± 0.15 to 1.96 ± 0.19; n = 8 vs. 1.75 ± 0.11 to 1.43 ± 0.10; n = 8; p = 0.02). Compared to N, NC experienced a significant increase in plasma NOx (N: 94.2 ± 15.5 μmol/L; NC: 128.7 ± 29.1 μmol/L; p = 0.01). Although there was no significant difference in oxLDL change between treatments (N: -1.08 ± 9.8 U/L; NC: -6.07 ± 9.14 U/L; p = 0.19), NC elicited significant reductions in LDL (N: 2.2 ± 2; NC: -10.7 ± 23; p = 0.049), triglycerides (N: 14.6 ± 43; NC: -43.7 ± 45; p = 0.03), and no change in serum high density lipoprotein. Within treatment group comparisons showed that only NC reduced oxLDL significantly from baseline to 4 weeks (p = 0.01).
Conclusions
No between intervention differences were observed in RHI. RHI only improved in NC subjects with ED at intervention baseline. Four weeks of NC enriched the NO pool and promoted reduction of blood lipids and oxidative stress in subjects with hypercholesterolemia. These preliminary findings highlight a supplementation strategy that may reduce the progression of atherosclerotic disease and deserves further attention in studies using flow mediated dilation methods.
Clinical trial registration
www.clinicaltrials.gov (NCT04283630).
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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