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
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. We aimed to examine whether co-administration of vitamin...
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| Veröffentlicht in: | Clinical nutrition (Edinburgh, Scotland) Jg. 40; H. 4; S. 1851 - 1860 |
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| Abstract | 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.
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).
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.
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 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >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).
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.
www.clinicaltrials.gov (NCT04283630). |
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| AbstractList | Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO
) to nitrite (NO
) to NO. The combined effect of vitamin C and NO
supplementation is relatively unexplored in untreated hypercholesterolemia.
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).
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 (NO
+ NO
(NOx)), oxidized LDL (oxLDL), and serum lipids were assessed at baseline and at 4-weeks of each treatment period.
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 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >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).
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.
www.clinicaltrials.gov (NCT04283630). 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. 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). 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. 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 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >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). 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. www.clinicaltrials.gov (NCT04283630). 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.BACKGROUNDVitamin 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.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).AIMSWe 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).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.METHODSSubjects 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.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 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >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).RESULTSEighteen 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 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >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).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.CONCLUSIONSNo 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.www.clinicaltrials.gov (NCT04283630).CLINICAL TRIAL REGISTRATIONwww.clinicaltrials.gov (NCT04283630). 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.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).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.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 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >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).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.www.clinicaltrials.gov (NCT04283630). |
| Author | Skleres, Michealia Jayswal, Rani Thomas, D. Travis Basaqr, Reem |
| Author_xml | – sequence: 1 givenname: Reem surname: Basaqr fullname: Basaqr, Reem email: reem.basaqr@uky.edu organization: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, USA – sequence: 2 givenname: Michealia surname: Skleres fullname: Skleres, Michealia email: michealia.skleres@uky.edu organization: Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, USA – sequence: 3 givenname: Rani surname: Jayswal fullname: Jayswal, Rani email: rani.jayswal@uky.edu organization: Department of Biostatistics & Bioinformatics, University of Kentucky, USA – sequence: 4 givenname: D. Travis surname: Thomas fullname: Thomas, D. Travis email: dth225@uky.edu organization: Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33115598$$D View this record in MEDLINE/PubMed |
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| Keywords | Lipid profile Dietary nitrate Endothelial function Nitric oxide Oxidized low-density-lipoprotein Vitamin C |
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| Snippet | 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... Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO ) to nitrite (NO ) to NO. The combined effect of vitamin C... 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... |
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| SubjectTerms | age ascorbic acid atherosclerosis beets blood lipids blood serum clinical nutrition cross-over studies Dietary nitrate Endothelial function flow high density lipoprotein hypercholesterolemia hyperemia juices Lipid profile low density lipoprotein metabolites nitrates Nitric oxide nitrites oxidative stress Oxidized low-density-lipoprotein placebos triacylglycerols Vitamin C |
| Title | 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 |
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