The Effects of Vitamin C on Exercise-Induced Oxidative Stress in Postmenopausal Females
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Flow-Mediated Dilation (FMD%) - Brachial Artery Endothelial Function
研究概览
简要总结
This study is looking at whether vitamin C can help improve oxidative stress and blood vessel health in females after menopause. We will see if taking different amounts of vitamin C for a few days changes how the body handles stress from exercise. This could lead to safer ways to protect females from heart disease without using hormone therapy.
详细描述
Cardiovascular disease (CVD) remains the leading cause of death in the United States. After menopause, females face a significantly increased risk of CVD due to declines in estrogen, which negatively impact nitric oxide (NO) production and vascular health. This coincides with an increase in reactive oxygen species (ROS), leading to an imbalance in redox signaling that may blunt beneficial adaptations to exercise.
Vitamin C (ascorbic acid) is a potent antioxidant that may restore redox balance and endothelial function. However, most studies have been conducted in males using high doses that may suppress beneficial ROS signaling. In contrast, this trial focuses on the dose-response effects of short-term vitamin C supplementation (200 mg, 500 mg, and 1000 mg/day for 3 days) on ROS/NO balance, both at rest and in response to acute exercise, in PMF versus age-matched males.
The study includes 15 sedentary PMF and 15 sedentary age-matched males, ages 45 and older. Participants complete 5-6 total study visits: one baseline/screening visit and four intervention visits in a randomized crossover design. Each intervention visit consists of 3 days of supplementation followed by fasting blood draws, vascular testing, and a 200-kcal high-intensity exercise bout on a cycle ergometer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Post-menopausal (for females; defined as no menstrual cycle for 1-year)
- •Sedentary (<150min of moderate-intensity exercise per week or not engaged in a regular exercise program)
- •Non-smoking
- •Weight stable (+/-3 kg over the past 3 months)
排除标准
- •Overt CVD
- •Any condition or medication contraindicating safe exercise
- •Hormone replacement therapy (last 3-months)
- •Use of vasoactive medications (e.g., calcium channel blockers, statins, ACE inhibitors, ARBs, nitrates, alpha-/beta-blockers, diuretics), diabetes, or unstable medication regimens
- •Oral antibiotic use within previous four weeks
- •Oral disease or poor oral health as determined by the Oral Health Questionnaire
- •Using an antibacterial mouthwash or a mouthwash containing chlorhexidine and unwilling to discontinue use
- •Cancer diagnosis
研究组 & 干预措施
Active Comparator 1: 200mg vitamin C
Subjects will supplement with 200mg of vitamin C 2x a day for 3 days. 100mg will be taken in the morning and 100mg in the evening. On the 3rd day, subjects will be scheduled to return for post-supplementation testing and be instructed to take a full 200mg dose 30-minutes prior to arriving.
干预措施: Vitamin C (Ascorbic Acid) (Dietary Supplement)
Active Comparator 1: 500mg vitamin C
Subjects will supplement with 500mg of vitamin C 2x a day for 3 days. Subjects will take half the dose in the morning and half the dose in the evening. On the 3rd day, subjects will be scheduled to return for post-supplementation testing and be instructed to take a full dose 30-minutes prior to arriving.
干预措施: Vitamin C (Ascorbic Acid) (Dietary Supplement)
Active Comparator 1: 1000mg vitamin C
Subjects will supplement with 1000mg of vitamin C 2x a day for 3 days. Subjects will take half the dose in the morning and half the dose in the evening. On the 3rd day, subjects will be scheduled to return for post-supplementation testing and be instructed to take a full dose 30-minutes prior to arriving.
干预措施: Vitamin C (Ascorbic Acid) (Dietary Supplement)
Placebo Comparator 1: 0mg Vitamin C
Subjects will supplement with 0mg of vitamin C 2x a day for 3 days. Subjects will take half the dose in the morning and half the dose in the evening. On the 3rd day, subjects will be scheduled to return for post-supplementation testing and be instructed to take a full dose 30-minutes prior to arriving.
干预措施: Vitamin C (Ascorbic Acid) (Dietary Supplement)
结局指标
主要结局
Flow-Mediated Dilation (FMD%) - Brachial Artery Endothelial Function
时间窗: 5x: Baseline/un-supplemented; after 3-days of 200mg of vitamin C supplementation; after 3-days of 500mg of vitamin C supplementation; after 3-days of 1000mg of vitamin C supplementation; after 3-days of 0mg of vitamin C/placebo supplementation
Brachial artery endothelial function will be measured by flow-mediated dilation (FMD) in each participant 5x (at baseline and after 0mg (placebo) 200mg, 500mg, and 1000mg of vitamin C). Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The brachial artery will be imaged using a high-resolution 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation (250mmHg), and continuously for 2 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle.
Basal ROS Concentrations - plasma 8-Isoprostane (8-iso) and malondialdehyde (MDA)
时间窗: baseline and after 0mg/placebo, 200mg, 500mg, and 1000mg dose of vitamin C for 3-days each
A venous blood sample will be collected from a vein in the antecubital fossa. Plasma will be separated out and stored at -80C until concentrations of 8-Isoprostane (8-iso) and malondialdehyde (MDA) are measured via commerically available ELISA kits. ROS concentrations will be measured at 5x points: at baseline and after 0mg (placebo), 200mg, 500mg, and 1000mg of vitamin C
Resting ROS/NO Balance - plasma N-oxides (nitrite and nitrate)
时间窗: Baseline and after 3-days of placebo, 200mg, 500mg, and 1000mg doses of vitamin C
Venous blood samples will be collected from an antecubital fossa vein. Plasma will be separated out and stored at -80C until analysis. Plasma N-oxides (nitrite and nitrate) will be evaluated from the plasma via ozone-based chemiluminescence using a Sievers NOA model 280i. The N-oxides will be compared with the basal ROS also measured to calculate a ROS/NO balance.
Exercise-Induced ROS (plasma 8-Isoprostane (8-iso) and malondialdehyde (MDA)) and NO (plasma nitrate and nitrite)
时间窗: 16x points: 4 exercise session with blood will be collected immediately before, immediately after, 15-min after, and 30-min after exercise
An intravenous catheter will be placed into a vein in the antecubital fossa. Participants will complete 4 high-intensity exercise sessions (\~200kcals). Each exercise session will be after 3-days of vitamin C supplementation (0mg/placebo, 200mg, 500mg, and 1000mg). Blood will be collected immediately before, immediately after, 15-min after, and 30-min after exercise. Plasma will be separated out and used to evaluate the changes in ROS (plasma 8-Isoprostane (8-iso) and malondialdehyde (MDA)) and NO (plasma nitrate and nitrite) from baseline/rest.
次要结局
- Central Hemodynamics (Physioflow)(5x points over 5-6 weeks: (1) baseline/unsupplemented and after 3-days of (2) 0mg/placebo, (3) 200mg, (4) 500mg, and (5) 1000mg of vitamin C supplementation)
- Vitamin C(5x points over 5-6 weeks: (1) baseline/unsupplemented and after 3-days of (2) 0mg/placebo, (3) 200mg, (4) 500mg, and (5) 1000mg of vitamin C supplementation)
- Oral Nitrate Reducing Capacity(5x points over 5-6 weeks: (1) baseline/unsupplemented and after 3-days of (2) 0mg/placebo, (3) 200mg, (4) 500mg, and (5) 1000mg of vitamin C supplementation)
- Pulse Wave Analysis and Velocity(5x points over 5-6 weeks: (1) baseline/unsupplemented and after 3-days of (2) 0mg/placebo, (3) 200mg, (4) 500mg, and (5) 1000mg of vitamin C supplementation)
- Microvascular Function(5x points over 5-6 weeks: (1) baseline/unsupplemented and after 3-days of (2) 0mg/placebo, (3) 200mg, (4) 500mg, and (5) 1000mg of vitamin C supplementation)
- Exercise Capacity(Baseline only)
- Tissue Perfusion (NIRS)(5x points over 5-6 weeks: (1) baseline/unsupplemented and after 3-days of (2) 0mg/placebo, (3) 200mg, (4) 500mg, and (5) 1000mg of vitamin C supplementation)
研究者
Jason Allen
Professor
University of Virginia