Freeberg Kaitlin A, Craighead Daniel H, Martens Christopher R, You Zhiying, Chonchol Michel, Seals Douglas R
Integrative Physiology of Aging Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, Boulder, CO, United States.
Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, United States.
Front Cardiovasc Med. 2022 May 10;9:881703. doi: 10.3389/fcvm.2022.881703. eCollection 2022.
Aging is the primary risk factor for cardiovascular diseases, the leading cause of death worldwide. Age-related increases in systolic blood pressure (SBP) link advancing age to cardiovascular disease risk. A key mechanism mediating the increase in SBP with aging is stiffening of the large elastic arteries, which occurs due to increases in oxidative stress, inflammation, and vascular smooth muscle tone. Nicotinamide adenine dinucleotide (NAD) is a key molecule in energy metabolism and cellular functioning which declines with advancing age and chronic disease. Dietary supplementation with NAD precursors, such as nicotinamide riboside, boosts NAD bioavailability and may improve cardiovascular health. Here, we present the protocol for a randomized, controlled trial investigating the efficacy of 3 months of oral supplementation with nicotinamide riboside for decreasing SBP and arterial stiffness in midlife and older adults with initial above-normal (120-159 mmHg) SBP (ClinicalTrials.gov Identifier: NCT03821623). The primary outcome is casual (resting) SBP and secondary outcomes include 24-h SBP and aortic stiffness. Other outcomes include assessment of safety; tolerability; adherence; diastolic BP; systemic NAD bioavailability; and circulating biomarkers of oxidative stress, inflammation, and sympathoadrenal activity.
A randomized, double-blind, placebo-controlled, single-site parallel-group design clinical trial will be conducted in 94 (47/group) midlife and older (age ≥ 50 years) adults with initial above-normal SBP. Participants will complete baseline testing and then will be randomized to either nicotinamide riboside (500 mg, 2×/day, NIAGEN; ChromaDex Inc.) or placebo supplementation. Outcome measures will be assessed again after 3 months of treatment.
This study is designed to establish the safety and efficacy of the NAD boosting compound, nicotinamide riboside, for reducing casual and 24-h SBP and aortic stiffness in midlife and older adults with above-normal SBP at baseline, a population at increased risk of cardiovascular diseases.
[www.ClinicalTrials.gov], identifier [NCT03821623].
衰老为心血管疾病的主要风险因素，而心血管疾病是全球首要死因。收缩压（SBP）随年龄增长而升高，将年龄增长与心血管疾病风险联系起来。随着衰老，介导SBP升高的一个关键机制是大弹性动脉僵硬，这是由于氧化应激、炎症和血管平滑肌张力增加所致。烟酰胺腺嘌呤二核苷酸（NAD）是能量代谢和细胞功能中的关键分子，其水平会随着年龄增长和慢性疾病而下降。膳食补充NAD前体，如烟酰胺核糖，可提高NAD的生物利用度，并可能改善心血管健康。在此，我们展示一项随机对照试验的方案，该试验旨在研究口服烟酰胺核糖3个月对降低中年及老年且初始SBP高于正常水平（120 - 159 mmHg）人群的SBP和动脉僵硬度的疗效（ClinicalTrials.gov标识符：NCT03821623）。主要结局为日常（静息）SBP，次要结局包括24小时SBP和主动脉僵硬度。其他结局包括安全性评估；耐受性；依从性；舒张压；全身NAD生物利用度；以及氧化应激、炎症和交感肾上腺活动的循环生物标志物。
一项随机、双盲、安慰剂对照、单中心平行组设计的临床试验将在94名（每组47名）中年及老年（年龄≥50岁）且初始SBP高于正常水平的成年人中进行。参与者将完成基线测试，然后随机分为烟酰胺核糖组（500 mg，每日2次，NIAGEN；ChromaDex公司）或安慰剂组。治疗3个月后将再次评估结局指标。
本研究旨在确定NAD增强化合物烟酰胺核糖对降低基线SBP高于正常水平的中年及老年人心血管疾病风险增加人群的日常和24小时SBP以及主动脉僵硬度的安全性和疗效。
