Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults
Douglas Seals
Summary
Aging is the primary risk factor for cardiovascular diseases (CVD), the number one cause of death in developed societies. Systolic blood pressure (SBP) increase with age and is a key intermediary factor linking aging to increased CVD risk. The primary mechanisms underlying the age-associated increase in SBP is stiffening of the large elastic arteries, which is mediated by increases in oxidative stress, inflammation, and vascular smooth muscle tone. Regular caloric restriction is effective at lowering SBP in middle-aged and older adults; however, adherence to caloric restriction is poor and may be detrimental to normal weight older adults due to reduced skeletal muscle mass and bone mineral density. Therefore, identification of more practical alternative interventions that mimic the beneficial effects of caloric restriction, with stronger adherence and less risk of adverse consequences, is of significant biomedical importance. Nicotinamide riboside is a naturally occurring precursor of nicotinamide adenine dinucleotide (NAD+), a critical mediator of the beneficial effects of caloric restriction, and therefore a novel caloric restriction mimetic compound. We recently completed the first pilot study of nicotinamide riboside supplementation in healthy middle-aged and older adults and demonstrated that 6 weeks of supplementation decreased systolic blood pressure (SBP) by 8 mmHg in individuals with baseline SBP of 120-139 mmHg (elevated SBP/stage 1 hypertension) compared with placebo, and lowered arterial stiffness, a strong independent predictor of CVD and related morbidity and mortality. As a next translational step, we will conduct a randomized, placebo-controlled, double-blind clinical trial to further assess the safety and efficacy of oral nicotinamide riboside (3 months vs placebo) for decreasing SBP and arterial stiffness in middle-aged and older men and women with SBP between 120 and 139 mmHg at baseline.
Description
Study Overview: This is a randomized, double-blind, placebo-controlled, parallel design, single site phase IIa clinical trial assessing the efficacy of nicotinamide riboside supplementation to lower systolic blood pressure (SBP) and aortic stiffness in middle-aged to older (MA/O) adults (50-79 years) with elevated to stage-1 systolic hypertension (SBP: 120-139 mmHg). Nicotinamide riboside is an endogenously occurring precursor of NAD+ and a novel caloric restriction mimetic in humans that is now commercially available as a dietary ingredient/supplement. We have recently demonstrated that chron…
Eligibility
- Age range
- 50+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Ability to provide informed consent * Willing to accept random assignment to condition * Systolic blood pressure between 120 and 159 mmHg * Body mass index \<40 kg/m2 * Weight stable in the prior 3 months (\<2 kg weight change) and willing to remain weight stable throughout the study * Absence of other clinical disease as determined by medical history, physical examination, blood chemistries, ankle-brachial index, and 12-lead ECG at rest and during graded treadmill exercise * Ankle-brachial index \>0.7 * Total cholesterol \<240 mg/dL * Fasting plasma glucose \<126…
Interventions
- DrugNicotinamide riboside
Nicotinamide riboside, a dietary supplement available over the counter under the name NIAGEN®, (ChromaDex Inc) is an exogenous NAD+ precursor that reverses age-related arterial dysfunction in aged mice, suggesting that declining NAD+ may play a key role in cardiovascular aging.
- OtherPlacebo
Subjects will take placebo pills twice a day for 3 months
Location
- Integrative Physiology of Aging LaboratoryBoulder, Colorado