Nicotinamide Riboside for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults

Description

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.

Conditions

Hypertension, Aging

Study Overview

Study Details

Study overview

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.

Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults

Nicotinamide Riboside for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Middle-aged and Older Adults

Condition
Hypertension
Intervention / Treatment

-

Contacts and Locations

Boulder

Integrative Physiology of Aging Laboratory, Boulder, Colorado, United States, 80309

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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 mg/dL
  • * Normal 12-lead ECG at rest and during graded treadmill exercise to fatigue
  • * Systolic blood pressure \<120 or \>/= 160 mmHg
  • * Currently taking antihypertensive medications
  • * Other chronic medical condition (e.g., diabetes, chronic kidney disease, cancer)
  • * Current smoker
  • * Alcohol dependence or abuse
  • * Uncontrolled thyroid disease or change in thyroid medication within previous 3 months
  • * Abnormal blood pressure response to exercise (drop in SBP below resting pressure or SBP \>160 mmHg or DBP \>115 mmHg)
  • * Regular vigorous aerobic/endurance exercise (\>4 bouts/weeks, \>30 min/bout at a workload \>6 METS)

Ages Eligible for Study

50 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

Douglas Seals,

Study Record Dates

2024-12-31