Effect of Nicotinamide Mononucleotide (NMN) on Cardiometabolic Function

Study Overview
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Brief Summary
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The purpose of the study is to understand the effect of the dietary supplement Nicotinamide mononucleotide on metabolic health in people.

Detailed Description
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This study is is looking at the effect of the dietary supplement Nicotinamide mononucleotide (NMN) on key cardiovascular and metabolic functions, specifically those that are important risk factors for diabetes and cardiovascular disease. Accordingly, the investigators will evaluate the effect of NMN on how well the hormone insulin works to control blood sugar. The investigators will also look at the effects of NMN on blood lipids; body fat and liver fat; and other blood, fat tissue and muscle tissue markers of cardiovascular (heart) and metabolic health. Data from studies conducted in rodents have shown that NMN supplementation has beneficial effects on cardiovascular and metabolic health, but this has not yet been studied in people.

Official Title
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Effect of NMN (Nicotinomide Mononucleotide) Supplementation on Cardiometabolic Function

Conditions
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Glucose Metabolism Disorders

Intervention / Treatment
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* Dietary Supplement: NMN supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women 55-75 years old BMI 25.0-44.9 kg/m² Fasting plasma glucose concentration ≥100 mg/dl, OGTT 2 hour glucose ≥ 140 mg/dl, HbA1C ≥5.7%, or HOMA-IR ≥2.5 Exclusion Criteria: Diabetes Premenopausal or menopause <1 year Persons who have received hormone replacement therapy within the past 6 months Persons who take vitamin B supplementation and are not willing to discontinue supplementation for 3 weeks before and during the entire study period. Structured exercise: ≥75 min/wk of vigorous exercise (e.g., jogging, activity that causes heavy breathing and sweating) or ≥150 min/wk of low intensity physical activity (e.g., brisk walking). Unstable weight (>3% change during the last 2 months before entering the study) Significant organ system dysfunction or disease Present cancer or history of cancer that has been in remission for <5 years Polycystic ovary syndrome Major psychiatric illness Use of medications known to affect study outcome measures (e.g., steroid) or increase the risk of study procedures (e.g., anticoagulants) that cannot be temporarily discontinued for the study Metal implants Smokes cigarettes Persons who consume >14 units of alcohol per week Unable or unwilling to follow the study protocol or who, for any reason, is considered an inappropriate candidate for the study by the research team.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Intervention will last at least 8 weeks in the form of two capsules.<br>|
| Experimental: NMN supplementation<br> | Dietary Supplement: NMN supplement<br>* Intervention will last at least 8 weeks in the form of two capsules (250 mg total).<br>* Other names: nicotinamide mononucleotide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle insulin sensitivity | The outcome will be assessed by hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopic tracer infusion before and after intervention period. | before and after at least 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in liver insulin sensitivity | The outcome will be assessed during hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopic tracer infusion before and after intervention period. | before and after at least 8 weeks of treatment | 
| Change in adipose tissue insulin sensitivity | The outcome will be assessed during hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopic tracer infusion before and after intervention period. | before and after at least 8 weeks of treatment | 
| Change in body fat mass | The outcome will be measured by using dual-energy X-ray absorptiometry before and after intervention period. | before and after at least 8 weeks of treatment | 
| Change in fat free mass | The outcome will be measured by using dual-energy X-ray absorptiometry before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in intra-abdominal adipose tissue volume | The outcome will be measured by using magnetic resonance imaging before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in intrahepatic triglyceride content | The outcome will be measured by using magnetic resonance imaging before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in blood pressure | The outcome will be assessed by measuring blood pressure at rest before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in plasma glucose concentration | The outcome will be determined by plasma glucose concentration after overnight fasting, before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in fasting insulin | The outcome will be determined by plasma insulin concentration after overnight fasting, before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in fasting free fatty acid | The outcome will be determined by plasma free fatty acid concentration after overnight fasting, before and after intervention period. | before and after at least 8 weeks of treatment | 
| Changes in tissue NAD content | The outcome will be assessed by measuring NAD content before and after intervention period | before and after at least 8 weeks of treatment | 
| Changes in protein levels in skeletal muscle insulin signaling | The outcome will be determined by Western blot by using samples collected before and after intervention period | before and after at least 8 weeks of treatment |