Nicotinamide Riboside for Low Milk Supply

(MOONRISE Trial)

Overseen By Bruce German, PhD

Age: Any Age

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: University of California, Davis

Must not be taking: Narcotics, Amphetamines, Contraceptives, others

Disqualifiers: Breast surgery, Cancer treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using narcotics, amphetamines, cancer treatments, lithium, gold therapies, contraceptives, and galactagogues (substances that increase milk supply). If you are taking any of these, you would need to stop before participating.

What evidence supports the effectiveness of the drug Nicotinamide Riboside Chloride for increasing milk supply?

Nicotinamide riboside (NR) is known to boost levels of NAD+ (a vital molecule for energy and metabolism) in the body, which has shown benefits in treating various metabolic and cardiovascular conditions. While there is no direct evidence for increasing milk supply, its role in enhancing metabolic pathways might indirectly support lactation. ^{1 2 3 4 5}

Is Nicotinamide Riboside safe for human use?

Nicotinamide Riboside (NR) is generally considered safe for human use. Studies show that it does not cause significant side effects and is well-tolerated at various doses in healthy adults. However, its safety for pregnant and lactating women is less certain, and further research is needed. ^{1 2 6 7 8}

How does the drug Nicotinamide Riboside Chloride differ from other treatments for low milk supply?

Nicotinamide Riboside Chloride is unique because it is a form of vitamin B3 that boosts NAD+ levels, which are important for cellular energy and metabolism. Unlike other treatments, it is generally recognized as safe and has been shown to increase NAD+ levels significantly without adverse effects, making it a novel approach for potentially improving milk supply. ^{1 3 4 5 9}

What is the purpose of this trial?

Breastfeeding has well-established immunity and developmental benefits for newborns, yet mothers of preterm infants often struggle to provide sufficient breast milk. The investigators hypothesize that supplementing mothers of preterm infants with nicotinamide riboside (NR) during early postpartum will result in increased milk production. NR is a unique precursor to NAD+, which functions in whole-body metabolism, including that which supports the elevated energy demands of lactation. In lactating rats, NR supplementation improved milk quantity and quality, with metabolic benefits for the mother and lasting protective advantages for the offspring. No studies have been conducted to date that explore the short- or long-term use of NR for increasing milk supply in lactating women. This study will follow a small cohort of women and very preterm infants in the NICU throughout two intervention phases-- one in which each mother will randomly receive either NR or a placebo, then the opposite treatment-- to determine the effect of maternal NR supplementation on expressed milk volume and other markers of metabolism.

Research Team

Kara Khun-Riordon, MD

Principal Investigator

UC Davis

Nicole Cacho, DO

Principal Investigator

UC Davis

Luna Khanal, MD

Principal Investigator

UC Davis

Eligibility Criteria

This trial is for mothers who have given birth to extremely preterm infants (≤28 weeks gestation) at UC Davis Medical Center or transferred there within 6 days of birth. Participants must consent and be willing to express and measure milk volume.

Inclusion Criteria

My baby was born at or before 28 weeks of pregnancy.

Informed consent for participation of both mother and baby

Infant born at the UC Davis Medical Center or transferred to the UC Davis Medical Center NICU within the first 6 days of life

Exclusion Criteria

Mother plans to use any form of galactagogue (including fenugreek)

My mother cannot give her consent.

Mother is actively using narcotics or amphetamines

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Intervention Phase 1

Mothers receive either NR or placebo for 7 days

7 days

Daily monitoring in NICU

Washout Period

A washout period between intervention phases

7 days

Intervention Phase 2

Mothers receive the opposite treatment (NR or placebo) for 7 days

7 days

Daily monitoring in NICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide Riboside Chloride
• Placebo

Trial Overview The study tests if nicotinamide riboside (NR), a supplement, can increase breast milk production in these mothers. It involves two phases: one with NR supplementation and the other with a placebo, each assigned randomly.

Participant Groups

Group I: Placebo First Experimental Treatment 2 Interventions

Mothers will receive placebo during the first 7 days of intervention, then NR for the 7 days following washout.

Group II: NR First Experimental Treatment 2 Interventions

Mothers will receive NR during the first 7 days of intervention, then placebo for the 7 days following washout.

Nicotinamide Riboside Chloride is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Nicotinamide Riboside Chloride for:

• Food supplements
• Foods for special medical purposes (FSMP)
• Total Diet Replacements Products for Weight Control (TDRWC)

Approved in United States as Nicotinamide Riboside Chloride for:

• Dietary supplements

Approved in Canada as Nicotinamide Riboside Chloride for:

• Licensed Natural Health Products

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Findings from Research

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Conze, D., Brenner, C., Kruger, CL.[2023]

The EFSA Panel concluded that the safety of nicotinamide riboside chloride (NRC) has not been established for use in meal replacement products and nutritional drink mixes at proposed levels of 300 mg/day, due to concerns about potential adverse effects, especially in infants.

For food for special medical purposes and total diet replacement for weight control, NRC is considered as safe as pure nicotinamide at a maximum intake of 210 mg/day, which is below the established upper limit of 900 mg/day for adults, but further research is needed to assess long-term safety and potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2021]

Nicotinamide riboside (NR) is a promising NAD+ precursor that has shown potential health benefits in treating various conditions, including cardiovascular, neurodegenerative, and metabolic disorders, based on numerous animal and human studies.

Research indicates that NR may also have therapeutic applications against infections, such as SARS-CoV-2, but challenges related to its bioavailability and safety need to be addressed for effective translation into clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Mehmel, M., Jovanović, N., Spitz, U.[2021]

Nicotinamide riboside (NR), a form of vitamin B3, was found to be safe in various toxicity studies, including a 90-day rat study, with no genotoxic effects and no mortality at high doses (5000 mg/kg).

The lowest observed adverse effect level for NR was determined to be 1000 mg/kg/day, indicating that while it is generally safe, higher doses may lead to toxicity in organs such as the liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. Conze, DB., Crespo-Barreto, J., Kruger, CL.[2019]

Nicotinamide riboside chloride is considered safe for use in food supplements at levels up to 300 mg/day for healthy adults, with no safety concerns raised from human studies or animal data.

The substance effectively contributes to the body's nicotinamide levels and is bioavailable, making it a viable source of niacin, although caution is advised for pregnant and lactating women due to insufficient safety data for these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. Turck, D., Castenmiller, J., de Henauw, S., et al.[2020]

Nicotinamide riboside (NR) is a form of vitamin B3 that effectively increases NAD+ levels, which may help counteract age-related declines in this important metabolite.

In a 90-day safety study on Sprague Dawley rats, NR-E showed no significant adverse effects at doses up to 1,200 mg/kg/d, establishing a no-observed-adverse-effect-level (NOAEL) of 500 mg/kg/d for males and 1,200 mg/kg/d for females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. Marinescu, AG., Chen, J., Holmes, HE., et al.[2021]

Nicotinamide riboside hydride (NRH) is identified as a more effective and faster precursor for NAD+ synthesis compared to nicotinamide riboside (NR), utilizing a unique NRK1-independent pathway for NAD+ production.

NRH is orally bioavailable in mice and has shown potential in preventing acute kidney injury caused by cisplatin, suggesting its therapeutic promise in enhancing NAD+ levels and addressing metabolic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. Giroud-Gerbetant, J., Joffraud, M., Giner, MP., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Synthesis of β-Nicotinamide Riboside Using an Efficient Two-Step Methodology. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and nicotinamide adenine dinucleotide in milk by a novel enzyme-coupled assay. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. [2021]