Nicotinamide Riboside and Mitochondrial Metabolism

Obesity Clinical Trial

— VitaPower  

Official title:

Vitamin B3 as a Novel Mitochondrial Therapy for Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03951285
• Other study ID #: NRtwins_0001
• Status: Completed
• Phase: N/A
• Start date: May 25, 2016
• Est. completion date: May 31, 2019

Study information

• Verified date: December 2019
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Vitamin B3 has recently been found to be a potent modifier of energy metabolism, especially the function of mitochondria. Mitochondria power up all cells in our bodies, by generating fuel, ATP, for cellular functions. In previous studies, it has been discovered that mitochondrial biogenesis and oxidative metabolism in adipose tissue is severely impaired in obesity, already at a young adult age. Here the investigators describe a proposal where they use nicotinamide riboside (NR), a form of vitamin B3 naturally found in milk, to activate dysfunctional mitochondria, in particular the SIRT/NAD+ pathway, and to rescue signs of obesity-related diseases. The investigators use a unique human study design: monozygotic twins either discordant or concordant for obesity, to examine the effects of NR on mitochondrial function in muscle, adipose tissue and the metabolism of the whole body. The upcoming upcoming results are important for understanding the links between mitochondrial dysfunction and chronic metabolic diseases in humans, as well as for clarifying mechanisms of the novel nutritional therapeutic approaches.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: May 31, 2019
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. BMI >18.5 kg/m2 in both members of the twin pair

2. Agreed to maintain current level of physical activity throughout the study

3. Agreed to avoid vitamin supplementation or nutritional products with vitamin B3 14 days prior to the enrolment and during the study

4. Written, informed consent to participate in the study

Exclusion Criteria:

1. Unstable medical conditions as determined by the principal investigator

2. Clinically significant abnormal lab results at screening (e.g. AST and/or ALT > 2 x ULN, and/or bilirubin > 2 x ULN)

3. Subjects who have a planned surgery during the course of the trial

4. History of or a current diagnosis of any cancer (except for successfully treated basal cell carcinoma diagnosed less than 5 years prior to screening). Subjects with cancer in full remission more than 5 years after diagnosis are acceptable.

5. History of blood/bleeding disorders

6. Immunocompromised individuals such as subjects that had undergone organ transplantation or subjects diagnosed with human immunodeficiency virus (HIV)

7. Hepatitis

8. Blood donation in the previous 2 months

9. Anemia (hemoglobin <120)

10. Participation in a clinical research trial within 30 days prior to randomization

11. Allergy or sensitivity to study supplement ingredients

12. Individuals who are cognitively impaired and/or who are unable to give informed consent.

13. Any other condition, which in the principal investigator's opinion may adversely affect the subject's ability to complete the study or its measures or which may have posed significant risk to the subject.

Related Conditions & MeSH terms

• Obesity

Intervention

Dietary Supplement:
• NR in BMI-discordant twins
Water-soluble form of vitamin B3, nicotinamide riboside (NR) is used in this study. The NR product name is Niagen, produced by ChromaDex. NR does not cause the known side effects (vasodilation and flushing) of another vitamin B3, niacin.
• NR in BMI-concordant twins
Water-soluble form of vitamin B3, nicotinamide riboside (NR) is used in this study. The NR product name is Niagen, produced by ChromaDex. NR does not cause the known side effects (vasodilation and flushing) of another vitamin B3, niacin.

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Göteborg University, Helsinki University, National Institute for Health and Welfare, Finland, University of Iowa

References & Publications (6)

Airhart SE, Shireman LM, Risler LJ, Anderson GD, Nagana Gowda GA, Raftery D, Tian R, Shen DD, O'Brien KD. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017 Dec 6;12(12):e0186459. doi: 10.1371/journal.pone.0186459. eCollection 2017. — View Citation

Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022. — View Citation

Jukarainen S, Heinonen S, Rämö JT, Rinnankoski-Tuikka R, Rappou E, Tummers M, Muniandy M, Hakkarainen A, Lundbom J, Lundbom N, Kaprio J, Rissanen A, Pirinen E, Pietiläinen KH. Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins. J Clin Endocrinol Metab. 2016 Jan;101(1):275-83. doi: 10.1210/jc.2015-3095. Epub 2015 Nov 17. — View Citation

Naukkarinen J, Heinonen S, Hakkarainen A, Lundbom J, Vuolteenaho K, Saarinen L, Hautaniemi S, Rodriguez A, Frühbeck G, Pajunen P, Hyötyläinen T, Orešic M, Moilanen E, Suomalainen A, Lundbom N, Kaprio J, Rissanen A, Pietiläinen KH. Characterising metabolically healthy obesity in weight-discordant monozygotic twins. Diabetologia. 2014 Jan;57(1):167-76. doi: 10.1007/s00125-013-3066-y. Epub 2013 Oct 8. — View Citation

Rappou E, Jukarainen S, Rinnankoski-Tuikka R, Kaye S, Heinonen S, Hakkarainen A, Lundbom J, Lundbom N, Saunavaara V, Rissanen A, Virtanen KA, Pirinen E, Pietiläinen KH. Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue. J Clin Endocrinol Metab. 2016 Mar;101(3):1263-73. doi: 10.1210/jc.2015-3054. Epub 2016 Jan 13. — View Citation

Trammell SA, Weidemann BJ, Chadda A, Yorek MS, Holmes A, Coppey LJ, Obrosov A, Kardon RH, Yorek MA, Brenner C. Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Sci Rep. 2016 May 27;6:26933. doi: 10.1038/srep26933. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body weight and body composition	Change in body weight as well as fat mass and fat free mass measured with bioimpedance and DEXA scanning, fat distribution by magnetic resonance imaging	At baseline and 5 months after supplementation
Other	Ectopic lipid accumulation in liver and muscle (in vivo)	Change in liver and skeletal muscle lipid accumulation measured with H-MRS in vivo	At baseline and 5 months after supplementation
Other	Whole body insulin sensitivity	Insulin sensitivity as measured by oral glucose tolerance test (OGTT)-derived indexes	At baseline and 5 months after supplementation
Other	Circulating inflammation markers	Change in circulating levels of IL-2, IL-5, IL-6, IL-12 and TNF-alpha will be measured by multiplex	At baseline and 5 months after supplementation
Primary	Mitochondrial biogenesis - mitochondrial DNA quantification	Change in amount of mitochondrial DNA in skeletal muscle and adipose tissue (mtDNA quantification)	At baseline and 5 months after supplementation
Primary	Mitochondrial biogenesis - mitochondria-related mRNA expression	Change in mitochondria-related mRNA expression in skeletal muscle and adipose tissue (qPCR)	At baseline and 5 months after supplementation
Primary	Mitochondrial biogenesis - electron microscopy	Change in mitochondria histology by electron microscopy evaluation of skeletal muscle	At baseline and 5 months after supplementation
Secondary	NAD+ and related metabolite levels in blood	Change in levels of NAD+ and related metabolites such as: NADP+, nicotinic acid adenine dinucleotide, nicotinamide, and nicotinamide mononucleotide in blood using high performance liquid chromatography-mass spectrometry	At baseline and 5 months after supplementation
Secondary	Skeletal muscle mitochondrial oxidative capacity	Change in mitochondrial function in skeletal muscle by immunohistochemical respiratory chain enzyme analysis	At baseline and 5 months after supplementation