Niacin for Obesity

Overseen By Pamela Reich

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must not be taking: Statins, Niacin, Fibrates, others

Disqualifiers: Ischemic heart disease, Smokers, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications that can alter fat metabolism, such as high-dose fish oil, statins, niacin, fibrates, and others. If you are taking these, you may need to discontinue them for a specific period before joining the trial.

Is niacin safe for human use?

Niacin is generally safe for human use, but it can cause side effects like skin flushing, stomach issues, and liver problems, especially with certain formulations. Extended-release niacin has a better safety profile compared to other forms and is considered safe when used properly. ^{1 2 3 4 5}

How does the drug niacin work for obesity?

Niacin is unique in obesity treatment because it increases adiponectin (a protein that helps regulate glucose levels and fatty acid breakdown) and decreases inflammation in fat tissue, which may help manage weight. Unlike other treatments, niacin also has a role in improving blood lipid levels and is known for its effects on increasing good cholesterol (HDL). ^{6 7 8 9 10}

What is the purpose of this trial?

Adults who gain most of their excess weight in the abdominal area typically do not respond to things that "turn off" fat cells the same way as lean people. The researchers are trying to understand why fat tissue responds differently in people with different body types.

Research Team

Michael D Jensen, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This study is for men and women aged 18-65 who are overweight or obese, with a BMI of 29.0 - 40.0 kg/m2, especially those carrying extra weight around their abdomen. Participants must not have heart disease, high blood pressure that's uncontrolled by medication, be smokers, or take drugs affecting fat metabolism. They should also not be allergic to lidocaine or Niaspan.

Inclusion Criteria

No recent or current research participation in a study that involves an investigational drug

I am a man with most of my body fat around my waist.

I am not pregnant and follow the required birth control measures.

Exclusion Criteria

My blood pressure is still over 160/95 even with medication.

I am taking medication that affects how my body uses fats.

I am allergic to lidocaine, Niaspan, or indocyanine green.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Niacin to study fat cell response in different body regions

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Niacin

Trial Overview The trial is investigating how niacin affects fat tissue in people with different body types, particularly focusing on adults who carry excess abdominal weight and may react differently to factors that usually 'turn off' fat cells.

Participant Groups

Group I: Upper body obesity Experimental Treatment 1 Intervention

Subjects identify with upper body obesity will receive Niacin to lean how fat cells in different regions of the body the response.

Group II: Normal weight Experimental Treatment 1 Intervention

Subjects identify with normal body weight will receive Niacin to lean how fat cells in different regions of the body the response.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Niacin is highly effective in increasing HDL cholesterol and decreasing harmful lipoproteins, making it a valuable treatment for lipid metabolism disorders and cardiovascular disease, but it can cause side effects like flushing and gastrointestinal issues.

The discovery of the GPR109A receptor, which mediates some of niacin's effects, opens the door for developing new treatments that could provide similar benefits with fewer side effects, highlighting the need for careful management of niacin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Niacin in therapy]. Nagalski, A., Bryła, J.[2016]

Extended-release niacin/laropiprant (ERN/LRPT) demonstrated a favorable safety profile, with fewer flushing-related side effects compared to traditional niacin (ERN-NSP), based on data from 4747 participants across multiple studies lasting up to 52 weeks.

While there were slight increases in liver enzymes with ERN/LRPT, these were reversible and not linked to liver damage, indicating that ERN/LRPT can be safely used to enhance the lipid-modifying effects of niacin without significant adverse effects on muscle or liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of extended-release niacin/laropiprant in patients with dyslipidemia. McKenney, J., Bays, H., Koren, M., et al.[2015]

Niacin works by activating the GPR109A receptor, which helps reduce fat breakdown in fat cells and is also responsible for the flushing side effect, making it effective in cardiovascular prevention as shown in seven out of nine clinical trials involving various drug combinations.

While niacin can cause minor insulin resistance, it does not significantly worsen diabetes control or increase the risk of developing diabetes, and it is generally safe at lower doses, especially when combined with statins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niacin in cardiovascular prevention: mechanisms, efficacy, and safety. Guyton, JR.[2015]

In a study of 61 patients with ischemic heart disease and dyslipidemia, niacin significantly improved lipid profiles, reducing total cholesterol, LDL-cholesterol, and triglycerides while increasing HDL-cholesterol, particularly at a dose of 3.0 g/day.

Niacin was well tolerated by 62% of the patients, making it a safe and effective low-cost treatment option for managing dyslipidemia in patients with ischemic heart disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of immediate-release niacin in patients with ischemic cardiopathy. Experience of the Instituto Nacional de Cardiología "Ignacio Chávez"]. Morato Hernández, ML., Ichazo Cerro, MS., Alvarado Vega, AG., et al.[2015]

Niacin is the most effective approved drug for raising high-density lipoprotein (HDL) cholesterol levels, whether used alone or with other medications.

The extended-release formulation of niacin (niacin-ER) has a significantly better safety profile compared to other niacin formulations and is comparable in safety to commonly used lipid-altering drugs like statins, supporting its use in high-risk cardiovascular patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of niacin in the US Food and Drug Administration adverse event reporting database. Alsheikh-Ali, AA., Karas, RH.[2015]

Prolonged-release (PR) nicotinic acid (Niaspan) is effective in improving lipid profiles, particularly in increasing HDL-cholesterol and reducing lipoprotein(a), while being better tolerated than older formulations with less risk of flushing and hepatotoxicity.

PR nicotinic acid can be safely used alongside statins to enhance lipid management in patients, including those with type 2 diabetes, without negatively impacting blood sugar control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. McCormack, PL., Keating, GM.[2018]

Nicotinamide (NAM), a form of vitamin B3, has been shown to prevent weight gain in mice by increasing overall energy expenditure and altering adipose tissue metabolism, particularly in white adipose tissue.

High-dose NAM treatment led to significant improvements in liver health, including reduced fat accumulation and inflammation, suggesting its potential as a therapeutic option for obesity and related metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Protects Against Diet-Induced Body Weight Gain, Increases Energy Expenditure, and Induces White Adipose Tissue Beiging. Méndez-Lara, KA., Rodríguez-Millán, E., Sebastián, D., et al.[2021]

Niacin treatment in obese mice increased serum levels of adiponectin, an anti-inflammatory protein, by 21%, indicating its potential to reduce inflammation associated with obesity.

The study found that niacin reduced the expression of pro-inflammatory markers in adipose tissue, suggesting that it can help mitigate obesity-induced inflammation through mechanisms that depend on the niacin receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice. Wanders, D., Graff, EC., White, BD., et al.[2021]

Nicotinamide, when taken with glucose, significantly increased plasma hydrogen peroxide and insulin levels while lowering blood glucose levels, suggesting it may influence glucose metabolism positively in healthy individuals.

The study found a strong association between increased niacin consumption and rising obesity rates among US children, indicating that excessive niacin intake could contribute to obesity prevalence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic niacin overload may be involved in the increased prevalence of obesity in US children. Li, D., Sun, WP., Zhou, YM., et al.[2023]

Nicotinamide mononucleotide (NMN) supplementation in obese mice led to significant changes in body composition, including reduced fat mass and increased lean mass, indicating its potential as a treatment for obesity.

The study suggests that NMN may improve metabolic health by enhancing NAD+ levels, which activates the NAD+/SIRT6/LKB1 pathway, leading to better glucose tolerance and reduced inflammation in adipose tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide mononucleotide alters body composition and ameliorates metabolic disorders induced by a high-fat diet. Zhang, Y., Zhu, W., Wang, M., et al.[2023]

References

1. Poland pubmed.ncbi.nlm.nih.gov

[Niacin in therapy]. [2016]

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

Safety of extended-release niacin/laropiprant in patients with dyslipidemia. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Niacin in cardiovascular prevention: mechanisms, efficacy, and safety. [2015]

4. Mexico pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of immediate-release niacin in patients with ischemic cardiopathy. Experience of the Instituto Nacional de Cardiología "Ignacio Chávez"]. [2015]

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

The safety of niacin in the US Food and Drug Administration adverse event reporting database. [2015]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Nicotinamide Protects Against Diet-Induced Body Weight Gain, Increases Energy Expenditure, and Induces White Adipose Tissue Beiging. [2021]

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

Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice. [2021]

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

Chronic niacin overload may be involved in the increased prevalence of obesity in US children. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Nicotinamide mononucleotide alters body composition and ameliorates metabolic disorders induced by a high-fat diet. [2023]