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N1-Methylnicotinamide (Niacin Metabolites)

SI UNITS (recommended)

CONVENTIONAL UNITS

Synonyms

  • N1-Methylnicotinamide
  • 1-Methylnicotinamide
  • MNA
  • N-Methylnicotinamide
  • Niacin metabolite
  • Nicotinamide methylated metabolite

Units of Measurement

  • nmol/L
  • µg/L
  • µg/dL
  • µg/100 mL
  • µg%
  • ng/mL

Molecular Weight

137.15 g/mol

Key Unit Conversions

Mass ↔ Molar

1 nmol/L=0.13715 µg/L1\ \text{nmol/L} = 0.13715\ \text{µg/L}1 nmol/L=0.13715 µg/L 1 µg/L=7.29 nmol/L1\ \text{µg/L} = 7.29\ \text{nmol/L}1 µg/L=7.29 nmol/L

µg/dL ↔ µg/L

1 µg/dL=10 µg/L1\ \text{µg/dL} = 10\ \text{µg/L}1 µg/dL=10 µg/L

ng/mL

1 ng/mL=1 µg/L1\ \text{ng/mL} = 1\ \text{µg/L}1 ng/mL=1 µg/L

µg%

\text{µg%} = \text{µg/dL}

Description

N1-Methylnicotinamide (MNA) is the major methylated metabolite of:

  • Niacin (Vitamin B3)
  • Nicotinamide
  • Tryptophan → NAD⁺ pathway

It reflects:

  • Niacin intake
  • Vitamin B3 nutritional status
  • NAD⁺ biosynthesis capacity
  • Methylation activity (via nicotinamide N-methyltransferase, NNMT)

MNA is measured particularly in:

  • Nutritional deficiency assessment (pellagra)
  • Metabolic research (NAD⁺ metabolism, aging studies)
  • Tryptophan/kynurenine pathway disorders
  • Liver disease and methylation abnormalities

Physiological Role

N1-Methylnicotinamide itself has physiological activity:

  • Vasodilation
  • Anti-inflammatory actions
  • Antithrombotic effects
  • Marker of NNMT activity (important in obesity, diabetes, malignancy)

Produced by:

Nicotinamide→NNMTN1-Methylnicotinamide\text{Nicotinamide} \xrightarrow{\text{NNMT}} \text{N1-Methylnicotinamide}NicotinamideNNMT​N1-Methylnicotinamide

Metabolized further to:

  • N1-Methyl-2-pyridone-5-carboxamide (2-Py)
  • N1-Methyl-4-pyridone-3-carboxamide (4-Py)

Measurement of all 3 may be used to assess niacin status.

Clinical Significance

HIGH N1-Methylnicotinamide

1. High Niacin / Nicotinamide Intake

  • Supplementation
  • Energy drinks
  • Fortified foods

2. Liver Disease

Impaired degradation increases MNA.

3. Hyper-methylation / High NNMT Activity

Seen in:

  • Obesity
  • Type 2 diabetes
  • Metabolic syndrome
  • Polycystic ovary syndrome (PCOS)
  • Cancers (NNMT overexpression)

4. Renal impairment

Reduced clearance → elevated serum/urine levels.

LOW N1-Methylnicotinamide

1. Niacin Deficiency (Pellagra)

Classic triad:

  • Dermatitis
  • Diarrhea
  • Dementia

Low urinary MNA is a sensitive early marker.

2. Poor Nutrition / Malabsorption

  • Alcoholism
  • Malnutrition
  • Anorexia
  • Intestinal diseases (IBD, celiac)

3. Defects in Tryptophan–NAD Pathway

  • Hartnup disorder
  • Tryptophan deficiency
  • Carcinoid syndrome (tryptophan shunted to serotonin)

4. Low Methylation Capacity

  • SAM deficiency
  • Folate/B12 deficiency

Reference Intervals

Serum / Plasma

  • 20 – 150 µg/L
     (= 20–150 ng/mL ≈ 146–1090 nmol/L)

Urine Excretion (24-hr)

  • > 5.8 µmol/day → adequate niacin status
  • < 1.0 µmol/day → severe deficiency
  • 1–5 µmol/day → marginal deficiency

Clinical Cutoffs

  • Low MNA (< 20 µg/L or < 150 nmol/L) → niacin deficiency likely
  • Very high MNA (> 200 µg/L) → supplementation, liver disease, or high NNMT activity

Diagnostic Uses

1. Niacin Deficiency (Pellagra) Diagnosis

Low MNA = sensitive early marker.

2. Nutritional Assessment

Useful in:

  • Alcoholism
  • Elderly malnutrition
  • Chronic diarrheal diseases
  • Eating disorders

3. Tryptophan / NAD⁺ Pathway Evaluation

In:

  • Hartnup disease
  • Carcinoid syndrome
  • Inborn errors of metabolism

4. Metabolic Syndrome Research Marker

High MNA reflects high NNMT activity → associated with:

  • Obesity
  • Insulin resistance
  • Fatty liver disease

5. Toxicology / Supplement Overuse

Niacin overdose → flushing, liver injury.

Analytical Notes

  • Sample: plasma, serum, or urine (24-hr most informative)
  • Technique: LC–MS/MS (gold standard)
  • Protect sample from heat and light
  • Fasting sample preferred
  • Renal impairment influences serum levels

Clinical Pearls

  • Low urinary MNA is one of the earliest indicators of subclinical niacin deficiency.
  • High MNA indicates high NNMT activity, a pathway linked to metabolic syndrome.
  • Pellagra still occurs in malnutrition, alcoholism, and poor diets in developing regions.
  • MNA levels reflect overall NAD⁺ metabolism, increasingly important in aging research.

Interesting Fact

N1-Methylnicotinamide was once thought to be an inert waste product-modern research now shows it has vascular protective and anti-inflammatory roles, reshaping our understanding of niacin metabolism.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Vitamins & Metabolic Pathways
  2. WHO Niacin Deficiency Assessment Protocol
  3. Mayo Clinic Laboratories - Nicotinamide Metabolites
  4. ARUP Consult - Vitamin Testing
  5. Nutritional Biochemistry Texts - NAD⁺/NNMT Pathway
  6. MedlinePlus / NIH Niacin (Vitamin B3) Testing

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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