Berberine vs NMN (Nicotinamide Mononucleotide)

Mechanism

Berberine activates AMP-activated protein kinase (AMPK), the master metabolic sensor, mimicking many effects of caloric restriction and exercise. It inhibits mitochondrial Complex I, increasing the AMP:ATP ratio which triggers AMPK. Downstream effects include enhanced GLUT4 translocation (glucose uptake), inhibition of HMG-CoA reductase (cholesterol synthesis), upregulation of LDL receptor expression, and suppression of PCSK9. It also modulates gut microbiome composition, increasing short-chain fatty acid-producing bacteria.

Standard Dosing

500mg 2-3x daily (1000-1500mg total)

Timing

With meals or immediately before meals (reduces postprandial glucose spike). Must be taken with food.

Cycle Duration

Cycle 8-12 weeks on, 4 weeks off (or continuous under practitioner supervision)

Side Effects

• GI cramping/diarrhea (dose-dependent)
• Constipation in some
• Abdominal distension
• Potential for hypoglycemia

Contraindications

• Pregnancy (uterotonic — may induce contractions)
• Lactation
• Concurrent use of multiple CYP3A4 metabolized drugs
• Severe liver disease
• Children under 12

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Mechanism

NMN is a direct biosynthetic precursor to NAD+ via the salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT). Elevated NAD+ activates sirtuins (SIRT1-7), PARP DNA repair enzymes, and CD38/CD157 signaling. SIRT1 activation deacetylates PGC-1alpha (mitochondrial biogenesis), FOXO transcription factors (stress resistance), and NF-kB (anti-inflammatory). NMN also enters cells via the Slc12a8 transporter, recently identified in the gut.

Standard Dosing

500-1000mg daily

Timing

Morning on empty stomach. Sublingual absorption bypasses first-pass metabolism.

Cycle Duration

ongoing

Side Effects

• Mild GI discomfort
• Flushing (rare, unlike niacin)
• Mild headache during initial use

Contraindications

• Active cancer (theoretical concern: NAD+ may fuel rapidly dividing cells)
• Pregnancy/lactation (insufficient data)
• Theoretical concern in active cancer (NAD+ fuels all rapidly dividing cells)

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