MAOB Gene rs1799836: MAO-B Enzyme and Your Dopamine Breakdown Rate
Monoamine oxidase B (MAO-B) is the primary enzyme that degrades dopamine and phenylethylamine (PEA) in the striatum and prefrontal cortex. Unlike its sibling enzyme MAO-A (which primarily metabolizes serotonin), MAO-B is the dopamine-clearing system. How quickly it works determines how long dopamine lingers after release — affecting motivation, focus, reward processing, and Parkinson's disease vulnerability. The rs1799836 variant in the MAOB gene changes this clearance speed with meaningful downstream consequences.
Key Variant
MAOB intron 13 A/G
Located in intron 13 of the MAOB gene on the X chromosome. G allele is associated with higher MAO-B activity; A allele with lower activity. Because MAOB is X-linked, males are hemizygous (one allele), females are homozygous or heterozygous. Males with the G allele have high MAO-B activity; males with the A allele have low activity. The A allele is associated with higher dopamine/PEA levels and modestly reduced Parkinson's risk; the G allele with faster dopamine clearance and higher Parkinson's risk in some studies.
X-linked gene: males have one copy (hemizygous), so G vs A is the complete genotype. Females are either GG (high activity), GA (intermediate), or AA (low activity). Effect sizes in males are cleaner because there is no heterozygote ambiguity.
MAO-B vs MAO-A: The Important Distinction
Monoamine oxidase exists in two isoforms with overlapping but distinct substrate preferences:
MAO-A
- Primary substrate: serotonin
- Also: norepinephrine, dopamine
- Gene: MAOA (X-linked)
- Distribution: gut, liver, neurons
- Clinical relevance: depression, anxiety, "warrior gene" associations
- Inhibitors: phenelzine, tranylcypromine (old MAOIs)
MAO-B
- Primary substrate: dopamine, PEA, benzylamine
- Also: tyramine (shared with MAO-A)
- Gene: MAOB (X-linked)
- Distribution: platelets, brain, astrocytes
- Clinical relevance: Parkinson's disease, dopamine duration
- Inhibitors: selegiline, rasagiline (Parkinson's drugs)
This distinction matters practically. COMT is another dopamine-clearing enzyme, but it operates in the prefrontal cortex (working memory, attention). MAO-B is the primary dopamine clearance mechanism in the striatum (reward, motivation, movement). The MAOB genotype therefore has disproportionate effects on striatal dopamine tone and motor-reward circuit function.
MAO-B Activity and Parkinson's Disease Risk
Parkinson's disease is caused by the selective loss of dopaminergic neurons in the substantia nigra — the same neurons whose dopamine is cleared by MAO-B. The MAO-B connection is mechanistically direct: when MAO-B metabolizes dopamine (or some exogenous substrates like MPTP), it produces H2O2 as a byproduct — the same hydrogen peroxide that, in the presence of iron, generates hydroxyl radicals via the Fenton reaction. These hydroxyl radicals preferentially damage dopaminergic neurons, creating a self-consuming cycle.
The MAOB rs1799836 G allele (higher MAO-B activity) is associated with modestly higher Parkinson's disease risk in some studies — consistent with the model that higher MAO-B turnover produces more oxidative stress in dopaminergic neurons. Conversely, the A allele (lower activity) is associated with slightly lower Parkinson's risk.
This is the biological rationale for MAO-B inhibitors (selegiline, rasagiline) as first-line Parkinson's treatment: reducing MAO-B activity slows dopamine degradation (extending dopamine action), reduces H2O2 production in dopaminergic neurons, and may slow neuronal loss. The same reasoning supports antioxidant protocols for high-MAO-B individuals.
Behavioral and Cognitive Consequences
Beyond Parkinson's disease risk, MAO-B activity affects moment-to-moment dopaminergic function in behavioral terms:
High MAO-B activity (G allele, males): Dopamine is cleared more rapidly. The dopamine "pulse" following reward stimuli is shorter. This is associated with lower reward sensitivity per event, higher threshold for dopamine-driven motivation, and potentially more novelty-seeking to compensate for faster dopamine clearance. Some research links high MAO-B with lower mood in older adults — MAO-B activity increases with age (by approximately 4-fold between age 20 and 80), which is one mechanism of age-related anhedonia and motivation loss.
Low MAO-B activity (A allele, males): Dopamine and especially phenylethylamine (PEA) persist longer. PEA is a neuromodulator sometimes called the "endogenous amphetamine" — it enhances dopamine release and extends dopamine signaling. Low-MAO-B individuals have naturally higher PEA tone, which may partially explain the behavioral phenotype (more naturally energetic, higher ambient motivation in some individuals). However, high PEA can also contribute to anxiety and cardiovascular stimulation — the trade-off is not uniformly positive.
Age-Related MAO-B Elevation: Why This Gets Worse
One of the most clinically significant features of MAO-B is that its activity increases substantially with age. MAO-B expression in the brain rises progressively from young adulthood through old age, with approximately 4-fold higher activity in 80-year-olds compared to 20-year-olds in autopsy studies. This age-related increase correlates with: reduced dopamine levels in the striatum, declining cognitive function, reduced motivation and emotional blunting, and the dramatic increase in Parkinson's disease prevalence with aging.
For individuals who already have elevated MAO-B from the G allele genotype, this age-related increase starts from a higher baseline and reaches higher peak levels. The practical consequence is a steeper age-related trajectory of dopaminergic decline.
Natural MAO-B inhibiting compounds that modify this trajectory include: deprenyl (selegiline, prescription), green tea EGCG (modest inhibition), resveratrol, quercetin, and several other dietary polyphenols. These are not pharmacologically equivalent to prescription MAO-B inhibitors, but they provide meaningful attenuation of the age-related increase.
Protocol for High MAO-B Activity (G Allele / GG)
- L-tyrosine 500-1,000mg in the morning: The dietary precursor to dopamine. With faster dopamine clearance (G allele), ensuring substrate availability is important — the enzyme clears what's there more quickly, so starting with adequate precursor reduces the amplitude difference.
- Quercetin 500mg/day: Quercetin is a moderate MAO-B inhibitor (Ki approximately 0.5-1 µM in enzyme assays — lower than prescription inhibitors but meaningful for chronic dietary exposure). Also an antioxidant that reduces H2O2 damage in dopaminergic neurons.
- Green tea EGCG 400-600mg standardized extract: EGCG inhibits MAO-B and is neuroprotective in multiple Parkinson's disease models. Observational studies consistently show lower Parkinson's risk in populations with high green tea consumption.
- Coenzyme Q10 200-400mg/day: Dopaminergic neurons have very high mitochondrial density. CoQ10 supports mitochondrial electron transport and reduces the H2O2 generated by MAO-B activity, specifically protecting the dopaminergic neuron population. The NINDS-sponsored CoQ10 trial in Parkinson's showed slower functional decline at 1,200 mg/day.
- Regular aerobic exercise: Exercise increases BDNF in the substantia nigra and improves dopaminergic neuron survival. Consistent aerobic exercise is the lifestyle factor most consistently associated with lower Parkinson's disease risk — likely through the combined effects of BDNF elevation, improved mitochondrial function, and reduced oxidative stress in dopaminergic neurons.
Know your MAOB genotype and get a personalized dopamine metabolism and neuroprotection protocol.
Analyze Your Genome →References
Fowler JS et al. (1997)
Age and sex influence brain MAO B in normal subjects. Neurobiology of Aging. Age-related MAO-B elevation in human brain.
Tan EK et al. (2003)
MAOB intron 13 variant associated with Parkinson's disease in Chinese patients. Neurology. rs1799836 and Parkinson's risk.
Youdim MB, Riederer PF (2004)
A review of the mechanisms and role of monoamine oxidase inhibitors in Parkinson's disease. Neurology. MAO-B mechanism and inhibitor rationale.
Checkoway H et al. (2002)
Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. American Journal of Epidemiology. Lifestyle MAO-B modification and Parkinson's risk.