BH4 (Tetrahydrobiopterin)
The hidden bottleneck in mood and circulation. Without BH4, you can't make serotonin, dopamine, or nitric oxide—no matter how much precursor you take.
What BH4 Does
BH4 is a cofactor—an essential helper molecule. Three critical enzymes need BH4 to function:
Tryptophan Hydroxylase
Converts tryptophan → 5-HTP → serotonin
Low BH4 = can't make serotonin even with plenty of tryptophan
Tyrosine Hydroxylase
Converts tyrosine → L-DOPA → dopamine
Low BH4 = can't make dopamine even with plenty of tyrosine
Nitric Oxide Synthase
Converts arginine → nitric oxide
Low BH4 = poor circulation, high blood pressure, erectile dysfunction
The BH4 Cycle
How BH4 Works
- 1.BH4 donates electrons to enzymes (TPH, TH, NOS)
- 2.Becomes oxidized to BH2 (inactive)
- 3.DHFR enzyme regenerates BH4 from BH2
- 4.Cycle repeats—BH4 is recycled, not consumed
When Things Go Wrong
- !Oxidative stress converts BH4 → BH2 faster than it can recycle
- !BH2 competes with BH4 for enzyme binding sites
- !NOS with BH2 makes superoxide instead of NO (more damage)
- !MTHFR mutations impair folate cycle → less BH4 regeneration
Signs of Low BH4
Depression
Low serotonin + dopamine. SSRIs don't help if BH4 is the issue.
Anxiety
Neurotransmitter imbalance. Often with depression.
Poor Circulation
Cold hands/feet, Raynaud's, poor wound healing.
High Blood Pressure
Low NO = vessels can't relax.
Chronic Pain
Fibromyalgia, migraines—BH4 involved in pain processing.
Erectile Dysfunction
NO required for erection. BH4 often overlooked cause.
What Depletes BH4
Oxidative Stress
Inflammation, toxins, poor diet oxidize BH4 to BH2
MTHFR Mutations
Impaired folate → impaired BH4 recycling
Aluminum
Directly inhibits BH4 synthesis
Chronic Infections
Immune activation consumes BH4
Supporting BH4 Production
Methylfolate (5-MTHF)
Active folate helps regenerate BH4. Essential if MTHFR+.
Vitamin C
Protects BH4 from oxidation. Keep recycling faster than depletion.
NAC / Glutathione
Master antioxidants protect BH4 from oxidative stress.
SAMe
Methyl donor that helps regenerate BH4.
Reduce Inflammation
Less oxidative stress = less BH4 depletion.
BH4 Supplement
Direct supplementation available (Kuvan). Usually prescription.
Why Precursors Alone Don't Work
Taking 5-HTP for serotonin or tyrosine for dopamine won't help if BH4 is low—the enzymes can't convert them without the cofactor. This is why some people don't respond to amino acid therapy. Fix BH4 first, then precursors work.
