Glutathione doesn't work alone.
It's the master antioxidant. But it depends on a network of systems - NAD+, methylation, and minerals - to actually function.
Glutathione needs support infrastructure.
When glutathione neutralizes a toxin, it becomes oxidized glutathione (GSSG). Useless until recycled.
Recycling requires glutathione reductase. Which requires NADPH. Which comes from the pentose phosphate pathway.
Block any link in this chain, and glutathione can't do its job - no matter how much you supplement.
This is why isolated glutathione supplementation often fails. The regeneration system matters as much as the molecule itself.
NAD+ is the bottleneck.
NAD+ (and its phosphorylated form NADP+) drives glutathione recycling. Low NAD+ means glutathione gets stuck in its oxidized, inactive form.
- -NAD+ declines with age - dropping approximately 50% by middle age
- -Chronic inflammation depletes NAD+ through PARP activation
- -High toxic load increases NAD+ consumption
- -Many chronic conditions show depleted NAD+ levels
Niacin (B3) is the precursor. Without adequate B3, the whole system slows.
Methylation feeds the system.
Essential amino acid that provides the raw material for glutathione synthesis via cysteine.
Intermediate that can either recycle to methionine or convert to cysteine for glutathione.
Required to recycle homocysteine back to methionine. Deficiency blocks the cycle.
Converts homocysteine to cysteine - the rate-limiting amino acid for glutathione production.
Poor methylation = poor glutathione production. The cycles are linked.
Minerals are the forgotten cofactors.
Required for glutathione peroxidase - the enzyme that allows glutathione to neutralize peroxides
Supports glutathione S-transferase enzymes that conjugate toxins for excretion
Required for ATP production - and glutathione synthesis is energy-dependent
Required for sulfite oxidase - prevents sulfite accumulation that can inhibit glutathione
Depleted soils mean depleted minerals. Modern food often can't supply adequate levels.
Why taking glutathione often doesn't work.
- -Oral absorption is poor
Most gets broken down in the gut before reaching cells
- -Recycling is still blocked
Without NAD+ and cofactors, even absorbed glutathione quickly becomes useless
- -Production pathways remain impaired
External glutathione doesn't fix the underlying synthesis problems
- -Can worsen detox reactions
Mobilizing toxins without supporting excretion pathways creates problems
Build the network instead.
Support NAD+
Niacin or niacinamide provides the precursor. Some prefer NR or NMN for direct NAD+ boosting.
Support methylation
B12, folate (methylfolate if MTHFR variants), B6, and methionine or SAMe.
Provide precursors
NAC (N-acetyl cysteine) provides the rate-limiting cysteine. Glycine is often overlooked but equally important.
Add the minerals
Selenium, zinc, magnesium, molybdenum. Testing can identify specific deficiencies.
Glutathione is an endpoint.
It's the result of healthy NAD+ levels, functional methylation, adequate minerals, and available precursors.
Fix the network and glutathione takes care of itself.