P5P+

P5P+ is Marek's neuroendocrine support formula — a multi-ingredient capsule designed for daily foundational support of mental clarity, stress resilience, and healthy neurotransmitter pathways.‡

The formula combines an enzymatic cofactor, amino acid precursors, botanical extracts, and a membrane-supportive nucleotide derivative — each chosen for a specific role in neurotransmitter synthesis, stress physiology, or cognitive support:‡

• Active vitamin B6 as P5P (pyridoxal-5-phosphate) — the cofactor for 100+ enzymes involved in neurotransmitter production.‡
• L-tyrosine — amino acid precursor for neurotransmitters such as dopamine, norepinephrine, and epinephrine.‡
• Rhodiola rosea extract — adaptogen studied for stress resilience and mental fatigue recovery.‡
• Ginkgo biloba extract (standardized to 24% flavone glycosides) — supports healthy cognitive function.‡
• Apigenin — plant flavonoid with neuroendocrine modulating activity.‡
• Triacetyluridine — uridine derivative supporting healthy brain phospholipid pathways.‡

One capsule daily with food, taken earlier in the day. Designed for steady cognitive and stress-tolerance support, not acute stimulation.

P5P (pyridoxal-5-phosphate) is the biologically active coenzyme form of vitamin B6 — the form your body's enzymes actually use. More than 100 enzymes across amino acid metabolism, neurotransmitter synthesis, one-carbon (methylation) pathways, and heme production rely on P5P as a cofactor.‡

Most vitamin B6 supplements provide pyridoxine HCl, the inactive form. Pyridoxine has to be converted to P5P — primarily in the liver, via the enzyme PNPO — before it can do any of that work. The efficiency of that conversion varies across individuals depending on liver function, zinc status, and PNPO activity.‡ Two people taking the same dose of pyridoxine can end up with quite different active-B6 status.

P5P+ uses the active P5P form directly, which sidesteps the conversion step entirely.

Reference: P5P and neurotransmitter synthesis — https://pubmed.ncbi.nlm.nih.gov/30037155/

Because of a counterintuitive finding sometimes called the "vitamin B6 paradox."‡

In a 2017 paper in Toxicology In Vitro, researchers showed that pyridoxine — the inactive form of B6 — can competitively inhibit pyridoxal-5-phosphate at the active sites of PLP-dependent enzymes. Translation: unconverted pyridoxine may block the form your body actually uses. The authors named the phenomenon directly: symptoms of high-dose pyridoxine supplementation, including peripheral neuropathy, can resemble those of vitamin B6 deficiency.‡

This is the underlying mechanism behind the well-documented peripheral neuropathy risk associated with long-term high-dose pyridoxine HCl supplementation. Even at moderate doses, individuals with reduced PNPO conversion capacity (genetic variants, zinc insufficiency, hepatic impairment) may accumulate unconverted pyridoxine without proportionally raising P5P levels — getting the worst of both worlds.

By starting with P5P, P5P+ delivers the active coenzyme form directly. The conversion step is bypassed, and so is the potential competitive-inhibition mechanism.‡

Reference: Vrolijk et al., Toxicology In Vitro, 2017 — https://pubmed.ncbi.nlm.nih.gov/28716455/

Yes but with two specific notes:

First, the ingredient overlap. P5P+ and Calm both contain rhodiola. Stacking them increases total daily rhodiola intake, which is generally within the 100-500 mg daily dose typically found in supplements, but worth knowing if you're sensitive to adaptogens. The two formulas serve different purposes — P5P+ for neuroendocrine support‡, Calm for relaxation without sedation‡ — and many people use them at different times of day rather than at the same meal.

Second, the B6 audit. P5P is also present in Methylate and Thyroid Support. If you take P5P+ with either of those, your total daily B6 intake adds up — verify it stays within the 100 mg upper daily limit.

Consult your healthcare provider before starting P5P+ if you:

• Take blood-thinning medication (warfarin, aspirin, clopidogrel, or other anticoagulants and antiplatelets). Ginkgo has antiplatelet effects and may amplify the action of these medications.
• Take MAOI antidepressants, levodopa (carbidopa-levodopa, Sinemet), or thyroid hormone medications. L-tyrosine is a catecholamine precursor and a thyroid hormone precursor; interactions with these medications are documented.
• Take other B6-containing supplements or multivitamins — especially those with high-dose pyridoxine. Verify total daily B6 intake stays within the 100 mg upper limit.
• Have existing peripheral nerve symptoms (tingling, numbness, burning sensation in the hands or feet).
• Have a seizure disorder. Both ginkgo and high-dose B6 have specific considerations in seizure contexts.
• Have a diagnosed psychiatric condition under active management, particularly those involving dopamine or catecholamine pathways.
• Are pregnant, nursing, or trying to conceive.
• Are scheduled for surgery in the near term — ginkgo's antiplatelet effects typically warrant discontinuation 1–2 weeks before surgical procedures.

P5P+ is a dietary supplement and is not intended to diagnose, treat, cure, or prevent any disease. If you're managing a condition or under medical supervision, work with your provider to determine whether P5P+ fits your protocol.