Seeking mechanistic and protocol-level insights on pantothenic acid (vitamin B5) and pantethine: transporter competition, circadian timing, and phenotype-specific outcomes
I am interested in assembling a transporter- and metabolism-aware framework for pantothenic acid use in adult acne, dyslipidemia, and stress-related phenotypes. Rather than general anecdotes, I’m looking for data-driven experiences, mechanistic rationale, and monitoring strategies that could make B5 interventions more predictable and safer. Specific questions:
Transporter competition (SMVT/SLC5A6): At high intake levels, pantothenate shares the sodium-dependent multivitamin transporter with biotin and lipoic acid. For those who have trialed ≥1 g/day, have you observed functional biotin insufficiency signals (e.g., elevated urinary 3-hydroxyisovalerate or methylcrotonylglycine, brittle nails, dermatitis) or altered lipoate response? Any mitigation strategies that seem to work (divided dosing, with-meal vs fasting, spacing from biotin/lipoate, alternating-day schedules, or use of alternative forms like pantethine or 4′-phosphopantetheine)?
Form-specific pharmacology: Pantethine (600-900 mg/day) is reported to favorably modulate triglycerides and ApoB in some clinical contexts. Have users or clinicians observed differential effects between calcium pantothenate vs pantethine on:
- Lipids (TG, LDL-P/apoB, sdLDL)
- Glycemic markers (fasting insulin, HOMA-IR)
- Inflammatory markers (hs-CRP)
Do you have evidence that pantethine’s uptake or intracellular conversion meaningfully bypasses SMVT saturation compared with pantothenate?
Sebum and skin lipidomics: For individuals trialing high-dose B5 for acne/seborrhea, did you quantify:
- Sebum excretion rate (e.g., Sebumeter)
- Skin surface lipid composition (squalene, peroxide products, free fatty acid profile)
- Time course to effect and durability after discontinuation
Mechanistic observations (e.g., changes in facial shine, pore size appearance, comedone formation) alongside any lab or imaging data would be particularly valuable.
Cholinergic tone and sleep architecture: Given B5’s role in acetyl-CoA and acetylcholine synthesis, have you tracked REM metrics, dream recall/intensity, or heart rate variability with different dosing times? Any clear dose-timing relationships (morning vs evening) that affect sleep continuity or REM density?
Adrenal and steroidogenesis dynamics: Although evidence is limited, some report changes in perceived stress tolerance. Has anyone run before/after LC-MS/MS steroid panels (cortisol, cortisone, THF/allo-THF/THE ratios, DHEA-S) during B5 or pantethine trials, especially under controlled stressors or shift work?
Microbiome interactions: Because gut microbes synthesize and consume pantothenate, have stool metabolomics or shotgun sequencing datasets shown shifts in pantothenate pools, SMVT-expressing enterocyte gene signatures, or community composition during supplementation? Any observed interplay with antibiotic use or pre/probiotics that altered response to B5?
Safety signals and thresholds: Beyond GI effects, has anyone documented:
- Biotin-dependent carboxylase impairment (OA panel: 3-HIA, 3-methylcrotonylglycine)
- Acylcarnitine profile shifts (C2/C3/C5) indicative of altered CoA flux
- Neurologic sensations, palpitations, or blood pressure changes
- Liver enzymes or platelet function alterations
What intake thresholds and durations appear to precipitate issues, and which reverse on dose reduction or form-switch?
Protocol design variables that seem to matter:
- Dose-finding and escalation (e.g., 250 mg titrations vs gram-level step-ups)
- Co-factors (carnitine, riboflavin/FAD for fatty acid oxidation, alpha-lipoic acid, magnesium)
- Circadian dosing aligned with diurnal sebum production or work-sleep schedules
- Cycling/washout to reduce transporter competition
If you have n-of-1 data with objective endpoints (lipids, sebumetrics, OAs, acylcarnitines, HRV/sleep staging), please share protocols and outcomes.
Biomarker suite for responders vs non-responders: Proposed minimal panels to stratify and monitor could include plasma/urine pantothenate, RBC CoA if available, organic acids (with biotin markers), acylcarnitines, fasting lipid subfractions, hs-CRP, and sebum output. Has anyone correlated baseline status or genetic variants (e.g., SLC5A6, PANKs) with response?
The goal is to move toward transporter-aware, phenotype-specific, and monitored use of pantothenic acid or pantethine. Rigorous negative data are as useful as positive. References, lab snapshots, and device-based measures welcome.