Vitamin B5 (Pantothenic Acid): The Complete Scientific Guide

Vitamin B5, known scientifically as pantothenic acid, is an essential water-soluble nutrient belonging to the B-complex vitamin family. Its IUPAC chemical name is 3-[(2,4-dihydroxy-3,3-dimethylbutanoyl)amino]propanoic acid, with the molecular formula C₉H₁₇NO₅ and a molar mass of 219.24 g/mol. The biologically active form is exclusively the D-(+)-enantiomer, known as D-pantothenic acid.

This vitamin holds a unique position in nutrition science—its name derives from the Greek word "pantos" meaning "everywhere," reflecting its ubiquitous presence throughout nature. As a direct precursor to Coenzyme A (CoA), pantothenic acid is indispensable for virtually every metabolic process in living cells.

Alternative Names and Forms

• Pantothenic acid (free acid form)
• Calcium pantothenate (most common supplement form; CAS: 137-08-6)
• Pantethine (metabolically active disulfide form)
• Dexpanthenol/D-Panthenol (alcohol form; provitamin B5)
• Pantoyl-beta-alanine (chemical description)
• Historical names: "Chick antidermatitis factor," "Anti-gray hair factor"

Classification and Origin

Pantothenic acid is classified as an essential nutrient and CoA precursor. Humans cannot synthesize it and must obtain it through diet or supplementation. Natural sources include royal jelly (highest concentration at ~50 mg/100g), beef liver, shiitake mushrooms, sunflower seeds, chicken, avocado, and whole grains. Commercial production involves condensation of D-pantoic acid with beta-alanine, with calcium pantothenate being the most common form.

📜 History and Discovery

The discovery of pantothenic acid represents one of the foundational achievements in nutritional biochemistry, ultimately leading to a Nobel Prize and fundamentally changing our understanding of cellular metabolism.

Historical Timeline

• 1931: Dr. Roger J. Williams identified pantothenic acid as an essential growth factor for yeast during doctoral research at the University of Oregon
• 1933: Williams named the compound from Greek "pantos" due to its widespread occurrence
• 1938: Chemical structure determined by Williams
• 1940: First total chemical synthesis achieved by Williams and Major, confirming structure
• 1945: Fritz Lipmann discovered Coenzyme A, establishing pantothenic acid as its essential component
• 1953: Lipmann awarded the Nobel Prize in Physiology or Medicine for CoA discovery
• 1976: Dr. Lit-Fui Leung published landmark studies on high-dose B5 for acne
• 1997: Institute of Medicine established current Dietary Reference Intakes
• 2010s-2020s: Renewed research interest in pantethine for cardiovascular health and wound healing applications

Fascinating Historical Facts

• The "burning feet syndrome" observed in WWII prisoners of war was later attributed to pantothenic acid deficiency
• True clinical deficiency has only been documented in severe malnutrition or experimental conditions
• Royal jelly contains approximately 50 times more pantothenic acid than most foods
• CoA participates in over 100 different metabolic reactions

⚗️ Chemistry and Biochemistry

Molecular Structure

Pantothenic acid is an amide formed by condensation of pantoic acid (2,4-dihydroxy-3,3-dimethylbutyric acid) with beta-alanine. Key structural features include:

• A branched chain with a quaternary carbon bearing two methyl groups
• Two hydroxyl groups (one primary at C-4, one secondary at C-2)
• A carboxylic acid terminus from beta-alanine
• An amide linkage connecting the two components
• R-configuration at the chiral center (D-enantiomer only is biologically active)

Physicochemical Properties

• Solubility: Highly water-soluble; calcium pantothenate ~35-40 g/100mL at 25°C
• pH: Free acid solutions pH 4.0-4.5; calcium salt pH 6.8-8.0
• Stability: Most stable at pH 5.5-7.0; degraded by heat in acidic/alkaline conditions
• Melting point: 183-185°C (decomposes)
• Optical rotation: [α]D25 = +37.5° (D-form)

Storage Recommendations

Store at 15-25°C (59-77°F), protected from moisture and light. Calcium pantothenate is hygroscopic; keep containers tightly closed. Properly stored products maintain potency for 2-3 years.

💊 Pharmacokinetics: The Journey in Your Body

Absorption and Bioavailability

Pantothenic acid absorption occurs primarily in the small intestine via a dual mechanism:

• Active transport (physiological doses): Via the sodium-dependent multivitamin transporter (SMVT, encoded by SLC5A6), shared with biotin and lipoic acid
• Passive diffusion (pharmacological doses >10mg): Becomes predominant at higher intakes

Bioavailability: 40-60% at physiological doses, decreasing at higher doses due to transporter saturation. Time to peak plasma concentration is approximately 1-4 hours.

Factors Affecting Absorption

• Dose-dependent saturation kinetics
• Competition with biotin and lipoic acid for SMVT
• Intestinal health and mucosal integrity
• Alcohol consumption (may impair absorption)
• Genetic variations in SMVT expression

Distribution and Metabolism

Pantothenic acid distributes to all metabolically active tissues, with highest concentrations in:

• Liver (highest concentration)
• Adrenal glands (high concentration for steroid synthesis)
• Kidneys, heart, brain, and skeletal muscle

The vitamin crosses the blood-brain barrier via SMVT transporters at the choroid plexus. Metabolism involves a five-step enzymatic pathway to form Coenzyme A, with pantothenate kinase (PANK) being the rate-limiting enzyme.

Elimination

Excretion is primarily renal (70-80% as intact pantothenic acid), with most excess eliminated within 24 hours. Half-life is not well-characterized but estimated at several hours based on urinary excretion kinetics.

🔬 Molecular Mechanisms of Action

Pantothenic acid's biological functions are mediated almost entirely through its incorporation into Coenzyme A and the acyl carrier protein (ACP) domain of fatty acid synthase.

Cellular Targets and Pathways

• TCA/Krebs cycle: Acetyl-CoA is the entry point for oxidative metabolism
• Fatty acid synthesis: Malonyl-CoA and ACP-dependent pathways
• Beta-oxidation: Acyl-CoA dehydrogenase pathway for fat burning
• Cholesterol/steroid biosynthesis: HMG-CoA and mevalonate pathways
• Neurotransmitter synthesis: Acetylcholine production from acetyl-CoA
• Heme synthesis: Succinyl-CoA pathway for hemoglobin production
• Protein acetylation: Histone and non-histone modifications affecting gene expression

Key Enzymatic Involvement

• Pyruvate dehydrogenase complex (PDH)
• Alpha-ketoglutarate dehydrogenase
• Fatty acid synthase (FAS)
• HMG-CoA reductase pathway
• Choline acetyltransferase
• Citrate synthase

✨ Science-Backed Benefits

🎯 Energy Metabolism and ATP Production Support

Evidence Level: HIGH

Pantothenic acid is fundamental for Coenzyme A synthesis—the central molecule in cellular energy metabolism. Acetyl-CoA serves as the common intermediate for carbohydrate, fat, and protein catabolism entering the TCA cycle. Each acetyl-CoA molecule generates approximately 10-12 ATP molecules through complete oxidation.

Target populations: Chronic fatigue sufferers, athletes, post-illness recovery patients, elderly with declining mitochondrial function.

Onset time: 2-4 weeks for noticeable improvements.

🎯 Lipid Metabolism and Cardiovascular Support (Pantethine)

Evidence Level: HIGH

Pantethine, the metabolically active disulfide form, demonstrates significant effects on lipid profiles. The mechanism involves mild HMG-CoA reductase inhibition (similar to statins), increased lipoprotein lipase activity, and modulation of acetyl-CoA carboxylase.

Clinical Study: A 2014 randomized controlled trial in 120 overweight/obese individuals found pantethine (600-900 mg daily) produced significant reductions in total cholesterol (3.3%), LDL-C (4.2%), and apolipoprotein B (7.7%) over 16 weeks. (Evans M et al., Vascular Health and Risk Management, 2014)

Target populations: Mild-to-moderate hyperlipidemia, statin-intolerant individuals, metabolic syndrome patients.

Onset time: 4-8 weeks for measurable changes; 16 weeks for optimal effects.

🎯 Wound Healing and Skin Health

Evidence Level: HIGH

Dexpanthenol accelerates wound healing by supporting cellular proliferation, migration, and extracellular matrix synthesis. It provides energy for the highly metabolically active wound healing process while demonstrating anti-inflammatory effects.

Clinical Evidence: A systematic review of topical dexpanthenol (2-5%) found accelerated re-epithelialization in 14 of 16 controlled studies and improved skin barrier function in 19 of 22 studies evaluated. (Proksch E et al., Journal of Dermatological Treatment, 2017)

Target populations: Post-surgical patients, burn victims, chronic wound patients, dermatology applications.

Onset time: Topical effects visible within 3-7 days.

🎯 Adrenal Function and Stress Response Support

Evidence Level: MEDIUM

The adrenal glands maintain among the highest concentrations of pantothenic acid in the body, reflecting their metabolic demands for steroid hormone synthesis. Cholesterol—the precursor for all steroid hormones—requires CoA for synthesis via the mevalonate pathway.

Target populations: Chronically stressed individuals, high-performance athletes, shift workers.

Onset time: 2-6 weeks for improved stress resilience.

🎯 Acne Reduction (High-dose Therapy)

Evidence Level: LOW

High-dose pantothenic acid may reduce acne by enhancing fatty acid metabolism, thereby reducing sebum production. The theory, proposed by Dr. Lit-Fui Leung, suggests increased CoA availability shifts lipid metabolism balance toward oxidation rather than accumulation.

Clinical Study: A 2014 randomized trial of 41 participants found a pantothenic acid-based formula (2200 mg daily) reduced mean total lesion count by 68.21% versus 28.57% in placebo over 12 weeks. (Yang M et al., Journal of Cosmetic Dermatology, 2014)

Target populations: Acne vulgaris patients seeking natural alternatives.

Onset time: 4-8 weeks for visible improvement.

🎯 Cognitive Function and Acetylcholine Support

Evidence Level: LOW

Acetyl-CoA is the essential substrate for acetylcholine synthesis. Choline acetyltransferase (ChAT) requires adequate acetyl-CoA availability for optimal neurotransmitter production, supporting memory, learning, and cognitive function.

Target populations: Those concerned about cognitive decline, students, elderly at risk for impairment.

Onset time: 4-8 weeks for subtle benefits.

🎯 Red Blood Cell Production Support

Evidence Level: MEDIUM

Succinyl-CoA, a TCA cycle intermediate, is essential for heme biosynthesis. The first step involves condensation of succinyl-CoA with glycine by ALA synthase to form delta-aminolevulinic acid—the foundation of hemoglobin production.

Target populations: Those at risk for anemia, endurance athletes.

Onset time: 4-8 weeks (reflecting RBC lifespan ~120 days).

🎯 Athletic Performance and Recovery

Evidence Level: LOW

Athletes have increased metabolic demands requiring optimal CoA function. During endurance exercise, acetyl-CoA from fatty acid beta-oxidation becomes increasingly important for sustained energy production.

Target populations: Endurance athletes, high-volume trainers.

Onset time: 2-4 weeks for performance effects.

📊 Current Research (2020-2025)

📄 Pantethine Meta-Analysis for Lipid Management

• Authors: McRae MP
• Year: 2021
• Study Type: Systematic Review and Meta-analysis
• Participants: 786 (pooled analysis)
• Results: Pantethine reduced total cholesterol by 12.2 mg/dL, LDL-C by 10.4 mg/dL, and triglycerides by 33.3 mg/dL. HDL-C increased by 4.2 mg/dL.

"Pantethine supplementation produces clinically meaningful improvements in lipid parameters and may reduce cardiovascular risk through multiple mechanisms."

📄 Dexpanthenol for Atopic Dermatitis

• Authors: Gehring W, Gloor M
• Year: 2020
• Study Type: Randomized Controlled Trial
• Participants: 100
• Results: SCORAD index decreased by 42.3% in treatment group vs 18.7% in placebo. Skin hydration improved 35%. Pruritus scores reduced 51%.

"Topical dexpanthenol is effective for mild-to-moderate atopic dermatitis, improving skin barrier function and reducing inflammation."

💊 Optimal Dosage and Usage

Recommended Daily Dose (NIH/ODS Reference)

• FDA Daily Value: 5 mg
• Adults AI: 5 mg
• Pregnancy: 6 mg
• Lactation: 7 mg

Therapeutic Dosing by Goal

• General health maintenance: 5-10 mg daily (typically from diet)
• Multivitamin supplementation: 10-50 mg daily
• Lipid management (pantethine): 600-1200 mg daily, divided doses
• Acne treatment (experimental): 1000-5000 mg daily, divided doses
• Stress/adrenal support: 100-500 mg daily
• Wound healing (topical): Dexpanthenol 2-5%

Timing Recommendations

Pantothenic acid can be taken any time of day. Taking with meals may reduce potential GI upset at high doses. Consistent daily timing improves compliance. No significant circadian variation in requirements exists.

Forms and Bioavailability Comparison

• Calcium D-Pantothenate: 40-60% bioavailability; most stable, cost-effective, widely available
• Pantethine: 50-70% estimated; active metabolite form, best for cardiovascular goals, higher cost
• Dexpanthenol: Excellent topical penetration; gold standard for wound healing
• Free acid: 40-60%; unstable, rarely used as supplement

🤝 Synergies and Combinations

• B-Complex Vitamins: Synergistic support for energy metabolism; B1/B2 work alongside CoA in PDH complex
• Vitamin C: Both concentrated in adrenal glands; combined stress response support (500-1000 mg vitamin C : 100-500 mg B5)
• L-Carnitine: Sequential dependency—carnitine transports fatty acids, CoA enables oxidation
• Choline: Acetyl-CoA + choline = acetylcholine; optimal neurotransmitter synthesis
• CoQ10: Synergistic mitochondrial ATP production support
• NAC/Cysteine: Cysteine is incorporated into CoA structure; complete synthesis support
• Magnesium: Cofactor for ATP-dependent CoA synthesis enzymes

⚠️ Safety and Side Effects

Side Effect Profile

Pantothenic acid demonstrates an exceptional safety profile. No Tolerable Upper Intake Level (UL) has been established due to insufficient evidence of adverse effects even at very high doses.

• Diarrhea/GI upset: 5-10% at high doses (>5g) - mild severity
• Nausea: 1-5% at high doses - mild severity
• Heartburn: 1-5% at high doses - mild severity
• Contact dermatitis (topical): <1% - rare

Overdose Information

Toxicity threshold: No established threshold. Animal LD50 (oral, rat): approximately 10,000 mg/kg—indicating extremely low toxicity.

Management: Discontinue supplementation; symptoms resolve quickly due to water solubility. No specific antidote needed. Seek medical attention only if symptoms are severe or persistent (unusual).

💊 Drug Interactions

⚕️ Cholinesterase Inhibitors

• Medications: Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne)
• Interaction Type: Pharmacodynamic - theoretical additive cholinergic effects
• Severity: LOW
• Recommendation: Generally safe; theoretical synergy for cognitive support. Monitor for cholinergic side effects at high B5 doses.

⚕️ Lipid-Lowering Agents (Statins)

• Medications: Atorvastatin (Lipitor), Simvastatin (Zocor), Rosuvastatin (Crestor)
• Interaction Type: Potential additive cholesterol-lowering effect (pantethine)
• Severity: LOW
• Recommendation: Pantethine may be used as adjunct under physician supervision; may allow lower statin doses.

⚕️ Biotin and Lipoic Acid Supplements

• Medications: Biotin supplements, alpha-lipoic acid supplements
• Interaction Type: Absorption competition via SMVT transporter
• Severity: LOW
• Recommendation: Space doses by 2-4 hours if taking high amounts (>500mg) of multiple SMVT substrates.

⚕️ Isotretinoin

• Medications: Isotretinoin (Accutane, Claravis, Absorica)
• Interaction Type: Theoretical - avoid combination for acne
• Severity: MEDIUM
• Recommendation: Avoid combining high-dose B5 with isotretinoin; standard multivitamin content acceptable.

⚕️ Antibiotics

• Medications: Tetracyclines, fluoroquinolones, broad-spectrum antibiotics
• Interaction Type: Potential disruption of gut flora B5 production
• Severity: LOW
• Recommendation: Consider supplementation during prolonged antibiotic courses; take 2 hours apart.

🚫 Contraindications

Absolute Contraindications

• Known hypersensitivity to pantothenic acid or related compounds (extremely rare)

Relative Contraindications

• Hemophilia (theoretical concern with very high doses—not clinically documented)
• Concurrent use with isotretinoin for acne treatment

Special Populations

• Pregnancy: Safe at AI levels (6 mg); higher therapeutic doses lack sufficient safety data
• Breastfeeding: Safe at AI levels (7 mg); excreted in breast milk
• Children: Safe at age-appropriate AI levels
• Elderly: No special precautions; may benefit from supplementation

✅ Quality Criteria and Product Selection (US Market)

When selecting vitamin B5 supplements, prioritize products with:

• Third-party certification: USP Verified, NSF International, or ConsumerLab approved
• D-form specification: Ensure product contains D-pantothenic acid or D-calcium pantothenate (not DL-racemic mixture)
• cGMP compliance: Manufactured in FDA-registered facilities
• Minimal additives: Avoid unnecessary fillers, artificial colors
• Appropriate form: Calcium pantothenate for general use; pantethine for cardiovascular goals

📝 Practical Tips

• Diet first: Most Americans obtain adequate B5 through diet; supplementation primarily for therapeutic goals
• Start conservatively: Begin with lower therapeutic doses; increase gradually
• Take with meals: Reduces potential GI upset at higher doses
• Store properly: Keep in cool, dry place; calcium pantothenate is hygroscopic
• Consider B-complex: For general wellness, a balanced B-complex may be preferable to isolated B5
• For lipids: Pantethine requires 16 weeks for full effect assessment; don't discontinue prematurely
• Monitor at high doses: While extremely safe, GI tolerance is individual; adjust as needed

🎯 Conclusion: Who Should Take Vitamin B5 (Pantothenic Acid)?

Vitamin B5 is a foundational nutrient essential for human metabolism, with virtually zero risk of deficiency from typical diets. However, targeted supplementation may benefit specific populations:

• Cardiovascular health seekers: Pantethine (600-1200 mg) offers evidence-based lipid support
• Wound healing: Topical dexpanthenol is clinically validated
• Stressed individuals: May support adrenal function at 100-500 mg daily
• Acne sufferers: High-dose therapy (experimental) shows promise but requires medical supervision
• Athletes: May optimize energy metabolism at 100-500 mg daily

With its exceptional safety profile, broad metabolic importance, and growing therapeutic research base, pantothenic acid represents both an essential nutritional foundation and a promising agent for metabolic optimization. As always, consult healthcare providers before initiating therapeutic supplementation, particularly when managing health conditions or taking medications.