Pantothenic acid is one of the B-vitamins which is critical in the formation of Co-enzyme A, a molecule which helps a large amount of enzymes function in the body, and for energy production in general. While it is important, it is rare to be deficient and further supplementation shows little promise.
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Table of Contents:
- 1 Sources and Structure
- 2 Molecular Targets
- 3 Pharmacology
- 4 Neurology
Exercise and Performance
- 5.1 Mechanisms
- 6 Interactions with Oxidation
Interactions with Organ Systems
- 7.1 Liver
- 8 Interactions with Aesthetics
- 9.1 Ethanol
- 10 Safety and Toxicology
Pantothenic acid (also known as pantothenate) is the essential vitamin known as Vitamin B5. The origin of the name is derived from the Greek word "pantos" (meaning "everywhere") as it is not only present in the majority of food products but also a required cofactor in numerous enzymes; the molecule it produces, a coenzyme known as Coenzyme A (CoA) is ubiquitous in the human body.
Generally speaking, pantothenic acid is found in most food groups with chicken, beef, egg yolk, and organs being high sources for animal products while root vegetables (potatoes), whole grains, tomatoes, and broccoli also have a large level of pantothenic acid.
Pantothenic acid can also be found in human breast milk mostly in free form (85-90%) and some in a conjugated form (10-15%) and appears to correlate with the amount of pantothenic acid circulating in the mother at the time of providing milk.
Pantothenic acid appears to be somewhat susceptible to losses during preservation (freezing and canning) of meats and vegetables.
Co-enzyme A (CoA) is required in approximately 4% of all known enzymes as a cofactor, mostly known for being involved in energy production. Dietary pantothenic acid, whether in the form of CoA itself (broken down into pantothenic acid before absorption) or as supplemental pantothenic acid, is initially converted via pantothenate kinases (PanKs) into 4'-phosphopantothenate; this step is the rate-limiting step of CoA synthesis and consumes ATP in the process.
Subsequently the metabolite is converted into 4'-phospho-N-pantothenoylcysteine (via phosphopantothenoylcysteine synthetase adding a cysteine molecule), into 4'-phosphopantetheine (by phosphopantothenoylcysteine decarboxylase), into dephospho-CoA (by phosphopantetheine adenylyl transferase), and finally dephospho-CoA gains a phosphorus group via dephosphocoenzyme A kinase and becomes CoA.
Pantothenic acid's major role in the human body is to be provided as a substrate that is required to form Co-enzyme A, a required cofactor for many enzymes in the human body
Pantothenic acid has an AI (adequate intake) value of:
1.7 mg for infants younger than six months
1.8 mg for infants between the ages of 6-12 months
2 mg for children between the ages of 1-3 years
3 mg for children between the ages of 4-8 years
4 mg for children between the ages of 9-13 years
5 mg for everybody above the age of 14
The AI for pantothenic acid scales with bodyweight up until adolescence until it holds steady at 5 mg for the rest of life, with the only exceptions being pregnancy and lactation where requirements are boosted slightly to 6 mg and 7 mg respectively.
Pantothenic acid deficiency is mostly unheard of in free-living adults due to the prevalence of this vitamin in the diet. Most studies on the topic are in vitro or in animal models of pantothenic acid deficiency.
When it comes to animals, a deficiency of pantothenic acid impairs numerous systems and organs such as fatty acid metabolism by elevating serum, hepatic, and perinephrical levels of triglycerides. A deficiency impairs the function of the adrenals and testicles resulting in impaired fertility.
Surprisingly, studies in young rats investigating CoA metabolism find that levels are similar between pantothenic acid deficient rats and those fed normal levels despite abnormalities to nearly all organs and slowed growth; pantothenic acid concentrations were also reduced to less than 10% in all organs except the liver where they reached 30% of normal levels. Other studies in adult rats do note decreases in CoA, hypothesized to be due to a resilience in this pathway in younger rats.
While it is near unheard of in humans with an even decent diet (as pantothenic acid in found in most foods), a deficiency of pantothenic acid reduces growth thought to be related to impairing the activity of CoA. While a deficiency does not appear outright fatal, most systems in the body are adversely affected
There is currently no tolerable upper limit (TUL) known for pantothenic acid due to no adverse effects being reported in excessive intake.
A study using higher than normal doses have failed to find harm with 200-900 mg of pantothenic acid in humans.
Dexpanthenol is the name for D-panthenol, the biologically active enantiomer of an alcohol analogue of pantothenic acid known as 'Panthenol' (aka. pantothenylalcohol). This form is hygroscopic similar to pantothenic acid but more stable, the increased stability being relevant when used on the skin as an external cosmetic. It does, however, convert directly into pantothenic acid and is considered to be a more stable prodrug for pantothenic acid due to being highly soluble and stable in water and alcohol solutions.
Dexpanthenol/D-Panthenol is a more stable form of pantothenic acid suited for cosmetic purposes
Consuming CoA from the diet provides pantothenic acid to the body as it is hydrolyzed in the intestinal lumen into phosphopantetheine, pantetheine, and subsequently pantothenate.
Panthothenic acid can be absorbed in both the small and large intestines via the sodium-dependent multivitamin transporter (SMVT), similar to biotin and can compete for absorption with an Ki of 14.4μM which appears to be wholly responsible for panthothenic acid uptake as knocking the gene out in mice (via siRNA) ablates uptake of the vitamin. The rate of uptake in all three segments of the small intestine seems similar in the rat.
There is bacteria in the large intestine that is able to produce panthothenic acid. When dividing the gut biome into enterotypes (clusters of similarly acting bacteria) enterotype 1 appears to contain many enzymes capable of synthesizing pantothenic acid (as well as biotin, Vitamin C, and Riboflavin).
In rats given either pantothenic acid restricted diets or sufficient diets, higher fat intakes (20% rather than 5%) and exercise both appear to reduce the amount of pantothenic acid detected in plasma and muscle tissue when compared to their controls; suggesting a higher intake required if either of these two variables are present.
It has been reported that pantothenic acid does not appear to have many interactions with pharmaceuticals and high doses of oral contraceptives have been found to not interact with pantothenic acid status in young women.
Pantothenic acid exists at higher concentrations in the brain relative to plasma, being about 50-fold higher and almost exclusively due to the sodium dependent multivitamin transporter (SLC5A6) which accounted for 98.6% of uptake in cells of the blood brain barrier in vitro. The pantothenic acid that exists in cerebrospinal fluid and brain plasma is usually intact (neither metabolized nor conjugated) and even within neuron cells where it accumulates a large amount remains unmetabolized rather than forming CoA or phorphorylated metabolites. While SLC5A6 is known to be inhibited by many compounds in vitro such as medium chain triglycerides, a deficiency of pantothenic acid in the brain appears highly unlikely due to these high levels.
Due to being the substrate which eventually produces CoA, pantothenic acid serves its role in the brain in assisting the synthesis of various neurotransmitters.
Pantothenic acid has been investigated for its role in sports performance since it is required for the production of Coenzyme A (CoA), which among other things is required to transport fatty acyls (via the conjugated fatty acyl-CoA) to the mitochondria so fats can be used for energy production and is used at many other points in the energy production cycle. A study investigating the role of pantothenic acid in exercise notes that other studies suggest that reduced availability of free CoA to be used in the above processes may be a rate limiting step in fat oxidation during exercise.
Supplementation of both L-cysteine (1,500 mg; thought to buffer decreases in CoA during exercise) and pantothenic acid (1,500 mg) in recreationally active men for one week failed to affect levels of free CoA, respiratory exchange ratios, and performance when participants were subject to a cycling test.
When tested in vitro, pantothenic acid and a few variants (sodium and calcium pantothenate, phosphopantothenate, pantothenol, and pantethine) had minor antioxidant effects against lipid peroxidation.
In a mouse model of nonalcoholic fatty liver disease (NAFLD), a disease state where production of Coenzyme A (CoA) is impaired leading to complications, supplementation of both N-Acetylcysteine and pantothenic acid (both at 250mg/kg) failed to improve the rate-limiting step of CoA production and failed to improve complications of NAFLD.
It has been hypothesized that pantothenic acid deficiency could be related to acne.
It was initially found that, in an eight week trial using a supplement which contains pantothenic acid (Panthogen; containing 2,200 mg pantothenic acid, 733.3 mg L-carnitine, and other B-vitamins in two divided doses) found benefits to skin health of which less acne was noted and later the same formulation was found (in subjects with mild to moderate blemishes) to reduce facial lesions by 68.21% with an improvement in quality of life (assessed by DLQI) over the course of 12 weeks when taken orally.
Panthothenic acid may be able to reduce acne, but current studies only use formulations that are highly confounded with the other B-vitamins and L-carnitine. The role of panthothenic acid alone is not yet known
In humans who underwent tattoo removal surgery who were given both Vitamin C and pantothenic acid, supplementation of these two (1-3 g and 0.2-0.9 g respectively; no placebo control) for 21 days after surgery appeared to benefit the strength of the skin in the group given the higher doses; the energy required to break scar tissue was greater (indicative of stronger tissue) and, while both groups showed beneficial changes in scar content of magnesium, manganese (increases) and iron (a decrease) both groups had significant increases relative to baseline with the higher doses having a faster rate. The effort required to break scar tissue has previously been associated with the changes in the content of these minerals within the scar and the overall count of fibroblasts and hydroxyproline content appeared to increase when compared to placebo.
Supplementation of pantothenic acid (and Vitamin C) appears to improve some aspects of scarring, but a direct increase in the time required to heal a scar has not yet been found
found that 2.5% dexpanthenol (with 6% borage oil) improved stratum corneum hydration without effect on transepidermal water loss (TEWL); borage oil alone was also effective but to a lesser degree than the combination. When tested without an oil carrier, both 1% and 2.5% dexpanthenol appear to improve stratum corneum hydration while reducing TEWL relative to control.
When irritation or skin abnormalities are considered a factor, dexpanthenol has been found to be beneficial in reducing inflammation and helping the rate of repair of the skin following irritation from sodium lauryl sulphate and had been noted (in a correspondence) to be of aid cheilitis associated with isotretinoin (form of Vitamin A) in the form of a 5% dexpanthenol cream.
Pantothenic acid has been long linked to hair health (dating back to at least 1946). It was known that a deficiency of pantothenic acid in rats caused graying of the hair and a connection between the two, among other topics such as hormonal and adrenal factors, was questioned. The only relatively modern evidence for pantothenic acid on hair health involves one study confounded with numerous other components (caffeine, Niacin, dimethicone and an acrylate polymer) and used neither an oral nor shampoo delivery method.
Elimination of pantothenic acid in the urine doesn't seem to differ between control subjects and those with graying hair (achromotrichia) or hair loss (alopecia), suggesting increased elimination may not be leading to a deficiency state that impairs hair health.
Despite being known as a hair health supplement, there is a stark lack of evidence conducted in the past half-century on the topic and only a few small trials conducted around 1950; many of which cannot be located online
Alcohol (ethanol) is generally known to impair absorption of numerous vitamins and minerals during excessive intake (ie. alcoholism) due to its effects on the intestines and liver, hindering absorption and storage of many vitamins and minerals respectively.
In rats given 15% ethanol in their diets, pantothenic acid levels did not appear to decrease in the liver after a month of ethanol ingestion when the level of pantothenic acid in the diet was sufficient. When the diet lacked this vitamin, however, ethanol was able to reduce not only pantothenic acid but that of thiamine, riboflavin, and pyridoxine. This may be related to the effects of ethanol on the liver itself as, according to a rat study, administering ethanol to the liver causes release of pantothenic acid and its presence may impair the ability of pantothenic acid to convert into CoA.
- Vaxman F et al.. Can the wound healing process be improved by vitamin supplementation? Experimental study on humans. Eur Surg Res. (1996)
- Vaxman F et al.. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. Eur Surg Res. (1995)
- Jillian L. Capodice. Feasibility, Tolerability, Safety and Efficacy of a Pantothenic Acid Based Dietary Supplement in Subjects with Mild to Moderate Facial Acne Blemishes. J Cosmetics, Dermatology Science and Applications. (2012)
- Yang M et al.. A randomized, double-blind, placebo-controlled study of a novel pantothenic Acid-based dietary supplement in subjects with mild to moderate facial acne. Dermatol Ther (Hejdelb). (2014)
- Davis MG et al.. A novel cosmetic approach to treat thinning hair. Br J Dermatol. (2011)
- Wall BT et al.. Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans. J Appl Physiol (1985). (2012)
- Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. . (1998)
- Ren XN et al.. Application of UPLC-MS/MS Method for Analyzing B-vitamins in Human Milk. Biomed Environ Sci. (2015)
- Song WO et al.. Effect of pantothenic acid status on the content of the vitamin in human milk. Am J Clin Nutr. (1984)
- Schroeder HA. Losses of vitamins and trace minerals resulting from processing and preservation of foods. Am J Clin Nutr. (1971)
- Leonardi R, et al. Coenzyme A: back in action. Prog Lipid Res. (2005)
- Leonardi R et al.. Modulation of pantothenate kinase 3 activity by small molecules that interact with the substrate/allosteric regulatory domain. Chem Biol. (2010)
- Leonardi R, et al. Coenzyme A: back in action. Prog Lipid Res. (2005)
- Yao J, Dotson GD. Kinetic characterization of human phosphopantothenoylcysteine synthetase. Biochim Biophys Acta. (2009)
- Strauss E et al.. Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping of an enethiolate intermediate with a mechanism-based inactivating agent. Biochemistry. (2004)
- de Jonge BL et al.. Discovery of inhibitors of 4'-phosphopantetheine adenylyltransferase (PPAT) to validate PPAT as a target for antibacterial therapy. Antimicrob Agents Chemother. (2013)
- Gudkova D et al.. EDC4 interacts with and regulates the dephospho-CoA kinase activity of CoA synthase. FEBS Lett. (2012)
- Wittwer CT et al.. Mild pantothenate deficiency in rats elevates serum triglyceride and free fatty acid levels. J Nutr. (1990)
- Shibata K et al.. Pantothenic acid refeeding diminishes the liver, perinephrical fats, and plasma fats accumulated by pantothenic acid deficiency and/or ethanol consumption. Nutrition. (2013)
- Hurley LS, Mackenzie JB. Adrenal function in the pantothenic acid-deficient rat; liver glycogen, blood glucose, adrenal cholesterol and adrenal ascorbic acid levels. J Nutr. (1954)
- Yamamoto T et al.. Effects of pantothenic acid on testicular function in male rats. J Vet Med Sci. (2009)
- Barboriak JJ et al.. Effect of partial pantothenic acid deficiency on reproductive performance of the rat. J Nutr. (1957)
- Reibel DK, et al. Coenzyme A metabolism in pantothenic acid-deficient rats. J Nutr. (1982)
- Srinivasan V, Belavady B. Alterations in gluconeogenesis in experimental pantothenic acid deficiency. Indian J Biochem Biophys. (1976)
- Olson RE, Kaplan NO. The effect of pantothenic acid deficiency upon the coenzyme A content and pyruvate utilization of rat and duck tissues. J Biol Chem. (1948)
- Gehring W, Gloor M. Effect of topically applied dexpanthenol on epidermal barrier function and stratum corneum hydration. Results of a human in vivo study. Arzneimittelforschung. (2000)
- Abiko Y, Tomikawa M, Shimizu M. Enzymatic conversion of pantothenylalcohol to pantothenic acid. J Vitaminol (Kyoto). (1969)
- Ebner F, et al. Topical use of dexpanthenol in skin disorders. Am J Clin Dermatol. (2002)
- Shibata K, Gross CJ, Henderson LM. Hydrolysis and absorption of pantothenate and its coenzymes in the rat small intestine. J Nutr. (1983)
- Said HM et al.. Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. Am J Physiol. (1998)
- Said HM. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas. Am J Physiol Gastrointest Liver Physiol. (2013)
- Ghosal A et al.. Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption. Am J Physiol Gastrointest Liver Physiol. (2013)
- Balamurugan K, Ortiz A, Said HM. Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system. Am J Physiol Gastrointest Liver Physiol. (2003)
- Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. (2011)
- Arumugam M et al.. Enterotypes of the human gut microbiome. Nature. (2011)
- Takahashi K, Fukuwatari T, Shibata K. Exercise and a High Fat Diet Synergistically Increase the Pantothenic Acid Requirement in Rats. J Nutr Sci Vitaminol (Tokyo). (2015)
- Lewis CM, King JC. Effect of oral contraceptives agents on thiamin, riboflavin, and pantothenic acid status in young women. Am J Clin Nutr. (1980)
- Uchida Y et al.. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. J Neurochem. (2015)
- Spector R. Pantothenic acid transport and metabolism in the central nervous system. Am J Physiol. (1986)
- Spector R. Development and Characterization of Pantothenic Acid Transport in Brain. J Neurochem. (1986)
- Spector R, Johanson CE. Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E. 2007. (2007)
- Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients. (2016)
- Bremer J, Wojtczak AB. Factors controlling the rate of fatty acid -oxidation in rat liver mitochondria. Biochim Biophys Acta. (1972)
- Sahlin K, et al. Turning down lipid oxidation during heavy exercise--what is the mechanism?. J Physiol Pharmacol. (2008)
- Sahlin K. Control of lipid oxidation at the mitochondrial level. Appl Physiol Nutr Metab. (2009)
- Stephens FB et al.. New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle. J Physiol. (2007)
- Slyshenkov VS, et al. Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation. Free Radic Biol Med. (1995)
- Machado MV et al.. Vitamin B5 and N-Acetylcysteine in Nonalcoholic Steatohepatitis: A Preclinical Study in a Dietary Mouse Model. Dig Dis Sci. (2016)
- Leung LH. Pantothenic acid deficiency as the pathogenesis of acne vulgaris. Med Hypotheses. (1995)
- Proksch E, Nissen HP. Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation. J Dermatolog Treat. (2002)
- Romiti R, Romiti N. Dexpanthenol cream significantly improves mucocutaneous side effects associated with isotretinoin therapy. Pediatr Dermatol. (2002)
- Unknown. Pantothenic acid, the adrenal cortex, and gray hair. Nutr Rev. (1946)
- Schmidt V. The excretion of pantothenic acid in patients with achromotrichia and alopecia. J Gerontol. (1951)
- Miyazaki A, et al. Effects of ethanol consumption on the B-group vitamin contents of liver, blood and urine in rats. Br J Nutr. (2012)
- Sorrell MF, et al. Release by ethanol of vitamins into rat liver perfusates. Am J Clin Nutr. (1974)
- Israel BC, Smith CM. Effects of acute and chronic ethanol ingestion on pantothenate and CoA status of rats. J Nutr. (1987)
(Common misspellings for Vitamin B5 include panthenic acid)