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Pantothenic Acid

Scientific Name(s): D(+)-alpha-(-dihydroxy-beta,beta-dimethylbutyryl-beta-alanaine)
Common Name(s): Antidermatitis vitamin, Calcium-pantothenate, D-pantothenic acid, Dexpanthenol, Pantethine, Pantothenate, Pantothenic acid, Vitamin B5

Clinical Overview

Use

Clinical studies are limited. Pantothenic acid and its derivatives may have a role in the management of dyslipidemia and in wound healing.

Dosing

The US recommended dietary allowance (RDA) for pantothenic acid in nutritional supplements and foods is age dependent and ranges from 0.2 mg/kg in infants to 5 mg in adults. The RDA during pregnancy and lactation is slightly higher, at 6 and 7 mg daily, respectively.

Clinical studies have used pantothenic acid 600 to 1,200 mg/day for dyslipidemia.

Contraindications

Avoid use if hypersensitivity to pantothenic acid exists.

Pregnancy/Lactation

Pantothenic acid has been assigned US Food and Drug Administration (FDA) Pregnancy Category A (studies have failed to demonstrate risk). When dosed above the recommended dietary allowance (6 to 7 mg/day), pantothenic acid is designated Category C.

Interactions

None well documented. Caution may be warranted with concomitant use of biotin.

Adverse Reactions

In high doses, pantothenic acid may inhibit the absorption of biotin produced by the microflora in the large intestine. Diarrhea may occur with large doses of pantothenic acid. Allergic contact dermatitis has been reported with topical use of dexpanthenol.

Toxicology

A tolerable upper intake level for pantothenic acid has not been set because reports of adverse effects are lacking. An oral median lethal dose of 10 g/kg for mice has been reported.

Source

Pantothenic acid is found in all animal and plant tissues. Common sources of pantothenic acid include liver, queen bee jelly, yeast, rice bran, molasses, peanuts, tree nuts, whole grains, mushrooms, eggs, milk, and potatoes. Pantothenic acid is commercially available as D-pantothenic acid and its synthetic derivatives dexpanthenol and calcium pantothenate. It is frequently included in various vitamin B-complex formulations. Liquid preparations of pantothenic acid are commercially available as D-pantothenyl alcohol or panthenol.1, 2

History

The name pantothenic acid is derived from the Greek pantothen, meaning "from all sides" or "everywhere." The vitamin was first isolated in 1931, and its role as an essential component in the growth of yeast cells was demonstrated in 1933. The involvement of pantothenic acid in coenzyme A and cellular metabolism was elucidated in the late 1940s and early 1950s.

Knowledge of pantothenic acid resulted from experimentation on microorganisms and chicks. Chick antidermatitis factor was the name given to purified concentrates of this substance, as was vitamin B5, but these terms are now obsolete. Pantothenic acid deficiency is rare. Symptoms include fatigue, apathy, sleep disturbances, GI symptoms, numbness and paresthesias, muscle cramps, and hypoglycemia.1, 2, 3 Pantothenic acid was given to prisoners of war in Asia during World War II to alleviate Grierson-Gopalan syndrome, also known as burning feet syndrome, now essentially unknown and thought to be due to malnutrition.1, 2

Chemistry

Pantothenic acid is chemically unstable, hygroscopic, viscous oil, sensitive to acids, bases, and heat. It is sweet with a bitter aftertaste. Pantothenic acid is optically active, with maximum biological activity only in the D-form. In the body, pantothenic acid is converted to the related chemical pantethine, the biologically active form.

Pantothenic acid is a member of the B-complex of vitamins and is essential for the biosynthesis of coenzyme A, an important substance involved in energy release from carbohydrates; metabolism of amino acids and fatty acids; syntheses of compounds, including sterols, steroid hormones, and acetylcholine; and other reactions.

The primary marketed supplemental form of pantothenic acid is calcium D-pantothenate (D-calcium pantothenate). Dexpanthenol, considered a provitamin form, is the corresponding alcohol of pantothenic acid. Pantothenic acid, its salts, and its alcohol derivative can be assayed by chemical and microbiological methods.1, 2, 4, 5

Uses and Pharmacology

Dermatological effects

Animal data

Despite positive findings in rodent studies, little positive clinical data exist regarding the use of pantothenic acid in the condition or growth of human hair.

Clinical data

In an older clinical study, acne vulgaris was effectively treated with both oral and topical pantothenic acid in 100 patients.6 Mucocutaneous adverse reactions caused by isotretinoin therapy have been effectively treated with dexpanthenol 5% cream.7 A pilot study found dexpanthenol 5% as effective as hydrocortisone in atopic dermatitis.8

Dyslipidemia

Pantothenic acid is converted to pantethine in the body. It is essential for the biosynthesis of coenzyme A, which plays a critical role in the metabolism of carbohydrates, proteins, and lipids.

Animal data

Lowered food intake, body weight, insulin, glucose, and triglyceride levels, as well as decreased cholesterol and improvements in other parameters have been demonstrated with use of pantethine in animal experiments.9, 10, 11, 12, 13, 14

Clinical data

A review of pantethine's use as a nutraceutical option for the treatment of hypertriglyceridemia as well as a meta-analysis of pantethine's efficacy and tolerability covering 28 studies from 1966 to 2002 was published. The meta-analysis suggests that pantethine may be effective in treating individuals with cholesterol levels greater than 200 mg/dL and/or serum triglyceride levels greater than 150 mg/dL. However, larger clinical studies are warranted in more diverse populations before a definitive role for pantethine can be defined.15, 16

Ophthalmic effects

Animal data

Limited animal experiments have studied the role of pantethine in lens opacification and light scattering during cataract formation. Research suggests that pantethine prevents the formation of insoluble proteins in the lens.17, 18, 19, 20

Clinical data

A study evaluated the effect of dexpanthenol 5% following phototherapeutic keratectomy. No significant difference over the placebo ointment was found; however, the study may have been underpowered.21

Wound healing

Animal data

In vivo and animal studies have been undertaken to elucidate a potential mechanism of action for the use of pantothenic acid and its derivatives in enhancing wound healing.22, 23, 24

Clinical data

Dexpanthenol as a pastille and as a spray has been evaluated in small clinical trials for wound healing in postoperative tonsillectomy, endotracheal intubation, and endoscopic sinus surgery.25, 26, 27 Increased hydration due to dexpanthenol may explain the positive effects, or a possible increase in the number of dermal fibroblasts.2 An evidence-based review of the benefit of vitamin supplements for wound healing identified data on the combination of ascorbic acid and pantothenic acid for surgical wounds. Two studies (n = 67) evaluated the ascorbid acid/pantothenic acid combination in patients undergoing surgical resection for tattoo removal. Treatment that was initiated pre-procedure improved mechanical properties of wound scars.39 Further studies are warranted.

Other uses

Pantethine stimulates GI motility in laboratory animals.28, 29 A clinical role for this effect has not been established, and no efficacy in treating ulcerative colitis was found in a small open-label study.30

Dexpanthenol has been used intravenously in combination with other micronutrients ("Myers' Cocktail") in fibromyalgia31 and in arthritis in older studies.2

Older studies in animals suggest that pantothenic acid increases levels of coenzyme A and glutathione, protecting against oxygen-radical species and ionizing radiation as well as against induced hepatotoxicity.32, 33

A role for pantothenic acid in epilepsy therapy34 and in exercise performance have not been pursued to any extent in the literature.35

A small study (n = 8) looked at the effective of daily doses of 1.5 g of pantothenic acid combined with an equal amount of L-cysteine. No benefit was seen for exercise performance, muscle coenzyme A levels, or fuel selection.40

Dosing

The US RDA for pantothenic acid in nutritional supplements and foods is age dependent and ranges from 0.2 mg/kg in infants to 5 mg in adults. The RDA during pregnancy and lactation is slightly higher, at 6 and 7 mg daily, respectively.2, 36

Pantothenic acid is available in capsule, liquid, and tablet doseforms from numerous commercial manufacturers. Clinical studies have used pantethine 600 to 1,200 mg/day for dyslipidemia, 200 to 300 mg/day for wound healing, and 1.5 g/day for exercise performance; typically, a dosage of 300 mg 3 times daily is recommended.15, 16, 37, 38

Pregnancy / Lactation

Pantothenic acid has been assigned US FDA Pregnancy Category A (ie, adequate, well-controlled studies have failed to demonstrate a risk to the fetus). When dosed above the recommended dietary allowance, pantothenic acid is designated Category C (ie, Risk cannot be ruled out. Human studies are lacking, and animal studies are either positive for fetal risk or lacking. However, potential benefits may justify the potential risks). During pregnancy and lactation, the adequate intake is pantothenic acid 6 and 7 mg/day, respectively. Pantothenic acid concentrations in human breast milk weakly correspond with maternal intake.2, 36

Interactions

None well documented. A case report of life-threatening eosinophilic pleuropericardial effusion with concomitant use of biotin 10 mg/day and pantothenic acid 300 mg/day exists.37

Adverse Reactions

In high doses, pantothenic acid may inhibit the absorption of biotin produced by microflora in the large intestine; diarrhea may occur. Allergic contact dermatitis has been reported with topical use of dexpanthenol and panthenol cream.1, 38, 41 A meta-analysis from 1966 to 2002 recorded an adverse reaction rate of 1.4 per 100 subjects. The majority of these events were mild GI complaints.16

Toxicology

Pantothenic acid is considered to be relatively safe. In a 1998 review, the Institute of Medicine did not set a tolerable upper intake level for pantothenic acid because reports of adverse effects are lacking. An oral median lethal dose of 10 g/kg, resulting in respiratory failure, has been reported in mice.2, 36

References

1. Gennaro AR, ed. Panthothenic acid. In: Troy DB, ed. Remington: The Science and Practice of Pharmacy. 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000: 1809.
2. Trumbo PR. Pantothenic acid. In: Shils ME, Shike M, Ross AC, Cabellero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
3. Ames BN, Atamna H, Killilea DW. Mineral and vitamin deficiencies can accelerate the mitochondrial decay of aging. Mol Aspects Med. 2005;26(4-5):363-378.16102804
4. Webb ME, Smith AG, Abell C. Biosynthesis of pantothenate. Nat Prod Rep. 2004;21(6):695-721.15565250
5. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011;437(3):357-372.21749321
6. Leung LH. Pantothenic acid deficiency as the pathogenesis of acne vulgaris. Med Hypotheses. 1995;44(6):490-492.7476595
7. Romiti R, Romiti N. Dexpanthenol cream significantly improves mucocutaneous side effects associated with isotretinoin therapy. Pediatr Dermatol. 2002;19(4):368.12220290
8. Udompataikul M, Limpa-o-vart D. Comparative trial of 5% dexpanthenol in water-in-oil formulation with 1% hydrocortisone ointment in the treatment of childhood atopic dermatitis: a pilot study. J Drugs Dermatol. 2012;11(3):366-374.22395588
9. Tanaka K, Hsu Jennshung, Ohtani S. Effects of dietary pantethine on plasma lipid fractions and on hepatic lipogenesis of growing chicks. Nippon Chikusan Gakkaiho. 1989;60(12):1150-1160.
10. Naruta E, Buko V. Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Exp Toxicol Pathol. 2001;53(5):393-398.11817109
11. Kirilina V, Rabinkov A, Kopelevich V, Gunar V. Hypolipidemic activity of pantethine and other acetylation coenzyme precursors [in Russian]. Eksp Med (Riga). 1991;27:71-75.
12. Kumerova AO, Silova AA, Utno LIa. Effect of pantethine on post-heparin lipolytic activity and lipid peroxidation in the myocardium [in Russian]. Biull Eksp Biol Med. 1991;111(1):33-35.2054471
13. Sasuga M, Yoshida Y, Mogaki M, et al. Effect of pantethine, soysterol, and their combinations on serum lipoprotein metabolism and the incidence of atheromatous lesions in cholesterol-fed rabbits. Domyaku Koka. 1990;18(9/10):839-850.
14. Tanaka K, Morimoto E, Makino Y, Ohtani S. Effects of pantethine on gluconeogenesis and fatty acid synthesis in Japanese native goats with fatty liver induced by ethionine administration [in Japanese]. Gifu Daigaku Nogakubu Kenkyu Hokoku. 1992;57:53-63.
15. Pins JJ, Keenan JM. Dietary and nutraceutical options for managing the hypertriglyceridemic patient. Prog Cardiovasc Nurs. 2006;21(2):89-93.16760691
16. McRae MP. Treatment of hyperlipoproteinemia with pantethine: a review and analysis of efficacy and tolerability. Nutr Res. 2005;25(4):319-333.
17. Matsushima H, David LL, Hiraoka T, Clark JI. Loss of cytoskeletal proteins and lens cell opacification in the selenite cataract model. Exp Eye Res. 1997;64(3):387-395.9196390
18. Clark JI, Livesey JC, Steele JE. Delay or inhibition of rat lens opacification using pantethine and WR-77913. Exp Eye Res. 1996;62(1):75-84.8674515
19. Fisher DH, Szulc ME. Reduction of pantethine in rabbit ocular lens homogenate. J Pharm Biomed Anal. 1997;15(5):653-662.9127277
20. Hiraoka T, Clark JI. Inhibition of lens opacification during the early stages of cataract formation. Invest Ophthalmol Vis Sci. 1995;36(12):2550-2555.7591646
21. Baumeister M, Buhren J, Ohrloff C, Kohnen T. Corneal re-epithelialization following phototherapeutic keratectomy for recurrent corneal erosion as in vivo model of epithelial wound healing. Ophthalmologica. 2009;223(6):414-418.19648776
22. Akdeniz Y, Tarhan OR, Barut I. Can dexpanthenol prevent peritoneal adhesion formation? An experimental study [in Turkish]. Ulus Travma Acil Cerrahi Derg. 2007;13(2):94-100.17682950
23. Etensel B, Ozkisacik S, Ozkara E, et al. Dexpanthenol attenuates lipid peroxidation and testicular damage at experimental ischemia and reperfusion injury. Pediatr Surg Int. 2007;23(2):177-181.16983563
24. Heise R, Skazik C, Marquardt Y, et al. Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacol Physiol. 2012;25(5):241-248.22759998
25. Celebi S, Tepe C, Yelken K, Celik O. Efficacy of dexpanthenol for pediatric post-tonsillectomy pain and wound healing. Ann Otol Rhinol Laryngol. 2013;122(7):464-467.23951700
26. Gulhas N, Canpolat H, Cicek M, et al. Dexpanthenol pastille and benzydamine hydrochloride spray for the prevention of post-operative sore throat. Acta Anaesthesiol Scand. 2007;51(2):239-243.17073853
27. Tantilipikorn P, Tunsuriyawong P, Jareoncharsri P, et al. A randomized, prospective, double-blind study of the efficacy of dexpanthenol nasal spray on the postoperative treatment of patients with chronic rhinosinusitis after endoscopic sinus surgery. J Med Assoc Thai. 2012;95(1):58-63.22379743
28. Kan S, Taniyama K, Goto Y. Mechanism of stimulatory effect of pantethine on the colonic motility in relation to the cholinergic neurons [in Japanese]. Yakuri to Chiryo. 1995;23(9):2215-2220.
29. Ryokawa Y, Komada T, Goto Y, Taniyama K. Effect of intravenous pantethine on rat gastrointestinal motility [in Japanese]. Yakuri to Chiryo. 1995;23(9):2207-2214.
30. Loftus EV Jr, Tremaine WJ, Nelson RA, et al. Dexpanthenol enemas in ulcerative colitis: a pilot study. Mayo Clin Proc. 1997;72(7):616-620.9212762
31. Ali A, Njike VY, Northrup V, et al. Intravenous micronutrient therapy (Myers' Cocktail) for fibromyalgia: a placebo-controlled pilot study. J Altern Complement Med. 2009;15(3):247-257.19250003
32. Slyshenkov VS, Omelyanchik SN, Moiseenok AG, Trebukhina RV, Wojtczak L. Pantothenol protects rats against some deleterious effects of gamma radiation. Free Radic Biol Med. 1998;24(6):894-899.9607598
33. Nagiel-Ostaszewski I, Lau-Cam CA. Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat. Res Commun Chem Pathol Pharmacol. 1990;67(2):289-292.2333416
34. Poverennova IE, Iakunina AV, Kalinin VA, Savel'eva NN. Efficacy and tolerability of Pantogam Activ in patients with partial epilepsy [In Russian]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(2):54-59.21350425
35. Wall BT, Stephens FB, Marimuthu K, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL. 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;112(2):272-278.22052867
36. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its panel on folate, other B vitamins, and choline. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington (DC): National Academies Press (US); 1998. 10, Pantothenic Acid. Available from: http://www.ncbi.nlm.nih.gov/books/NBK114311/. Accessed May 15, 2014.
37. Debourdeau PM, Djezzar S, Estival JL, Zammit CM, Richard RC, Castot AC. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother. 2001;35(4):424-426.11302404
38. Chin MF, Hughes TM, Stone NM. Allergic contact dermatitis caused by panthenol in a child. Contact Dermatitis. 2013;69(5):311-322.24117747
39. Ellinger S, Stehle P. Efficacy of vitamin supplementation in situations with wound healing disorders: results from clinical intervention studies. Curr Opin Clin Nutr Metab Care. 2009;12(6):588-595.19770648
40. Wall BT, Stephens FB, Marimuthu K, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL. 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;112(2):272-278.22052867
41. Bregnbak D, Johansen JD, Zachariae C. Contact dermatitis caused by panthenol used for aftercare treatment of a new tattoo. Contact Dermatitis. 2016;75(1):50-52.27264289

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