Pantothenic Acid

Common Name(s): Pantothenic acid , D-pantothenic acid , pantethine , Vitamin B-5

Uses

Vitamin B-5 may be beneficial in lipid, ophthalmic, and skin disorders. It also has possible radioprotective and adaptogen effects.

Dosing

Pantothenic acid is available in capsule, liquid, and tablet dosage forms from numerous commercial manufacturers. Clinical studies have used pantethine 600 to 1,200 mg per day for hyperlipidemias; however, most commercial Web sites document a typical dose of 300 mg 3 times a day. The US recommended daily allowance (RDA) for pantothenic acid in nutritional supplements and foods is 1 to 7 mg/day.

Contraindications

Avoid use if hypersensitive to pantothenic acid.

Pregnancy/Lactation

US Food and Drug Administration Pregnancy category A (Controlled studies show no risk. Adequate, well-controlled studies in pregnant women have failed to demonstrate risk to the fetus). Pantothenic acid is classified as category C (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.) when dosed above the recommended dietary allowance. During pregnancy and lactation, the daily maximum dosages are 6 and 7 mg/day of pantothenic acid, respectively.

Interactions

None well documented.

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. A meta-analysis from 1966 to 2002 recorded an adverse reaction rate of 1.4 per 100 subjects. The majority of these reactions were mild GI complaints.

Toxicology

Overall, pantothenic acid is considered to be safe.

History

Pantothenic acid comes from the Greek pantothen , meaning “from all sides” or “everywhere.” It is found in all animal and plant tissues. Common sources of pantothenic acid include liver, queen bee jelly, yeast, rice bran, molasses, peanuts, nuts, whole grains, mushrooms, eggs, milk, and potatoes. 1 , 2 , 3 Pantothenic acid is a member of the B-complex of vitamins and is essential for the biosynthesis of coenzyme A (CoA), 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. 1 , 2 , 4

Knowledge of pantothenic acid came about from experimentation on microorganisms and chicks. Chick dermatitis factor was the name given to purified concentrates of this substance, as was vitamin B-3, but these terms are now obsolete. 1

Vitamin B-5 is commercially available as D-pantothenic acid and its synthetic derivatives dexpanthenol and calcium pantothenate. Pantothenic acid is frequently seen in various vitamin B-complex formulations. Liquid preparations of pantothenic acid are commercially available as D-pantothenyl alcohol or panthenol. 1 In the body, pantothenic acid is converted to the related chemical pantethine, the biologically active form.

Chemistry

Pantothenic acid is an unstable, hygroscopic, viscous oil, sensitive to acids, bases, and heat. Its taste is sweet with a bitter aftertaste. 1 , 2 Pantothenic acid is optically active, with maximum biological activity only in the D-form. Pantothenic acid, its salts, and its and alcohol derivative can be assayed by chemical and microbiological methods. 1 High performance liquid chromatography methods have been used to determine synthetic pantethine. 5 , 6 , 7 At least one article reports pantethine to be the natural substrate for CoA biosyntheses. 8

The principal biologically active forms of pantothenic acid are CoA and acyl carrier protein. The primary marketed supplemental form of pantothenic acid is calcium D-pantothenate (D-calcium pantothenate). Dexpanthenol is considered a provitamin form and is the corresponding alcohol of pantothenic acid. Dexpanthenol is used in various cosmetic products and is available in topical dosage forms to promote wound healing.

Uses and Pharmacology

Review of the scientific literature documents the clinical use of pantothenic acid in skin and cardiovascular disorders.

Acne
Clinical data

Acne vulgaris was effectively treated in 100 patients with both oral and topical pantothenic acid. Patients were treated orally with 10 g/day of pantothenic acid in 4 divided doses and topical pantothenic acid cream (20% by weight) applied 4 to 6 times a day. Outcome measures included decreased sebum secretion after 1 to 2 days of treatment; both acne lesions and eruptions regressed within 1 to 2 weeks. Thirty-five patients were monitored for 18 months, and a maintenance dose of 1 to 5 g/day was needed to control the acne. 9 The mucocutaneous adverse reactions of isotretinoin therapy were effectively treated with 5% dexpanthenol cream. 10

Hyperlipidemia

Pantothenic acid is converted to pantethine in the body. It is essential for the biosynthesis of CoA, which plays a critical role in the metabolism of carbohydrates, proteins, and lipids. Some studies have evaluated pantothenic acid and pantethine as supplements and therapeutic agents in treating dyslipidemias.

Animal data

Decreased cholesterol levels in the liver and plasma of growing chicks fed a cholesterol-supplemented diet with pantethine was observed. 11 Administration of pantothenic acid derivatives given to mice with induced hypothalamic obesity lowered food intake, body weight, insulin, glucose and triglyceride levels, as well as decreased cholesterol and improved other parameters. 12 Hypolipidemic effects were also observed in rats given certain pantethine preparations. 13 Pantethine administration in rats stimulated lipolytic activity, decreased free fatty acid levels, and inhibited lipid peroxidation. 14 Atheromatous lesions in aortas and coronary arteries of rabbits were lowered by diets containing pantethine. 15 Pantethine given to affected goats accelerated normalization of liver triglycerides. 16

Clinical data

A review of pantethine use, which included other nutraceutical options, to treat hypertriglyceridemia 17 and a meta-analysis of pantethine's efficacy and tolerability covering reports from 1966 to 2002 have been published. The meta-analysis indicated that pantethine was an effective therapeutic option in treating individuals with cholesterol levels greater than 200 mg/dL and/or serum triacylglycerol levels greater than 150 mg/dL. The report also notes that the full benefit of pantethine may not be realized until at least 4 months of therapy have been completed. 18

Small, double-blind studies conducted in the early to mid-1980s document pantethine's efficacy in reducing the known risk factors of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B in patients with hyperlipidemia. 19 , 20 , 21 , 22 One postmarketing surveillance study of over 1,000 subjects documented improved cholesterol and triglyceride levels with pantethine in diabetic patients. 23

A study of 24 hypercholesterolemic perimenopausal women supplemented with pantethine 900 mg/day demonstrated an efficacy rate of approximately 80% with marked reductions in total cholesterol, LDL cholesterol, and LDL/high-density lipoprotein ratios after 16 weeks. 24 Another study evaluated administration of pantethine 600 mg/day to 16 patients with hypertriglyceridemia and fatty liver. Nine of these patients were no longer diagnosed with fatty liver after the study period. In addition, visceral fat was reduced. 25 In another study, pantethine 600 mg/day in combination therapy with probycol improved certain cholesterol parameters. 26

Several patent applications substantiate the use of pantethine in lipid disorders. 27 , 28 , 29 , 30

Ophthalmic effects

The mechanism of action involves pantethine preventing the formation of insoluble proteins in the lens. 31

Animal data

Several animal models 32 , 33 document that pantethine inhibits lens opacification and light scattering during cataract formation. The protective effect of pantethine was most efficacious when administered within 8 hours of exposure. 34

Radioprotective and adaptogen effects

Pantothenic acid and its derivatives may act by increasing levels of CoA and glutathione, leading to protection from oxygen radical species and ionizing radiation. 35 Pantethine and other botanical substances may allow animals and humans to sustain an adaptive response and minimize effects of stress by enhancing adrenal cortex functioning. 36

Animal data

In 2 studies, pantothenic acid protected rats against exposure to gamma radiation. 35 , 37 Pantothenic acid and related compounds make the plasma membrane of ascites tumor cells more resistant to the damaging effects of digitonin. 38 Pantethine offers a protective effect on the drug-metabolizing system in rat liver. 39 Pantethine versus pantothenic acid or cystamine provided the greatest protection against induced hepatotoxicity in rats. 40 A review concludes that pantethine plays a role in adaptive reactions in the myocardium as well as adaptation to deep hypothermia. 41

Other pharmacologic effects
GI activity

Pantethine stimulates GI motility in laboratory animals. 42 , 43 Interestingly, a patent from Japan describes the use of pantethine and derivatives as therapeutic agents for diarrhea. 44 Pantethine stimulates food intake in satiated rats, but is inhibitory to food intake in fasted animals. 45 In an open-label pilot study, 3 patients were administered a dexpanthenol 1,000 mg enema. No efficacy in treating ulcerative colitis was found. 46

Wound healing

Several studies document the use of pantothenic acid and its derivatives in enhancing wound healing. 47 , 48 , 49 In one study, calcium D-pantothenate accelerated the wound-healing process by increasing the migration, proliferation, and synthesis of human dermal fibroblast cells. 49

Dosage

Pantothenic acid is available in capsule, liquid, and tablet dosage forms from numerous commercial manufacturers. Clinical studies have used pantethine 600 to 1,200 mg per day for hyperlipidemias; typically, 300 mg 3 times a day is recommended. The US RDA for pantothenic acid, which is used for determining percent daily values on nutritional supplement and food labels, is 1 to 7 mg/day. 50

Pregnancy/Lactation

US Food and Drug Administration Pregnancy category A. Pantothenic acid is classified as category C when dosed above the recommended dietary allowance. During pregnancy and lactation, the daily maximum dose is 6 and 7 mg/day of pantothenic acid, respectively. 50

Interactions

None well documented.

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. Older sources report that deficiency of pantothenic acid in the diet results in neuromuscular disorders, loss of response to adrenocorticotropic hormone, fatigue, abdominal cramping, and other effects. 1 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.

Toxicology

Overall, pantothenic acid is considered to be safe.

Bibliography

1. Gennaro AR, ed. Panthothenic acid . Remington: The Science and Practice of Pharmacy . 20th ed. Lippincott Williams & Wilkins, Baltimore MD; 2000: 1809.
2. Pantothenic acid. Merck Index . 14th ed. Rahway, NJ: Merck & Co; 2006.
3. Bourre JM , Galea F . An important source of omega-3 fatty acids, vitamins D and E, carotenoids, iodine and selenium: a new natural multi-enriched egg . J Nutr Health Aging . 2006;10(5):371-376.
4. Bratman S , Kroll D , eds. Panthothenic acid and pantethine . Natural Health Bible . Roseville, CA: Prima Publishing; 2000:275-276.
5. Kopelevich VM , Gunmar VL . Methods for obtaining D-pantethine [in Russian]. Eksp Med (Riga) . 1991;27:128-131.
6. Chen X , Luo J , Zeng S . Amount determination of panthethine by RP-HPLC . Zhongguo Yaoye . 2006;15(2):38-39.
7. He X , Xu S , Jiang L , Chen A . Determination of pantethine and related substances in panthetine tablets by HPLC . Zhongguo Yiyuan Yaozue Zazhi . 2005;25(4):375-376.
8. Khomich TI . Pantethine and the biosynthetic regulation of the coenzyme of acetylation [in Russian]. Eksp Med (Riga) . 1991;27:112-118.
9. Leung LH . Pantothenic acid deficiency as the pathogenesis of acne vulgaris . Med Hypotheses . 1995;44(6):490-492.
10. Romiti R , Romiti N . Dexpanthenol cream significantly improves mucocutaneous side effects associated with isotretinoin therapy . Pediatr Dermatol . 2002;19(4):368.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. Pins JJ , Keenan JM . Dietary and nutraceutical options for managing the hypertriglyceridemic patient . Prog Cardiovasc Nurs . 2006;21(2):89-93.
18. McRae MP . Treatment of hyperlipoproteinemia with pantethine: A review and analysis of efficacy and tolerability . Nutr Res . 2005;25(4):319-333.
19. Prisco D , Rogasi PG , Matucci M , et al. Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia . Angiology . 1987;38(3):241-247.
20. Bertolini S , Donati C , Elicio N , et al. Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children . Int J Clin Pharmacol Ther Toxicol . 1986;24(11):630-637.
21. Arsenio L , Caronna S , Lateana M , Magnati G , Strata A , Zammarchi G . Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine [in Italian]. Acta Biomed Ateneo Parmense . 1984;55(1):25-42.
22. Donati C , Barbi G , Cairo G , Prati GF , Degli Esposti E . Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial . Clin Nephrol . 1986;25(2):70-74.
23. Donati C , Bertieri RS , Barbi G . Pantethine, diabetes mellitus and atherosclerosis. Clinical study of 1045 patients [in Italian]. Clin Ter . 1989;128(6):411-422.
24. Binaghi P , Cellina G , Lo Cicero G , Bruschi F , Porcaro E , Penotti M . Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age [in Italian]. Minerva Med . 1990;81(6):475-479.
25. Osono Y , Hirose N , Nakajima K , Hata Y . The effects of pantethine on fatty liver and fat distribution . J Atheroscler Thromb . 2000;7(1):55-58.
26. Nomura H , Kimura Y , Okamoto O , Shiraishi G . Effects of antihyperlipidemic drugs and diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia . Clin Ther . 1996;18(3):477-482.
27. Dasseux J-LH, inventor; Esperion Therapeutics Inc, assignee. Pharmaceutical compositions containing pantethine for treating, preventing, and managing cholesterol, dyslipidemia and related disorders . US patent application 20,050,101,565. May 12, 2005.
28. Guo X, Lou Y, inventors; Hangzhuo Xinfu Pharmaceutical Co, assignee. Application of medicinal composition for regulating blood lipid . Canadian patient application CN 1004-9207. January 24, 2005.
29. Pins JJ, inventor. Dietary supplement for treatment of lipid risk factors . US patent application 20,061,539,00. January 10, 2006.
30. Hanawa M, inventor; Daliichi Seiyaku Co, assignee. Compositions for prophylactic and or therapeutic treatment of hypercholesterolemia . Japanese patent application 20,060,163,56. January 19, 2006.
31. 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.
32. 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.
33. Fisher DH , Szulc ME . Reduction of pantethine in rabbit ocular lens homogenate . J Pharm Biomed Anal . 1997;15(5):653-662.
34. Hiraoka T , Clark JI . Inhibition of lens opacification during the early stages of cataract formation . Invest Ophthalmol Vis Sci . 1995;36(12):2550-2555.
35. 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.
36. Kelly GS . Nutritional and botanical interventions to assist with the adaptation to stress . Altern Med Rev . 1999;4(4):249-265.
37. Slyshenkov VS , Omelyanchik SN , Moiseenok AG , Petushok NE , Wojtczak L . Protection by pantothenol and beta-carotene against liver damage produced by low-dose gamma radiation . Acta Biochim Pol . 1999;46(2):239-248.
38. Slyshenkov VS , Rakowska M , Wojtczak L . Protective effect of pantothenic acid and related compounds against permeabilization of Ehrlich ascites tumour cells by digitonin . Acta Biochim Pol . 1996;43(2):407-410.
39. Hiramatsu N , Kishida T , Natake M . Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate . J Nutr Sci Vitaminol (Tokyo) . 1989;35(4):303-313.
40. 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.
41. Utno L . Major metabolic pathways regulatable with pantethine [in Russian]. Eksp Med (Riga) . 1991;27:5-8.
42. 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.
43. 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.
44. Tadano T, Hanawa M, inventors; Daiichi Sankyo Healthcare Co, assignee. Preventive and therapeutic agents for diarrhea . Japanese patent application 20,062,825,07. March 31, 2005.
45. Abucham J , Bollinger-Gruber J , Reichlin S . Pantethine, a somatostatin depleting agent, increases food intake in rats . Pharmacol Biochem Behav . 1989;33(3):585-589.
46. 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.
47. Weimann BI , Hermann D . Studies on wound healing: effects of calcium D-pantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture . Int J Vitam Nutr Res . 1999;69(2):113-119.
48. 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.
49. 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.
50. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline: A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine . Washington, DC: National Academy Press; 2000: 357-373.

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