Synonyms
Vitamin B5, antidermatosis vitamin, chick antidermatitis factor, chick antipellagra factor
Chemistry Pantothenic acid is composed of beta-alanine and 2,4-dihydroxy-3,3- dimethyIbutyric acid (pantoic acid), acid amide-linked. Pantetheine consists of pantothenic acid linked to a ß-mercaptoethylamine group.
Calcium pantothenate crystals in polarised light CH3 OH
HO CH2 C C C N CH2 CH2 COOH
H CH3 H O
Molecular formula of pantothenic acid 75
Introduction Dietary sources tothenic acid are ingested as nutri- tional supplements, they must first be converted to pantetheine by intestin- Pantothenic acid was discovered in The active vitamin is present in vir- al enzymes before being absorbed. 1933 and belongs to the group of tually all plant, animal and microbial Topical and orally applied D-pan- water-soluble B vitamins. Its name cells. Thus pantothenic acid is widely thenol (the alcoholic form of pan- originates from the Greek word distributed in foods, mostly incorpo- tothenic acid that can, e.g., be found “pantos”, meaning “everywhere”, as rated into coenzyme A. Its richest in many cosmetic products) is also it can be found throughout all living sources are yeast and organ meats absorbed by passive diffusion and cells. (liver, kidney, heart, brain), but eggs, transformed to pantothenic acid by milk, vegetables, legumes and whole- enzymatic oxidation. The highest grain cereals are more common concentrations in the body are in the sources. liver, adrenal glands, kidneys, brain, Functions heart and testes. Total pantothenic Pantothenic acid is synthesised by acid levels in whole blood are at least Pantothenic acid, as a constituent of intestinal micro-organisms, but the 1 mg/L in healthy adults; most of it coenzyme A (a coenzyme of acetyla- extent and significance of this enteral exists as coenzyme in the red blood tion), plays a key role in the metabo- synthesis is unknown. cells. Urinary excretion in the form of lism of carbohydrates, proteins and pantothenic acid generally correlates fats, and is therefore important for with dietary intake, but variation is the maintenance and repair of all cells large (2-7 mg daily). During lactation, and tissues. Coenzyme A is involved Pantothenic acid content of foods a large proportion of the intake in reactions that supply energy, in the reaches the milk (1-5 mg daily). synthesis of essential lipids (e.g. Food Pantothenic acid sphingolipids, phospholipids), sterols (mg/100g) (e.g. cholesterol), hormones (e.g. Veal liver 7.9 Measurement growth, stress and sex hormones), Brewer’s yeast 7.2 neurotransmitters (e.g. acetylcholine), Peanuts 2.1 porphyrin (a component of haemo- Due to the fact that dietary deficiency White mushrooms 2.1 globin, the oxygen-carrying red blood is practically unknown, little research cell pigment) and antibodies, and in Egg 1.6 has been conducted through assays the metabolism of drugs (e.g. Wheat germ 1 to assess pantothenate status in sulphonamides) and in alcohol detox- Herring 0.94 man. Nutritional status can be ification. Another essential role of Milk 0.35 deduced from amounts of pantothen- pantothenic acid concerns acyl carri- Vegetables 0.2-0.6 ate excreted in urine. Less than 1 mg er protein, an enzyme involved in the daily is considered abnormally low. A synthesis of fatty acids. In the (Souci, Fachmann, Kraut) more convenient approach is deter- process of fat burning, pantothenic mination of pantothenate in serum, or acid works in concert with coenyzme preferably whole blood, by microbio- Q10 and L-carnitine. logical methods. Although these Absorption and assays are highly sensitive and specific, they are slow and tedious to Main functions in a nutshell: body stores perform. New methods, such as • Metabolism of carbohydrates, HPLC/MS (High Performance Liquid proteins and fats Most of the pantothenic acid in food Chromatography / mass spectrome- • Supply of energy from foods exists in the form of coenzyme A, and try) and immunologic methods, have • Synthesis of essential lipids, pantothenic acid is released by a also been applied. Another method sterols, hormones, neurotrans- series of enzyme reactions in the suggested for assessing nutritional mitters, and porphyrin small intestine. It is then absorbed by status is the sulphanilamide acetyla- • Metabolism of drugs and passive diffusion into the portal circu- tion test, which measures the activity alcohol detoxification lation and transported to the tissues, of coenzyme A in the blood. Whole where re-synthesis of the coenzyme blood levels typically range from 0.9 – occurs. About half of the pantothenic 1.5 µmol/L. acid in the diet is actually absorbed. If calcium pantothenate or pan- 76
Stability Deficiency Homopantothenate is a pantothenic acid antagonist that has been used in Japan to enhance mental function, Pantothenic acid is stable under neu- Since pantothenic acid occurs to especially in Alzheimer's disease. A tral conditions, but is readily some extent in all foods, it is general- rare side effect was an abnormal destroyed by heat in alkaline or acid ly assumed that dietary deficiency of brain function resulting from the fail- solutions. Up to 50% may be lost this vitamin is extremely rare. ure of the liver to eliminate toxins during cooking (due to leaching) and However, pantothenic acid deficiency (hepatic encephalopathy). This condi- up to 80% as a result of food pro- in humans is not well documented tion was reversed by pantothenic cessing and refining (canning, freez- and probably does not occur in isola- acid supplementation, suggesting it ing, milling etc.). Pasteurisation of tion but in conjunction with deficien- was due to pantothenic acid deficien- milk only causes minor losses. cies of other B vitamins. Clinical man- cy caused by the antagonist. In ifestations that can be clearly experiments with mice it has been ascribed to dietary deficiency of pan- shown that a deficiency of pan- tothenic acid have not been identi- tothenic acid leads to skin irritation Interactions fied, although it has been implicated and greying of the fur, which were in “burning feet” syndrome, a condi- reversed by giving pantothenic acid. Positive interactions tion observed among malnourished Pantothenic acid has since been Various studies have indicated that prisoners of war in the 1940s. added to shampoo, although it has vitamin B12 may aid in the conver- Deficiency symptoms have been pro- never been successful in restoring sion of free pantothenic acid into duced experimentally by administer- hair colour in humans. coenzyme A. In the absence of B12, ing the antagonist omega-methyl coenzyme A production is pantothenic acid. They include Groups at risk of deficiency decreased and fat metabolism fatigue, headaches, insomnia, nau- • Alcoholics impaired. In animal experiments, sea, abdominal cramps, vomiting and • Women on oral contraceptives ascorbic acid (vitamin C) was shown flatulence. The subjects complained • People with insufficient food intake to lessen the severity of symptoms of tingling sensations in the arms and (e.g. elderly, post-operative) due to pantothenic acid deficiency; legs, muscle cramps and impaired • People with impaired absorption vitamin A, vitamin B6, folic acid and coordination. There was cardiovascu- (due to certain internistic diseases) biotin are also necessary for proper lar instability and impaired responses utilisation of pantothenic acid. to insulin, histamine and ACTH (a stress hormone). Negative interactions Ethanol causes a decrease in the amount of pantothenic acid in tis- sues, with a resulting increase in serum levels. It has therefore been Current recommendations in the USA suggested that pantothenic acid utili- sation is impaired in alcoholics. Birth RDA* control pills containing estrogen and Infants < 6 months 1.7mg (AI) progestin may increase the require- Infants 7-12 months 1.8mg (AI) ment for pantothenic acid. The most Children 1-3 years 2mg (AI) common antagonist of pantothenic acid used experimentally to acceler- Children 4-8 years 3mg (AI) ate the appearance of deficiency Children 9-13 years 4mg (AI) symptoms is omega-methyl pan- Adults >14 years 5mg (AI) tothenic acid. L-pantothenic acid has Pregnancy 6mg (AI) also been shown to have an antago- Lactation 7mg (AI) nistic effect in animal studies. Methyl bromide, a fumigant used to control *The Dietary Reference Intakes (DRIs) are actually Allowances (RDAs). The RDA was established as vermin in places where food is a set of four reference values: Estimated Average a nutritional norm for planning and assessing stored, destroys the pantothenic acid Requirements (EAR), Recommended Dietary dietary intake, and represents intake levels of in foods exposed to it. Allowances (RDA), Adequate Intakes (AI), and essential nutrients considered to meet adequately Tolerable Upper Intake Levels, (UL) that have the known needs of practically all healthy people replaced the 1989 Recommended Dietary 77
Disease Recommended application, aerosols, tablets, oint- ments and creams). Pantethine, a prevention and Dietary Allowance derivative of pantothenic acid, is used therapeutic use (RDA) as a cholesterol and triglyceride-low- ering drug in Europe and Japan and is available in the U.S. as a dietary sup- Although isolated deficiency states are It is widely agreed that there is insuf- plement. rarely observed, various investigators ficient information available on which Pantothenate is added to a variety of have noted changes in pantothenic to base an RDA for pantothenic acid. foods, the most important of which acid levels in various diseases, and Most countries that make are breakfast cereals and beverages, pharmacological amounts of the vita- recommendations therefore give an dietetic and baby foods. min are used in the treatment of estimate of safe and adequate levels D-Panthenol is often used in cosmetic numerous conditions. In most cases, for daily intake. These adequate products. In skin care products, it however, the claimed therapeutic intake levels (AI) are based on esti- helps to keep the skin moist and sup- responses have not been confirmed mated dietary intakes in healthy pop- ple, stimulates cell growth and tissue by controlled studies in humans. ulation groups and range, depending repair, and inhibits inflammation and For the treatment of deficiency due to on the health authority concerned, reddening. As a moisturiser and con- impaired absorption, intravenous or from 2 to 14 mg for adults. ditioner in hair care products, it pro- intramuscular injections of 500 mg tects against and repairs damage due several times a week are recommend- to chemical and mechanical proce- ed. Postoperative ileus (paralysis of dures (brushing, combing, shampoo- the intestine) requires doses of up to Safety ing, perming, colouring etc.), and 1000 mg every six hours. imparts sheen and luster. Panthenol is applied topically to skin Pantothenic acid is essentially consid- and mucosa to speed healing of ered to be nontoxic, and no cases of wounds, ulcers and inflammation, hypervitaminosis have ever been such as cuts and grazes, burns, sun- reported. As much as 10 g daily in Industrial burn, nappy rash, bed sores, laryngitis humans produces only minor gastroin- production and bronchitis. In combination, pan- testinal disturbance (diarrhoea). Due to tothenic acid and ascorbic acid signif- the lack of reports of adverse effects icantly enhance post surgical therapy the main regulatory authorities have Pantothenic acid is chemically and wound healing. The healing not defined a tolerable upper level of synthesised by condensation of process of conjunctiva and the cornea intake (UL) for pantothenic acid. D-pantolactone with P-alanine. after reconstructive surgery of the Addition of a calcium salt produces epithelium has also been accelerated. colourless crystals of calcium pan- Pantothenic acid has been tried, with tothenate. Panthenol is produced as varying results, to treat various liver Supplements, food a clear, almost colourless, viscous conditions, arthritis, and constipation fortification and hygroscopic liquid. in the elderly; to prevent urinary reten- tion after surgery or childbirth; and cosmetics (together with biotin) to prevent bald- ness. It has also been reported to have a protective effect against radia- Pure pantothenic acid is a viscous tion sickness. hygroscopic oil that is chemically not Pantethine is used to normalise lipid very stable. Supplements therefore profiles, as it lowers elevated triglyc- usually contain the calcium salt, or erides and LDL cholesterol while rais- alcohol, panthenol. Both are highly ing levels of the beneficial HDL choles- water soluble and are rapidly convert- terol. Pantethine actually consists of ed to free acid in the body. Calcium two molecules of pantetheine joined pantothenate is often included in mul- by two molecules of sulphur (a disul- tivitamin preparations; panthenol is phide bridge). It is especially effective the more common form used in mono- at lowering elevated blood lipids in preparations, which are available in a patients with diabetes without hinder- wide variety of pharmaceutical forms ing blood sugar control. (e.g. solutions for injection and local 78
History
1931 Williams and Truesdail separate an acid fraction from “bios”, the growth factor for yeast discovered in 1901 by Wildiers.
1933 Williams and coworkers show this fraction to be a single acid substance essential for the growth of yeast. Because they find it in a wide range of biological materials, they suggested calling it “pantothenic acid”.
1938 Williams and associates establish the structure of pantothenic acid
1939 Jukes and colleagues show the similarity between pantothenic acid and the chick antidermatitis factor.
1940 Total synthesis of the vitamin is achieved independently by Williams and Major, Stiller and associates, Reichstein and Grüssner, and Kuhn and Wieland.
1947 Lipmann and his associates identify pantothenic acid as one of the components of the coenzyme they had discovered in liver two years earlier.
1953 The full structure of coenzyme A is elucidated by Baddiley and colleagues. Lipmann receives the Nobel Prize, together with Roger John Williams Krebs, for his work on coenzyme A and its role in metabolism.
1954 Bean and Hodges report that pantothenic acid is essential in human nutrition. Subsequently, they and their colleagues conduct several further studies to produce deficiency symptoms in healthy humans using the antagonist omega-methyl pantothenic acid.
1965 Pugh and Wakil identify the acyl carrier protein as an additional active form of pantothenic acid.
1976 Fry and her associates measure the metabolic response of humans to deprivation of pantothenic acid without involvement Fritz Albert Lipmann of an antagonist.
Tadeusz Reichstein