By Dr. Vaishali Kulkarni

Introduction:

Pantothenic acid, previously known as Vitamin B5 is a water soluble B-complex vitamin. It was first extracted and isolated from liver in1938 and latter synthesized in 1940. Chemically, it is N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)-B-alanine1.The name Pantothenic acid has its origin from the Greek word ‘Panthos’ meaning ‘found everywhere’ 2. It is found in high amounts in avacodo, whole grain cereals, legumes, eggs, meat and yogurt3.  Mostly, chemically synthesized Vitamin B5 and its derivatives or precursors are added to food and beverages or consumed as dietary supplement. But, D-Pantothenic acid is the only naturally occurring, biologically active form4.

STRUCTURE OF PANTOTHENIC ACID

Biochemistry and Functions of Pantothenic acid :

Pantothenic acid is a component of Coenzyme A (CoA), and therefore used in CoA and acyl carrier proteins, which carry and transfer acetyl and acyl groups respectively. Coenzyme A is an essential cofactor in fatty acid oxidation, lipid elongation and fatty acid synthesis. Panthothenic acid is a precursor for synthesis of 4′-phosphopanthetheine moiety of CoA and acyl carrier protein5. Interestingly, only plants and microorganism are known to synthesize panthothenate de novo and represent a significant source of dietary pantothenate. However, our understanding of biosynthetic pathways in plants is still limited. On the contrary, biosynthetic pathways in bacteria are well established, comprising of four enzymatic reactions6,7. Pantothenic acid is synthesized by bacterial flora in the intestine.

Functions:

Pantothenic acid is a component of Coenzyme A, an essential coenzyme in many biochemical reactions such as synthesis of fatty acids, carbohydrates, cholesterol, porphyrins and neurotransmitter acetylcholine, steroid hormones and melatonin. Pantethine, a disulphide form of panthothenic acid is considered to be most active form of vitamin B5 because it contains a sulfhdryl-group needed for biological activities8. CoA plays an important role in acetylating proteins, modifying its structural conformation and eventually its function. Most proteins are modified by addition of acetyl group donated by COA. Protein acetylation plays a important role in cell division, DNA replication, repair of cells and tissues and gene expression.

Sources of Pantothenic acid:

Pantothenic acid is available from a wide range of food sources. Food sources considered as exceptionally high source of pantothenic acid include peanut butter (5-8 mg/100 g), liver (5-7 mg/100 g), kidney (4-6 mg/100 g), peanuts (2-3 mg/100 g), almonds (2-3 mg/100 g), wheat bran (2-3 mg/100 g), cheese (1.5 mg/100 g), and lobster (1.5 mg/100g)10. Fish, chicken and shellfish, milk, yogurt, mushrooms, legumes, lentils, avocados and sweet potatoes are also good sources of pantothenic acid. However, modern practices of refining foods cause loss of pantothenic acid. Hence, whole grains are good source of pantothenic acid but refined grains are not 9. Similarly, freezing and canning of food results in loss of pantothenic acid10,11.

Pantothenic acid can also be consumed in form of dietary supplements. These supplements commonly contain pantothenol, a stable alcohol derivative which is rapidly converted into pantothenic acid. Calcium and sodium salts of pantothenic acids are also available12.

Intake of Pantothenic acid:

Due to insufficient data from , nationwide surveys, information regarding the intake of pantothenic acid is based on er studies. The Food and Nutrition Board of the Institute of Medicine has set an adequate intake level (AI) for pantothenic acid due to insufficient scientific evidence to calculate the recommended dietary allowance (RDA)11. These studies estimated the average intake of pantothenic acid to be 5-6mg/day in adults9.

Deficiency of Pantothenic acids:

Pantothenic acid deficiencies are rare in humans and observed only in cases of malnutrition therefore most of the information available is from animal studies. Pantothenic acid deficient rats showed adrenal gland damage whereas monkeys showed decreased in hemoglobin9,13. Interestingly, nutritional research on pantothenic deficit chickens and rats produced dermatitis and loss of fur coat color respectively. This lead to the thought that pantothenic acid might act as a potential anti-gray and anti-dermatitis factor14. Chickens also showed spine nerve damage due to myelin sheath degeneration while mice showed diminished storage of glucose tolerance in liver and muscles 9.

Most extensive study on pantothenic acid in humans was done in 1950s, where in a diet low in pantothenic acid in combination with the drug omega-methyl pantothenate was used to induce deficiency in healthy subjects. Many subjects mirrored the set of symptoms from the animal studies .i.e. fatigue, headache weakness gastro-intestinal disturbances, sleep and emotional disturbances15. Furthermore, to study the significance of pantothenic acid, deficiencies were experimentally induced in humans subjects by administering a pantothenic acid antagonist and a panthothenic deficient diet. The participants of this study complained of headache, fatigue, insomnia, intestinal disturbances, numbness and tingling of their hands and feet13. Schizophrenic patients with damaged adrenal gland showed improved adrenal function on administration of panthothenic acid,16,17,18. Historical account of malnourished prisoners of war during World War II reported numbness and burning sensations in feet that was cured using pantothenic acid supplements. This information supports the other studies on pantothenic acid deficiencies.

The list of diverse symptoms due to pantothenic acid deficiency indicate a significant role of panthothenic acid – CoA in particular in various biochemical pathways.

Toxicity, dosing and side effects:

Toxicity studies in mice and rats reported that acute oral LD 50 value for pantothenic acid is 10,000mg/kg. Lethal doses resulted in death by respiratory failure19. Chronic administration for 6 months did not produce any signs of toxicity such as weight loss or histopathological changes in rats with doses up to 2,000 mg/kg, dogs(50 mg/kg), monkeys(200-250mg/kg)19. The lowest observed adverse side effects when calcium pantothenate at 3% of the diet given in rats included symptoms such as enment of testes, diarrhea, hair damage, weight loss, and less food intake. No observed side-effects were reported with 1% calcium pantothenate20. The most commonly reported side effect is mild gastrointestinal disturbance such as nausea, heartburn and diarrhea. Typically, adverse effects do not occur until a dose exceeds 1 gm daily21,22,23. The Dietary reference Intake(DIR) establishes by the Institute of Medicine for pantothenic acid is as below24:

• 1-3 years old- 2 mg/d
• 4-8 years old- 3 mg/d
• 9-13 years old: 4 mg/d
• 14 years and older: 5 mg/d
• Pregnancy: 6 mg/d
• Lactation: 7mg/d

References:

1. Scientific Opinion on the safety and efficacy of pantothenic acid (calcium Dpantothenate and D-panthenol) as a feed additive for all animal species based on a dossier submitted by Lohmann Animal Health. EFSA Journal 2011;9(11):2409
2. Williams RJ. Pantothenic acid – a vitamin. Science 1939;89:486.
3.  “Pantothenic Acid”. Linus Pauling Institute at Oregon State University. Micronutrient Information Center. Retrieved 7 November 2010.
4. Webb ME, Smith AG, Abell C. Biosynthesis of pantothenate. Nat Prod Rep 2004; 21:695-721.
5. Kleinkauf,H. The role of 4′-phosphopanthelene in the biosynthesis of fatty acids, polyketides and peptides. Biofactors, 2000; 11, 91-92
6. Cronan,J.E., Jr. Beta-alanine synthesis in Escherichia coli. J. Bactyeriol. 1980; 141, 1291-1297.
7. Lobley, C.M.C., Schitzberger,F., Kilkenny,M.L.et al. Structural insights into the evolution of the panthothenate biosynthesis pathways. Biochem.Soc.Trans. 2003; 31, 563-571.
8. Khomich TI . Pantethine and the biosynthetic regulation of the coenzyme of acetylation. Eksp Med (Riga) 1991; 27:112-118.
9. Oregaon State University- Linus Pauling Institute-Micronutrient Information Center. http://lpi.oregonstate.edu/mic/vitamins/pantothenic-acid
10. Rucker RB, Bauerly K. Pantothenic acid. In: Zempleni J, Rucker RB, McCormickDB, Suttie JW, eds. Handbook of Vitamins. New York, NY: CRC Press;2007:289-305.
11. Food and Nutrition Board, Institute of Medicine. Panthothenic acid. Dietary Reference intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vit B12, Panthothic acid, biotin and Choline. Washiongton, DC. National Academy Press, 1998: 357-373.
12. Plesofsky-Vig N. Pantothenic acid. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and disease.9th ed. Philadelphia:Lippincott WIlliams and Wilkins; 1999:423-432.
13. Hurley LS, Morgan AF. Carbohydrate metabolism and adrenal cortical function in the pantothenic acid-deficient rat. J Biol Chem 1952;195:583-590.
14. Davenport RE, Spaide J, Hodges RE. An evaluation of various survival rations. Am J Clin Nutr 1971; 24:513-523..
15.  Hodges RE, Ohlson MA, Bean WB. Pantothenic acid deficency in man. J.Clin Invest.1958; 37:1642-1657
16. Monro J. Pantothenic acid in schizophrenia. Lancet 1973;1:262-263.
17. Hodges RE, Bean WB , Ohlson MA, Bleiler R. Human pantothenic acid deficiency produced by omega-methyl pantothenic acid. J Clin Invest 1959;38:1421-1425.
18. ornton GH, Bean WB, Hodges RE. Effect of pantothenic acid deficiency of gastric secretion and motility. J Clin Invest 1955;34:1085-1091.
19. Bean WB, Hodges RE, Daum K. Pantothenic acid deficiency induced in human subjects. J Clin Invest

1955;34:1073-1084.

20. Scientific Committee on Food: Opinion of the Scientific Committee on Food on the tolerable upper intake level of pantothenic acid. Report of the European Commission: Health and consumer protection directorate general 2002SCF/CS/NUT/UPPLEV/61Final:1-6 (http://ec.europa.eu/food/fs/sc/scf/out80k_en.pdf)

21. Shibata K, Takahashi C, Fukuwatari T, Sasaki R. Effects of excess pantothenic acid administration on the other water-soluble vitamin metabolisms in rats. J Nutr Sci Vitaminol (Tokyo) 2005; 51:385-391.
22. http://www.drugs.com/npp/pantothenic- acid.html [Accessed August 1,2011]
23. Cosmetic Ingredient Review. Final report on the safety assessment of panthenol and pantothenic acid. J Am Coll Toxicol 1987;6:139-162
24. Unna K, Greslin JG. Studies on the toxicity and pharmacology of pantothenic acid. J Pharmacol Exp

1941; 73:85-90.

25. Institute of Medicine. Dietary Reference Intakes for “iamin, Ribo#avin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998:367-368.