PANTOTHENIC ACID
Pantothenic acid, also known as vitamin B-5, is essential to all forms of life (1). Pantothenic acid is found throughout living cells in the form of coenzyme A (CoA), a vital coenzyme in numerous chemical reactions (2).
FUNCTION
Coenzyme A: Pantothenic acid is a component of coenzyme A (CoA), an essential coenzyme in a variety of reactions that sustain life. CoA is required for chemical reactions that generate energy from food (fat, carbohydrates, and proteins). The synthesis of essential fats, cholesterol, and steroid hormones requires CoA, as does the synthesis of the neurotransmitter, acetylcholine, and the hormone, melatonin. Heme, a component of hemoglobin, requires a CoA-containing compound for its synthesis. Metabolism of a number of drugs and toxins by the liver requires CoA (3).
Coenzyme A was named for its role in acetylation reactions. Most acetylated proteins in the body have been modified by the addition of an acetate group that was donated by CoA. Protein acetylation affects the 3-dimensional structure of proteins, potentially altering their function. Protein acetylation affects the activity of peptide hormones and appears to play a role in cell division and DNA replication. Protein acetylation also affects gene expression by facilitating the transcription of mRNA. A number of proteins are also modified by the attachment of long-chain fatty acids donated by CoA. These modifications are known as protein acylation, and appear to play a central role in cell signaling.
Acyl-carrier protein: The acyl-carrier protein requires pantothenic acid in the form of 4'-phosphopantetheine for its activity as an enzyme (1,4). Both CoA and the acyl-carrier protein are required for the synthesis of fatty acids. Fatty acids are a component of some lipids, which are fat molecules essential for normal physiological function. Among these essential fats are sphingolipids, which are a component of the myelin sheath that enhances nerve transmission, and phospholipids in cell membranes.
DEFICIENCY
Naturally occurring pantothenic acid deficiency in humans is very rare and has been observed only in cases of severe malnutrition. World War II prisoners in the Phillipines, Burma, and Japan experienced numbness and painful burning and tingling in their feet, which was relieved specifically by pantothenic acid (1). Pantothenic acid deficiency in humans has been induced experimentally by administering a pantothenic acid antagonist together with a pantothenic acid deficient diet. Participants in this experiment complained of headache, fatigue, insomnia, intestinal disturbances, and numbness and tingling of their hands and feet (5). In a more recent study, participants fed only a pantothenic acid free diet did not develop clinical signs of deficiency, though some appeared listless and complained of fatigue (6). Homopantothenate is a pantothenic acid antagonist with cholinergic effects (similar to those of the neurotransmitter, acetylcholine). It was used in Japan to enhance mental function, especially in Alzheimer's disease. A rare side effect was the development of hepatic encephalopathy, a condition of abnormal brain function resulting from the failure of the liver to eliminate toxins. The encephalopathy was reversed by pantothenic acid supplementation suggesting, but not proving, it was due to pantothenic acid deficiency caused by the antagonist (4).
Because it is so rare, most information regarding the effects of pantothenic acid deficiency comes from experimental research in animals. The diversity of symptoms emphasizes the numerous functions of pantothenic acid in its coenzyme forms (see Function). Pantothenic acid deficient rats developed damage to the adrenal glands, while monkeys developed anemia due to decreased synthesis of heme, a component of hemoglobin. Dogs with pantothenic acid deficiency developed low blood glucose, rapid breathing and heart rates, and convulsions. Chickens developed skin irritation, feather abnormalities, and spinal nerve damage associated with the degeneration of the myelin sheath. Pantothenic acid deficient mice showed decreased exercise tolerance and diminished storage of glucose (in the form of glycogen) in muscle and liver. Mice also developed skin irritation and graying of the fur, which was reversed by giving pantothenic acid. This finding led to the idea of adding pantothenic acid to shampoo, although it has not been successful in restoring hair color in humans (7).
The Adequate Intake Level (AI): The Food and Nutrition Board of the Institute of Medicine felt the existing scientific evidence was insufficient to calculate an RDA for pantothenic acid, so they set an Adequate Intake level (AI). The AI for pantothenic acid was based on estimated dietary intakes in healthy population groups (8).
The AI for adult men and women of all ages: 5 milligrams (mg) of pantothenic acid/day
DISEASE TREATMENT
Wound healing: Administration of pantothenic acid orally and application of pantothenol ointment to the skin have been shown to accelerate the closure of skin wounds and increase the strength of scar tissue in animals. Adding calcium-D-pantothenate to cultured human skin cells given an artificial wound increased the number of migrating skin cells, and their speed of migration, effects likely to accelerate wound healing (9). However, little data exists in humans to support the findings of accelerated wound healing in cell culture and animal studies. A randomized, double blind study examining the effect of supplementing patients undergoing surgery for tattoo removal with 1,000 mg of vitamin C and 200 mg of pantothenic acid could not document any significant improvement in the wound healing process in those that received the supplements (10).
High cholesterol: A pantothenic acid derivative called pantethine has been reported by a number of investigators to have a cholesterol lowering effect. Pantethine is actually two molecules of pantetheine joined by a disulfide bond (chemical bond between two molecules of sulfur). In the synthetic pathway of coenzyme A (CoA), pantetheine is closer to CoA than pantothenic acid, and is the functional component of CoA and acyl carrier proteins (see Function). Several studies found doses of 900 mg of pantethine daily (300 mg, three times daily) to be significantly more effective than placebo in lowering total cholesterol and triglyceride levels in the blood of both diabetic and non-diabetic individuals (11). Pantethine was also found to lower cholesterol and triglyceride levels in diabetic patients on hemodialysis without adverse side effects. The low side effect profile of pantethine was especially attractive for hemodialysis patients because of the increased risk of drug toxicity in patients with renal (kidney) failure (12). Pantethine is not a vitamin; it is a derivative of pantothenic acid. The decision to use pantethine to treat elevated blood cholesterol or triglycerides should be made in collaboration with a qualified health care provider, who can provide appropriate follow up.
SOURCES
Food sources: Pantothenic acid is available in a variety of foods. Rich sources of pantothenic acid include liver and kidney, yeast, egg yolk, and broccoli. Fish, shellfish, chicken, milk, yogurt, legumes, mushrooms, avocado, and sweet potatoes are also good sources. Whole grains are good sources of pantothenic acid, but processing and refining grains may result in a 35% to 75% loss. Freezing and canning of foods have been found to result in similar losses (8). Large national nutritional surveys were unable to estimate pantothenic acid intake due to the scarcity of data on the pantothenic acid content of food. Smaller studies estimate average daily intakes of pantothenic acid to be from 5 to 6 mg/day in adults. The table below lists some rich sources of pantothenic acid along with their content in milligrams (mg). For more information on the nutrient content of foods you eat frequently, search the USDA food composition database.
| Food | Serving | Pantothenic Acid (mg) |
| Fish, cod (cooked) | 3 ounces | 0.15 |
| Tuna (canned) | 3 ounces | 0.18 |
| Chicken, cooked | 3 ounces | 0.98 |
| Egg (cooked) | 1 large | 0.61 |
| Milk | 1 cup (8 ounces) | 0.79 |
| Yogurt | 8 ounces | 1.35 |
| Broccoli (steamed) | 1/2 cup (chopped) | 0.40 |
| Lentils (cooked) | 1/2 cup | 0.64 |
| Split peas (cooked) | 1/2 cup | 0.59 |
| Avocado, California | 1 whole | 1.68 |
| Sweet potato (cooked) | 1 medium (1/2 cup) | 0.74 |
| Mushrooms (raw) | 1/2 cup (chopped) | 0.51 |
| Lobster (cooked) | 3 ounces | 0.24 |
| Bread, whole wheat | 1 slice | 0.16 |
Intestinal bacteria: The bacteria that normally colonize the colon (large intestine) are capable of making their own pantothenic acid. It is not yet known whether humans can absorb the pantothenic acid synthesized by their own intestinal bacteria in meaningful amounts. However, a specialized process for the uptake of biotin and pantothenic acid was recently identified in cultured cells derived from the lining of the colon, suggesting that humans may be able to absorb pantothenic acid and biotin produced by the bacteria normally present in the colon (13).
Supplements: Supplements commonly contain pantothenol, a more stable alcohol derivative, which is rapidly converted by humans to pantothenic acid. Calcium and sodium D-pantothenate, the calcium and sodium salts of pantothenic acid are also available as supplements (1).
SAFETY
Toxicity: Pantothenic acid is not known to be toxic in humans. The only adverse effect noted was diarrhea resulting from very high intakes of 10 to 20 grams/day of calcium D-pantothenate (14). Due to the lack of reports of adverse effects, the Food and Nutrition Board did not set a tolerable upper level of intake (UL) for pantothenic acid (8).
Drug interactions: Oral contraceptives (birth control pills) containing estrogen and progestin may increase the requirement for pantothenic acid (14).
THE LINUS PAULING INSTITUTE RECOMMENDATION
Little is known regarding the amount of dietary pantothenic acid required to promote optimal health or prevent chronic disease. The Linus Pauling Institute supports the recommendation by the Food and Nutrition Board of 5 milligrams (mg) of pantothenic acid/day for adults. A varied diet should provide enough pantothenic acid for most people. Following the Linus Pauling Institute recommendation to take a daily multivitamin-mineral supplement, containing 100 % of the Daily Value (DV), will ensure an intake of at least 5 mg of pantothenic acid/day.
Older adults (65 years and older): Presently there is little evidence that older adults differ in their intake or requirement for pantothenic acid. Most multivitamin/multimineral supplements provide at least 5 mg/day of pantothenic acid.
REFERENCES
1. Plesofsky-Vig, N. Pantothenic acid. In Shils, M. et al. Eds. Nutrition in Health and Disease, 9th Edition. Baltimore: Williams & Wilkins, 1999: pages 423-432.
2. Tahiliani, A.G. & Beinlich, C.J. Pantothenic acid in health and disease. Vitamins and Hormones. 1990; volume 46: pages165-228. (PubMed)
3. Brody, T. Nutritional Biochemistry. San Diego, CA: Academic Press, 1999: pages 613-617.
4. Bender, D.A. Optimum nutrition: thiamin, biotin and pantothenate. Proceedings of the Nutrition Society. 1999; volume 58: pages 427-433. (PubMed)
5. Hodges, R. E. et al. Pantothenic acid deficiency in man. Journal of Clinical Investigation. 1958; volume 37: pages 1642-1657.
6. Fry. P.C. et al. Metabolic response to a pantothenic acid deficient diet in humans. Journal of Nutrition Science and Vitaminology. 1976; volume 22: pages 339-346.
7. Plesofsky-Vig, N. Pantothenic acid. In Ziegler, E.E. & Filer, L.J. Eds. Present Knowledge in Nutrition. Washington D.C.: ILSI Press, 1996: pages 237-244.
8. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press, 1998: pages 357-373. (National Academy Press)
9. Weinmann, B.J. & Hermann, D. Studies on wound healing: effects of calcium d-pantothenate on the migration, proliferation, and protein synthesis of human dermal fibroblasts in culture. International Journal of Vitamin and Nutrition Research. 1999; volume 69: pages 113-119. (PubMed)
10. Vaxman, F. et al. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double blind, prospective randomized trial. European Surgery Research. 1995; volume 27: pages 158-166. (PubMed)
11. Gaddi, A. et al. Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia. Atherosclerosis. 1984; volume 50: pages 73-83. (PubMed)
12. Coronel, F. et al. Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance. American Journal of Nephrology. 1991; volume 11: pages 32-36. (PubMed)
13. Said, H.M. et al. Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. American Journal of Physiology. 1998; volume 275: pages C1365-C1371. (PubMed)
14. Flodin, N. Pharmacology of Micronutrients. New York, NY: Alan R. Liss, Inc., 1988: page 191.
Reviewed
by:
Nora Plesofsky, Ph.D.
College of Biological Sciences
University of Minnesota
Last updated 10/19/2000 Copyright 2000 by The Linus Pauling Institute
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