Pantothenic Acid

Pantothenic acid, also known as vitamin B5, 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.

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.

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, 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. 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. 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. 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. 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.

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. 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.

The Adequate Intake (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.

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. 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.

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), pantethine is closer to CoA than pantothenic acid, and is the functional component of CoA and acyl carrier proteins. 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. 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. 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.

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.

Supplements

Pantothenic acid

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.

Pantethine

Although it is used as a cholesterol-lowering agent in Europe and Japan, pantethine is available in the U.S. as a dietary supplement.

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. However, there is one case report of life-threatening eosinophilic pleuropericardial effusion in an elderly woman who took a combination of 10 mg/day of biotin and 300 mg/day of pantothenic acid for two months. Due to the lack of reports of adverse effects when the Dietary Reference Intakes (DRI) for pantothenic acid were established in 1998, the Food and Nutrition Board of the Institute of Medicine did not establish a tolerable upper level of intake (UL) for pantothenic acid. Pantethine is generally well tolerated in doses up to 1,200 mg/day. However gastrointestinal side effects like nausea and heartburn have been reported.

Drug interactions

Oral contraceptives (birth control pills) containing estrogen and progestin may increase the requirement for pantothenic acid. Use of pantethine in combination with HMG-CoA reductase inhibitors (statins) or nicotinic acid may produce additive effects on blood lipids.

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 mg/day of pantothenic acid 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/day of pantothenic acid.

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.

Reference: http://lpi.oregonstate.edu/infocenter/vitamins/pa/