Human Pantothenic Acid Deficiency The Burning Foot Syndrome

In the 1940s, prisoners of war in the Far East who were severely malnourished showed, among other signs and symptoms of vitamin deficiency diseases, a new condition of paresthesia and severe pain in the feet and toes, which was called the burning foot syndrome or nutritional melalgia. Although it was tentatively attributed to pantothenic acid deficiency, no specific trials of pantothenic acid were conducted; rather the subjects were given yeast extract and other rich sources of all vitamins as part of an urgent program of nutritional rehabilitation. There seem to be no reports of neurological damage in deficient animals which may explain the burning foot syndrome.

Experimental pantothenic acid depletion, sometimes together with the administration of «-methyl pantothenic acid, results in the following signs and symptoms alter 2 to 3 weeks:

1. Neuromotor disorders, including paresthesia of the hands and feet, hyperactive deep tendon reflexes and muscle weakness. These can be explained by the role of acetyl CoA in the synthesis of the neurotransmit-ter acetylcholine and the impaired formation of threonine acyl esters in myelin. Dysmyelination may explain the persistence and recurrence of neurological problems many years after nutritional rehabilitation in people who had suffered from burning foot syndrome.

2. Mental depression, which again may be related to either acetylcholine deficit or impaired myelin synthesis.

3. Gastrointestinal complaints, including severe vomiting and pain, with depressed gastric acid secretion in response to insulin and gastrin. As with the development of ulcers in deficient animals, this may reflect hypersensitivity to glucocorticoid stimulation.

4. Increased insulin sensitivity and a flattened glucose tolerance curve, which may reflect decreased antagonism by glucocorticoids.

5. Decreased serum cholesterol and decreased urinary excretion of 17-ketosteroids, reflecting the impairment of steroidogenesis.

6. Decreased acetylation of p-aminobenzoic acid, sulfonamides, and other drugs, thus reflecting reduced availability of acetyl CoA for these reactions.

7. Increased susceptibility to upper respiratory tract infections, which presumably reflects the impairment of immune responses.


Urinary excretion of pantothenic acid mirrors intake, albeit with wide range of individual variation, and may provide a means of assessing status. Urinary excretion of less than 1 mg (4.5 ^mol) of pantothenic acid per 24 hours is considered to be abnormally low (Sauberlich et al., 1974).

Sauberlich(1974) suggested that a whole blood totalpantothenicacidbelow 4.5 ^mol per L was indicative of inadequate intake. However, few studies have reported mean blood concentrations of pantothenic acid as high as 4.5 ^mol per L in normal subjects. Eissenstat and coworkers (1986) showed that serum or plasma free pantothenic acid was not a good index of nutritional status.

There are no functional tests of pantothenic acid nutritional status that are generally applicable. Deficiency of pantothenic acid impairs the ability to acetylate a variety of drugs, such as p-aminobenzoic acid, but this has not been developed as an index of vitamin status. The capacity to acetylate drugs is genetically determined; neither experimental pantothenate deficiency nor the administration of supplements affects the determination of fast or slow acetylator status (Pietrzik et al., 1975; Vas et al., 1990).


From the limited studies thathave beenperformeditis notpossible to establish requirements for pantothenic acid. Average intakes are between 2 to 7 mg per day. This is obviously adequate, because, as discussed previously, deficiency is unknown under normal conditions. The U.S./Canadian adequate intake for adults is 5 mg per day (Institute of Medicine, 1998).


Fibroblasts in culture undergo faster proliferation and migration when the concentration of pantothenic acid is high, and this has led to the topical use of pantothenol in skin disorders and wound healing. There is no evidence that oral supplements have any effect on wound healing (Vaxmanetal., 1995,1996; Egger et al., 1999; Weimann and Hermann, 1999; Ebner et al., 2002).

Some of the side effects of valproate administration to young children to control seizures (ketosis and liver damage) are associated with sequestration of CoA as valproyl CoA, which is poorly metabolized, and the administration of pantothenate supplements (generally together with carnitine; Section 14.1) prevents depletion of CoA and reduces the risk of liver damage (Thurston and Hauhart, 1992). In the same way, pantothenate supplements protect mice against neural tube defects caused by valproate (Sato et al., 1995).

Homopantothenic acid (pantoyl-GABA or hopanthate; see Figure 12.1) has been reported to enhance cholinergic function in the central nervous system. It seems to act by binding to GABA receptors and stimulating the release of acetylcholine in the cerebral cortex and hippocampus, rather than by any direct effect on acetylcholine synthesis or cholinergic receptors. It appears to have some beneficial effect in Alzheimer's disease, reducing loss of memory and cognitive impairment in some patients (Nakahiro et al., 1985).

Pantothenic acid seems to have very low toxicity. Intakes of up to 10 g of calcium pantothenate per day (compared with a normal dietary intake of 2 to 7 mg per day) have been given for up to 6 weeks, with no apparent ill effects.


Begley TP, Kinsland C, and Strauss E (2001) The biosynthesis of coenzyme A in bacteria. Vitamins and Hormones 61, 157-71. Plesofsky-Vig N and Brambl R (1988) Pantothenic acid and coenzyme A in cellular modification of proteins. Annual Reviews of Nutrition 8, 461-82. Tahiliani AG and Beinlich CJ (1991) Pantothenic acid in health and disease. Vitamins and Hormones 46, 165-228.

References cited in the text are listed in the Bibliography.


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