Pantothenic acid, also called pantothenate or vitamin B5 (a B vitamin), is a water-soluble vitamin discovered by Roger J. Williams in 1919. For many animals, pantothenic acid is an essential nutrient. Animals require pantothenic acid to synthesize coenzyme-A (CoA), as well as to synthesize and metabolize proteins, carbohydrates, and fats.
Pantothenic acid is the amide between pantoic acid and β-alanine. Its name derives from the Greek pantothen (πάντοθεν) meaning “from everywhere” and small quantities of pantothenic acid are found in nearly every food, with high amounts in whole-grain cereals, legumes, eggs, meat, royal jelly, avocado, and yogurt. It is commonly found as its alcohol analog, the provitamin panthenol, and as calcium pantothenate. Pantothenic acid is an ingredient in some hair and skin care products.
|CAS number||599-54-2, 79-83-4 R|
|PubChem||988, 6613 R, 5748353 S|
|ChemSpider||963 , 6361 R , 4677898 S|
|Beilstein Reference||1727062, 1727064 R|
|Jmol-3D images||Image 1
|Molar mass||219.23 g mol−1|
|Density||1.266 g mL−1|
|Melting point||183.83 °C, 457 K, 363 °F|
|Boiling point||551.5 °C, 825 K, 1025 °F|
|Related alkanoic acids|
Only the dextrorotatory (D) isomer of pantothenic acid possesses biologic activity. The levorotatory (L) form may antagonize the effects of the dextrorotatory isomer.
Pantothenic acid is used in the synthesis of coenzyme A (CoA). Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. CoA is important in energy metabolism for pyruvate to enter the tricarboxylic acid cycle (TCA cycle) as acetyl-CoA, and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine. CoA is incidentally also required in the formation of ACP, which is also required for fatty acid synthesis in addition to CoA.
Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively.
Since pantothenic acid participates in a wide array of key biological roles, it is essential to all forms of life. As such, deficiencies in pantothenic acid may have numerous wide-ranging effects, as discussed below.
Small quantities of pantothenic acid are found in most foods. The major food source of pantothenic acid is meat. The concentration found in animal muscle is about half that in human muscle. Whole grains are another good source of the vitamin, but milling removes much of the pantothenic acid, as it is found in the outer layers of whole grains. Vegetables, such as broccoli and avocados, also have an abundance. In animal feeds, the most important sources are rice, wheat bran, cereal, alfalfa, peanut meal, molasses, yeasts, and condensed fish solutions. The most significant sources of pantothenic acid in nature are coldwater fish ovaries and royal jelly.
The derivative of pantothenic acid, pantothenol, is a more stable form of the vitamin and is often used as a source of the vitamin in multivitamin supplements. Another common supplemental form of the vitamin is calcium pantothenate. Calcium pantothenate is often used in dietary supplements because, as a salt, it is more stable than pantothenic acid in the digestive tract, allowing for better absorption.
Possible benefits of supplementation: Doses of 2 g/day of calcium pantothenate may reduce the duration of morning stiffness, degree of disability, and pain severity in rheumatoid arthritis patients. Although the results are inconsistent, supplementation may improve oxygen utilization efficiency and reduce lactic acid accumulation in athletes.
Pantothenate in the form of 4’phosphopantetheine is considered to be the more active form of the vitamin in the body; however, any derivative must be broken down to pantothenic acid before absorption. 10 mg of calcium pantothenate is equivalent to 9.2 mg of pantothenic acid.
|Infants||0–6 months||1.7 mg|
|Infants||7–12 months||1.8 mg|
|Children||1–3 years||2 mg|
|Children||4–8 years||3 mg|
|Children||9–13 years||4 mg|
|Adult men and women||14+ years||5 mg|
|Pregnant women||(vs. 5)||6 mg|
|Breastfeeding women||(vs. 5)||7 mg|
- United Kingdom RDA: 6 mg/day
When found in foods, most pantothenic acid is in the form of CoA or acyl carrier protein (ACP). For the intestinal cells to absorb this vitamin, it must be converted into free pantothenic acid. Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4′-phosphopantetheine. The 4′-phosphopantetheine is then dephosphorylated into pantetheine. Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid.
Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system. At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be absorbed via passive diffusion. As intake increases 10-fold, however, absorption rate decreases to 10%.
Pantothenic acid deficiency is exceptionally rare and has not been thoroughly studied. In the few cases where deficiency has been seen (victims of starvation and limited volunteer trials), nearly all symptoms can be reversed with the return of pantothenic acid.
Symptoms of deficiency are similar to other vitamin B deficiencies. There is impaired energy production, due to low CoA levels, which could cause symptoms of irritability, fatigue, and apathy. Acetylcholine synthesis is also impaired; therefore, neurological symptoms can also appear in deficiency; they include numbness, paresthesia, and muscle cramps. Deficiency in pantothenic acid can also cause hypoglycemia, or an increased sensitivity to insulin. Insulin receptors are acylated with palmitic acid when they do not want to bind with insulin. Therefore, more insulin will bind to receptors when acylation decreases, causing hypoglycemia Additional symptoms could include restlessness, malaise, sleep disturbances, nausea, vomiting, and abdominal cramps. In a few rare circumstances, more serious (but reversible) conditions have been seen, such as adrenal insufficiency and hepatic encephalopathy.
One study noted painful burning sensations of the feet were reported in tests conducted on volunteers. Deficiency of pantothenic acid may explain similar sensations reported in malnourished prisoners of war.
Deficiency symptoms in other nonruminant animals include disorders of the nervous, gastrointestinal, and immune systems, reduced growth rate, decreased food intake, skin lesions and changes in hair coat, and alterations in lipid and carbohydrate metabolism.
Toxicity of pantothenic acid is unlikely. In fact, no Tolerable Upper Level Intake (UL) has been established for the vitamin. Large doses of the vitamin, when ingested, have no reported side effects and massive doses (e.g., 10 g/day) may only yield mild intestinal distress, and diarrhea at worst. It has been suggested, however, that high doses of pantothenic acid might worsen panic attacks in those with panic disorder by prolonging the duration until adrenal exhaustion.
There are also no adverse reactions known following parenteral or topical application of the vitamin.
Given pantothenic acid’s prevalence among living things and the limited body of studies in deficiency, many uses of pantothenic acid have been the subject of research.
Testicular torsion can severely affect fertility if it occurs. One study on a rat model indicated a treatment of 500 mg of dexpanthenol/kg body weight 30 minutes prior to detorsion can greatly decrease the risk of infertility after torsion. Pantothenic acid has the ability to spare reduced glutathione levels. Reactive oxygen species play a role in testicular atrophy, which glutathione counteracts.
Foot ulceration is a problem commonly associated with diabetes, which often leads to amputation.A preliminary study completed by Abdelatif, Yakoot and Etmaan indicated that perhaps a royal jelly and panthenol ointment can help cure the ulceration. People with foot ulceration or deep tissue infection in the study had a 96% and 92% success rate of recovery. While these results appear promising, they need to be validated, as this was a pilot study; it was not a randomized, placebo-controlled, double-blind study.
Pantothenic acid derivatives, panthenol, phosphopantethine and pantethine, have also been seen to improve the lipid profile in the blood and liver. In this mouse model, they injected 150 mg of the derivative/kg body weight. All three derivatives were able to effectively lower low-density lipoprotein (LDL), as well as triglyceride (TG) levels; panthenol was able to lower total cholesterol, and pantethine was able to lower LDL-cholesterol in the serum. The decrease in LDL is significant, as it is related to a decrease the risk of myocardial infarction and stroke. In the liver, panthenol was the most effective, as it lowered TG, total cholesterol, free cholesterol and cholesterol-ester levels.
A study in 1999 showed pantothenic acid has an effect on wound healing in vitro. Wiemann and Hermann found cell cultures with a concentration of 100 μg/mL calcium D-pantothenate increased migration, and the fibers ran directionally with several layers, whereas the cell cultures without pantothenic acid healed in no orderly motion, and with fewer layers. Cell proliferation or cell multiplication was found to increase with pantothenic acid supplementation. Finally, increased concentrations of two proteins, both of which have yet to be identified, were found in the supplemented culture, but not in the control. Further studies are needed to determine whether these effects will stand in vivo.
Mouse models identified skin irritation and loss of hair color as possible results of severe pantothenic acid deficiency. As a result, the cosmetic industry began adding pantothenic acid to various cosmetic products, including shampoo. These products, however, showed no benefits in human trials. Despite this, many cosmetic products still advertise pantothenic acid additives.
Following from discoveries in mouse trials, in the late 1990s, a small study was published promoting the use of pantothenic acid to treat acne vulgaris.
According to a study published in 1995 by Dr. Lit-Hung Leung, high doses of vitamin B5 resolved acne and decreased pore size. Dr. Leung also proposed a mechanism, stating that CoA regulates both hormones and fatty acids, and without sufficient quantities of pantothenic acid, CoA will preferentially produce androgens. This causes fatty acids to build up and be excreted through sebaceous glands, causing acne. Leung’s study gave 45 Asian males and 55 Asian females varying doses of 10–20g of pantothenic acid (100000% of the US Daily Value), 80% orally and 20% through topical cream. Leung noted improvement of acne within one week to one month of the start of the treatment.
In a report published in 1997 by Lit-Hung Leung, it was hypothesized that pantothenic acid also has an effect on weight management. Leung proposed that those who were deficient in pantothenic acid would feel the effects of hunger and weakness more strongly. To access fat storages in the body in times of fasting or dieting requires CoA. Diets high in pantothenic acid produce more CoA. In a study done on 100 Chinese individuals from age range 15–55 it was observed that on a diet of 1000 calories a day and 10 g pantothenic acid, the dieters could lose on average 1.2 kg/week with lessened effects from hunger or weakness. Ketone bodies in urine indicated that some dieters required more than 10 g of pantothenic acid a day. The possibilities of pantothenic acid in weight management have not been fully explored, but remain an area of research.
Diabetic peripheral polyneuropathy
Twenty-eight out of 33 patients (84.8%) previously treated with alpha-lipoic acid for peripheral polyneuropathy reported further improvement after combination with pantothenic acid. The theoretical basis for this is that both substances intervene at different sites in pyruvate metabolism and are, thus, more effective than one substance alone. Additional clinical findings indicated diabetic neuropathy may occur in association with a latent prediabetic metabolic disturbance, and that the symptoms of neuropathy can be favorably influenced by the described combination therapy, even in poorly controlled diabetes.
Cholesterol and Triglyceride
Pantothenic acid was originally studied on rats. Studies showed that those fed a diet with less pantothenic acid were more likely to have higher cholesterol. Pantethine, a more active form of pantothenic acid, has been used to lower cholesterol and triglyceride levels. Clinical trials have shown that taking pantethine can lower cholesterol by 19% and triglyceride levels by 32%. Although not all studies agree, pantethine has also been shown to raise high-density lipoprotein cholesterol (often referred to as “good” cholesterol).
No dietary requirement for pantothenic acid has been established as synthesis of pantothenic acid by ruminal microorganisms appears to be 20 to 30 times more than dietary amounts. Net microbial synthesis of pantothenic acid in the rumen of steer calves has been estimated to be 2.2 mg/kg of digestible organic matter consumed per day. The degradation of dietary intake of pantothenic acid is considered to be 78 percent. Supplementation of pantothenic acid at 5 to 10 times theoretic requirements did not improve performance of feedlot cattle.