Pantothenic acid
IUPAC name 3-[(2,4-Dihydroxy-3,3-dimethylbutanoyl)amino]propanoic acid
Identifiers
CAS number	79-83-4 Y
PubChem	6613
ChemSpider	6361 Y
UNII	568ET80C3D Y
DrugBank	DB01783
KEGG	D07413 Y
ChEBI	CHEBI:46905 Y
ChEMBL	CHEMBL1594 Y
ATC code	A11HA31,D03AX04 (calcium salt)
Jmol-3D images	Image 1
SMILES O=C(NCCC(=O)O)[C@H](O)C(C)(C)CO
InChI InChI=1S/C9H17NO5/c1-9(2,5-11)7(14)8(15)10-4-3-6(12)13/h7,11,14H,3-5H2,1-2H3,(H,10,15)(H,12,13)/t7-/m0/s1 Y Key: GHOKWGTUZJEAQD-ZETCQYMHSA-N Y InChI=1/C9H17NO5/c1-9(2,5-11)7(14)8(15)10-4-3-6(12)13/h7,11,14H,3-5H2,1-2H3,(H,10,15)(H,12,13)/t7-/m0/s1 Key: GHOKWGTUZJEAQD-ZETCQYMHBS
Properties
Molecular formula	C9H17NO5
Molar mass	219.23 g mol−1
Density	1.266 g/cm³
Melting point	183.83 °C, 457 K, 363 °F
Boiling point	551.5 °C, 825 K, 1025 °F
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Pantothenic acid, also called pantothenate or vitamin B₅ (a B vitamin), is a water-soluble vitamin. 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 pantoate and beta-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.^[1] 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.

Pantothenic acid was discovered by Roger J. Williams in 1919.^[2]

Biological role[link]

Only the dextrorotatory (D) isomer of pantothenic acid possesses biologic activity.^[3] The levorotatory (L) form may antagonize the effects of the dextrorotatory isomer.^[4]

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.^[5] 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.^[6] CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine.^[6] CoA is incidentally also required in the formation of ACP,^[7] which is also required for fatty acid synthesis in addition to CoA.^[5]

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.^[8]

Since pantothenic acid participates in a wide array of key biological roles, it is essential to all forms of life.^[9] As such, deficiencies in pantothenic acid may have numerous wide-ranging effects, as discussed below.

Sources[link]

Dietary[link]

Small quantities of pantothenic acid are found in most foods.^[10] The major food source of pantothenic acid is in meats, although the concentration found in food animals' muscles is only about half that in humans' muscles. [2] Whole grains are another good source of the vitamin, but milling often removes much of the pantothenic acid, as it is found in the outer layers of whole grains.^[11] Vegetables, such as broccoli and avocados, also have an abundance of the acid.^[12] In animal feeds, the most important sources of the vitamin are rice, wheat brans, 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.^[13]

Supplementation[link]

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.^[14] 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.^[15]

Daily requirement[link]

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.^[16] 10 mg of calcium pantothenate is equivalent to 9.2 mg of pantothenic acid.

• United Kingdom RDA: 6 mg/day

Absorption[link]

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.^[16] Within the lumen of the intestine, CoA and ACP are hydrolyzed into 4'-phosphopantetheine.^[16] The 4'-phosphopantetheine is then dephosphorylated into pantetheine.^[16] Pantetheinase, an intestinal enzyme, then hydrolyzes pantetheine into free pantothenic acid.^[16]

Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system.^[6] At high levels of intake, when this mechanism is saturated, some pantothenic acid may also be absorbed via passive diffusion.^[17] As intake increases 10-fold, however, absorption rate decreases to 10%.^[6]

Deficiency[link]

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.^[6]

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.^[6] Acetylcholine synthesis is also impaired; therefore, neurological symptoms can also appear in deficiency;^[12] they include numbness, paresthesia, and muscle cramps.^[12] Deficiency in pantothenic acid can also cause hypoglycemia, or an increased sensitivity to insulin.^[6] Insulin receptors are acylated with palmitic acid when they do not want to bind with insulin.^[16] Therefore, more insulin will bind to receptors when acylation decreases, causing hypoglycemia.^[5] Additional symptoms could include restlessness, malaise, sleep disturbances, nausea, vomiting, and abdominal cramps.^[12] 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.^[9] 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.^[18]

Toxicity[link]

Toxicity of pantothenic acid is unlikely. In fact, no Tolerable Upper Level Intake (UL) has been established for the vitamin.^[16] 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.^[6] 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.^[19]

Uses[link]

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[link]

Testicular torsion can severely affect fertility if it occurs.^[20] 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.^[20] Pantothenic acid has the ability to spare reduced glutathione levels.^[21] Reactive oxygen species play a role in testicular atrophy, which glutathione counteracts.^[20]

Diabetic ulceration[link]

Foot ulceration is a problem commonly associated with diabetes, which often leads to amputation.^[22] A preliminary study completed by Abdelatif, Yakoot and Etmaan indicated that perhaps a royal jelly and panthenol ointment can help cure the ulceration.^[22] People with foot ulceration or deep tissue infection in the study had a 96% and 92% success rate of recovery.^[22] 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.^[22]

Hypolipidemic effects[link]

Pantothenic acid derivatives, panthenol, phosphopantethine and pantethine, have also been seen to improve the lipid profile in the blood and liver.^[23] In this mouse model, they injected 150 mg of the derivative/kg body weight.^[23] 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.^[23] The decrease in LDL is significant, as it is related to a decrease the risk of myocardial infarction and stroke.^[6] In the liver, panthenol was the most effective, as it lowered TG, total cholesterol, free cholesterol and cholesterol-ester levels.^[23]

Wound healing[link]

A study in 1999 showed pantothenic acid has an effect on wound healing in vitro.^[24] 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.^[24] Cell proliferation or cell multiplication was found to increase with pantothenic acid supplementation.^[24] 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.^[24] Further studies are needed to determine whether these effects will stand in vivo.

Hair care[link]

Mouse models identified skin irritation and loss of hair color as possible results of severe pantothenic acid deficiency.^[25] 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.^{[citation needed]} Despite this, many cosmetic products still advertise pantothenic acid additives. ^{[26][27][28][29][30][31]}

Acne[link]

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,^[32] 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.

Obesity[link]

In a report published in 1997 by Lit-Hung Leung,^[33] 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[link]

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.^{[citation needed]} 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.^[34]

Ruminant nutrition[link]

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 ^[35]

See also[link]

• Coenzyme A
• Panthenol
• Roger J. Williams (discoverer of pantothenic acid)
• Acyl carrier protein (ACP)

References[link]

External links[link]

• PDRhealth.com - Pantothenic acid
• Pantothenate at Klotho
• B5 chapter from Vitamin Tolerance of Animals (1987) an open book

B vitamin supplement tablets

B vitamins are a group of water-soluble vitamins that play important roles in cell metabolism. The B vitamins were once thought to be a single vitamin, referred to as vitamin B (much as people refer to vitamin C or vitamin D). Later research showed that they are chemically distinct vitamins that often coexist in the same foods. In general, supplements containing all eight are referred to as a vitamin B complex. Individual B vitamin supplements are referred to by the specific name of each vitamin (e.g., B₁, B₂, B₃ etc.).

List of B vitamins[link]

• Vitamin B₁ (thiamine)
• Vitamin B₂ (riboflavin)
• Vitamin B₃ (niacin or niacinamide)
• Vitamin B₅ (pantothenic acid)
• Vitamin B₆ (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride)
• Vitamin B₇ (biotin)
• Vitamin B₉ (folic acid)
• Vitamin B₁₂ (various cobalamins; commonly cyanocobalamin in vitamin supplements)

Health benefits[link]

The B vitamins are necessary to:

• Support and increase the rate of metabolism^{[citation needed]}
• Maintain healthy skin, hair and muscle tone^{[citation needed]}
• Enhance immune and nervous system function^{[citation needed]}
• Promote cell growth and division, including that of the red blood cells that help prevent anemia
• Reduce the risk of pancreatic cancer - one of the most lethal forms of cancer^[1] - when consumed in food, but not when ingested in vitamin tablet form.^[2][3]

All B vitamins are water-soluble, and are dispersed throughout the body. Most of the B vitamins must be replenished regularly, since any excess is excreted in the urine.^[4] This can result in the urine produced being a neon green-yellow colour.

B vitamins have also been hypothesized to reduce the symptoms of attention deficit hyperactivity disorder.^[5]

B vitamin deficiency[link]

Several named vitamin deficiency diseases may result from the lack of sufficient B-vitamins. Deficiencies of other B vitamins result in symptoms that are not part of a named deficiency disease.

B vitamin toxicity[link]

Although most B vitamins are eliminated regularly in the urine, taking large doses of certain B vitamins may produce harmful effects.

B vitamin sources[link]

B vitamins are found in whole unprocessed foods. Processed carbohydrates such as sugar and white flour tend to have lower B vitamin than their unprocessed counterparts. B vitamins are particularly concentrated in meat such as turkey and tuna, in liver and meat products.^[14] Good sources for B vitamins include kombucha, whole grains, potatoes, bananas, lentils, chili peppers, tempeh, beans, nutritional yeast, brewer's yeast, and molasses. Although the yeast used to make beer results in beers being a source of B vitamins,^[15] their bioavailability ranges from poor to negative as drinking ethanol inhibits absorption of thiamine (B₁),^[16][17] riboflavin (B₂),^[18] niacin (B₃),^[19] biotin (B₇),^[20] and folic acid (B₉).^[21][22] In addition, each of the preceding studies further emphasizes that elevated consumption of beer and other ethanol-based drinks results in a net deficit of those B vitamins and the health risks associated with such deficiencies.

The B₁₂ vitamin is of note because it is not available from plant products, making B₁₂ deficiency a concern for vegans. Manufacturers of plant-based foods will sometimes report B₁₂ content, leading to confusion about what sources yield B₁₂. The confusion arises because the standard US Pharmacopeia (USP) method for measuring the B₁₂ content does not measure the B₁₂ directly. Instead, it measures a bacterial response to the food. Chemical variants of the B₁₂ vitamin found in plant sources are active for bacteria, but cannot be used by the human body. This same phenomenon can cause significant over-reporting of B₁₂ content in other types of foods as well.^[23]

Vitamin B may also be delivered by injection to reverse deficiencies.^[24]

Another popular means of increasing one's vitamin B intake is through the use of dietary supplements. B vitamins are also commonly added to energy drinks, many of which have been marketed with large amounts of B vitamins^[25] with claims that this will cause the consumer to "sail through your day without feeling jittery or tense."^[25] Nutritionists, such as Case Western University Professor Hope Barkoukis, dismiss these claims: "It's brilliant marketing, but it doesn't have any basis [in fact]."^[25]

While B vitamins do "help unlock the energy in foods," just about everyone in America already gets all of the B vitamins they could possibly need in their diets.^{[citation needed]} In general, extra B vitamins are just flushed out of the system, although everyone's limit of absorption is different in regards to B complex vitamins, and no one knows how much is needed on an individual basis of these vitamins…"^[25] The elderly and athletes may need to supplement their intake of B₁₂ and other B vitamins due to problems in absorption and increased needs for energy production. Both type 1 and type 2 diabetics may also be advised to supplement thiamine based on high prevalence of low plasma thiamine concentration and increased thiamine clearance associated with diabetes.^[26] Also, Vitamin B₉ (folic acid) deficiency in early embryo development has been linked to neural tube defects. Thus, women planning to become pregnant are usually encouraged to increase daily dietary folic acid intake and/or take a supplement.^[27] However, for "most typical consumers of energy supplements or drinks, B vitamins are nothing more than a 'gimmick'."^[25]

Related nutrients[link]

Many of the following substances have been referred to as vitamins because they were believed to be vitamins at one time. They are not considered vitamins anymore and the numbers that were assigned to them now form the "gaps" in the true series of B-complex vitamins described above (e.g. there is no vitamin B₄). Some of them, though not essential to humans, are essential in the diets of other organisms; others have no known nutritional value and may even be toxic under certain conditions.

• Vitamin B₄: adenine, a nucleobase, is synthesized by the human body.^[28]

• Vitamin B₇: is also known as "vitamin I" of Centanni E. (1935)—also called "Enteral factor"—is a water and alcohol-soluble rice-bran factor that prevents digestive disturbance in pigeons. It governs the anatomical and functional integrity of the intestinal tract. Later found in yeast. Possible candidates for this substance are inositol, niacin (nicotinic acid), and biotin. Carnitine was also claimed to be a candidate but is not soluble in alcohol. Ref: Biochim, e terap. sper. 22:137 (April 30)1935 E. Centenni. Presse med. 51 No6 66-7 1943 R. Jacquot (on enteral B7 in Yeast) et al.
• Vitamin B₈: adenosine monophosphate, or alternately myo-inositol, is synthesized by the human body.^{[citation needed]}
• Vitamin B₁₀: para-aminobenzoic acid (PABA)
• Vitamin B₁₁: pteryl-hepta-glutamic acid—chick growth factor, which is a form of folic acid. Later found to be one of five folates necessary for humans; also known as vitamin S or factor S.
• Vitamin B₁₃: orotic acid, now known not to be a vitamin.
• Vitamin B₁₄: cell proliferant, anti-anemia, rat growth factor, and antitumor pterin phosphate named by Earl R. Norris. Isolated from human urine at 0.33ppm (later in blood), but later abandoned by him as further evidence did not confirm this. He also claimed this was not xanthopterin.
• Vitamin B₁₅: pangamic acid
• Vitamin B₁₆: dimethylglycine (DMG)
• Vitamin B₁₇: nitrilosides, amygdalin or Laetrile. These substances are found in a number of seeds, sprouts, beans, tubers, and grains. While toxic in large quantities, proponents claim that it is effective in cancer treatment and prevention despite a lack of scientific evidence.^[29]
• Vitamin B₁₈:
• Vitamin B₁₉:
• Vitamin B₂₀: carnitine
• Vitamin B₂₁:
• Vitamin B₂₂: often claimed as an ingredient of Aloe vera extracts but also in many other foods. Claimed by one source to be vitamin B₁₂b-δ.^{[citation needed]}
• Vitamin B_h: biotin
• Vitamin B_m: "mouse factor": also used to designate inositol
• Vitamin B_p: choline^{[dubious – discuss]} Choline is only required for survival of some mutants. Most commonly it is synthesized in vivo de novo.^[30] May be added as supplement especially when methionine supply is limited^[why?]

• Vitamin B_t: L-carnitine
• Vitamin B_v: a type of B₆ but not pyridoxine^{[clarification needed]}
• Vitamin B_w: a type of biotin but not d-biotin^{[clarification needed]}
• Vitamin B_x: para-aminobenzoic acid

Note: B₁₆, B₁₇, B₁₈, B₁₉, B₂₀, B₂₁ & B₂₂ do not appear to be animal factors but are claimed by some naturopaths as human therapeutic factors.^{[citation needed]}

References[link]