Vitamin B5

1.1. Sources

Pantothenic acid (also known as pantothenate) is the essential vitamin known as Vitamin B5. The origin of the name is derived from the Greek word "pantos" (meaning "everywhere") as it is not only present in the majority of food products but also a required cofactor in numerous enzymes; the molecule it produces, a coenzyme known as Coenzyme A (CoA) is ubiquitous in the human body.

Generally speaking, pantothenic acid is found in most food groups with chicken, beef, egg yolk, and organs being high sources for animal products while root vegetables (potatoes), whole grains, tomatoes, and broccoli also have a large level of pantothenic acid.^[7]

Pantothenic acid can also be found in human breast milk^[8] mostly in free form (85-90%) and some in a conjugated form (10-15%)^[9] and appears to correlate with the amount of pantothenic acid circulating in the mother at the time of providing milk.^[9]

Pantothenic acid appears to be somewhat susceptible to losses during preservation (freezing and canning) of meats and vegetables.^[10]

1.2. Biological Significance

Co-enzyme A (CoA) is required in approximately 4% of all known enzymes as a cofactor, mostly known for being involved in energy production.^[11] Dietary pantothenic acid, whether in the form of CoA itself (broken down into pantothenic acid before absorption) or as supplemental pantothenic acid, is initially converted via pantothenate kinases (PanKs) into 4'-phosphopantothenate;^[12][13] this step is the rate-limiting step of CoA synthesis and consumes ATP in the process.^[12]

Subsequently the metabolite is converted into 4'-phospho-N-pantothenoylcysteine (via phosphopantothenoylcysteine synthetase adding a cysteine molecule^[14]), into 4'-phosphopantetheine (by phosphopantothenoylcysteine decarboxylase^[15]), into dephospho-CoA (by phosphopantetheine adenylyl transferase^[16]), and finally dephospho-CoA gains a phosphorus group via dephosphocoenzyme A kinase^[17] and becomes CoA.

Pantothenic acid's major role in the human body is to be provided as a substrate that is required to form Co-enzyme A, a required cofactor for many enzymes in the human body

1.3. Recommended Intake

Pantothenic acid has an AI (adequate intake) value of:^[7]

• 1.7 mg for infants younger than six months

• 1.8 mg for infants between the ages of 6-12 months

• 2 mg for children between the ages of 1-3 years

• 3 mg for children between the ages of 4-8 years

• 4 mg for children between the ages of 9-13 years

• 5 mg for everybody above the age of 14

The AI for pantothenic acid scales with bodyweight up until adolescence until it holds steady at 5 mg for the rest of life, with the only exceptions being pregnancy and lactation where requirements are boosted slightly to 6 mg and 7 mg respectively.^[7]

1.4. Deficiency

Pantothenic acid deficiency is mostly unheard of in free-living adults due to the prevalence of this vitamin in the diet. Most studies on the topic are in vitro or in animal models of pantothenic acid deficiency.

When it comes to animals, a deficiency of pantothenic acid impairs numerous systems and organs such as fatty acid metabolism by elevating serum,^[18] hepatic, and perinephrical^[19] levels of triglycerides. A deficiency impairs the function of the adrenals^[20] and testicles resulting in impaired fertility.^[21][22]

Surprisingly, studies in young rats investigating CoA metabolism find that levels are similar between pantothenic acid deficient rats and those fed normal levels despite abnormalities to nearly all organs and slowed growth; pantothenic acid concentrations were also reduced to less than 10% in all organs except the liver where they reached 30% of normal levels.^[23] Other studies in adult rats do note decreases in CoA,^[24][25] hypothesized to be due to a resilience in this pathway in younger rats.^[23]

While it is near unheard of in humans with an even decent diet (as pantothenic acid in found in most foods), a deficiency of pantothenic acid reduces growth thought to be related to impairing the activity of CoA. While a deficiency does not appear outright fatal, most systems in the body are adversely affected

1.5. Sufficiency and Excess

There is currently no tolerable upper limit (TUL) known for pantothenic acid due to no adverse effects being reported in excessive intake.^[7]

A study using higher than normal doses have failed to find harm with 200-900 mg of pantothenic acid in humans.^[1]

1.6. Formulations and Variants

Dexpanthenol is the name for D-panthenol, the biologically active enantiomer of an alcohol analogue of pantothenic acid known as 'Panthenol' (aka. pantothenylalcohol). This form is hygroscopic similar to pantothenic acid but more stable, the increased stability being relevant when used on the skin as an external cosmetic.^[26] It does, however, convert directly into pantothenic acid^[27] and is considered to be a more stable prodrug for pantothenic acid due to being highly soluble and stable in water and alcohol solutions.^[26][28]

Dexpanthenol/D-Panthenol is a more stable form of pantothenic acid suited for cosmetic purposes

3.1. Absorption

Consuming CoA from the diet provides pantothenic acid to the body as it is hydrolyzed in the intestinal lumen into phosphopantetheine, pantetheine, and subsequently pantothenate.^[29]

Panthothenic acid can be absorbed in both the small and large intestines via the sodium-dependent multivitamin transporter (SMVT), similar to biotin and can compete for absorption with an K_i of 14.4μM^[30][31] which appears to be wholly responsible for panthothenic acid uptake as knocking the gene out in mice (via siRNA) ablates uptake of the vitamin.^[32][33] The rate of uptake in all three segments of the small intestine seems similar in the rat.^[29]

There is bacteria in the large intestine that is able to produce panthothenic acid.^[34] When dividing the gut biome into enterotypes (clusters of similarly acting bacteria^[35]) enterotype 1 appears to contain many enzymes capable of synthesizing pantothenic acid (as well as biotin, Vitamin C, and Riboflavin).^[35]

3.2. Distribution

In rats given either pantothenic acid restricted diets or sufficient diets, higher fat intakes (20% rather than 5%) and exercise both appear to reduce the amount of pantothenic acid detected in plasma and muscle tissue when compared to their controls; suggesting a higher intake required if either of these two variables are present.^[36]

3.3. Drug-Drug Interactions

It has been reported that pantothenic acid does not appear to have many interactions with pharmaceuticals^[7] and high doses of oral contraceptives have been found to not interact with pantothenic acid status in young women.^[37]

4.1. Neuropharmacology

Pantothenic acid exists at higher concentrations in the brain relative to plasma, being about 50-fold higher and almost exclusively due to the sodium dependent multivitamin transporter (SLC5A6) which accounted for 98.6% of uptake in cells of the blood brain barrier in vitro.^[38] The pantothenic acid that exists in cerebrospinal fluid and brain plasma is usually intact (neither metabolized nor conjugated)^[39] and even within neuron cells where it accumulates a large amount remains unmetabolized rather than forming CoA or phorphorylated metabolites.^[40] While SLC5A6 is known to be inhibited by many compounds in vitro such as medium chain triglycerides, a deficiency of pantothenic acid in the brain appears highly unlikely due to these high levels.^[41][42]

Due to being the substrate which eventually produces CoA, pantothenic acid serves its role in the brain in assisting the synthesis of various neurotransmitters.^[42]

5.1. Mechanisms

Pantothenic acid has been investigated for its role in sports performance since it is required for the production of Coenzyme A (CoA), which among other things is required to transport fatty acyls (via the conjugated fatty acyl-CoA) to the mitochondria so fats can be used for energy production and is used at many other points in the energy production cycle.^[43] A study investigating the role of pantothenic acid in exercise^[6] notes that other studies^[44][45] suggest that reduced availability of free CoA to be used in the above processes may be a rate limiting step in fat oxidation during exercise.

Supplementation of both L-cysteine (1,500 mg; thought to buffer decreases in CoA during exercise^[46]) and pantothenic acid (1,500 mg) in recreationally active men for one week failed to affect levels of free CoA, respiratory exchange ratios, and performance when participants were subject to a cycling test.^[6]

6.1. Lipid Peroxidation

When tested in vitro, pantothenic acid and a few variants (sodium and calcium pantothenate, phosphopantothenate, pantothenol, and pantethine) had minor antioxidant effects against lipid peroxidation.^[47]

7.1. Liver

In a mouse model of nonalcoholic fatty liver disease (NAFLD), a disease state where production of Coenzyme A (CoA) is impaired leading to complications, supplementation of both N-Acetylcysteine and pantothenic acid (both at 250mg/kg) failed to improve the rate-limiting step of CoA production and failed to improve complications of NAFLD.^[48]

8.1. Skin

It has been hypothesized that pantothenic acid deficiency could be related to acne.^[49]

It was initially found that, in an eight week trial using a supplement which contains pantothenic acid (Panthogen; containing 2,200 mg pantothenic acid, 733.3 mg L-carnitine, and other B-vitamins in two divided doses) found benefits to skin health of which less acne was noted^[3] and later the same formulation was found (in subjects with mild to moderate blemishes) to reduce facial lesions by 68.21% with an improvement in quality of life (assessed by DLQI) over the course of 12 weeks when taken orally.^[4]

Panthothenic acid may be able to reduce acne, but current studies only use formulations that are highly confounded with the other B-vitamins and L-carnitine. The role of panthothenic acid alone is not yet known

In humans who underwent tattoo removal surgery who were given both Vitamin C and pantothenic acid, supplementation of these two (1-3 g and 0.2-0.9 g respectively; no placebo control) for 21 days after surgery appeared to benefit the strength of the skin in the group given the higher doses;^[1] the energy required to break scar tissue was greater (indicative of stronger tissue) and, while both groups showed beneficial changes in scar content of magnesium, manganese (increases) and iron (a decrease) both groups had significant increases relative to baseline with the higher doses having a faster rate.^[1] The effort required to break scar tissue has previously been associated with the changes in the content of these minerals within the scar^[2] and the overall count of fibroblasts and hydroxyproline content appeared to increase when compared to placebo.^[2]

Supplementation of pantothenic acid (and Vitamin C) appears to improve some aspects of scarring, but a direct increase in the time required to heal a scar has not yet been found

Dexpanthenol (D-Panthenol)

found that 2.5% dexpanthenol (with 6% borage oil) improved stratum corneum hydration without effect on transepidermal water loss (TEWL); borage oil alone was also effective but to a lesser degree than the combination.^[26] When tested without an oil carrier, both 1% and 2.5% dexpanthenol appear to improve stratum corneum hydration while reducing TEWL relative to control.^[26]

When irritation or skin abnormalities are considered a factor, dexpanthenol has been found to be beneficial in reducing inflammation and helping the rate of repair of the skin following irritation from sodium lauryl sulphate^[50] and had been noted (in a correspondence) to be of aid cheilitis associated with isotretinoin (form of Vitamin A) in the form of a 5% dexpanthenol cream.^[51]

8.2. Hair

Pantothenic acid has been long linked to hair health (dating back to at least 1946). It was known that a deficiency of pantothenic acid in rats caused graying of the hair and a connection between the two, among other topics such as hormonal and adrenal factors, was questioned.^[52] The only relatively modern evidence for pantothenic acid on hair health involves one study confounded with numerous other components (caffeine, Niacin, dimethicone and an acrylate polymer) and used neither an oral nor shampoo delivery method.^[5]

Elimination of pantothenic acid in the urine doesn't seem to differ between control subjects and those with graying hair (achromotrichia) or hair loss (alopecia), suggesting increased elimination may not be leading to a deficiency state that impairs hair health.^[53]

Despite being known as a hair health supplement, there is a stark lack of evidence conducted in the past half-century on the topic and only a few small trials conducted around 1950; many of which cannot be located online

9.1. Ethanol

Alcohol (ethanol) is generally known to impair absorption of numerous vitamins and minerals during excessive intake (ie. alcoholism) due to its effects on the intestines and liver, hindering absorption and storage of many vitamins and minerals respectively.

In rats given 15% ethanol in their diets, pantothenic acid levels did not appear to decrease in the liver after a month of ethanol ingestion when the level of pantothenic acid in the diet was sufficient. When the diet lacked this vitamin, however, ethanol was able to reduce not only pantothenic acid but that of thiamine, riboflavin, and pyridoxine.^[54] This may be related to the effects of ethanol on the liver itself as, according to a rat study, administering ethanol to the liver causes release of pantothenic acid^[55] and its presence may impair the ability of pantothenic acid to convert into CoA.^[56]