The water-soluble vitamin B5 (pantothenic acid) is an essential nutrient belongs to B vitamin family.
Its name is derived from the Greek pantothen (πάντοθεν) meaning "from everywhere" and small quantities of pantothenic acid are found almost in every food.
The molecular formula is C9H17NO5 and it is the amide between D-pantoate and beta-alanine; its IUPAC name is 3-[(2,4-dihydroxy-3,3-dimethylbutanoyl)amino]propanoic acid.
Figure 1 pantothenic acid structure
As already mentioned, the pantothenic acid can be found almost in every food; good sources of the vitamin (>1 mg/serving) include oranges, bananas, lobsters, poultry, soybeans, lentils, split peas, yogurt, egg, cheese, clam, artchoke, avocado, mushroom, broccoli, cauliflowers, carrots, potatoes, sweet potatoes, but the best source is surely the meat.
Whole grains also contain good quantity of B5 vitamin, but milling often removes much of the pantothenic acid that is contained in the outer layers of these cereals.
The most significant sources of pantothenic acid in nature are coldwater fish ovaries and royal jelly 1
Pantothenic acid is synthesised by intestinal micro-organisms 2 , but the extent and significance of this enteral synthesis is unknown.
Pantothenic acid can also be produced sintetically 3
It is widely agreed that there is insufficient information available on which to base an RDA for pantothenic acid.
Most countries that make recommendations therefore give an estimate of safe and adequate levels for daily intake. These adequate intake levels (AI) are based on estimated dietary intakes in healthy population groups and range, depending on the health authority concerned, from 2 to 14 mg/day for adults (10 mg for U.S.A., 6 mg for U.K.)
Pantothenate 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.
In the “Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline” (1998), the National Academy of Sciences. Institute of Medicine, Food and Nutrition Board, (USA) commended the follow AI:
0-6 months: 1,7 mg/day
7-12 months: 1,8 mg/day
1-3 years: 2 mg/day
4-8 years: 3 mg/day
9-13 years: 4 mg/day
14-18 years: 5 mg/day
19-50 years: 5 mg/day
51-70 years: 5 mg/day
>70 years: 5 mg/day
In pregnancy (14-50 years): 6 mg/day
In lactation (14-50 years): 7 mg/day
Absorption and excretion
Approximately 85% of pantothenic acid (PA) is found in many foods as CoA, which is an essential constituent, or Acyl Carrier Protein (ACP), an important component in both fatty acid and polyketide biosynthesis.
Figure 2 ACP structure
Figure 3 Co-enzyme A structure
After being introduced into the body through the diet, this vitamin to be adsorbed by intestinal cells must be converted into free pantothenic acid.
Enterocytes then absorb pantothenic acid using a saturable sodium-dependent active transport system. Studies in Caco-2 cells have shown that a sodium-dependent carrier-mediated transport mechanism, shared by both biotin and pantothenic acid, is present at the apical membrane of these cells. Absorbed pantothenic acid is transported to body tissues via the blood, primarily as bound forms in erythrocytes .
The kidney and gastrointestinal tract, working together, keep the plasma levels of PA relatively constant.
Toxicity of pantothenic acid is unlikely. Pantothenic acid is generally considered as safe, even at extremely high doses, as excesses of the compound are mostly excreted in the urine, rather than being stored in the tissues. Very high oral doses of pantothenic acid compounds have been associated with diarrhea and gastrointestinal disturbances.
There are also no adverse reactions known following parenteral or topical application of this vitamin. However, a large dosis of vitamin B5 (e.g: 5 - 9 gram) is known to cause nausea and a lack of fatigue.
Blood pantothenic acid levels have been reported to be low in patients with rheumatoid arthritis , and some reports suggest beneficial effects of supplementation in these subjects, as well as in patients with lupus erythematosus
Only the dextrorotatory isomer (D) of pantothenic acid has biologic activity, while the levorotatory one (L) may antagonize the D isomer’s effects.
Pantothenic acid is a precursor of coenzyme A (CoA), a coenzyme important for its role in the synthesis of fatty acids , cholesterol , and acetylcholine and in the oxidation of pyruvate in the citric acid cycle ( Krebs cycle )
The syntesis of CoA from pantothenate is regulated primarily by pantothenate kinasi, an enzyme that is inhibited by the pathway end products, CoA and acylCoA
The coenzyme A permits the transportation of carbon atoms into the cells because acts as an acyl group carrier to form acetyl-CoA .
As a consequence, pantothenic acid is involved in more than 100 different metabolic pathways including energy metabolism of carbohydrates , proteins and lipids , and the synthesis of lipids, neurotransmitters , steroid hormones , porphyrins and hemoglobin .
Pantothenic acid, as CoA, could also be required for acylation and acetylation , two essential mechanism for signal transduction and enzyme activation/deactivation.
Having the pantothenic acid these basic roles in many important byological activities, it is essential to all forms of life.
CoA in the diet is hydrolyzed in the intestinal lumen to dephosphoCoA, phosphopantetheine and pantetheine, with the pantetheine subsequently hydrolysed to pantothenic acid.
Absorption is by active transport at low concentration of the vitamin and by passive transport in higher concentration in animal models.
The pantothenic acid is excreted intact in urine, where it can be measured by using a Lactobacillus plantarum assay or a radioimmunoassay ; the ammount excreted varies proportionally with dietary intake.
Linus Pauling Institute - Micronutrient Research for Optimum Health
Deficiency of pantothenic acid in humans is extremely rare. Few examples of these deficiencies can be attributed to the victims of starvation and volunteers of the trials. Experimentally, pantothenic acid deficiency has been induced in human subjects by feeding diets virtually devoid of the vitamin or by the administration of a metabolic antagonist. Signs and symptoms exhibited by subjects given these tests included irritability and restlessness , fatigue(medical) , apathy , malaise , sleep disturbances, gastrointestinal complaints such as nausea, vomiting and abdominal cramps, neurobiological symptoms such as numbness , parasthesias , muscle cramps and staggering gait . 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. These symptoms are similar to other vitamin B deficiencies and deficiency of pantothenic acid may explain similar sensations reported in malnourished prisoners of war.
Pantothenic acid, after entry into cells and phosphorylation by pantothenate kinase PANK, the rate-limiting step, is then converted via a series of intermediates to coenzyme A in all tissues. This enzyme plays a role in the physiological regulation of the intracellular CoA concentration, it phophorylates pantothenate to form 4'-phosphopantothenate in the presence of ATP. PA isoform 1 is expressed at high levels in brain, heart, kidney, liver, skeletal muscle and testis. Isoform 2 is detected at much lower levels in kidney, liver, brain and testis and is not detected in heart or skeletal muscle.
A mutation in the gene for pantothenate kinase 2 PANK2 induces a very rare childhood neurodegenerative disorder, Pantothenate kinase-associated neurodegeneration PKAN, long known as Hallervorden-Spatz syndrome HSS, that is associated with the accumulation of iron in the brain, which causes progressively worsening abnormal movements and dementia.
OMIM – ONLINE MENDELIAN INHERITANCE in MAN
PANK2 - COASY - PPCDC - PPCS
Trials and clinical uses
The pantothenic acid and its derivates’s actions were subject of many studies; the first articles go back to the middle of 20th century.
Its most important demonstrated roles are the following:
Hypolipidemic effect: an experiment shows that serum triglycerides and free fatty acids levels were significantly elevated in mild pantothenate deficiency in rats (Mild Pantothenate Deficiency in Rats Elevates Serum Triglyceride and Free Fatty Acid Levels, Wittwer C.T.,1990).
A more recent study demonstrates the hypolipidemic effect of pantothenic acid derivatives (panthenol, phosphopantethine and pantethine) in liver and blood of mices with induced hypothalamic obesity (Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose. Naruta E, Buko V. 2001) ; in this animal model, all three derivatives were able to effectively lower low-density lipoprotein (LDL) as well as triglyceride levels.
Futrher, pantethine has beneficial effects in vascular disease, it able to decrease the hyperlipidaemia, moderate the platelet function and prevent the lipid-peroxidation (Current medical aspects of pantethine. Horváth Z, Vécsei L., 2009).
Acne: in 1995 Dr. Leung LH suggested a radically different theory for acne pathogenesis and related its basic pathology to a deficiency in pantothenic acid (Pantothenic acid deficiency as the pathogenesis of acne vulgaris. Leung LH., 1995).
He shown that 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.
Testicular funcion and sperm motility: a study conduced on male rats (Effects of pantothenic acid on testicular function in male rats. Yamamoto T. et al., 2009) clearly demonstrates that pantothenic acid is an essential factor in testicular endocrinology and sperm motility.
Testicular torsion: this is a pathology that can severely affect fertility.One study (The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Etensel B, 2007) on a rat model indicates that a treatment with provitamin B5 (dexpanthenol) in a dosage of 500mg /kg body weight 30 minutes prior to detorsion can greatly decrease the risk of infertility because pantothenic acid has the ability to avoid reduction of glutathione levels and this one can destroy reactive oxygen species that play a role in testicular atrophy.
Antitumor effect: in this in vitro experiment the antitumor properties of pantothenic acid against radiation-induced tumor were demonstrate in E. coli. (Radiation-induced antitumor properties of vitamin B5 and its effect on mitomycin C activity: experiments in vitro. Schittl H, Getoff N.,2007).
Wound healing: in 1988 Lacroix et al. shown that when cell cultures were incubated with pantothenic acid and ascorbic acid, the release of intracellular protein into the culture medium increases. This result suggests that the combined use of these two vitamins might be of interest in postsurgical therapy and in wound healing (Role of pantothenic and ascorbic acid in wound healing processes: in vitro study on fibroblasts. Lacroix B., 1988).
This vitamin B5’s ability cuold underlie the efficacy of a new ointment, prepared from natural royal jelly and panthenol, in the treatment of patients with limb-threatening diabetic foot infections, efficacy analyzed in a recent prospective pilot study (Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. Abdelatif M, 2008).
Adrenal steroid secretion: this experiment demonstrates that in male rats pantothenic acid supplementation stimulates the ability of adrenal cells to secrete corticosterone and progesterone ; furthermore, this vitamin induces hyperresponsiveness to ACTH stimulation (Effects of Pantothenic Acid Supplementation on Adrenal Steroid Secretion from Male Rats. Jaroenporn S. et al., 2007).
Sodium lauryl sulphate-induced irritation: treatment with a dexpanthenol-containing cream showed significantly enhanced skin barrier repair and stratum corneum hydration, while reducing skin roughness and inflammation after sodium lauryl sulphate (SLS) -induced irritation (Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation. Proksch E, Nissen HP., 2002).