Continuing Education Activity

Vitamin B5, also known as pantothenic acid, is a water-soluble nutrient necessary for various metabolic functions within the body. This essential vitamin participates in energy generation, synthesizing hormones, and maintaining optimal conditions for skin, hair, and nails. Supplemental vitamin B5 is employed to address and mitigate nutrient deficiencies. This activity discusses the mechanisms of action, adverse event profile, off-label applications, appropriate dosing strategies, pharmacodynamics, pharmacokinetics, monitoring procedures, and relevant interactions of vitamin B5. Participants gain insights and knowledge essential for managing cases involving nutritional deficiencies and related conditions.

Objectives:

• Identify sources of vitamin B5 (pantothenic acid) in various food sources and dietary supplements.

• Screen patients for potential vitamin B5 deficiency based on their medical history, symptoms, and laboratory tests.

• Implement appropriate strategies for vitamin B5 supplementation in patients with confirmed deficiency or inadequate intake.

• Develop communication with patients about the importance of adequate vitamin B5 intake and incorporating food sources rich in this vitamin into their diet.

Indications

Vitamin B5 (pantothenic acid) is a naturally occurring substance in various plants and animals (ie, eggs, milk, vegetables, beef, chicken, and whole grains). Vitamin B5 is also supplementally added to foods. Deficiency of this vitamin is rare but can present in people with severe malnutrition. A patient with vitamin B5 deficiency commonly has deficiencies in other nutrients, making it challenging to identify vitamin B5 deficiency specifically. An experimental vitamin B5 deficiency study associated the deficiency with symptoms such as fatigue, headache, malaise, personality changes, numbness, muscle cramps, paresthesia, muscle/abdominal cramps, nausea, and impaired muscle coordination.[1]

Discovery and Isolation

American biochemist Roger J. Williams isolated pantothenic acid as a growth factor in 1931. He derived its name from the Greek word "pantos," meaning "everywhere," as small quantities of pantothenic acid are found in nearly every food. Williams et al noted that a single acid substance could stimulate the growth of Saccharomyces cerevisiae and that this substance was a 'universal constituent of living matter.' 

The molecule's chemical structure was determined by Williams in 1940. Elvehjem et al and Jukes et al demonstrated that pantothenic acid was a growth and "anti-dermatitis" factor for chickens. In the 1950s, one of the functional forms of pantothenic acid, coenzyme A (CoA), was discovered as the cofactor essential for the acetylation of sulfonamides and choline. In the mid-1960s, pantothenic acid was identified as a component of an acyl carrier protein (ACP) in the fatty acid synthesis complex. Fritz Albert Lipmann won the Nobel Prize in Physiology and Medicine "for his discovery of coenzyme A and its importance for intermediary metabolism."[2] All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, the biosynthesis of which requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).[3]

FDA Approval

Vitamin B5 (pantothenic acid) supplements are not subject to initial review by the U.S. Food and Drug Administration (FDA). The agency does not have the authority to examine dietary supplement products for safety and effectiveness before marketing. Out of all the drugs listed in this indications section, only panthenol and dexpanthenol are approved by the FDA for use in cosmetics. All other indications listed are non-FDA approved.

Indications

The usage of vitamin B5 is prevalent within the field of dermatology.[4] This interest has led to a study that compares the effectiveness of dexpanthenol (an alcoholic analog of D-pantothenic acid) as an alternative treatment to atopic dermatitis against a standard treatment of hydrocortisone. The study found that dexpanthenol can potentially treat mild to moderate childhood atopic dermatitis therapy.[5] 

Other research suggests that dexpanthenol cream can help manage mucocutaneous side effects during isotretinoin therapy.[6] Isotretinoin therapy is used for acne treatment, and its mucocutaneous side effects include dry mucous membranes, cheilitis, and xerosis. 

Clinical studies have been conducted on dexpanthenol in wound healing applications. These small clinical trials used the drug as a pastille or spray to heal wounds in postoperative endotracheal intubation, endoscopic sinus surgery, and tonsillectomy.[7][8][9] The use of dexpanthenol shows better clinical outcomes in these clinical trials. Regardless, further studies are necessary to determine drug efficacy. 

Dyslipidemia is another field that can potentially benefit from vitamin B5 use. Since vitamin B5 is essential for the biosynthesis of coenzyme A, it plays a role in the metabolism of lipids. One study concluded that pantethine (a derivative of vitamin B5) lowered cardiovascular disease risk markers in low to moderate-risk participants.[10] These risk markers include LDL, HDL, and total cholesterol. 

Pantothenate deficiency can play a vital role in acetylcholine deficiency, neurodegeneration, myelin loss, and age-related dementias like Huntington disease.[11] Nevertheless, more studies are still needed to test the clinical efficacy of vitamin B5 in these conditions.

Off-Label Uses

Individuals with a pantothenate kinase 2 (PANK2) gene mutation are also likely to have a pantothenic acid inadequacy. PANK2 mutations can reduce the activity of pantothenate kinase 2, potentially decreasing the conversion of pantothenic acid to coenzyme A (CoA) and reducing CoA levels. PANK2 gene mutations also cause pantothenate kinase-associated neurodegeneration (PKAN). A common hallmark of individuals with PKAN is an iron accumulation in the brain, forming a pattern called the "eye of the tiger" sign.[12] 

PKAN also presents with a progressive movement disorder; other symptoms may vary significantly from case to case. Symptoms include dysarthria, dystonia, poor balance, spasticity, and muscle rigidity. Treatment of this condition focuses mainly on reducing symptoms. A few anecdotal reports indicate that vitamin B5 supplements can reduce symptoms, but the benefits of this supplement's general use in PKAN are unknown.[13]

Mechanism of Action

Vitamin B5 is exclusively a precursor in coenzyme A (CoA) synthesis and thus only directly affects this metabolic pathway. CoA has a role in hundreds of human biochemical reactions, such as cell growth, intermediary metabolism, and neurotransmitter synthesis.[14][15] The structure of CoA functions as a carbonyl-activating group and as an acyl group carrier to help facilitate these various reactions.[16]

Pharmacokinetics

Pantothenic acid is commonly found in the form of CoASH or peptide-bound 4′-phosphopantetheine.

Absorption: To be absorbed into the body, these substances must undergo hydrolysis by intestinal enzymes. This process occurs through the sequential action of 2 intestinal hydrolases: a pyrophosphatase and a phosphatase. Pantetheine, the resulting product, can then be metabolized into pantothenic acid with the help of another intestinal hydrolase called pantetheinase.

When proteins and peptides, such as those derived from ACP, are hydrolyzed, there is an almost complete release of pantothenic acid or pantetheine. Following the enzymatic release, the absorption of pantothenic acid or pantetheine takes place through a sodium-dependent multivitamin transporter, with a Km (Michaelis constant) value of 10 to 20 μM for pantothenic acid uptake in the intestines.[17]

Distribution: The absorption of free pantothenic acid occurs within intestinal cells through a saturable, sodium-dependent active transport system. When pantothenic acid intake is high, and the transport system reaches its maximum capacity, a portion of it may also be absorbed through passive diffusion. Consequently, when the intake of pantothenic acid increases by a factor of 10, the rate of absorption decreases to 10%.[17]

Metabolism: The synthesis of CoA from pantothenate is regulated primarily by pantothenate kinase, an enzyme inhibited by the pathway end products CoA and acyl CoA.[18]

Elimination: Pantothenic acid is excreted intact in urine, and the amount excreted varies proportionally with dietary intake.[18]

Administration

Available Dosage Forms 

Dietary supplements of vitamin B5 are available as vitamin B5 exclusively or in combination with other vitamins in multivitamin/multimineral products. Patients typically take these supplements orally. Depending on the application, derivatives of vitamin B5 can be applied topically and even through injection using IV formulas. Dexpanthenol administration can be administered via an oral spray in the mouth.[9]

Available Strengths 

Dietary supplements commonly contain varying amounts of pantothenic acid. The quantity typically varies between approximately 10 mg in multivitamin/multimineral products and can go up to 1,000 mg in supplements that specifically target B-complex vitamins or solely pantothenic acid.

Adult Dosage

Adults should take 5 mg/d.[19] Pregnant women should take 6 mg/d, and lactating women should take 7 mg/d. If administered orally, take it with food. 

Use in Hyperlipidemia

In patients with low to moderate cardiovascular risk, with a therapeutic lifestyle and change of diet enriched with pantethine during 16 weeks (600 mg/d from weeks 1 to 8 and 900 mg/d from weeks 9 to 16), a significant decrease in total cholesterol at 16 weeks and LDL cholesterol in 8 to 16 weeks compared to placebo was observed. The decreasing trend was also evident in non-high-density-lipoprotein cholesterol at weeks 8 and 12, which reached significance at 16 weeks. The level of CoQ10 significantly increased above the baseline in both groups, and homocysteine levels did not change.[10]

Pediatric Dosage

Specific Patient Population

Hepatic impairment: There are no adjustments provided in the manufacturer's labeling for liver disease.

Renal impairment: There are no adjustments provided in the manufacturer's labeling for kidney disease.

The following foods contain pantothenic acid 

• Beef, poultry, seafood, and organ meats
• Eggs and milk
• Vegetables such as mushrooms (especially shiitakes), avocados, potatoes, and broccoli
• Whole grains, such as whole wheat, brown rice, and oats
• Peanuts, sunflower seeds, and chickpeas 

Orphan Drug Use

Pantothenate kinase-associated neurodegeneration (PKAN), previously known as Hallervorden-Spatz syndrome, is an uncommon hereditary movement disorder affecting the central nervous system and includes a cluster of clinical conditions featuring progressive involuntary movements, changes in muscle tone, and disruptions in posture (extrapyramidal symptoms).

PKAN is a hereditary condition characterized by mutations in the PANK2 gene on chromosome 20, resulting in an autosomal recessive inheritance pattern. The PANK2 gene produces the enzyme pantothenate kinase, essential for metabolizing vitamin B5 (pantothenate). These gene mutations disrupt the normal metabolism of vitamin B5, which is crucial for synthesizing coenzyme A within cells. Consequently, the impairment of this enzyme profoundly impacts energy and lipid metabolism, potentially causing the accumulation of detrimental substances in the brain, including iron. Currently, PANK2 stands as the sole identified gene associated with PKAN.[20] 

The association between pantothenate kinase and PKAN suggests that supplemental pantothenate (eg, pantothenic acid, calcium pantothenate) taken orally could be beneficial; further clinical trials are needed to study this association.

Adverse Effects

As previously stated, vitamin B5 is considered generally safe.[21] There are no established upper limits since there have been no reports of vitamin B5 toxicity in humans with high intakes. However, there are still side effects involved with the administration of this drug, which include the following.

Common Adverse Effects

• Muscle pain
• Joint pain
• Diabetes mellitus, new-onset
• Sore throat
• Headache
• Weakness/lack of energy
• Dizziness 
• Creatine phosphokinase (CPK) elevation
• Nausea 
• Abdominal pain
• Alanine transaminase (ALT) elevation
• Constipation 
• Flulike illness
• Urinary tract infection (UTI) 
• Hypersensitivity reactions (including rash, itching, hives, and swelling)
• Pancreatitis

Less Common Adverse Effects

• Yellowing skin and eyes (jaundice)
• Muscle disease
• Muscle wasting (rhabdomyolysis)

Vitamin B5 doses are age-dependent and if the patient is pregnant or lactating. Doses greater than 10 g/d may cause mild diarrhea or mild intestinal distress.[21] Cases of allergic contact dermatitis with the topical use of panthenol cream and dexpanthenol have been reported.[22][23]

Contraindications

Drug-Drug Interactions

The following drugs have moderate interactions with vitamin B5:

• Azithromycin
• Clarithromycin
• Erythromycin base
• Erythromycin ethyl succinate
• Erythromycin lactobionate
• Erythromycin stearate
• Roxithromycin

Warnings and Precautions

Patients should not take vitamin B5 if they are allergic to pantothenic acid or any ingredients contained in the formulation.

At least 60 other drugs have mild interactions with vitamin B5. Other contraindications include patients with hypersensitivity or allergy to the drug or its derivatives. A report suggests that vitamin B5 intake might correlate with increased cerebral amyloid-beta peptide burden in individuals with cognitive impairment. Although further studies are still needed to confirm the findings and discover the molecular mechanisms of this pathway, the current research suggests those with cognitive impairment to be a potential contraindication.[24]

Monitoring

Vitamin B5 is considered relatively safe. Dosages above the recommended amount can induce mild diarrhea or intestinal distress. Allergic reactions and hypersensitivity can also occur with its derivatives.

Toxicity

Toxicity is likely at 10,000 mg daily and causes upset stomach and diarrhea as the most common symptoms, according to the National Institutes of Health (NIH) Office of Dietary Supplements.[18]

Enhancing Healthcare Team Outcomes

Vitamin B5 levels can be determined through blood or urine tests. Properly evaluating and classifying nutrient deficiencies leads to improved patient healthcare outcomes. Cohesiveness and open communication among a patient’s interprofessional healthcare team members allow optimal therapy and necessary interventions.