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PABA

Nutrient Name: PABA (para-aminobenzoic acid).
Synonyms: Para-amino benzoic acid, p-aminobenzoic acid, pABA; Potaba. Related Substance: Para-aminobenzoate.

physiology and function

Physiology and Function

Para-aminobenzoic acid (PABA) is a member of the vitamin-B complex but is not generally recognized as an official vitamin.

nutrient in clinical practice

Possible Uses

Arthritis, dermatitis herpetiformis, dermatomyositis, hair graying, infertility (female), insomnia, pemphigus, Peyronie's disease, scleroderma, sunscreen (topical UV obstruction), vitiligo.

Deficiency Symptoms

None established.

Dietary Sources

Whole grains and foods of animal origin, particularly brewer's yeast, wheat germ, bran, and liver.

Nutrient Preparations Available

As a single-ingredient over-the-counter nutraceutical, PABA is usually 100 to 500 mg per dose. More often, small amounts of PABA may be contained within multivitamin or B-complex formulations. Potaba, the potassium salt of PABA, is available by prescription.

Dosage Forms Available

Capsule, tablet.

Dosage Range

Dietary: None established.

Supplemental/Maintenance: Dietary requirement not established.

Pharmacological/Therapeutic: Dosage in clinical trial has ranged from 300 mg to 12 g per day.

Toxic: Toxicity possible with greater than 400 mg PABA; extended use of several grams daily is more likely the range necessary to induce adverse symptoms.

safety profile

Overview

PABA is generally considered to be safe and free of adverse effects at doses up to 400 mg, but minor adverse effects have been reported at doses as low as 30 mg/day. Some symptoms may be attributable to its mildly acidic nature when taken orally; these generally do not occur with the potassium salt of PABA (Potaba). Most reports of significant adverse effects, such as vitiligo or elevated liver enzymes, have been associated with daily doses of 8 to 12 g daily. 1,2Deaths have been reported at 20 g/day in children and as high as 48 g/day (for 6 days, followed by 7 months at 8 g/day). 3,4

Nutrient Adverse Effects

Dermatitis, fever, hypoglycemia, itching, liver toxicity, loss of appetite, nausea, vomiting.

Contraindications

Individuals taking sulfonamides and sulfones.

interactions review

Strategic Considerations

Increased PABA levels, resulting from increased endogenous production or increased exogenous (nutraceutical) sources, can cause increased resistance to sulfa drugs (sulfonamides and sulfones) through its effect on folic acid pathways. Patients receiving long-term sulfa drugs (e.g., HIV/AIDS patients on sulfa prophylaxis for Pneumocystis ) are at risk for folic acid deficiencies; for example, megaloblastic anemia is a possible complication. Homocysteine levels often rise with ordinary courses of sulfa antibiotics.

nutrient-drug interactions
Sulfonamides, Sulfones, and Related Sulfa Antibiotics
Evidence: Dapsone (DDS, diaminodiphenylsulphone; Aczone Gel, Avlosulfon), sulfasalazine (salazosulfapyridine, salicylazosulfapyridine, suphasalazine; Apo-Sulfasalazine, Azulfidine, Azulfidine EN-Tabs, PMS-Sulfasalazine, Salazopyrin, Salazopyrin EN-Tabs, SAS); combination drug: sulfamethoxazole and trimethoprim (cotrimoxazole, co-trimoxazole, SXT, TMP-SMX, TMP-sulfa; Bactrim, Bactrim DS, Cotrim, Septra, Septra DS, Sulfatrim, Uroplus); sulfamethoxazole (Gantanol). Extrapolated, based on similar properties: Sodium sulfacetamide (AK-Sulf, Bleph-10, Sodium Sulamyd), sulfanilamide (AVC), sulfisoxazole (Gantrisin), triple sulfa (Sultrin Triple Sulfa).
Minimal to Mild Adverse Interaction—Vigilance Necessary
Potentially Harmful or Serious Adverse Interaction—Avoid
Drug-Induced Nutrient Depletion, Supplementation Contraindicated, Professional Management Appropriate

Probability: 2. Probable
Evidence Base: Consensus

Effect and Mechanism of Action

Sulfones and sulfonamides exert their antimicrobial action by competitively displacing para-aminobenzoic acid (PABA) from its binding site on 7,8-dihydropteroate synthase (DHPS), an enzyme critical for de novo synthesis of folic acid by many pathogenic microorganisms. Specifically, DHPS catalyzes the condensation of PABA with 6-hydroxymethyl-7, 8-dihydropterin-pyrophosphate to form 7,8-dihydropteroate and pyrophosphate. Consequently, sulfonamide and sulfone drugs cause cell death by depleting the folate pool necessary to microbial growth. Furthermore, extended use of sulfa drugs can result in depletion of PABA as well as depletion of folate and subsequent elevation of homocysteine. Conscientious physicians are advised to coadminister folic acid when they prescribe sulfa drugs.

Research

The phenomenon of sulfonamide-resistant infections was first discussed in the late 1960s, but the mechanism of action underlying the effectiveness of sulfa drugs only gradually became known, with increasing knowledge of the interaction between PABA and this important class of antibiotics.

In a 1966 clinical trial involving 39 volunteers subjected to mosquito-borne malaria infections, Degowin et al. 5 observed that PABA intake impaired the antimalarial activity of dapsone (DDS) against chloroquine-resistant Plasmodium falciparum. The five subjects receiving both PABA (1 g four times daily) and dapsone (25 mg daily) demonstrated acute malaria, in contrast to subjects given dapsone only, before and for 1 month after exposure, in whom malaria was suppressed. Irshaid et al. 6 (1993) found that PABA substantially inhibited the acetylation of dapsone (DDS) by whole blood taken from both slow and rapid acetylators. In 1994, McConkey et al. 7 showed that auxotrophs of P. falciparumwere dependent on p-aminobenzoic acid for growth. That same year, Voeller et al. 8 described the interaction of Pneumocystis cariniiDHPS with sulfonamides and diaminodiphenyl sulfone (dapsone) and clarified that DHPS is the target enzyme for the sulfonamide compounds. In a subsequent study of the pharmacokinetic parameters of elimination of sulfamoyl benzoic acids, sulfonamides, and penicillins via tubular secretion, Ehlert et al. 9 observed inhibition of the conjugation of PABA with glycine in vitro.

In a 1999 paper, Vinnicombe and Derrick 10 investigated the enzymatic mechanism and sulfonamide inhibition of DHPS from the pathogen Streptococcus pneumoniae. Using equilibrium binding assays, they showed that binding of the substrate PABA to DHPS was absolutely dependent on the presence of pyrophosphate, which acts as an analog of the second substrate 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPPP), and that the product of the reaction, dihydropteroate, was also able to bind to DHPS. Sulfonamides were capable of displacing PABA in a competitive manner. Thus, the authors determined that the specific target for sulfonamide inhibition of S. pneumoniaeDHPS is the enzyme-DHPPP binary complex. Shortly thereafter, in an experiment using Saccharomyces cerevisiae, Castelli et al. 11 found that 15 sulfa drugs inhibited yeast growth in a manner indicating competition with PABA. Such competition resulted from direct addition of PABA or through increased expression of the PABA synthase gene.

Despite the axiomatic mechanism involved and the consistent evidence available in the interaction, its incidence and severity remain largely unclear.

Clinical Implications and Adaptations

Physicians prescribing sulfa drugs should advise patients to refrain from concomitant use of PABA, to avoid interference with the therapeutic activity of the medication. Although there is no known and agreed therapeutic ceiling for PABA dosing that would not interfere with sulfa therapy, daily doses greater than 100 mg twice daily are more likely to have a clinically significant effect. Whether it is also necessary to avoid B-complex or multivitamin formulas containing lower levels of PABA remains uncertain.

Further clinical research is warranted to determine the clinical significance of various dosage levels of pABA intake in relation to particular sulfa agents and respective pathogens, as well as the importance and implications of folate coadministration for patients undergoing long-term treatment with sulfones and sulfonamide antibiotics.

theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Chemotherapy and Radiation, Particularly Paclitaxel
Methotrexate
Citations and Reference Literature
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  • 2.Kantor GR, Ratz JL. Liver toxicity from potassium para-aminobenzoate. J Am Acad Dermatol 1985;13:671-672.View Abstract
  • 3.Zarafonetis CJD, Grekin RH, Curtis AC et al. Further studies on the treatment of lupus erythematosus with sodium para-aminobenzoate. J Invest Dermatol 1948;11:359.
  • 4.Worobec S, LaChine A. Dangers of orally administered para-aminobenzoic acid. JAMA 1984;251:2348.View Abstract
  • 5.Degowin RL, Eppes RB, Carson PE et al. The effects of diaphenylsulfone (DDS) against chloroquine-resistant Plasmodium falciparum. Bull World Health Organ 1966;34:671-681. View Abstract
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  • 9.Ehlert C, Strunz H, Visser K et al. Inhibition of the conjugation of PABA with glycine in vitro by sulfamoyl benzoic acids, sulfonamides, and penicillins and its relation to tubular secretion. J Pharm Sci 1998;87:785.View Abstract
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