Abstract:
Background: Carbohydrate derived fulvic acid (CHD-FA) is a synthetic heavy metal free
fulvic acid. Although CHD-FA has been suggested as a nutritional supplement and even a
medication, there is currently no data available with regards to the systemic kinetics of CHDFA
when ingested orally. Fulvic acid has shown equivalence when compared to diclofenac
sodium and betamethasone in a murine hypersensitivity model when applied topically with no
adverse side effects. Data from several animal studies indicate that fulvic acid administered
topically or orally is safe and effective as an anti-inflammatory agent. Human in vivo safety
and efficacy as well as potential in vitro genotoxicity still need to be assessed.
Aim: To determine whether carbohydrate derived fulvic acid shows any genotoxic effects and
whether it is safe, clinically effective as an anti-inflammatory and attempt to establish a
suitable CHD-FA marker for kinetic studies.
Methods: Genotoxicity was determined via an in vitro micronucleus assay. Systemic and
topical safety and efficacy of CHD-FA was established via two limited participant, double
blind, randomised, placebo controlled clinical trials. One to determine safety and efficacy in
30 adult male volunteers with a predetermined atopic hypersensitivity, using a skin prick test,
and the second trial to test topical safety and efficacy in 40 patients suffering from atopic
dermatitis. LC-MS/MS assays were conducted in order to determine whether a unique or
dominant ionic analyte could be found in plasma.
Discussion: In the in vitro genotoxicity tests, CHD-FA compared closely to that of the
negative control with respect to the number of micronuclei observed. All tested in vivo safety
parameters proved to remain constant throughout both the clinical trials. A significant
decrease in flare was observed in CHD-FA treated patients following a skin prick challenge.
Due to the complexity of the mass spectral fingerprints of both plasma and the fulvic acid no
suitable CHD-FA markers were found.
Conclusion: No genotoxicity was observed for CHD-FA treated cells. No severe adverse
events occurred in either the oral or topically administered CHD-FA trials, proving CHD-FA
to be systemically and topically safe. A significant decrease in wheal formation in the skin
prick test, and a significant clinical improvement in atopic dermatitis compared to placebo were observed implicating that CHD-FA may act as an anti-inflammatory agent in vivo in
humans. No suitable CHD-FA markers for pharmacokinetic studies in human plasma could be
identified.
