An investigation into the topical and systemic safety and efficacy of a new carbohydrate derived fulvic acid (CHD-FA) product

Abstract

Humic substances are a group of ubiquitous compounds formed during the decay of plant and animal residues in the environment. These substances can be divided into humic acid, fulvic acid and humin on the basis of its solubility in water as a function of pH. Fulvic acid is the fraction that is soluble in water under all pH conditions and is usually extracted from brown coal and is therefore associated with high levels of heavy metals. These heavy metal levels have become a point of concern and a unique method for synthesizing fulvic acid from a carbohydrate source has been subsequently developed and patented in an attempt to address this problem. The purpose of this study was therefore, to test the topical and systemic safety and efficacy of this new carbohydrate derived fulvic acid (CHD-FA) product. Initial in vitro screening using the Kirby-Bauer disk diffusion method indicated that the product was active against the Staphylococcus aureus test organisms used (ATCC 12600 and P3938). Results showed that not only was it as effective as the oxacillin control, but in the case of a more virulent strain of S. aureus, the CHD-FA (3.9% w/v) proved more active. Subsequently, the ability of the product to cross full-thickness skin was ascertained using Franz-type diffusion cells fitted with 100ìm skin disks obtained from rats. At the end of a 12-hr period, results indicated that up to 20% of the CHD-FA at a pH of 2.9 was able to cross the skin barrier. Divided into 6 phases, extensive animal safety studies were conducted on the product. In phase I, toxicity and sensitivity to topical application was examined by applying the product to the ears of mice over a period of 30 days. Phase II and III was undertaken to study the long term effects (6-weeks and 6-months) of CHD-FA ingestion (150 mg/kg body mass) whilst phase IV tested the effects of CHD-FA ingestion on pregnant rats and their off-spring. Phase V was an acute toxicity study in which rats received a single oral dose of CHD-FA (150mg/kg bw) and then observed for a period of 7 days. Phase VI was a 6-week chronic study in which the animals received 100mg/kg bw daily for the duration of the experiment. Results obtained in all studies showed that CHD-FA is safe for topical as well as, oral use at the doses tested. In addition, it is safe for use during pregnancy. Finally, the in vivo anti-microbial efficacy of the CHD-FA was examined using an infected wound healing model. A pilot study indicated that the animals used should be immunocompromised and the wounds inoculated with a Staphylococcus aureus (ATCC 12600) concentration of 1x1010 CFU/ml. Results from the main study showed that topical applications of the CHD-FA (pH 1.98) product at a concentration of 1.75% w/v over the 5-day period produced a wound healing pattern similar to that of the positive fuscidic acid control. In contrast, animals receiving an oral treatment of the product did not produce a pattern different from that of the water control group. In conclusion, CHD-FA has been shown to be safe and effective in treating S. aureus infections in vitro and in animal models. This study indicates that the next phase of human studies is certainly warranted.