Carbohydrate Derived Fulvic Acid Research Articles

Biostimulant effects on the herbage yield and nutritive composition of a mixed ryegrass–clover pasture

Dairy producers are continuously searching for environmentally friendly and economically sustainable alternatives to increase pasture herbage yield and reduce reliance on chemical fertilisers. A possible means to reduce fertiliser reliance is the use of biostimulants. Biostimulants such as fulvic acid and bioflavonoids help to increase N uptake efficiency, thereby increasing herbage quantity and quality. The aim of this study was to determine the effects of a soil application of a carbohydrate-derived fulvic acid and bioflavonoid biostimulant on herbage yield and nutritive composition of a mixed perennial ryegrass–clover pasture. Biostimulant treatment resulted in a lower ryegrass component of the mixed sward, in both winter and summer grazing cycles. However, the nutritive composition and total herbage yield of the pasture were not significantly affected by biostimulant treatment. The treatment did show a tendency to affect total herbage yield within a season. This suggests that total herbage yield could be increased if additional N fertiliser is applied together with a biostimulant soil treatment, although further investigation is needed to confirm this postulation. Biostimulant treatments have the potential to lead to reduced fertiliser inputs on perennial ryegrass–clover pastures as they may increase nutrient uptake efficiency.

Effect of 5% Carbohydrate Derived-Fulvic Acid on Smear Layer Removal and Root Dentin Microhardness - An In Vitro study.

ObjectiveTo compare the ability of 5% carbohydrate derived-fulvic acid (CHD-FA) with 17%ethylenediamine tetraaceticacid (EDTA) on smear layer removal when used as a final irrigant, and to assess their effect on root dentin microhardness.MethodsA total of 56 single-rooted human mandibular premolars were decoronated to obtain standardized root length of 12 mm. Canal patency was established using 10 size K-file, working length was determined. Based on the irrigation regimen, samples were assigned into three groups; 17% EDTA, 5% CHD-FA and distilled water (control). The canals were instrumented with Protaper till F3 size. A standardized volume of 5 mL of each testing solution was used for 1 min. Roots were longitudinally split into two halves with one half of the samples for SEM analysis to evaluate the smear layer removal at coronal, middle, and apical thirds of root dentin. The other halves of the samples were subjected to Vickers microhardness testing. The data was statistically analyzed using Kruskal Wallis and Post Hoc test (P<0.05).Results5% CHD-FA and 17% EDTA showed significant smear layer removal at all levels compared to distilled water (P<0.05). In the apical third, 5% CHD-FA showed significantly increased smear layer removal than EDTA (P<0.05). Microhardness testing of apical third showed significantly lesser reduction in microhardness for CHD-FA than EDTA (P<0.05).Conclusion5% CHD-FA could be a promising final irrigant for smear layer removal with decreased microhardness reduction on root dentin compared to 17% EDTA.

Carbohydrate-derived fulvic acid wellness drink: its tolerability, safety and effect on disease markers in pre-ART HIV-1 positive subjects

Background: Many people take wellness drinks on a daily basis to enhance physical and emotional well-being. The safety and/or efficacy of these are not always known or even established in the populations likely to consume these. The safety, tolerability and clinical impact of CHD-FA in a formulated wellness drink (F0210) (a pure and novel fulvic acid) were researched in a pre-ART HIV-1 positive population in India an area where patients are known to use organic acids such as fulvic acids (Shilajit) for health enhancement.Methods: This double-blind, placebo-controlled, parallel study recruited 332 patients (n = 166 on active; n = 166 on placebo). The study outcomes recorded safety and tolerability data, as well as the time to ART and/or the time to a decrease in CD4 count of 100 cells/mm3 for subjects in each treatment group. Change in immune status is an important clinical endpoint. The secondary outcomes were CD4 count, HIV-1 viral load changes and quality of life (the latter as a further proxy for tolerability).Results: The only notable side effect of the active medication was gastrointestinal intolerance such as diarrhoea, nausea and vomiting, which were more frequently experienced compared with placebo. The study was terminated before full recruitment due to regulatory changes in India and at the time of study termination there were too few clinical study endpoints reached to demonstrate any clinical difference between active and placebo treatments (no difference in hazard of experiencing an event (reaching indication for ART) between groups; p = 0.5724). An interesting trend was that patients’ CD4 counts in the study demonstrated a slower than anticipated decline compared with trends recorded in the literature for natural progression of disease.Conclusion: The CHD FA wellness drink is well tolerated in an ART-naive study population and does not negatively affect the disease-specific parameters and hence does not adversely affect the natural progression of the HIV-1 disease or patients’ general health. Further exploration of fulvic acids is therefore warranted.

Carbohydrate-derived fulvic acid wellness drink: its tolerability, safety and effect on disease markers in pre-ART HIV-1 positive subjects

Background: Many people take wellness drinks on a daily basis to enhance physical and emotional well-being. The safety and/or efficacy of these are not always known or even established in the popul...

Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens.

This work was intended as a proof-of-principle study to help establish carbohydrate-derived fulvic acid (CHD-FA) as a safe and effective agent that can be deployed to prevent the onset of drug-resistant bacterial and fungal infections in military and civilian personnel experiencing traumatic wound. Minimum inhibitory concentrations for CHD-FA were established on a total of 500 clinical isolates representing wound-associated drug-sensitive and drug-resistant bacterial and fungal pathogens. The efficacy of early use of CHD-FA to enhance healing of wounds infected with methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa was evaluated in an in vivo rat model. CHD-FA showed strong activity against a variety of bacterial and fungal pathogens with minimum inhibitory concentration values equal or less than 0.5%. Compared with infected but untreated wounds, improved wound healing upon CHD-FA treatment was observed in both infection models, demonstrated by wound surface area measurement, histopathologic examination, and expression profiling of wound healing genes. Up-regulation of proinflammatory cytokine interleukin 6 (IL-6) at Day 3 after infection was significantly dampened at Days 6 and 10 in the CHD-FA-treated wounds in both infection models, displaying an improved and accelerated wound healing. CHD-FA is a promising topical remedy for drug-resistant wound infections. It accelerated the healing process of wounds infected with methicillin-resistant S. aureus and multidrug-resistant P. aeruginosa in rats, which is linked to both its antimicrobial and anti-inflammatory properties.

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections

BackgroundA number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.MethodsMinimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.ResultsCHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.ConclusionsOverall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.

Antimicrobial compounds from natural sources

Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nowadays many infections are often caused by multi-resistant microorganisms resulting in difficult to treat diseases and, consequently, substantial increases in healthcare costs. The relative easy access to the antimicrobials and also the massive employment of these compounds for industrial purposes, including food production, have both strongly contributed to the progressive increase of resistant microorganisms. As a result, these multi-resistant microorganisms are reasserting themselves as worldwide threats. Research into natural products has demonstrated significant progress in the discovery of new compounds with antimicrobial activity. In fact, nature is a generous source of compounds with the potential to treat diseases, including infectious diseases. Among the known sources of natural compounds with valuable antimicrobial activity, we highlighted the medicinal plants and marine and terrestrial organisms, including fungi and bacteria. Nevertheless, there is still a vast fauna and flora that once systematically explored, could provide additional antimicrobial leads and new drugs. Thousands of natural products with the potential to act as antimicrobial compounds or as a structural lead compound still await further investigation. In this Research Topic Ebook, we present several scientific studies mainly focused on natural products with antimicrobial activity, which are the case of the natural antimicrobial peptides (AMPs) and host defense peptides (HDPs). This topic also includes recent studies on the roles of honey hydrogen peroxide in antimicrobial activity against resistant microbial strains, as well as the use of essential oils for food preservation. Such a wide and interesting topic also gave us an opportunity to include diverse sources, including plants, terrestrial and sea animals. Not to mention the interesting and unusual sources such as coal or lignite, which may provide future antimicrobial compounds candidates. The recent development of a patented process to GMP standards (PA107470/GB), rendering the obtainment of carbohydrate derived fulvic acid (CHD-FA), stimulated Sherry et al. (2012) to study and describe for the first time a highly effective novel antiseptic effect of fulvic acid with exquisite biofilm activity that acts by disrupting cell membranes. The antifungic peptide from Amazonian Pink Toe spider Juruin, described by Ayroza et al. (2012) is another outstanding example of the potential contribution of a systematic exploration of nature aiming to provide additional antimicrobial leads and drugs. In other words, nature is a generous source of compounds, with the potential to treat diseases, including infectious diseases. Studies exploiting the mechanism of action and the structure-activity aspects of these natural compounds may provide both additional antimicrobial leads and drugs, and also significant insight into potential possibilities to overcome the antimicrobial resistance.

Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid

BackgroundThe purpose of this research was to determine the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid (CHD-FA).MethodsIn this double-blind study, 30 male volunteers with predetermined atopy were randomly assigned to either Group A or Group B, each consisting of 15 participants. In part 1 of the study, the groups were administered increasing amounts of CHD-FA, ranging from 5 mL to 40 mL, provided that no adverse events had occurred at the previous dosage. In part 2, Group A participants received 20 mL of 3.8% CHD-FA twice daily for 3 days and were monitored for a week. Because no adverse events occurred, Group B received 40 mL of 3.8% CHD-FA twice daily for a period of 3 days. In part 3, both groups received either 40 mL of 3.8% CHD-FA or placebo twice daily for a period of one week, followed by a one-week washout period before crossover to the alternative treatment schedule. Parameters used to establish safety were electrocardiography, a physical examination, a health questionnaire, and hematology and biochemistry, determined at baseline, during regular calculated intervals, and at the end of each part of the study. A skin prick test was done as part of the screening process and, from the result, the allergen the participant was most allergic to was then selected, along with the positive histamine and negative control to be repeated at the start and end of each respective stage.ResultsSafety parameters remained constant throughout the trial. A significant decrease in skin prick test results was observed.ConclusionNo severe adverse events occurred, establishing that CHD-FA to be safe at doses up to 40 mL twice daily for a week and that at this dosage CHD-FA acts as an anti-inflammatory agent. These findings confirm earlier animal data.

Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms

Carbohydrate derived fulvic acid (CHD-FA) is a heat stable low molecular weight, water soluble, cationic, colloidal material with proposed therapeutic properties. The aim of this study was to evaluate the antifungal activity of CHD-FA against Candida albicans, and to characterize its mode of action. A panel of C. albicans isolates (n = 50) derived from a range of clinical specimens were grown planktonically and as biofilms, and the minimum inhibitory concentrations determined. Scanning electron microscopy was performed to examine ultrastructural changes and different cell membrane assays were used to determine its mode of action. In addition, the role of C. albicans biofilm resistance mechanisms were investigated to determine their effects on CHD-FA activity. CHD-FA was active against planktonic and sessile C. albicans at concentrations 0.125 and 0.25% respectively, and was shown to be fungicidal, acting through disruption of the cell membrane activity. Resistance mechanisms, including matrix, efflux, and stress, had a limited role upon CHD-FA activity. Overall, based on the promising in vitro spectrum of activity and minimal biofilm resistance of the natural and cheap antiseptic CHD-FA, further studies are required to determine its applicability for clinical use.

Carbohydrate Derived Fulvic Acid (CHD-FA) is a Novel Antifungal Product: Category: Scientific free paper

• Ala-Nap was added at a final concentration of 64mg/L, and the relative fluorescence measured for every 30s for 1 hour. • Isolates standardised to 1 × 106 and 1 x 10 7 cells for sessile and planktonic respectively, in assay buffer solution., and added to a black flat bottomed micro-titre plate. The aim of this study was to evaluate the antimicrobial activity of CHD-FA against a range of Candida albicans isolates associated with mucosal and systemic candidiasis. In addition, the toxicological properties of the compound were evaluated. The oral cavity contains a diverse and complex microbial ecology, which includes yeasts growing as biofilms. Oral candidiasis is a characteristic infection commonly observed in immunocomprimised patients, especially those with an HIV infection and causes oral discomfort, pain and taste distortion [1]. Despite Candida albicans being a commensal of the oral cavity in 30-40% of healthy individuals, it is also the most common fungal pathogen in humans [2]. In addition to infections in the oral cavity, C. albicans is also responsible for infections in the ICU. Bloodstream infections caused by this organism are associated with morbidity and mortality worldwide.

Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema

BackgroundThe purpose of this study was to evaluate the efficacy and safety of carbohydratederived fulvic acid (CHD-FA) in the treatment of eczema in patients two years and older.MethodsIn this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks.ResultsAll safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results.ConclusionCHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.

Carbohydrate‐derived Fulvic acid (CHD‐FA) inhibits Carrageenan‐induced inflammation and enhances wound healing: efficacy and Toxicity study in rats

AbstractThe objectives of this study were to evaluate the safety and anti‐inflammatory and wound‐healing characteristics of carbohydrate‐derived fulvic acid (CHD‐FA) in rats. CHD‐FA (≥100 mg/kg p.o.) effectively reduced carrageenan‐induced paw edema in rats, which was comparable to 10 mg/kg p.o. indomethacin. Topical application of CHD‐FA, formulated to contain 1.75% active product in a cetomicrogol cream at pH 1.98, compared favorably with fusidic acid cream (10 mg/g) in accelerating the healing of excised wounds infected with Staphylococcus aureus. No signs of toxicity were observed in rats during the 6‐day acute and 6‐month chronic treatment with CHD‐FA (100 mg/kg p.o.). Topical application of CHD‐FA, formulated in UEA cream and applied to the right ears of mice at 400 mg/g body weight on days 1 and 7–38, produced no adverse events. No signs of toxicity were observed in the teratogenicity study, in which CHD‐FA was administered at 100 mg/kg p.o. to pregnant female mice 3 days before fertilization to 14 days of pregnancy. In conclusion, CHD‐FA is a safe compound with anti‐inflammatory and wound‐healing properties and merits further evaluation in the treatment of patients suffering from similar conditions. Drug Dev Res 73: 18–23, 2012. © 2011 Wiley Periodicals, Inc.