Ernst Graf

Antioxidant potential of ferulic acid

Ferulic acid is a ubiquitous plant constituent that arises from the metabolism of phenylalanine and tyrosine. It occurs primarily in seeds and leaves both in its free form and covalently linked to lignin and other biopolymers. Due to its phenolic nucleus and an extended side chain conjugation, it readily forms a resonance stabilized phenoxy radical which accounts for its potent antioxidant potential. UV absorption by ferulic acid catalyzes stable phenoxy radical formation and thereby potentiates its ability to terminate free radical chain reactions. By virtue of effectively scavenging deleterious radicals and suppressing radiation-induced oxidative reactions, ferulic acid may serve an important antioxidant function in preserving physiological integrity of cells exposed to both air and impinging UV radiation. Similar photoprotection is afforded to skin by ferulic acid dissolved in cosmetic lotions. Its addition to foods inhibits lipid peroxidation and subsequent oxidative spoilage. By the same mechanism ferulic acid may protect against various inflammatory diseases. A number of other industrial applications are based on the antioxidant potential of ferulic acid.

Antioxidant functions of phytic acid.

Phytic acid is a natural plant antioxidant constituting 1-5% of most cereals, nuts, legumes, oil seeds, pollen and spores. By virtue of forming a unique iron chelate it suppresses iron-catalyzed oxidative reactions and may serve a potent antioxidant function in the preservation of seeds. By the same mechanism dietary phytic acid may lower the incidence of colonic cancer and protect against other inflammatory bowel diseases. Its addition to foods inhibits lipid peroxidation and concomitant oxidative spoilage, such as discoloration, putrefaction, and syneresis. A multitude of other industrial applications are based on the antioxidant function of phytic acid.

Suppression of colonic cancer by dietary phytic acid

Large differences exist between human populations in the frequency of colonic cancer. Epidemiological evidence indicates that these differences are strongly influenced by country of residence, and a negative correlation has been found between the fiber content of the diet and frequency of colonic cancer. This has prompted the hypothesis that high-fiber diets are in some way protective. However, reanalysis of the dietary data provides equally strong support for the hypothesis that the protective element may be phytic acid (inositol hexaphosphate). This heat- and acid-stable substance is present in high concentration in many food items, including cereal grains, nuts, and seeds. Phytic acid forms chelates with various metals and suppresses damaging iron-catalyzed redox reactions. Inasmuch as colonic bacteria have been shown to produce oxygen radicals in appreciable amounts, dietary phytic acid might suppress oxidant damage to intestinal epithelium and neighboring cells. Indeed, rapidly accumulating data from animal models indicate that dietary supplementation with phytic acid may provide substantial protection against experimentally induced colonic cancer. Should further investigations yield additional support for this hypothesis, purposeful amplification of dietary phytic acid content would represent a simple method for reducing the risk of colonic carcinogenesis.

Dietary suppression of colonic cancer fiber or phytate

The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high‐fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber‐rich diets. The authors have found that phytic acid is a potent inhibitor of iron‐mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.

Applications of phytic acid

Phytic acid (myo-inositol hexaphosphate) constitutes 1-3% of most plant seeds. Its tremendous chelating potential and its effects on the absorption of polycationic nutrilites such as Ca2+, Zn2+ and Fe3+ have been the subject of intense investigation for several decades. Yet in the American literature there is virtually no information available on other chemical properties of phytic acid or on its beneficial utilization. This review summarizes the present medical, dental, nutritional and industrial applications of phytic acid and suggests additional novel uses for this inexpensive and easily obtained chemical.

Antioxidant functions of Inositol 1,2,3-trisphosphate and Inositol 1,2,3,6-tetrakisphosphate

Iron chelates of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate lacked free coordination sites and prevented the iron-catalyzed oxidation of ascorbic acid and peroxidation of arachidonic acid. In contrast, iron chelates of inositol 1,2,6-trisphosphate and inositol 1,2,5,6-tetrakisphosphate contained available coordination sites, permitted iron-catalyzed ascorbic acid oxidation, and enhanced arachidonic acid peroxidation. It was concluded that the 1,2,3-trisphosphate grouping of inositol hexakisphosphate was responsible for the inhibition of iron-catalyzed hydroxyl radical formation. The structure of the chelate with the phosphates in an axial-equatorial-axial configuration appeared to be the only possible inositol trisphosphate that could form bonds between six oxygen atoms and the six coordination sites on iron. Km values for cleavage by Escherichia coli alkaline phosphatase were as follows: inositol 1,2,3-trisphosphate, 56 microM; inositol 1,2,6-trisphosphate, 35 microM; inositol 1,2,3,6-tetrakisphosphate, 139 microM; and inositol 1,2,5,6-tetrakisphosphate, 100 microM. The initial hydrolysis rates of 200 microM solutions of the latter three isomers by E. coli alkaline phosphatase were not affected by an equimolar concentration of iron, whereas the rate for inositol 1,2,3-trisphosphate decreased in the presence of iron to 50% of the control. Therefore, the antioxidant potential of inositol 1,2,3-trisphosphate and inositol 1,2,3,6-tetrakisphosphate in cells and other biological systems may be fortified by the resistance of their iron chelates to enzymatic hydrolysis of the functional 1,2,3-trisphosphate array.