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Ferulic Acid: an intriguing new supplement with some unusual antioxidant properties
by Russell Mills
Ferulic acid (FA) is a substance found in the seeds and leaves of most plants, especially in the brans of grasses such as wheat, rice, and oats. Its chemical structure strongly resembles that of curcumin, the substance responsible for the yellow color of the spice turmeric. 1, 2, 3
The amount of ferulic acid in plant materials varies widely depending on the species and growing conditions; supplements are therefore a more reliable source of this substance than food or unprocessed herbal materials. 2
Ferulic acid has antioxidant properties that make it an important anti-aging supplement, and they also contribute to FA’s other potential uses. These include applications in diabetes, cardiovascular disease, cancer, neuroprotection, bone degeneration, menopause, immunity, and (perhaps) athletic performance. Let us look at these uses in more detail.
Anti-aging
Free radicals are chemically reactive molecules produced in cells as byproducts of normal biochemical processes, particularly the metabolism of sugars and fats. Once produced, free radicals can damage almost any biological structure they come into contact with. Membranes within and surrounding cells contain many components that are prone to free radical damage. We perceive the results of such damage as ‘aging’.
Like many other dietary substances, FA is an antioxidant — but it is an unusually good one. It is especially good at neutralizing the free radicals known as ‘superoxide’, ‘hydroxyl radical’, and ‘nitric oxide’. It acts synergistically with other antioxidants, giving them extra potency. In addition, FA can be activated to even higher antioxidant activity by exposure to UV light, suggesting that it might help to protect skin from sun damage. 4, 5, 6, 7
Diabetes
Experiments with diabetic rats at Annamalai University in India showed that FA supplementation at relatively low doses increased the activities of antioxidant enzymes, thereby neutralizing free radicals which, in diabetics, are primary causes of acclerated tissue damage. FA also decreased blood glucose and lipid levels. 8, 9
Cardiovascular disease
In male rats fed a high cholesterol diet, FA supplementation significantly lowered total cholesterol and triglyceride concentrations in the blood, as compared to a control group. Moreover, HDL (‘good cholesterol’) is increased with FA supplementation. 10, 11
Cancer
Cancer in a variety of different tissues has been shown to be suppressed by ferulic acid supplementation. These include:
cancers of the digestive tract: tongue, eso****eal, stomach, intestinal and colorectal cancers 12, 13, 15, 16
prostate cancer 17, 18
lung cancer 14
liver cancer 16
breast cancer 19, 20
Some of FA’s anti-cancer effects appear to be due to its ability to prevent the conversion of the nitrites used in foods into cancer-causing chemicals. 21
Neuroprotection (Alzheimer’s, cognitive decline, macular degeneration)
By virtue of its antioxidant properties, ferulic acid greatly reduces free radical damage to the external and internal membranes of nerve cells without causing nerve cell death. FA also appears to encourage the proliferation of at least some types of nerve cells, such as retinal cells. These properties have attracted the interest of researchers looking for treatments for Alzheimer’s and other neurodegenerative diseases, and for certain diseases of the retina such as macular degeneration. 22, 23, 24
Bone degeneration (osteoporosis)
Studies of bone metabolism suggest that ferulic acid prevents bone loss by a mechanism different from that of estrogens. In an era when hormone replacement therapy is under fire from anti-technology crusaders, ferulic acid may be a welcome addition to the osteoporosis treatment arsenal. 25
Menopause
Ferulic acid has been shown effective in treating hot flashes in menopausal women, according to a review in the journal ‘Alternative Medicine Review’. 26
Immunity
Tissue culture experiments in Taiwan have shown that FA stimulates the production of human white blood cells and increases the secretion of IFN-gamma (gamma-interferon), an immune-system stimulatory protein. This suggests a possible value of FA as an immune stimulant, and provides some support for traditional usages of ferulic-acid-containing plants as treatments for cancer and infectious diseases. 27
Athletic performance
Ferulic acid (or its metabolic precursor, gamma oryzanol) has been widely used to enhance athletic performance, both in humans and in race horses. One rationale has been that it reduces fatigue by neutralizing free radicals that would otherwise damage the energy-producing structures in cells. This concept has merit theoretically, but has yet to be demonstrated in clinical trials. 28
Safety and dosage
The safety of ferulic acid is well-established both by animal studies and by its consumption as part of people’s daily diet for thousands of years — it is a significant component of grains, seeds, leafy vegetables and other food plants.
Effective dosages of FA for most of the applications mentioned above have not yet been established scientifically. Supplement companies therefore recommend dosages based on the usage of this supplement (or its precursor, gamma oryzanol) by athletes as a performance enhancer. A commonly recommended dose is 250 mg twice per day.
References
[1] Antioxidant potential of ferulic acid. [PubMed Abstract]
[2] Phytochemical profiles and antioxidant activity of wheat varieties. [PubMed Abstract]
[3] [Diagram]
[4] Radical scavenging activity and cytotoxicity of ferulic acid. [PubMed Abstract]
[5] Antioxidant effect of ferulic acid in isolated membranes and intact cells: synergistic interactions with alpha-tocopherol, beta-carotene, and ascorbic acid. [PubMed Abstract]
[6] Antioxidant potential of ferulic acid. [PubMed Abstract]
[7] Metal-chelating properties, electrochemical behavior, scavenging and cytoprotective activities of six natural phenolics. [PubMed Abstract] [PDF (337 KB)]
[8] Protective effects of ferulic acid on hyperlipidemic diabetic rats. [PubMed Abstract]
[9] Ferulic acid alleviates lipid peroxidation in diabetic rats. [PubMed Abstract]
[10] Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats. [PubMed Abstract]
[11] Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. [PubMed Abstract]
[12] Changing concepts of dietary fiber: implications for carcinogenesis. [PubMed Abstract]
[13] Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis. [PubMed Abstract]
[14] Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice. [PubMed Abstract]
[15] Inhibitory effects of phenolic compounds on benzo(a)pyrene-induced neoplasia. [PubMed Abstract]
[16] Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. [PubMed Abstract]
[17] Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate. [PubMed Abstract]
[18] Effect of trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) on polyamine level in the rat ventral prostate. [PubMed Abstract]
[19] Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells. [PubMed Abstract] [Publisher Full Text] [PDF (116 KB)]
[20] Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. [PubMed Abstract] [Publisher Full Text] [PDF (696 KB)]
[21] Teas and tea components as inhibitors of carcinogen formation in model systems and man. [PubMed Abstract]
[22] Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. [PubMed Abstract]
[23] Effect of ferulic acid on the proliferation of nerve cells of retinas in vitro [PubMed Abstract]
[24] Characterization of physicochemical properties of ferulic acid. [PubMed Abstract]
[25] Preventive effect of ferulic acid on bone loss in ovariectomized rats. [PubMed Abstract]
[26] Hot flashes—a review of the literature on alternative and complementary treatment approaches. [PubMed Abstract]
[27] Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. [PubMed Abstract]
[28] The effects of gamma-oryzanol supplementation during resistance exercise training. [PubMed Abstract]
by Russell Mills
Ferulic acid (FA) is a substance found in the seeds and leaves of most plants, especially in the brans of grasses such as wheat, rice, and oats. Its chemical structure strongly resembles that of curcumin, the substance responsible for the yellow color of the spice turmeric. 1, 2, 3
The amount of ferulic acid in plant materials varies widely depending on the species and growing conditions; supplements are therefore a more reliable source of this substance than food or unprocessed herbal materials. 2
Ferulic acid has antioxidant properties that make it an important anti-aging supplement, and they also contribute to FA’s other potential uses. These include applications in diabetes, cardiovascular disease, cancer, neuroprotection, bone degeneration, menopause, immunity, and (perhaps) athletic performance. Let us look at these uses in more detail.
Anti-aging
Free radicals are chemically reactive molecules produced in cells as byproducts of normal biochemical processes, particularly the metabolism of sugars and fats. Once produced, free radicals can damage almost any biological structure they come into contact with. Membranes within and surrounding cells contain many components that are prone to free radical damage. We perceive the results of such damage as ‘aging’.
Like many other dietary substances, FA is an antioxidant — but it is an unusually good one. It is especially good at neutralizing the free radicals known as ‘superoxide’, ‘hydroxyl radical’, and ‘nitric oxide’. It acts synergistically with other antioxidants, giving them extra potency. In addition, FA can be activated to even higher antioxidant activity by exposure to UV light, suggesting that it might help to protect skin from sun damage. 4, 5, 6, 7
Diabetes
Experiments with diabetic rats at Annamalai University in India showed that FA supplementation at relatively low doses increased the activities of antioxidant enzymes, thereby neutralizing free radicals which, in diabetics, are primary causes of acclerated tissue damage. FA also decreased blood glucose and lipid levels. 8, 9
Cardiovascular disease
In male rats fed a high cholesterol diet, FA supplementation significantly lowered total cholesterol and triglyceride concentrations in the blood, as compared to a control group. Moreover, HDL (‘good cholesterol’) is increased with FA supplementation. 10, 11
Cancer
Cancer in a variety of different tissues has been shown to be suppressed by ferulic acid supplementation. These include:
cancers of the digestive tract: tongue, eso****eal, stomach, intestinal and colorectal cancers 12, 13, 15, 16
prostate cancer 17, 18
lung cancer 14
liver cancer 16
breast cancer 19, 20
Some of FA’s anti-cancer effects appear to be due to its ability to prevent the conversion of the nitrites used in foods into cancer-causing chemicals. 21
Neuroprotection (Alzheimer’s, cognitive decline, macular degeneration)
By virtue of its antioxidant properties, ferulic acid greatly reduces free radical damage to the external and internal membranes of nerve cells without causing nerve cell death. FA also appears to encourage the proliferation of at least some types of nerve cells, such as retinal cells. These properties have attracted the interest of researchers looking for treatments for Alzheimer’s and other neurodegenerative diseases, and for certain diseases of the retina such as macular degeneration. 22, 23, 24
Bone degeneration (osteoporosis)
Studies of bone metabolism suggest that ferulic acid prevents bone loss by a mechanism different from that of estrogens. In an era when hormone replacement therapy is under fire from anti-technology crusaders, ferulic acid may be a welcome addition to the osteoporosis treatment arsenal. 25
Menopause
Ferulic acid has been shown effective in treating hot flashes in menopausal women, according to a review in the journal ‘Alternative Medicine Review’. 26
Immunity
Tissue culture experiments in Taiwan have shown that FA stimulates the production of human white blood cells and increases the secretion of IFN-gamma (gamma-interferon), an immune-system stimulatory protein. This suggests a possible value of FA as an immune stimulant, and provides some support for traditional usages of ferulic-acid-containing plants as treatments for cancer and infectious diseases. 27
Athletic performance
Ferulic acid (or its metabolic precursor, gamma oryzanol) has been widely used to enhance athletic performance, both in humans and in race horses. One rationale has been that it reduces fatigue by neutralizing free radicals that would otherwise damage the energy-producing structures in cells. This concept has merit theoretically, but has yet to be demonstrated in clinical trials. 28
Safety and dosage
The safety of ferulic acid is well-established both by animal studies and by its consumption as part of people’s daily diet for thousands of years — it is a significant component of grains, seeds, leafy vegetables and other food plants.
Effective dosages of FA for most of the applications mentioned above have not yet been established scientifically. Supplement companies therefore recommend dosages based on the usage of this supplement (or its precursor, gamma oryzanol) by athletes as a performance enhancer. A commonly recommended dose is 250 mg twice per day.
References
[1] Antioxidant potential of ferulic acid. [PubMed Abstract]
[2] Phytochemical profiles and antioxidant activity of wheat varieties. [PubMed Abstract]
[3] [Diagram]
[4] Radical scavenging activity and cytotoxicity of ferulic acid. [PubMed Abstract]
[5] Antioxidant effect of ferulic acid in isolated membranes and intact cells: synergistic interactions with alpha-tocopherol, beta-carotene, and ascorbic acid. [PubMed Abstract]
[6] Antioxidant potential of ferulic acid. [PubMed Abstract]
[7] Metal-chelating properties, electrochemical behavior, scavenging and cytoprotective activities of six natural phenolics. [PubMed Abstract] [PDF (337 KB)]
[8] Protective effects of ferulic acid on hyperlipidemic diabetic rats. [PubMed Abstract]
[9] Ferulic acid alleviates lipid peroxidation in diabetic rats. [PubMed Abstract]
[10] Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats. [PubMed Abstract]
[11] Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. [PubMed Abstract]
[12] Changing concepts of dietary fiber: implications for carcinogenesis. [PubMed Abstract]
[13] Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis. [PubMed Abstract]
[14] Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice. [PubMed Abstract]
[15] Inhibitory effects of phenolic compounds on benzo(a)pyrene-induced neoplasia. [PubMed Abstract]
[16] Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. [PubMed Abstract]
[17] Trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) inhibits the effect of androgens on the rat prostate. [PubMed Abstract]
[18] Effect of trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) on polyamine level in the rat ventral prostate. [PubMed Abstract]
[19] Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells. [PubMed Abstract] [Publisher Full Text] [PDF (116 KB)]
[20] Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. [PubMed Abstract] [Publisher Full Text] [PDF (696 KB)]
[21] Teas and tea components as inhibitors of carcinogen formation in model systems and man. [PubMed Abstract]
[22] Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. [PubMed Abstract]
[23] Effect of ferulic acid on the proliferation of nerve cells of retinas in vitro [PubMed Abstract]
[24] Characterization of physicochemical properties of ferulic acid. [PubMed Abstract]
[25] Preventive effect of ferulic acid on bone loss in ovariectomized rats. [PubMed Abstract]
[26] Hot flashes—a review of the literature on alternative and complementary treatment approaches. [PubMed Abstract]
[27] Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. [PubMed Abstract]
[28] The effects of gamma-oryzanol supplementation during resistance exercise training. [PubMed Abstract]
