GAMMA ORYZANOL
THE SECRET NUTRIENT
by Ronald L. Myers, CNC
Imagine a single nutrient that possesses the following properties: anti-oxidant, anti-carcinogenic, anti-ulcer, anti-stress, lipotrophic effects, hypothalamic effects, endocrinological effects, athletic benefits and benefits to the skin similar to Vitamin E. The nutrient with such wide-ranging power is Gamma Oryzanol. In this issue I will… cover this nutrient in detail; what is it, where does it come from and HOW does it work.
WHAT IS GAMMA ORYZANOL?
It is a nutrient with a strange sounding name that occurs naturally in many plants, especially the rice plant. The scientific name for rice is Oryza sativa, from which gamma oryzanol gets its name.
The chemical structure is that of two molecules in one, first a plant sterol and second ferulic acid. The sterol (triterpenyl alcohol) is the largest part of the molecule. Hormones such as testosterone, estrogen, progesterone, DHEA and corticosteroids, etc. are derived from cholesterol and can be thought of as modified sterols1. For this reason you may consider Gamma Oryzanol as a universal hormone precursor.
Ferulic acid is one of the hydroxycinnamic acids, a subgroup of plant phenolic acids2. In its purified state, it tastes and smells like cinnamon. Ferulic acid is a precursor for lignin, the polymer that makes up most physical support structures of plants. In rice, ferulic acid is added on to sterols, forming gamma oryzanol. In3other plants it is bound to sugars, cell walls, cellulose, etc., as well as being found in its free form .
There is no conclusive evidence of the presence of gamma oryzanol in any other plant than rice. This does not mean rice is the only source of gamma oryzanol in nature; methods of plant analysis for compounds similar to gamma oryzanol usually include hydrolysis, which could easily destroy it leaving sterols and ferulic acid as end products. Since rice is a plentiful and economic source of the nutrient there is not much incentive to do a systematic search for alternative sources.
Records indicate the Japanese were the first to isolate gamma oryzanol from rice in 1943. Today, rice is still the only known source of the nutrient.
BUT IS IT SAFE?
A long history of rice consumption by man and animals would suggest that gamma oryzanol does not cause much, if any toxicity. Still, Japanese companies have conducted safety tests on gamma oryzanol to satisfy Japanese government regulations regarding food additives and supplements. These tests began with determining if gamma oryzanol is toxic to animals by injecting ever increasing doses to arrive at the LD50 (lethal dose for 50% of the test animals). Such tests have revealed an acute LD50 of greater than 30gm/kg for mice, which would be equivalent to an average adult being injected with over 2100 grams (about 4 pounds) and surviving, meaning gamma oryzanol is extremely NON-TOXIC!4 Furthermore, feeding large daily doses to baby mice and chicks led to no harmful effects and even caused an increase in body weight over controls.5
The use of gamma oryzanol in dozens of human trials has found virtually no toxicity or side effects even at doses of 600mg daily for over 8 weeks. It’s safe.
ANTIOXIDANT EFFECTS
A standard model of tissue free radical damage is liver necrosis caused by carbon tetrachloride. Gamma oryzanol fed to rats at a dose of 100mg/kg 6 hours before exposure to carbon tetrachloride prevented half of the mortality, half of the decrease in cytochrome P450 levels and completely prevented lipid peroxidation of the liver.6
When rats were fed oxidized, rancid oil, significant growth reduction, red blood cell hemolysis and reduced polyunsaturated fatty acid levels were seen. Addition of gamma oryzanol to the rancid oil restored growth to normal, prevented red blood cell hemolysis and maintained normal tissue polyunsaturated fatty acids levels.7
Finally, when 300mg of gamma oryzanol per day was given for 4 – 8 weeks to 40 women with elevated serum lipid peroxide levels, a significant lowering to almost normal levels was seen. This shows that gamma oryzanol can provide useful antioxidant activity in humans when taken orally.8
ANTICARCINOGENIC EFFECTS
This is a function of antioxidant’s free radical scavenging potential as cancer is recognized as a free-radical pathology. Predicting cancer risk is difficult at best due to the complexity of the disease development. Some considerations are which carcinogens are encountered, what dose over what time period, subject response, stress and dietary effects, amounts of exogenous and endogenous antioxidants present, etc., etc.
Active carcinogens are electron deficient molecules (free radicals). These molecules react with electron rich molecules such as DNA, RNA, protein and membranes leading to genetic damage; loss of cell function and potential cell death; and cancer.
Those consuming diets high in fruits and vegetables present lower incidence of major cancers. 9 Research has identified numerous compounds in plants that are anticarcinogens such as vitamin A, vitamin C, vitamin E, selenium, cysteine and phenolic acids.10 Ferulic acid (part of the gamma oryzanol molecule) is a phenolic acid.
Let’s look at the activity of ferulic acid in preventing the conversion of nitrites to nitrosamines, a known carcinogen. Nitrites (sodium nitrite) are widely used as food preservatives to maintain color and prevent the growth of pathogens. Nitrosamines are continually formed and excreted by the human body, but consumption of nitrite preserved foods can lead to as much as 100 times the expected nitrosamine load.11
At acidic pH, nitrites can react with many compounds to produce nitrosamines. Because of its acidic pH, the stomach is believed to be the major site of nitrosamine formation from nitrites. Ferulic acid has been shown to prevent formation of nitrosamine from nitrites both in vitro and in vivo in humans and mice.12 13 It is 10 times more potent than equal amounts of vitamin C. Ferulic acid is one of many dietary phenolic acids that can block the actions of certain carcinogens. It can directly prevent the formation of nitrosamine from nitrites in humans. Its action is thought to be due to its ability to inhibit the activity of cytochrome P450 mixed function oxidases.
ANTI-ULCER EFFECTS
In a study conducted at the Gunma University School of Medicine in Maebashi, Japan, 29 patients with chronic gastritis were given 300mg of gamma oryzanol daily for four weeks. This protocol was effective in reducing nausea, fatigue, and post meal discomfort and fullness in 75% of the patients tested.14 A second study conducted at the University compared 13 patients with chronic gastritis to 7 normal controls.15 The same protocol was used for four weeks with surprising results. Gamma oryzanol administration reduced serum gastrin levels to 75% of pre- administration levels for gastritis patients, but did not affect gastrin levels in the healthy controls. THAT’S INCREDIBLE! The mechanism of activity seems to be normalization of autonomic nervous system function, specifically the vagus nerve, by altering brain neuron catecholamine levels.
ANTISTRESS EFFECTS
Several studies have shown gamma oryzanol to be as effective as many drugs in reducing objective, systemic effects of stress. Normalization (rather than suppression) of the autonomic nervous system is the proposed mechanism of action of gamma oryzanol in reducing stress.
Some of the complaints gamma oryzanol has been used to help are menopausal disturbances, head injuries, stomatitis, hormonal imbalances, non-specific psychogenic complaints, atrophic gastritis, stomach ache, loss of appetite, nausea, heartburn, fatigue, insomnia, palpitations, dizziness, headaches and lumbago.
Doses of Gamma Oryzanol used to treat the above complaints were from 25mg to 300mg daily.
LIPOTROPIC EFFECTS
Since gamma oryzanol is a chemical cousin to cholesterol, it makes sense that interactions between the two can occur in the body. Several studies have shown that when phytosterols (gamma oryzanol is a phytosterol) are fed with cholesterol containing meals, they inhibit the intestinal absorption of cholesterol from dietary and endogenous synthesis sources.16 17 18 Phytosterols work by forming an unabsorbable 1:1 complex with cholesterol molecules and by making cholesterol less soluble in bile.19 This means cholesterol will not be as readily absorbed by the intestinal cells and passes out of the body through the G.I. tract along with the unabsorbed phytosterols.
To inhibit cholesterol absorption, a ratio of 2:1 phytosterol to cholesterol must be achieved. It must be present at the same time as the cholesterol meal. In humans, this would work out to a minimum of 300mg of gamma oryzanol with the cholesterol containing meal. Higher doses do not result in a greater reduction of cholesterol levels. (Research indicates a normalizing as opposed to an inhibitory effect on HMG Co A reductase by gamma oryzanol.)
HYPOTHALAMIC EFFECTS
A family of releasing and release-inhibiting peptides secreted by the hypothalamus controls hormone secretion by the anterior pituitary.
Norepinephrine is the neurotransmitter for the sympathetic portion of the autonomic nervous system. This neurotransmitter is synthesized from the amino acid tyrosine. It is degraded primarily by the enzyme catechol-O-methyltransferase (COMT) into an inactive metabolite (normetanephrine). This is a continual, normal metabolic event of nerve cells. The chemical structure of ferulic acid and normetanephrine is strikingly similar. When ferulic acid (recall that gamma oryzanol is metabolized to ferulic acid) is present with COMT enzymes, a feedback inhibition may occur because of the similarity in structure between ferulic acid and the COMT metabolite normetanephrine. The net result is a slowing of COMT activity. Less COMT activity means less norepinephrine degradation, resulting in higher levels of norepinephrine and more effect from norepinephrine. In addition, it appears that ferulic acid may compete with norepinephrine for binding to COMT enzymes since these enzymes can also metabolize ferulic acid.20 The net result is less COMT activity and more norepinephrine.
ENDOCRINE EFFECTS
Pituitary hormones regulate the other endocrine glands. Secretions of these other endocrines control such functions as reproduction, growth, immune response and metabolism resulting in homeostasis (balance, normal function).
To make a long story short, gamma oryzanol exerts its influence on the autonomic nervous system (including the hypothalamus) not the endocrine glands specifically, as has already been presented. This is irrespective of the sex of the subject, male or female. In two studies conducted at the Gunma University Hospital in Maebashi Japan, gamma oryzanol was administered to normal subjects and patients suffering from primary hypothyroidism. No effects on TSH levels in the normal subjects were observed, but the hypothyroid patients had serum TSH levels reduced to 75% of basal values. Further investigations found no effect on the pituitary or thyroid, but hypothalamic effects mediated the observed changes.21
ATHLETIC USES
Gamma oryzanol is a plant sterol. It can exert steroid like activity if the subject is physically active (is exercising). An unpublished study by Bucci, L., Stiles, J., Sparks, W., and DeLuca, D., 1987, compared anabolic steroid users to those athletes supplemented with gamma oryzanol. Initially, the anabolic steroid users showed greater gains in girth measurements, but by 16 weeks, the gamma oryzanol users exhibited greater girth measurement increases that all steroid users, without ANY side effects! And the dose for gamma oryzanol is low, 75mg to 150mg a day.
SKIN USES OF GAMMA ORYZANOL
The beneficial effects of gamma oryzanol on the skin are at least equal to that of vitamin E. Research indicates this effect is achieved through topical application of gamma oryzanol containing creams. Creams claiming to contain gamma oryzanol are available in the market place today. They may be expensive for the patient to obtain, and a good quality vitamin E cream may be effective for much less cost.
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REF :
1 Hahlbrock, K., Grisebach, H., Enzymatic controls in the biosynthesis of lignin and flavonoids, Ann. Rev. Plant Physiol., 30,105, 1979.
2 Ibid.
3 Winter, M. and Herrmann, K., Esters and glucosides of hydroxycinnamic acids in vegetables, J. Agric. Food Chem., 34, 616, 1986.
4 Anonymous, Gamma-oryzanol reports, Amakasu Chemical Industries, Tokyo, Japan, 1980.
5 Ibid.
6 Okita, K., et al, A study on the interaction between liver diseases and their therapeutic agents: Etiological factors in carbon tetrachloride induced hepatic necrosis and its prevention with antioxidant, Acta Hepatol. Jap., 23(11), 1299, 1982.
7 Kajimoto, G., et al, Toxic character of rancid oil. XV. Biological effect of oryzanol on the growth of rats fed thermally oxidized oil, Yukagaku [J. Jap. Oil Chem. Soc.], 23(12), 771, 1974.
8 Ishihara, M., Ito, Y., et al, Clinical effect of gamma oryzanol on climacteric disturbance and serum lipid peroxides, Nippon Sanka Fujinka Gakkai Zasshi, 34(2), 243, 1982.
9 Mettlin, C., et al, Diet and cancer of the esophagus, Nutri. Cancer, 3, 145, 1981.
10 Newmark, H., A hypothesis for dietary components as blocking agents of chemical carcinogenesis: plant phenolics and pyrrole pigments, Nutri. Cancer, 6(1), 58, 1984.
11 Stich, H. F., et al, The effect of dietary factors on nitrosoproline levels in humans urine, Int. J. Cancer, 33, 625, 1984.
12 Kikugawa, K., et al, Reaction of p-hydroxycinnamic acid derivatives with nitrite and its relevance to nitrosamine formation, J. Agric. Food Chem., 31, 780, 1983
13 Kuenzig, W., Caffeic and ferulic acid as blockers of nitrosamine formation, Carcinogenesis, 5(3), 309, 1984.
14 Arai, T., Clinical studies on chronic gastritis 1. Effect of a few drugs on clinical evaluations and serum gastrin levels, Kitakanto Med. J., 30(3), 71, 1980.
15 Arai, T., Clinical studies on chronic gastritis 2. Endocrine effects of gamma oryzanol, Kitakanto Med. J., 30(3), 85, 1980.
16 Child, P., The absorption of cholesterol and plant sterols in the intestine, Fat Absorption, Vol. 2, Kuksis, A., Ed., CRC Press, Boca Raton, 1987, 1.
17 Subbiah, M., Dietary plant sterols-current status in human and animal sterol metabolism, Am. J. Clin. Nutr., 26, 219, 1973.
18 Subbiah, M., Significance of dietary plant sterols in man and experimental animals, Mayo Clin. Proc., 46, 549, 1971.
19 Child, P.
20 Finkle, B., Prologue: patterns of phenolic mediation in plants and animals, Phenolic Compounds and Metabolic Reactions, Appleton-Century Crofts, New York, 1967.
21 Shinomura, Y., et al, Effect of gamma oryzanol on serum TSH concentrations on primary hypothyroidism, Endocrin., Japan, 27(1), 83, 1980.
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