Gamma Oryzanol

Scientific Name(s): Oryza sativa L. Poaceae (grass) family.

Common Name(s): Rice bran oil , rice bran wax , rice bran protein , gamma oryzanol , gammariza

Uses

Rice bran oil is used extensively in Asia for cooking because of its high smoke point, and gamma oryzanol is widely used in the cosmetic industry. Clinical trial data are often of poor methodology, making it difficult to support suggested clinical applications; however, rice bran oil and its components may have applications in dyslipidemia, cancer, and dermatology.

Dosing

Rice bran oil has been used in doses of up to 800 mg daily in clinical studies in hyperlipidemia. Gamma oryzanol alone has been used at a daily dose of 500 mg/day.

Contraindications

Contraindications have not yet been identified; however, use of the component phytic acid in renal impairment is not advised.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Rice bran oil and extracts are considered to be very safe, with only a low incidence of minor allergic reactions reported.

Toxicology

Concerns regarding toxicity can be largely attributed to an incident in the late 1960s in Japan when contaminated rice bran oil affected at least 1,800 people. However, rice bran oil has not been shown to be mutagenic, clastogenic, or carcinogenic in short-term toxicity studies. An increase in bladder cancer has been associated with the sodium salt of phytic acid, but not the potassium or magnesium salts, and an increase of lung cancer has been suggested for high dose gamma oryzanol.

Botany

Rice bran oil is extracted from the bran fraction of rice kernels or seeds of the rice plant. The outer chaff of the rice seeds are milled off to produce brown rice; further milling removes the bran portion (the rest of the husk and the germ portions), creating white rice.

The rice plant grows up to 1.8 m tall, depending on location and conditions. It has long, slender leaves, and small wind-pollinated flowers. The species is native to South Asia and some parts of Africa but is cultivated widely. As a cereal grain, it is a major source of nutrition for a large portion of the world's population. 1 , 2

History

Rice bran oil is used extensively, especially in Asia, for cooking. It has a nut-like flavor and a high smoke point, making it suitable for deep frying and cooking at high temperatures. Rice bran extracts are used in the cosmetic industry.

Isolation, extraction, and purification of gamma oryzanol were first reported in the mid-1950s. It has been used in Japan as a medicine since 1962, first to treat anxiety, and later in menopause. Gamma oryzanol and rice bran oil therapy have been used to manage elevated cholesterol and triglyceride levels since the late 1980s. 2 , 3

Chemistry

Rice bran oil, gamma oryzanol, and phytic acid are chemical constituents of rice seed in the experimental and clinical realm.

The bran fraction is approximately 8% of the rice kernel and consists of saturated and unsaturated fatty acids and alcohols, phytosterols, tocotrienols, tocopherols, vitamins (including biotin, vitamin B 12 , thiamine, niacin), and minerals (including phosphorous, magnesium, potassium, zinc).

Gamma oryzanol is a mixture of esters of sterols (eg, campestrol, stigmasterol, beta-sitosterol) and triterpene alcohols and their ferulate esters. Approximately 7,500 tons of gamma oryzanol are processed from rice bran in Japan each year. Hydrolyzed rice bran protein containing a high portion of globulins and albumins is also extracted from the bran. 2 , 3 , 4

Uses and Pharmacology

Bodybuilding

Gamma oryzanol has been promoted for use in bodybuilding. Some studies suggest that gamma oryzanol is poorly absorbed, with the bulk of the dose excreted in the feces. 5

Animal data

Endocrinological studies in animals indicate that gamma oryzanol suppresses leutinizing-hormone release and reduces growth hormone. 6 Gamma oryzanol may reduce testosterone production. 7

Clinical data

Few well-controlled human trials exist, with the weight of evidence in studies of adequate methodology suggesting no influence on performance during resistance exercise training. 6 , 8

Cancer

Two compounds isolated from rice bran oil have been investigated for potential applications in cancer—the triterpene cycloartenol ferulate and phytic acid. Although rice bran oil contains tocotrienol and exhibits antioxidant activities, few studies have investigated mechanisms of action. 9

Animal data

Cycloartenol ferulate has demonstrated inhibition of tumor promotion in mouse skin models, as well as an anti-inflammatory action similar to that of indomethacin. 10 Phytic acid (also called IP6) is actively promoted as an anticancer agent, based on animal and in vitro studies in cancers such as breast, colon, liver, prostate, and skin, as well as leukemia. 11 , 12 However, caution is warranted because some of these studies using gamma oryzanol and phytic acid have produced increases in bladder and renal papillomas, as well as lung and bladder cancers at higher doses. 11 , 13

Clinical data

Clinical trials are lacking. 11

Dermatology
Animal data

Gamma oryzanol applied topically in rats increased sebaceous secretion and turnover of sebaceous gland cells. Increases in peripheral blood flow were also observed. 10 The ferulates in gamma oryzanol may adsorb ultraviolet radiation. 14 Squalene extracted from rice bran oil has been shown to exert emollient, hydrating, and antioxidant properties in skin models and has been used as a vehicle in lipid emulsions. 15

Clinical data

Based on animal experiments, proposed applications for gamma oryzanol include the repair of damaged or dry skin and anti-aging effects. Although clinical trials are lacking, gamma oryzanol is a component of many cosmetic preparations. 10 , 14

Dyslipidemia
Animal data

Several studies have indicated that gamma oryzanol and its related constituents (eg, tocotrienols) in rice bran oil exert marked hypocholesterolemic effects. However, there is some inconsistency in the data. 8 , 16 , 17 , 18 , 19 , 20 The availability of existing data from animal experiments and the relative safety of rice bran oil make data from further animal experiments largely redundant.

Clinical data

Human studies are promising; however, the methodology of many trials is poor. 8 , 9 , 21 Reduced total cholesterol and triglyceride levels and increases in the high-density lipoprotein:low-density lipoprotein ratio have been demonstrated in clinical studies. Mechanisms by which rice bran oil exerts its effect may include stimulation of cholesterol catabolism and suppression of HMG-CoA reductase; components involved include the tocotrienol content of the rice bran oil as well as beta-sitosterol and gamma oryzanol actions. 8 , 9 , 22 , 23 , 24 , 25 , 26

Other effects
CNS

The gamma oryzanol component cycloartenol ferulic acid ester has been shown to exert a suppressant effect on the CNS, causing sedation in rats at high doses and increasing levels of norepinephrine. 8 , 27 , 28 Tocotrienol from rice bran oil has demonstrated protective effects in hippocampal neurons from the effects of glutamate toxicity in vitro. 9

Endocrine

Gamma oryzanol has inhibited luteinizing, thyroid-stimulating, growth, and prolactin-secreting hormones in animal and limited human studies. 8

GI effects

Animal data and limited clinical studies suggest that gamma oryzanol exerts an antiulcer effect, inhibiting gastric secretion and improving healing. It has been used in humans to reduce dyspepsia; however, data from more recent studies are lacking. 8

Menopause

Earlier studies suggesting a role for gamma oryzanol in managing the symptoms of menopause have not been validated. Effects of gamma oryzanol on pituitary hormones, including luteinizing- and prolactin-secreting hormones, have been described in animal studies. 8

Dosage

Rice bran oil has been investigated in clinical studies to evaluate its effect in hyperlipidemia at doses of 50 mg/day for up to 25 weeks 9 to 800 mg daily for 4 weeks. 23

Gamma oryzanol has been studied for improvement in exercise training at a dose of 500 mg/day. 29 An increase of lung cancer has been observed at high doses of gamma oryzanol in animal experiments. 11 , 13

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Because effects on the pituitary gland have been demonstrated in animal experiments, gamma oryzanol should be avoided during pregnancy. 8

Interactions

None well documented. A study on the effect of gamma oryzanol on cytochrome P450 reactions showed little inhibition of CYP activity. Therefore, interactions dependent on these pathways are unlikely. 29 Chelation of certain elements has been demonstrated for phytic acid in animal studies, and iron absorption with concurrent rice bran product intake has been studied, but case reports for such interactions are lacking. 11

Adverse Reactions

Rice bran oil and extracts are considered to be very safe, with only a low incidence of minor allergic reactions reported despite the common understanding that rice is hypoallergenic. Case reports exist of urticaria to raw rice. Lotions containing rice bran oil show a low incidence of minor skin irritation. 3 In experimental animal studies on phytic acid, renal papillae changes have been observed, including necrosis and calcification. Therefore, use in renal impairment is not advised. 11

No adverse effects have been reported in gamma oryzanol animal or human studies. 2

Toxicology

Short-term toxicity studies in rodents suggest the LD 50 of rice bran oil to be more than 5 g/kg. Gamma oryzanol has not been shown to be mutagenic or clastogenic in models and is not carcinogenic in mice or rats. No gross abnormalities have been found on necropsy in short-term studies. Data from long-term studies are lacking. 3 , 8 , 30 , 31 , 32 An increase in bladder cancer has been associated with the sodium salt of phytic acid, but not the potassium or magnesium salts, and an increase of lung cancer has been suggested with high-dose gamma oryzanol. 11 , 13

Concern regarding toxicity can be largely attributed to an incident in the late 1960s in Japan when contaminated rice bran oil affected at least 1,800 people. Rice bran oil was contaminated with polychlorinated biphenyls (a dioxin) as well as polychlorinated quaterphenyls and dibenzofurans that resulted from the heating process. The subsequent “Yusho syndrome” has been described, with skin, eyes, and teeth effects, and intractable headache, hyperglyceridemia, and pulmonary symptoms persisting for as long as 30 years. It has also been suggested that this population of affected people have a higher risk of developing type 2 diabetes. 33 , 34 , 35

Bibliography

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