Gamma oryzanol is a compound extracted primarily from rice bran oil. Since the 1950s, it has been studied for various health applications including cholesterol management, exercise performance, and menopausal symptoms. In Japan, it has been used as a prescription medication for autonomic nervous system disorders and menopausal complaints.

But does the research support these uses? This article examines what we actually know about gamma oryzanol based on published clinical studies.

What is gamma oryzanol?

The name comes from Oryza sativa, the scientific name for rice. When Japanese researchers first isolated this compound from rice bran oil in 1954, they thought it was a single substance. Later analysis revealed it to be a mixture of compounds called ferulic acid esters of plant sterols and triterpene alcohols.

The main components include:

Cycloartenyl ferulate
24-methylenecycloartanyl ferulate
Campesteryl ferulate
Beta-sitosteryl ferulate

These four compounds account for roughly 80% of what we call gamma oryzanol. Small amounts also occur in barley, corn, wheat, oats, and various fruits and vegetables, though rice bran remains the primary commercial source.

In Japan, gamma oryzanol has been approved as a drug for treating autonomic nervous system disorders since 1962. Elsewhere, it is sold as a dietary supplement, often marketed to athletes or people seeking cholesterol support.

What does the research say about gamma oryzanol?

1. Blood lipid regulation

The most researched application for gamma oryzanol is its effect on cholesterol levels. Dyslipidaemia affects a substantial portion of adults worldwide and contributes to cardiovascular disease risk over time.

A study involving 20 patients with chronic schizophrenia who also had abnormal lipid profiles examined the effects of 100 mg gamma oryzanol taken three times daily for 16 weeks. The researchers found reductions in total cholesterol and LDL cholesterol, along with increases in HDL cholesterol [1].

I should note the obvious limitation here: this was a small study in a specific patient population, and results may not generalise to healthy adults.

A more rigorous double-blind randomised controlled trial looked at 59 people with hyperlipidaemia who consumed rice bran oil rich in gamma oryzanol for four weeks. Compared to controls, the rice bran oil group showed reduced LDL cholesterol levels. The researchers also measured improved antioxidant status using oxygen radical absorbance capacity and ferric reducing antioxidant power assays [2].

The proposed mechanism involves two pathways: gamma oryzanol appears to inhibit HMG-CoA reductase, the same enzyme targeted by statin medications, and may also increase activity of cholesterol 7-alpha-hydroxylase (CYP7A1), which helps convert cholesterol to bile acids for excretion.

Whether these effects are clinically meaningful compared to established treatments remains unclear. The existing studies are small and short-term. If you have diagnosed hyperlipidaemia, standard medical treatments have far more evidence behind them.

2. Exercise performance and muscle strength

Gamma oryzanol gained popularity among bodybuilders in the 1980s and 1990s based on claims it could increase testosterone levels and muscle mass. The initial excitement came from one early study, but subsequent research has not supported these claims.

A randomised double-blind trial assigned 30 healthy volunteers to receive either 600 mg gamma oryzanol or placebo daily during a nine-week resistance training programme [3]. The results were mixed at best. There was no significant difference in body composition or skinfold thickness between groups. The supplementation group did show some improvement in muscle strength measurements after training, but the effect was modest.

I would be cautious about reading too much into this. The sample size was small, and the strength improvements could reflect normal variation. Athletes looking for proven performance enhancers would be better served by focusing on adequate protein intake, proper training programmes, and sufficient recovery time.

A separate study found that gamma oryzanol did not significantly increase testosterone, growth hormone, or other anabolic hormones in weight-training males [4]. This contradicts the marketing claims that drove its initial popularity in fitness circles.

3. Cognitive function

Animal research has explored whether gamma oryzanol might protect against age-related cognitive decline. In rodent models, the compound has shown some neuroprotective properties, potentially related to its antioxidant effects and ability to modulate inflammation in brain tissue [5].

The animal data is interesting from a mechanistic standpoint, but we have very little human evidence. Extrapolating from mouse studies to human cognitive outcomes is problematic. Many compounds that show promise in animal models fail to demonstrate benefits in human trials.

If you are concerned about cognitive decline or dementia, the best-supported interventions remain physical exercise, maintaining social connections, managing cardiovascular risk factors, and treating conditions like diabetic bladder dysfunction and related metabolic disorders that can affect brain health indirectly.

4. Anti-tumour effects

Laboratory and animal studies have found that gamma oryzanol can inhibit tumour growth through several mechanisms, including activating natural killer cells, stimulating macrophage activity, and reducing angiogenesis (the formation of new blood vessels that tumours need to grow) [6].

I want to be direct here: these are test tube and animal findings. They tell us gamma oryzanol has certain biological properties, but they do not mean it can prevent or treat cancer in humans. Many compounds that kill cancer cells in a petri dish have no clinical utility. The leap from laboratory findings to effective human treatment is enormous.

The research into gamma oryzanol and cancer is preliminary. Anyone with cancer should work with oncologists and follow evidence-based treatment protocols.

5. Blood sugar regulation

Type 2 diabetes involves insulin resistance and eventual decline in insulin-producing beta cells in the pancreas. Animal studies suggest gamma oryzanol may improve insulin sensitivity and protect pancreatic beta cells from dysfunction and death [7, 8].

One proposed mechanism involves gamma oryzanol reducing endoplasmic reticulum stress in beta cells, which could help preserve their function. In mouse models, supplementation improved glucose tolerance and insulin secretion.

Again, these are animal findings. We lack good human trials examining whether gamma oryzanol actually helps people with diabetes or those at risk. People managing blood sugar should focus on proven approaches: dietary modifications, physical activity, weight management, and medications as prescribed.

Side effects of gamma oryzanol

In the limited human studies conducted to date, gamma oryzanol appears to be well tolerated. Most trials have not reported significant adverse effects at doses up to 300-600 mg daily.

However, the safety data is not extensive. Most studies have been short-term, and long-term effects are not well characterised.

There is one concerning finding from animal research. A study in rats suggested gamma oryzanol might promote lung cancer development, though the effect was weak and only occurred at very high doses [9]. Other animal studies found no carcinogenic effects even at doses of 2000 mg per kilogram of body weight [10, 11], which is enormously higher than any human would take.

Common sense applies: if you experience any unusual symptoms while taking gamma oryzanol supplements, discontinue use and consult a healthcare provider.

Safety precautions (2 contraindications)

Based on current knowledge, two groups should avoid gamma oryzanol:

1. Pregnant and breastfeeding women

Safety during pregnancy and lactation has not been established. In the absence of data showing it is safe, the prudent approach is to avoid supplementation during these periods. The potential risks to a developing foetus or nursing infant are unknown.

2. People with thyroid disorders

Research indicates gamma oryzanol may reduce thyroid-stimulating hormone (TSH) levels [12]. This could potentially interfere with thyroid function or complicate the management of existing thyroid conditions.

If you have hypothyroidism, hyperthyroidism, or any thyroid disorder, discuss gamma oryzanol with your endocrinologist before considering supplementation. The effect on TSH could alter the effectiveness of thyroid medications or complicate diagnostic testing.

Dosage considerations

Human studies have typically used doses ranging from 100 mg to 600 mg daily. The Japanese prescription form for autonomic disorders uses doses around 10-30 mg three times daily.

Because gamma oryzanol is a dietary supplement rather than a regulated medication in most countries, product quality can vary significantly. Independent testing has found that some supplements do not contain the amounts listed on labels.

If you choose to try gamma oryzanol, look for products from reputable manufacturers who conduct third-party testing.

The bottom line

Gamma oryzanol has a long history of use in Japan and has been studied for cholesterol management, exercise performance, and other applications. The evidence base is modest. Most human studies have been small and short-term.

For cholesterol management, the data is perhaps most encouraging, though conventional treatments have far stronger evidence. Claims about muscle building and testosterone enhancement are not supported by research. The cognitive and anti-cancer findings come from animal and laboratory studies that cannot be directly applied to humans.

If you are interested in trying gamma oryzanol for cholesterol support, it is reasonable to discuss this with your doctor. It may have a role as an adjunct to diet and lifestyle modifications, particularly for people who prefer to explore options before starting medication.

References

Sasaki J, Takada Y, Handa K, et al. Effects of gamma-oryzanol on serum lipids and apolipoproteins in dyslipidemic schizophrenics receiving major tranquilizers. Clin Ther. 1990;12(3):263-268. https://pubmed.ncbi.nlm.nih.gov/1974170/
Bumrungpert A, Chongsuwat R, Phosat C, et al. Rice bran oil containing gamma-oryzanol improves lipid profiles and antioxidant status in hyperlipidemic subjects: a randomized double-blind controlled trial. J Altern Complement Med. 2019;25(3):353-358. https://pubmed.ncbi.nlm.nih.gov/30265563/
Fry AC, Bonner E, Lewis DL, et al. The effects of gamma-oryzanol supplementation during resistance exercise training. Int J Sport Nutr. 1997;7(4):318-329. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164998/
Wheeler KB, Garleb KA. Gamma oryzanol-plant sterol supplementation: metabolic, endocrine, and physiologic effects. Int J Sport Nutr. 1991;1(2):170-177.
Rungratanawanich W, Cenini G, Voos W, et al. Gamma-oryzanol improves cognitive function and modulates hippocampal proteome in mice. Nutrients. 2019;11(4):753. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520752/
Kim SP, Kang MY, Nam SH, et al. Dietary fermented brown rice bran by Lentinus edodes enhances NK cell immune function and reduces tumor metastasis. J Nutr Biochem. 2012;23(9):1001-1008. https://pubmed.ncbi.nlm.nih.gov/22707268/
Kozuka C, Yabiku K, Sunagawa S, et al. Brown rice and its component, gamma-oryzanol, attenuate the preference for high-fat diet by decreasing hypothalamic endoplasmic reticulum stress in mice. Diabetes. 2012;61(12):3084-3093. https://pubmed.ncbi.nlm.nih.gov/20533244/
Kozuka C, Yabiku K, Takayama C, et al. Natural food science based novel approach toward prevention and treatment of obesity and type 2 diabetes: recent studies on brown rice and gamma-oryzanol. Obes Res Clin Pract. 2013;7(3):e165-e172. https://pubmed.ncbi.nlm.nih.gov/25594697/
Tamagawa M, Shimizu Y, Hayashi T, et al. Carcinogenicity test of gamma-oryzanol in B6C3F1 mice. Food Chem Toxicol. 1992;30(1):49-56. https://pubmed.ncbi.nlm.nih.gov/10625936/
Tamagawa M, Shimizu Y, Takahashi T, et al. Carcinogenicity test of gamma-oryzanol in F344 rats. Food Chem Toxicol. 1992;30(1):41-48. https://pubmed.ncbi.nlm.nih.gov/1544605/
Tamagawa M, Otaki Y, Takahashi T, et al. Carcinogenicity study of gamma-oryzanol in B6C3F1 mice. Food Chem Toxicol. 1992;30(1):49-56. https://pubmed.ncbi.nlm.nih.gov/1544606/
Ishihara M. Effect of gamma-oryzanol on serum lipid peroxide level and clinical symptoms of patients with climacteric disturbances. Asia Oceania J Obstet Gynaecol. 1984;10(3):317-323. https://pubmed.ncbi.nlm.nih.gov/7389672/