Gamma Oryzanol

Gamma Oryzanol (γ-Oryzanol) is a mixture of compounds in Rice Bran Oil and other sources that share a common structure. Promising but unproven cholesterol lowering agent with some skin health properties, does not increase Testosterone.

This page features 34 unique references to scientific papers.


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Also Known As

γ-Oryzanol


The dosages of Gamma-oryzanol used are highly variable, with some studies using a lower dose (50mg once daily or 20mg thrice daily) and other studies using a markedly higher dosage (300-800mg daily). As there are no reliable benefits associated with Gamma-oryzanol supplementation in the first place, it is unsure what dosage should be recommended (if this supplement is to be recommended at all).


The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Gamma Oryzanol has in your body, and how strong these effects are.
GradeLevel of Evidence
ARobust research conducted with repeated double blind clinical trials
BMultiple studies where at least two are double-blind and placebo controlled
CSingle double blind study or multiple cohort studies
DUncontrolled or observational studies only
Level of Evidence
EffectChange
Magnitude of Effect Size
Scientific ConsensusComments
CLDL-C

Although rice bran oil may reduce LDL cholesterol, there is insufficient evidence to support the role of gamma-oryzanol in this role

CTotal Cholesterol

No significant alterations seen in total cholesterol levels with supplementation

CHDL-C

No detectable influences on HDL cholesterol, although rice bran oil (a source of gamma oryzanol) may have a slight positive effect

CTestosterone

No detectable influence on testosterone levels in otherwise healthy men

CCortisol

No significant influence on cortisol levels with prolonged supplementation

CEstrogen

No significant influence on circulating estrogen levels in healthy men given gamma-oryzanol over a few weeks

CGrowth Hormone

No significant alterations in growth hormone following ingestion of gamma-oryzanol

CInsulin

No significant alterations noted in fasting insulin levels following prolonged ingestion of gamma-oryzanol in healthy persons

CPlasma Endorphins

Plasma beta-endorphin is unaltered following ingestion of standard doses of gamma-oryzanol

CPower Output

No interactions with power output have been noted with gamma-oryzanol ingestion

CTriglycerides

No significant alterations in plasma triglycerides seen with supplementation


Disagree? Join the Gamma Oryzanol Discussion

Table of Contents:


Edit1. Sources and Composition

1.1. Sources

Gamma-oryzanol is most well known for being a component of Rice Bran Oil[1] as well as rice itself[2][3][4] and is credited alongside Policosanol and tocotrienols (alternate forms of Vitamin E) for cholesterol reducing properties as a combination of unsaponifiable constitients.[5][6]

The aforementioned 'unsaponifiable' constitients are merely a subset of the fatty acids which do not undergo saponification reactions (similar to soap making processes), in this scenario it is due to the sterols known as Gamma-Oryzanol being bound to a molecule known as Ferulic Acid; Gamma-Oryzanol is essentially a term used to refer to a collection of ferulated sterols.

Rice bran itself (10% of unprocessed rice by weight) is 18-22% oil, of which up to 5% is the unsaponifiable fraction.[7] Due to this, the benefits associated with Gamma-Oryzanol may not be easily achieved with oral Rice Bran, due to Gamma-Oryzanol being at best 0.1% of Rice Bran by weight; Rice Brain Oil is plausible, but requires an oral dose of 6g to mimick 300mg Gamma-Oryzanol.[7]

1.2. Composition

Gamma-oryzanol is a term used to refer to a collection of molecules build on a ferulic acid backbone, with 4-4'dimethylsterol or 4-desmethylsterol groups esterified to the ferulic acid. The compounds commonly referred to as Gamma-Oryzanol include:

  • Cycloartenol and Cycloartenyl Ferulate, the latter of which is seen as the primary ingredient[8]
  • Beta-sitosterol (common in many plants)[8]
  • 24-methylenecycloartanol[8]
  • Campesterol[8]

The content of Gamma-Oryzanol varies depending on strain of rice, but tends to be around 244.1-342.6mg/kg with most content being attributed to cycloartenyl ferulate (27-30%) and 24-methylene cycloartenyl ferulate (53-57%).[2]

Gamma-Oryzanol is a term used to refer to the above four molecules; fairly common structures but all bound to a Ferulic Acid molecule (and thus, Ferulated). The constitient molecules per se are not unique and are found in many vegetables, but are not too common when ferulated.


Edit2. Pharmacology

2.1. Dermal Transporter

Gamma Oryzanol has demonstrated to pass through the skin membranes (transdermal application) when entrapped with Niosomes, transporter molecules composed of Tween 61 and cholesterol at equal ratios.[9][10]

2.2. Serum

As Gamma Oryzanol is a collection of ferulated sterols, these molecules can be metabolized to provide circulating ferulic acid; with 300mg of Gamma-Oryzanol orally elevating serum levels of Gamma Oryzanol and Ferulic Acid on average to 37.6ng/mL and 36.6ng/mL, respectively.[11] A later test noted that acute dosing of 600mg led to significant variability in serum Gamma-Oryzanol (21-106.8ng/mL), and that thrice daily dosing of 100mg was able to provide a relatively constant serum level of 111.7ng/mL.[11]

Ferulic acid is excreted in the urine at 2.4-2.8% of the oral dose, with no detectable urinary Gamma-Oryzanol.[11]

Repeated dosing may be more effective than single dosing, but pharmacokinetic data is limited

2.3. Enzymatic Interactions

Gamma-Oryzanol, at 1-30ug/mL, failed to significantly inhibit CYP1A1/2, CYP2A6, CYP2B6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4; with the most inhibitory potential being a mere 16% at 30ug/mL on CYP1A1/2.[11]

Not yet found to inhibit any enzymes that would precede drug-drug interactions


Edit3. Neurology

3.1. Appetite

One study in rats noted that there appeared to be preference for a diet containing Gamma-Oryzanol (high carb diet, via brown rice) in preference of a high fat diet. This was said to be possibly influenced by Gamma Oryzanol as injection of a chemical into they hypothalamis to reduce endoplasmic reticulum (ER) stress also induced preference for the high carb diet, and Gamma Oryzanol was found to control excess ER stress in high-fat fed rats and ER stress induced by a toxin.[12] This study also noted suppression of a high-fat diet induced increase of TNF-a and IL-6 expression, normalizing the levels to that of the high carb control.[12]

Studies using Gamma-Oryzanol in animals given a high fat diet fail to find reductions of overall food intake associated with 0.5% Gamma-Oryzanol of the diet. [13][14]

Some evidence that it may alter preference for food, with unknown potency or practical relevance; does not appear to really reduce food intake in animals

3.2. Menopausal Symptoms

Gamma-Oryzanol is sometimes referred to as a supplement against symptoms of menopause.

The first studies to assess this claim noted that 1,500mg of gamma-oryzanol particulate (300mg total gamma-oryzanol) over 8 weeks was associated with improvements in menopausal symptoms in 90% of the study population (40% reporting the improvements as excellent)[15] which has elsewhere been attributed to the ferulic acid content.[16] More recently, thrice daily dosing of 20mg Gamma-Oryzanol has failed to outperform acupuncture (no control used in this study, and cited vicariously through two reviews[17][18] as the full text cannot be located online).

The evidence to support gamma-oryzanol for usage in menopause is somewhat lacklustre, with one quite old study showing promising but the more recent study showing no benefit being underdosed. More research on this topic is needed


Edit4. Cardiovascular Health

4.1. Mechanisms

Gamma-Oryzanol appears to negatively influence the intestinal absorption of cholesterol directly, with high concentrations also impairing micelle formation.[19] At 0.5% of the diet in rats, Gamma-Oryzanol can increase the amount of sterols and bile acids in the feces by 107% and 246%, respectively.[14]

May reduce choleterol absorption, practical significance and potency relative to other cholesterol-inhibiting compounds is uncertain

4.2. Artherosclerosis

Secondary to NF-kB inhibition (of which Gamma-Oryzanol components are moderately potent) one in vitro study noted that less inflammatory response from NF-kB resulted in less expression of adhesion molecules. Less VCAM-1 and E-selectin were expressed at 3uM while increasing the concentration to 30uM reduced both of those as well as ICAM-1; this led to less monocyte adhesion, reducing a 7-fold increase under inflammatory conditions to 1.7-fold under the influence of 30uM Gamma-Oryzanol, and was twice as effect as the control drug Pyrrolidine dithiocarbamate (PDTC)[20]

Possesses anti-artherogenic properties secondary to it being anti-inflammatory

4.3. Interventions

One study conducted in 30 hypercholesterolemic men with dietary guidance over 6 weeks were randomized to one of two Rice Bran Oils, varying in only their Gamma-Oryzanol content; one being low (50mg/50g; 0.1%) and the other high (800mg/50g; 1.6%).[21] There was no significant difference between groups at any time-point.[21]

This study noted a 11.9% reduction in LDL-C within two weeks of Rice Bran Oil, which was met with a slight reduction of HDL-C; there was a decrease in total cholesterol relative to baseline, but this decrease was met with peanut oil used as a control during dietary lead-in.[21]


Edit5. Interactions with Glucose Metabolism

A diet consisting of 0.5% Gamma-Oryzanol in rats over 4 weeks was able to attenuate the rise in serum glucose concentrations induce by a high-fat diet secondary to increasing glycogen carbohydrate content and insulin levels.[13] There was a suppression of G6Pase and PEPCK enzyme activity associated with Gamma-Oryzanol, and this was also seen with Ferulic Acid at 0.5% at similar potency.[13]

One rat study noted a lesser AUC of insulin in a rat group fed 0.525% Gamma-Oryzanol, but no influence on glucose AUC or either glucose or insulin response to an intraperitoneal glucose tolerance test.[14]

May benefit glucose metabolism secondary to its Ferulic Acid components, unknown practical relevance


Edit6. Exercise and Performance

6.1. Interventions

A 9 week resistance training program in 22 recreationally active males was sufficient to reduce skinfold measurements while increasing body mass, with the addition of daily 500mg Gamma-Oryzanol failing to be significantly different than placebo.[22] This study did not measure power output.[22]

No notable benefits with Gamma-Oryzanol and physical performance


Edit7. Inflammation and Immunology

7.1. Mechanisms

Gamma-Oryzanol (specifically Cycloartenyl Ferulate, 24-methyene Cyloartenylferulate, and B-Sitosteryl Ferulate) can inhibit NF-kB translocation in LPS-stimulated Macrophages at a concentration of 10ng/mL, with Cycloartenyl Ferulate reducing translocation of NF-kB to below 20% at 10ng/mL with other components between 20-40%.[23] This inhibition has subsequently been noted in endothelial cells, reducing the LPS-induced NF-kB translocation down to 12.5% at 30uM Gamma-Oryzanol, which was more potent than the active control drug Pyrrolidine dithiocarbamate (PDTC).[20]

The ferulated saponins are actually quite potent in vitro on one of the prototypical mechanisms of inflammation; NF-kB translocation. At nanogram concentrations is more effective than Feverfew and becomes slightly less effective at higher (10-30ug/mL) concentrations; both are quite effective at this mechanism

7.2. Natural Killer (NK) Cells

One study in rats with implanted colonic tumors who were fed either 0.2, 0.5, or 1% Gamma-Oryzanol orally for 2 weeks noted an increase in NK cell activity by 130%, 170%, and 220% above control when measuring splenic NK cell activity.[24]

Appears to increase NK cell activity, unknown mechanisms; not remarkable potent when compared to other nutraceuticals

7.3. Macrophages

Gamma-Oryzanol at oral doses of 0.2, 0.5, or 1% of the diet for 2 weeks was able to increase activity of macrophages that were suppressed by the presence of a colonic tumor with 1% of the diet increasing the activity seen in tumor planted mice (50% or so) to 80% of control (when assessing nitric oxide release) and normalization of phagocytosis.[24] This was accompanied by preservation of TNF-a, IL-b, and IL-1b.[24]


Edit8. Interactions with Cancer

8.1. Mechanisms

Gamma-Oryzanol appears to be able to regulate angiogenesis, suppressing blood vessel formation in tumor implanted mice by 61% at 1% of the diet.[24]

8.2. Skin Cancer

Gamma-Oryzanol is able to reduce melanin concentration in B16F1 Melanoma cells, by 13% at 3uM and 38% at 30uM; this correlated highly with a reduction in PKA activity that reduced microphthalmia-associated transcription factor (MTIF) which reduces melanin synthesis.[25] A downregulation of Tyrosinase protein content and mRNA was also noted.[25]

8.3. Tumors

One rat study assessing components of Rice Bran (Gamma-Oryzanol, Ferulic Acid, Tocotrienols, or Phytic Acid all at 0.2%) noted that after implantation of a colonic tumor in mice, all compounds reduced tumor size slightly but Gamma-Oryzanol (and to a degree, Phytate) was most effective.[24] Testing doses of 0.2, 0.5, and 1% of the diet led to dose-dependent reductions in colonic tumor size in these rats, with 1% reducing the tumor size by 44% yet 10% Rice Bran (used as an active control) reduced size by 7%.[24]


Edit9. Interactions with Aesthetics

9.1. Skin

Gamma Oryzanol can be applied topically when trapped in Niosomes (Tween 61:Cholesterol transport molecule) and, after 28 days of application, is associated with improvements on skin hydration (in about a third of subjects) and skin lightening (in 90% of subjects).[10]


Edit10. Interactions with Hormones

10.1. Testosterone

It has been noted that a supercritical carbon extraction of rice bran itself (Oryza sativa) appears to be able to inhibit the 5α reductase type I enzyme,[26] suggesting it may increase testosterone and reduce DHT concentrations in the body. Subsequently, 500mg of gamma-oryzanol has been tested in healthy male athletes alongside a weight training program and failed to influence testosterone concentrations.[22]

Does not appear to cause an increase in testosterone concentrations

10.2. Estrogen

9 weeks of 500mg daily Gamma-Oryzanol combined with a resistance training program in 22 healthy male athletes failed to significantly influence estrogen levels.[22]

10.3. Growth Hormone

9 weeks of 500mg daily Gamma-Oryzanol combined with a resistance training program in 22 healthy male athletes failed to significantly influence circulating levels of growth hormone.[22]

10.4. Cortisol

9 weeks of 500mg daily Gamma-Oryzanol combined with a resistance training program in 22 healthy male athletes failed to significantly influence cortisol.[22]

10.5. Adiponectin

Adiponectin is a hormone secreted by fat tissue, and known as an adipokine that increases insulin sensitivity;[27] its decrease with obesity is correlated with an increase in insulin resistance.[28][29] Its oral administration to mice appears to increase adiponectin in circulation, yet incubating an adipocyte (fat cell) with Gamma-Oryzanol fails to induce secretion of adiponectin.[30]

An animal study that reduced circulating adiponectin levels with palmitate (a fatty acid) and beef tallow fed to rats noted that Gamma-Oryzanol (0.025mmol) was able to preserve adiponectin levels under the influence of palmitate and acted to increase circulating adiponectin in control (corn oil).[31] As palmitate activates NF-kB[32] which then acts to suppress adiponectin secretion from mouse 3T3-L1 adipocytes[30] secondary to binding to PPARy and inhibiting its genomic actions,[33] it is possible that these observed effects are secondary to Gamma-Oryzanol inhibiting NF-kB.

It was later confirmed that Gamma-Oryzanol (290mcg/kg) was able to increase adiponectin levels, and alongside GABA (also found in rice bran, 600mcg/kg) there appeared to be slightly better effects, but did not appear to be significantly synergistic.[34]

Appears to increase Adiponectin in animals, which may be secondary to preventing a decline of adiponectin and thus causing a relative increase; which is greater than control animals

References

  1. Angelis A, et al. One-step isolation of γ-oryzanol from rice bran oil by non-aqueous hydrostatic countercurrent chromatography. J Sep Sci. (2011)
  2. Zubair M, et al. Characterization of High-Value Bioactives in Some Selected Varieties of Pakistani Rice (Oryza sativa L.). Int J Mol Sci. (2012)
  3. Huang SH, Ng LT. An improved high-performance liquid chromatographic method for simultaneous determination of tocopherols, tocotrienols and γ-oryzanol in rice. J Chromatogr A. (2011)
  4. Huang SH, Ng LT. Quantification of tocopherols, tocotrienols, and γ-oryzanol contents and their distribution in some commercial rice varieties in Taiwan. J Agric Food Chem. (2011)
  5. Afinisha Deepam LS, Arumughan C. Effect of saponification on composition of unsaponifiable matter in rice bran oil. J Oleo Sci. (2012)
  6. Kaup RM, Khayyal MT, Verspohl EJ. Antidiabetic Effects of a Standardized Egyptian Rice Bran Extract. Phytother Res. (2012)
  7. Cicero AF, Gaddi A. Rice bran oil and gamma-oryzanol in the treatment of hyperlipoproteinaemias and other conditions. Phytother Res. (2001)
  8. Fang N, Yu S, Badger TM. Characterization of triterpene alcohol and sterol ferulates in rice bran using LC-MS/MS. J Agric Food Chem. (2003)
  9. Manosroi A, et al. Transdermal absorption enhancement of rice bran bioactive compounds entrapped in niosomes. AAPS PharmSciTech. (2012)
  10. Manosroi A, et al. Anti-aging efficacy of topical formulations containing niosomes entrapped with rice bran bioactive compounds. Pharm Biol. (2012)
  11. Umehara K, Shimokawa Y, Miyamoto G. Effect of gamma-oryzanol on cytochrome P450 activities in human liver microsomes. Biol Pharm Bull. (2004)
  12. Kozuka C, et al. Brown Rice and Its Component, γ-Oryzanol, Attenuate the Preference for High-Fat Diet by Decreasing Hypothalamic Endoplasmic Reticulum Stress in Mice. Diabetes. (2012)
  13. Son MJ, et al. Effect of oryzanol and ferulic acid on the glucose metabolism of mice fed with a high-fat diet. J Food Sci. (2011)
  14. Cheng HH, et al. Gamma-oryzanol ameliorates insulin resistance and hyperlipidemia in rats with streptozotocin/nicotinamide-induced type 2 diabetes. Int J Vitam Nutr Res. (2010)
  15. Ishihara M, et al. Clinical effect of gamma-oryzanol on climacteric disturbance -on serum lipid peroxides (author's transl). Nihon Sanka Fujinka Gakkai Zasshi. (1982)
  16. Philp HA. Hot flashes--a review of the literature on alternative and complementary treatment approaches. Altern Med Rev. (2003)
  17. Borud E, Grimsgaard S, White A. Menopausal problems and acupuncture. Auton Neurosci. (2010)
  18. Cho SH, Whang WW. Acupuncture for vasomotor menopausal symptoms: a systematic review. Menopause. (2009)
  19. Mäkynen K, et al. Effect of gamma-oryzanol on the bioaccessibility and synthesis of cholesterol. Eur Rev Med Pharmacol Sci. (2012)
  20. Sakai S, et al. γ-Oryzanol reduces adhesion molecule expression in vascular endothelial cells via suppression of nuclear factor-κB activation. J Agric Food Chem. (2012)
  21. Berger A, et al. Similar cholesterol-lowering properties of rice bran oil, with varied gamma-oryzanol, in mildly hypercholesterolemic men. Eur J Nutr. (2005)
  22. Fry AC, et al. The effects of gamma-oryzanol supplementation during resistance exercise training. Int J Sport Nutr. (1997)
  23. Islam MS, et al. Antioxidant, free radical-scavenging, and NF-kappaB-inhibitory activities of phytosteryl ferulates: structure-activity studies. J Pharmacol Sci. (2009)
  24. Kim SP, et al. Dietary rice bran component γ-oryzanol inhibits tumor growth in tumor-bearing mice. Mol Nutr Food Res. (2012)
  25. Jun HJ, et al. Dual Inhibition of γ-Oryzanol on Cellular Melanogenesis: Inhibition of Tyrosinase Activity and Reduction of Melanogenic Gene Expression by a Protein Kinase A-Dependent Mechanism. J Nat Prod. (2012)
  26. 5α-Reductase type 1 inhibition of Oryza sativa bran extract prepared by supercritical carbon dioxide fluid
  27. Heilbronn LK, Smith SR, Ravussin E. The insulin-sensitizing role of the fat derived hormone adiponectin. Curr Pharm Des. (2003)
  28. Statnick MA, et al. Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res. (2000)
  29. Yamauchi T, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. (2001)
  30. Ohara K, et al. The effects of hydroxycinnamic acid derivatives on adiponectin secretion. Phytomedicine. (2009)
  31. Nagasaka R, et al. γ-Oryzanol recovers mouse hypoadiponectinemia induced by animal fat ingestion. Phytomedicine. (2011)
  32. Cacicedo JM, et al. Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Diabetes. (2005)
  33. Suzawa M, et al. Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade. Nat Cell Biol. (2003)
  34. Ohara K, et al. Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia. Phytomedicine. (2011)

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