Perilla Oil

Perilla Oil is a nutty oil derived from the seeds of perilla frutescens after roasting, and is supplemented for its high omega-3 fatty acid content and Rosmarinic Acid content. Benefits are secondary to either of those components, and it may be kidney healthy.

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Summary

All Essential Benefits/Effects/Facts & Information

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Perilla Oil is the term used to refer to any oil derived from the plant perilla frutescens, and it almost always refers to an oil that is pressed from roasted seeds which is used in the diet as a condiment to confer a nutty taste. It is sold as a dietary supplement or 'health oil' due to having the standard phenolic and Vitamin E content that many 'healthy' oils do, but is also quite a large source of omega-3 fatty acids (in the form of alpha-linolenic acid; the plant based form not to be confused with Fish Oil) comparable to flaxseed oil.

The leaves of perilla frutescens are less frequently used, by are sometimes used medicinally for the purpose of easing the stomach (served alongside some seafood); the oil pressed from the leaves, which is much less common, may have different properties than the seed oil and the two should be seen as somewhat different supplements.

Perilla Oil appears to have some promise associated with its Rosmarinic Acid content and the omega-3 fatty acid content, but the unique properties of perilla oil are not well researched nor is there much evidence on the benefits these isolated molecules confer. The benefits of perilla oil can possible be mimicked by flaxseed (if the omega-3 fatty acids are what does the benefit) or either supplementation of pure rosmarinic acid or plants that have a higher rosmarinic acid content (such as lemon balm).

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects perilla oil has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
C-Reactive Protein - - See study
HDL-C - - See study
LDL-C - - See study
Liver Enzymes - - See study
Plasminogen Inhibitor 1 - - See study
TNF-Alpha - - See study
Total Cholesterol - - See study
Triglycerides - - See study


1Sources and Composition

1.1. Sources

Perilla oil refers to the fat soluble component (oil) of the seeds from the plant perilla frutescens (of the family lamiaceae), where the seeds are initially roasted and then pressed to provide the oil.[1] This oil is frequently used as a condiment (Asian cuisine) due to its nutty taste and novel aromatic profile,[2]

There is also an oil that can be derived from the leaves of perilla frutescens which is the medicinal component of the plant,[3][4] and this oil may have a different composition than the seed oil (due to some volatiles also removed in the extraction process that remain in the oil)

Perilla seed oil is a dietary oil which confers a nutty taste after it is roasted and processed into an oil, and appears to be used in some asian cuisine. Perilla oil may also refer to an oil taken from the leaves which is sometimes used medicinally, and while the oil itself is similar there may be different minor components depending on which plant part it came from

It is sought after as a dietary supplement since, among vegetable sources of oil, perilla contains the highest proportion of omega-3 fatty acids relative to omega-6 fatty acids with omega-3 (as alpha-linolenic acid) being in the 54-65% range and omega-6 (as linoleic acid) being in the 14-20% range.[5] This is the same fatty acid (alpha-linolenic acid; ALA) which comprises the omega-3 profile of other plant products such as flaxseed oil (55% ALA[6]), Salvia hispanica (Chia), borage oil, and walnuts but not animal based Fish Oil products.[5]

Perilla oil (seed and leaf) is a source of plant-based omega-3 fatty acids, and appears to be one of the better sources when looking at the omega-3 content relative to omega-6 fatty acid content

1.2. Composition

Perilla frutescens (Perilla seeds; unless otherwise specified) include:

  • Dietary lipids (35-45% raw seed weight[6][2]), the leaves contain only 0.2% lipids by weight[6]

  • Rosmarinic Acid in free form (average 1716.9μg/g in the seeds[7]) and the 3-O-glucoside (average 1752.7μg/g in the seeds)[7][8] totalling almost all phenolics (49% and 48%, respectively)[8]

  • Caffeic acid and its 3-O-glucoside (Minimally in seeds[8] and up to 0.4% in leaves after methanolic extraction[7])

  • Luteolin and its 3-O-glucoside (Minimum in seeds[8] and up to 7.1% in the leaves after methanolic extraction[7])

  • Apigenin and its 3-O-glucoside (Minimal in seeds[8])

  • Chrysoeriol (Minimal in seeds[8])

  • Scutellarin (Leaves at 1.9% after 50% methanolic extraction[7]

  • Perilla ketone (ie. 1-(3-furanyl)-4-methyl-1-pentanone) which is doubled to tripled in the roasting process[2]

  • Perilla aldehyde (doubled in the roasting process[2]) thought to be unique to perilla, except for a small content in orange juice (0.1ppm or less[9])

  • Pyrazine compounds such as 2-methyl-3-propylpyrazine,[10]tetramethylpyrazine,[10]2,3-diethyl-5-methylpyrazine,[10]2-methylpyrazine,[1]2,5-dimethylpyrazine,[1]trimethylpyrazine,[1]2-ethyl-3,5-dimethylpyrazine,[1]

  • Furan compounds such as vinylfuran,[1]3-methylfuran,[1]5-Methylfurfuraldehyde,[1]2-Furanmethanol,[1]2-Furancarboxaldehyde[1]

  • Sulfur compounds such as Dimethyl sulfide[1] and methanethiol[1]

The final oil product of perilla frutescens (Perilla oil derived from seeds) contains:

  • Alpha-linolenic acid (ALA in a 54-65% range[5] with isolated studies reporting 64.19%[1] and 59.08%[11])

  • Oleic acid (13-21% range,[5] isolated studies at 14.20%[1] and 16.70%[11])

  • Linoleic acid (14-21% range,[5] isolated studies at 12.79%[1] and 14.79%[11])

  • Palmitic acid (5.95-7.38%[11][1])

  • Stearic acid (1.85-1.93%[11][1])

  • Glycolipids in the 4-6% range[5]

  • Phospholipids in the 2-3% range[5]

  • Polyphenolis (mostly rosmarinic acid) at 80.56+/-1.79µg/g[11]

  • Vitamin E at 641.15+/-17.36µg/g which is mostly γ-tocopherol at 89% (comparable to corn oil overall, slightly more γ-tocopherol[11])

Whereas Perilla oil derived from the leaves may contain:

1.3. Physicochemical Properties

Roasting of perilla seeds is sometimes the only processing technique prior to oil extraction,[1] and the composition of the final oil can vary depending on whether or not seeds are lightly or heavily roasted which can be determined by a heavy browning of the seeds during the roasting process.[1]

In regards to the fatty acid composition, roasting appears to note minor content of butyric (short chain saturated fatty acid) and palmitoleic (monounsaturated fatty acid) which are not detectable in unroasted oils;[1] either through oxidation of fatty acids or better yield seen with roasting.[1]

Despite heat treatment (which may oxidize the lipids in oils[12]), roasted perilla seeds seem to have less oxidation in the oil as assessed by DPPH.[1] Such an unorthodox phenomena (heat treatment causing oxidative stability) has been noted with sesame seed oil[13] thought to be due to alterations in the lignan content such as Sesamin; since some of the bioactives in perilla (perilla ketone and perilla aldehyde) have been noted to be more than doubled during the roasting process[2] it is thought that freeing these molecules up (by destroying the cell walls with heat) adds to the antioxidative properties.

Roasting in general is known to alter pyrazine molecules[14] which applies to perilla oil pyrazines, with roasting causing a relative increase in 2-methylpyrazine (relative to 2,5-dimethylpyrazine) the more it is roasted;[10] an overall increase in pyrazine quantity (16.78-fold) is seen in dark roasted seeds relative to light roasted[10] and their content is further increased in a linear manner when heat treated at 190°C (34.75%) relative to 150°C (3.66%).[2]


2Pharmacology

2.1. Serum

Acute ingestion of perilla oil results in a peak in plasma alpha-linolenic acid (ALA) levels approximately five hours after ingestion returning to near baseline levels after 24 hours[5] and this change in ALA is not met with changes in either eicosapentaenoic acid (EPA) nor docosahexaenoic acid (DHA);[5] enteric coated capsules may provide more overall exposure following a single dose (2.2-fold increase in plasma with 6g ALA enteric coated capsules relative to a 1.56-fold increase seen with noncoasted capsules).[5]


3Neurology

3.1. Anxiety and Stress

Oral ingestion of 3-6mg/kg of the essential oil (derived from leaves) to mice subject to chronic unpredictable manageable stress (CUMS) testing over the course of four weeks noted that the oil had anti-stress properties in the latter two weeks with the higher dose being comparbale to 20mg/kg fluoxetine.[3] Both treatments only saw benefits in the forced swim test but not open-field test, and it appeared that the reduction in BDNF mRNA that is seen during stress was attenuated with both treatments.[3]

The leaf oil extract has shown benefits to stress prevention in mice, but it is not sure if this applies to the seed oil component (most commonly sold form of 'perilla oil')


4Cardiovascular Health

4.1. Atherosclerosis

Perilla oil (dosage unspecified) for 12 weeks in hyperlipidemic adults appears to improve inflammatory parameters (TNF-α, CRP, PAI-1) relative to baseline and with a potency comparable to mild-moderate exercise.[15] This is thought to be beneficial for atherosclerosis as PAI-1 (via thrombis formation[16]) TNF-α (via promoting inflammation[17]) and C-reactive protein (via platelets[18] and as a biomarker for plaque[19]) are thought to be positively associated with cardiovascualar disease and atherosclerosis.

4.2. Cholesterol

Supplementation of perilla oil for 12 weeks (dosage unspecified), relative to baseline values due to no placebo group, showed a minor increase in HDL-C (14%) and reductions in LDL-C (18%) and total cholesterol (11%) which was comparable in potency to brisk walking four times weekly (30-60 minutes, voluntarily increasing intensity over the 12 weeks) in these hyperlipidemic patients yet not additive.[15]


5Peripheral Organ Systems

5.1. Kidneys

A methanolic extract from the leaves of perilla frutescens appears to have antiproliferative effects in isolated mesangial cells induced to proliferate with IgA with an IC50 of 8.8μg/mL, mostly due to the Rosmarinic Acid content (7.3% by weight) which had an IC50 of 3.6μM and in part due to the luteolin glycoside content (IC50 of 17.5μM and a 7.1% content)[7] This is thought to be a protective effect against glomerulonephritis, which is characterized by hypercellularity of mesangial cells[20] and has been replicated with an acetone extract (but again thought to be due to the luteolin and rosmarinic acid content[21]) and basic seed oil[22] while a fourth study has noted that the effects were fully reproducible with pure rosmarinic acid.[23]

In a mouse model of spontaneous nephritis characterized by high serum IgA[24][25] from gut‐associated lymphoid tissue,[26] perilla leaf extract (50-500mg/kg of the 9% rosmarinic acid extract) over the course of 16 weeks appeared to reduce serum IgA levels and concentrations of IgA in glomeruli of treated mice relative to control.[23] This was thought to be due to less IgA release from lymphoid tissue (replicated in vitro with perilla leaf extract and rosmarinic acid, mostly in spleen cells).[23]

Perilla oil appears to be associated with a reduced rate of IgA nephropathy in in vitro and rodent research which is thought to be mostly (if not fully) due to the rosmarinic acid content

Scientific Support & Reference Citations

References

  1. Park MH, et al Effects of roasting conditions on the physicochemical properties and volatile distribution in perilla oils (Perilla frutescens var. japonica) . J Food Sci. (2011)
  2. The effects of roasting temperatures on the formation of headspace volatile compounds in perilla seed oil
  3. Yi LT, et al Essential oil of Perilla frutescens-induced change in hippocampal expression of brain-derived neurotrophic factor in chronic unpredictable mild stress in mice . J Ethnopharmacol. (2013)
  4. Analysis of the volatile oil of perilla furtescens drawing with two kinds of method by GC/MS
  5. Kurowska EM, et al Bioavailability of omega-3 essential fatty acids from perilla seed oil . Prostaglandins Leukot Essent Fatty Acids. (2003)
  6. Asif M Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant oils . Orient Pharm Exp Med. (2011)
  7. Makino T, et al Inhibitory effect of decoction of Perilla frutescens on cultured murine mesangial cell proliferation and quantitative analysis of its active constituents . Planta Med. (2001)
  8. Lee JH, et al Identification, characterisation, and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds of Korean perilla (Perilla frutescens) cultivars . Food Chem. (2013)
  9. Quantitative Determination of 46 Volatile Constituents in Fresh, Unpasteurized Orange Juices Using Dynamic Headspace Gas Chromatography
  10. Kwon TY, Park JS, Jung MY Headspace-Solid Phase Microextraction-Gas Chromatography-Tandem Mass Spectrometry (HS-SPME-GC-MS2) Method for the Determination of Pyrazines in Perilla Seed Oils: Impact of Roasting on the Pyrazines in Perilla Seed Oils . J Agric Food Chem. (2013)
  11. Wang S, et al Temperature dependence of autoxidation of perilla oil and tocopherol degradation . J Food Sci. (2010)
  12. Yaacoub R, et al Formation of lipid oxidation and isomerization products during processing of nuts and sesame seeds . J Agric Food Chem. (2008)
  13. Effects of roasting conditions of sesame seeds on the oxidative stability of pressed oil during thermal oxidation
  14. Jung MY, et al Effects of roasting on pyrazine contents and oxidative stability of red pepper seed oil prior to its extraction . J Agric Food Chem. (1999)
  15. Wei M, et al Perilla oil and exercise decrease expressions of tumor necrosis factor-alpha, plasminogen activator inhibitor-1 and highly sensitive C-reactive protein in patients with hyperlipidemia . J Tradit Chin Med. (2013)
  16. Wiman B, Hamsten A The fibrinolytic enzyme system and its role in the etiology of thromboembolic disease . Semin Thromb Hemost. (1990)
  17. Horrevoets AJ, et al Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes . Blood. (1999)
  18. Vigo C Effect of C-reactive protein on platelet-activating factor-induced platelet aggregation and membrane stabilization . J Biol Chem. (1985)
  19. Zhang YX, et al Coronary C-reactive protein distribution: its relation to development of atherosclerosis . Atherosclerosis. (1999)
  20. Mené P, Simonson MS, Dunn MJ Physiology of the mesangial cell . Physiol Rev. (1989)
  21. Makino T, et al Inhibitory effect of Perilla frutescens and its phenolic constituents on cultured murine mesangial cell proliferation . Planta Med. (1998)
  22. Sakurai K, et al Dietary Perilla seed oil supplement increases plasma omega-3 polyunsaturated fatty acids and ameliorates immunoglobulin A nephropathy in high immunoglobulin A strain of ddY mice . Nephron Exp Nephrol. (2011)
  23. Makino T, et al Suppressive effects of Perilla frutescens on spontaneous IgA nephropathy in ddY mice . Nephron. (1999)
  24. Muso E, et al Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice . Kidney Int. (1996)
  25. Miyawaki S, et al Selective breeding for high serum IgA levels from noninbred ddY mice: isolation of a strain with an early onset of glomerular IgA deposition . Nephron. (1997)
  26. Kamata T, et al Increased frequency of surface IgA-positive plasma cells in the intestinal lamina propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of IgA nephropathy with hyperserum IgA . J Immunol. (2000)
  27. Wei M, et al Perilla oil and exercise decrease expressions of tumor necrosis factor-alpha, plasminogen activator inhibitor-1 and highly sensitive C-reactive protein in patients with hyperlipidemia . J Tradit Chin Med. (2013)