Supercritical pomegranate seed extract for health and nutrition

Pomegranate – Punica granatum – is a fruit-bearing deciduous tree growing to 5–8 m tall. It is native from Iran to the Himalayas in northern India and has been cultivated and naturalized over the whole Mediterranean region including Armenia since ancient times. Pomegranate fruit has been used worldwide as dietary item and as medicine for centuries as well as for culinary purpose.

Investigations have been done regarding the properties of the different fractions of the fruit. More than 200 peer reviewed scientific papers are published about pomegranate´s positive health effects. In vitro, in vivo and clinical studies revealed positive effects of the antioxidative, antiinflammatory, antisclerotic and anticancerogenic properties of pomegranate ingredients (1,2).

However, only until very recently, the importance of the seed oil has been largely overlooked. Recent studies have also begun to suggest possible synergistic interactions between aqueous and lipid phases of the whole fruit including its seeds.

Composition of CO₂-extracted pomegranate seed oil

Pomegranate seed oil contains a valuable fatty oil with more than 80 % conjugated fatty acids. The most important one with more than 60% is punicic acid, a conjugated linolenic acid of cis-9, trans-11, cis-13 C18:3n5 configuration (3). Other fatty acids found in pomegranate seed oil include linoleic, oleic, palmitic, stearic, arachidic, and palmitoleic acid (4). In addition, weak estrogens such as 17-α-estradiol, estrone and estriol were found in pomegranate seeds (5-10). Recently lignans were detected and quantified for the first time in pomegranate seeds by means of GC-MS (11).

Flavex offers a high grade pomegranate seed oil, which is produced by supercritical CO₂-extraction under gentle conditions, exclusion of oxygen and without the need of refinement, free of proteins and polysaccharides, solvent residues  and additives. It is therefore practically sterile. Cold pressed oils are manufactured normally at higher temperatures whereas CO₂-extracted oils are produced at 40-50°C. In comparison to cold pressed oils, which may contain metal traces acting as catalysts for oxidation processes, CO₂-extracted fatty oils are free of heavy metals and they are stabilised with rosemary antioxidant in order to guarantee a long shelf life. CO₂-extracted fatty oils are therefore ideal for food supplements and encapsulation.

Pomegranate seed oil - phytosterols

In recent years, phytosterols have been gaining increasing interest, since more and more evidence is rising that they play an important role in preventing a range of diseases, including the hormonally dependent cancers.  Epidemiological data demonstrate, that diets rich in phytosterols protect against breast, prostate and colon cancers as well as cardiovascular diseases and osteoporosis (12-14).

Phytosterols have the ability to bind to the estrogen receptors (ER) due to their structure and they can act as partial ER agonists or antagonists.

The pomegranate seed oil contains a range of phytosterols with synergistic health effects on estrogen related physiological processes. One of the phytosterols newly found in pomegranate seeds is the weak estrogen 17-a-estradiol, which is an enantiomer of the very potent estrogen 17-b-estradiol. In vitro studies as well as studies on mice have shown that this and other estrogens from pomegranate inhibit the activity of stronger estrogens. Additionally researchers noted that the conjugated fatty acid isomers found in punica granatum are selective estrogen receptor modulators (SERMs) in vitro. Punicic acid inhibits other estrogens from binding with receptor sites in a manner similar to the anticancer drug tamoxifen. Punicic acid and its isomer a-eleostearic acid seemed especially potent in inhibiting estrogen insensitive and estrogen-sensitive breast and prostate cancer cells (15-17). Overall, the results show punicic acid and a-eleostearic acid are SERMs.

It was demonstrated that the whole pomegranate seed extract is more chemopreventive against breast cancer than the unrefined pomegranate juice  polyphenols alone (18). Flavex with its recently established High Pressure Ethanol (HPE) extraction offers the key technology for this purpose.

Other physiological effects

Pomegranate seed oil has also other physiological benefits. For example the pomegranate seed oil is normalizing lipid metabolism in case of obese and hyperlipidemic conditions. Conjugated linolenic acids were found to reduce adipose tissue (19-20).

A study with mice fed a high-fat diet demonstrates that consuming oil from pomegranate seeds may prevent the development of diabetes. Pomegranate seed oil, rich in conjugated linolenic acid, was found to change weight gain, reduce body weight and improve insulin sensitivity in mice, indicating reduced risk of developing type 2 diabetes (21).

The effects of dietary pomegranate seed oil, which contains high levels of punicic acid  on immune function in mice were also investigated. According to these results  pomegranate seed oil may enhance B-cell function in vivo (22).

Toxicological evaluation of pomegranate seed oil

The toxicology and safety of pomegranate seed oil was evaluated by in vitro Ames tests, chromosomal aberration tests as well as by in vivo acute toxicity and 28-days toxicity tests in Wistar rats. No mutagenicity of pomegranate seed oil was observed in Ames and chromosome aberration tests. The acute oral toxicity study revealed no significant findings at 2000 mg pomegranate seed oil/kg body weight. The maximum administered dose of pomegranate seed oil was much higher than the level of pomegranate seed oil that elicits beneficial antidiabetic and antiinflammatory efficacy. Increased hepatic enzyme activities and increased liver-to-body weight ratios were observed at maximum dose. However, these effects might be the result of a physiological response to exposure to a very high level of fatty acids which are not part of the normal diet, and are most likely not toxicologically relevant (23).

Outlook

The CO₂-extracted pomegranate seed oil and possibly a total HPE pomegranate extract containing lipophilic and polar components could play an important role for dietary supplements. The additive or synergistic effects of the multiple phytochemicals found in pomegranate were already demonstrated.

Hippocrates´ statement "Let food be your medicine, and let your medicine be food"

is based on a deep understanding and proves true more and more in nutrition research. High-quality food and food supplements preserve the natural composition and synergy of their ingredients and they are characterized by a high concentration of effective plant ingredients. Pomegranate ingredients can supplement standard therapies and probably improve the effect/side-effect profile. Supercritical extraction technology holds the advantage of producing well-characterized, reproducible and standardized whole pomegranate extracts with promising health effects.

References

(1) Seeram NP, Schulman RN, Heber D (2006) Pomegranates: Ancient Roots to Modern Medicine. CRC Press, 1 edition

(2) Lansky E, Newman RA (2007) Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. Journal of Ethnopharmacology 109, 177-206

(3) El-Shaarawy MI and Nahapetian A (1983) Studies on pomegranate seed oil. Fette Seifen Anstrichmittel 85: 123-126

(4) Melgarejo P, et al (1995) Total lipids content and fatty acid composition of seed oils from six pomegranate cultivars. J. Sci. Food and Agric, 69, 253

(5) Heftmann E, et al (1966) Identification of estrone in pomegranate seeds. Phytochemistry, 5,1337-40

(6) Moneam NM, et al (1988) Oestrogen content of pomegranate seeds. J Chromatogr., 438:438-42

(7) Kim ND, et al (2002) Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat, 71:203-17

(8) Abd El Wahab, SM, et al (1998) Characterization of certain steroid hormones in Punica granatum L. seeds. Bull Fac Pharm (Cairo University) 36:11-5

(9) Farnsworth NR, et al (1975) Potential value of plants as sources of new antifertility agents. J Pharm Sci., 64:717-54

(10) Toi M, et al (2003) Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis, 6:121-8

(11) Bonzanini F, Bruni R, Palla G, Serlataite N, Caligiani A (2009) Identification and distribution of lignans in Punica granatum L. fruit endocarp, pulp, seeds, wood knots and commercial juices by GC-MS. Food Chemistry Volume 117, 4, 745-749

(12) Bingham SA et. al (1998) Phyto-oestrogens: where are we now?  Br. J. Nutr. 79, 393

(13) Ziegler RG (1993) Migration patterns and breast cancer risk in Asian_American women. J. Natl. Cancer Int. 85, 1819

(14) Shimizu H, Ross RK, Bernstein L, et al (1991) Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 63 (6): 963-6

(15) Grossmann ME, Mizuno NK, Schuster T, Cleary MP (2010) Punicic acid, a fatty acid from pomegranate seed oil, inhibits breast cancer cell proliferation. Cancer Prevention Research 3 (Meeting Abstract Supplement), A72, January 7

(16) Albrecht M et al (2004) Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. Journal of Medicinal Food 7: 274-283

(17) Tran HNA, Bae S-Y, Song, BH, Lee, B-H, Bae, Y-S, Kim, Y-H, Lansky, E, Newman, RA (2010) Pomegranate (Punica granatum) Seed Linolenic Acid Isomers: Concentration-Dependent Modulation of Estrogen Receptor Activity. Endocrine Research, 35, 1, 1-16

 (18)  Mehta R, Lansky E (2004) Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev, 13(4):345-8

(19) Koba et al (2002) Dietary conjugated linolenic acid in relation to CLA differently modifies body fat mass and serum and liver lipid levels in rats. Lipids 37(4), 343-350

(20) Keisuke et al (2004) Dietary effect of pomegranate seed oil rich in 9 cis, 11 trans, 13 cis conjugated linolenic acid on lipid metabolism in obese, hyperlipidemic OLETF Rats. Lipids in Health and Disease, 3

(21) McFarlin BK, Strohacker KA, Kueht ML (2009) Pomegranate seed oil consumption during a period of high-fat feeding reduces weight gain and reduces type 2 diabetes risk in CD-1 mice. British Journal of Nutrition Volume 102, Pages 54-59

(22) Yamasaki M, Kitagawa T, Koyanagi N, Chujo H, Maeda H, Kohno-Murase J, Imamura J, Tachibana H, Yamada K (2006) Dietary effect of pomegranate seed oil on immune function and lipid metabolism in mice. Nutrition, Volume 22(1), 54-9

(23) Meerts IATM, Verspeek-Rip CM, Buskens CAF, Keizer HG, Bassaganya-Riera J, Jouni ZE, van Huygevoort AHBM, van Otterdijk, FM, van de Waart EJ (2009) Toxicological evaluation of pomegranate seed oil. Food and Chemical Toxicology, 47, 6, 1085-1092

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