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Studies that use pomegranate seed oil use 400mg of a 72% punicic acid seed oil. While this appears to be in the bioactive range of punicic acid, it is not known if this is an optimal dosage or not.
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects punicic acid 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.
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.
|HDL-C||Minor||Moderate See 2 studies|
|Triglycerides||Minor||Moderate See 2 studies|
|Fat Mass||-||- See study|
|Insulin||-||- See study|
|Insulin Sensitivity||-||- See study|
|LDL-C||-||Very High See 2 studies|
|Lean Mass||-||- See study|
|TNF-Alpha||-||- See study|
|Total Cholesterol||-||- See study|
|Weight||-||- See study|
Studies Excluded from Consideration
NOTE: The above table includes studies on Pomegranate Seed Oil as Punicic Acid is the main bioactive. Water extracts of pomegranate such as juice is gathered on the Punicalagins page
Table of Contents:
- 1 Sources and Structure
- 2 Pharmacology
- 3 Obesity and Fat Mass
- 4 Inflammation and Immunology
Interactions with Lipid Metabolism
- 5.1 Triglycerides
Interactions with Cancer
- 6.1 Breast Cancer
Interactions with Hormones
- 7.1 Estrogen
- 8.1 Xanthigen
Punicic Acid is found in:
Pomegranates at 63.5% total fatty acid profile, with another 14.2% possibly being isomers of Punicic Acid. As pomegranates contain slightly over 1% fatty acids on a wet weight basis, 300g of fresh pomegranate confers 3g Punicic acid (estimate)
Trichosanthes kirilowii seeds, at 24.3% of the fatty acids by weight and 3g Punicic acid per 24.5g seeds
Punicic acid is named after its source, Pomegranates, which have the vernacular name of Punica granatum.
Punicic Acid is a conjugated linoleic acid molecule, but not one of the fatty acids referred to as supplemental CLA; typical Conjugated Linoleic Acid (CLA) supplements contain linoleic acid molecules with two double bonds in various locations; Punicic Acid contains a third double bond, is known as cis9, trans11, cis13, and is referred to as an 18:3 fatty acid rather than an 18:2 fatty acid (amount of carbons in the side chain: amount of double bonds). Structurally, it is the c9t11 Conjugated Linoleic Acid isomer with a cis double bond added on the side closer to the tail.
It is one of the main 5 18:3 conjugated linoleic acid molecules, with the others being alpha-eleostearic acid (cis9, trans11, trans13), jacaric acid (cis8,trans10,cis12), catalpic acid (9trans,11trans,13cis) and calendic acid (8trans,10trans,12cis).
Similar to Conjugated Linoleic Acid, Punicic acid may eventually refer to a category of 18:3 conjugated linoleic acids and may not be a single molecule; the above is the standard Punicic acid molecules found in Pomegranates
Ingestion of 3g Punicic acid for 28 days (via the seeds of Trichosanthes kirilowii) increases the content of Punicic acid in circulating phospholipids from negligible amounts to 0.34+/-16% of total lipids and similar study design, when replicated, led to an increase from negligible to 0.47+/-0.04%.
It was found in rats that Punicic acid, which is a c9t11c13 fatty acid, could be rapidly metabolized into circulating c9t11 conjugated linoleic acid, similar to another 18:3 fatty acid mentioned earlier, the c9t11t13 alpha-eleostearic acid. This, if replicated in humans, would mean some of the bioactivity of Punicic Acid is due to c9t11 CLA. A study designed with a 7 day adaptation period where participants were advised to not consume sources of CLA (ruminant foods) followed by 28 days punicic acid intervention (via Trichosanthes seeds) found that while the control group had CLA levels circulating from 0.05-0.06% of total fatty acids, the Punicic Acid intervention rose to 0.23+/-0.03% of total fatty acids (although Punicic acid itself was found, suggesting partial metabolism). This replicated the effects found in a previous phamacokinetic study noting higher than normal CLA levels, but did not control for dietary intake. It appears Punicic acid can incompletely get metabolized into c9t11 Conjugated Linoleic Acid
Punicic Acid can be metabolized into the lesser potent isomer of Conjugated Linoleic Acid known as c9t11
Punicic acid, via the seeds of Trichosanthes kirilowii, has been shown to increase lipid peroxidation via measurements of 8-iso-PGF2α; if motifs from Conjugated Linoleic Acid research are carried over (due to similar structures), this may be indicative of peroxisomal oxidation of Punicic acid and not actually indicative of lipid peroxidation. Regardless of the mechanisms, 28 days of ingesting 20.8g of the seeds (12.5g fatty acids with 3g Punicic Acid) daily, relative to control (sunflower seeds), increased urinary 8-iso-PGF2α by approximately 50% without influencing C-reactive protein or IL-6.
In interventions where weight is measured although not the primary goal of the research, 28 days of 3g Punicic acid shows no effects on weight reduction and 800mg of Pomegranate seed oil with 72% Punicic acid content in hyperlipidemic individuals shows no benefit to weight reduction.
In a rat model of Necrotizing Enterocolitis (NES), Pomegranate Seed Oil at 1.5% of the diet was able to suppress the occurrence of NES (from 61% to 26%) and normalizing inflammatory biomarkers (TNF-α and interleukins) were measured in the ileum.
4 weeks of Pomegranate Oil supplementation (800mg, 72% Punicic Acid) has been shown to reduce triglycerides in hyperlipidemic adults from 3.45+/-1.56mmol/L to 2.75+/-1.40mmol/L (20% decrease) without significantly affecting body weight. Secondary to the lower triglycerides, a better ratio of HDL:TG was seen as HDL-C was nonsignificantly increased from baseline values. These effects were replicated by the same researcher(s) 2 years later, where 45 hyperlipidemic adults had similar decreases in TGs with exactly the same magnitude and variance.
A study done on healthy youth noted no influence on triglyceride levels, or any measured lipoprotein (HDL-C, LDL-C).
Appears to have the ability to reduce triglycerides, but I would not put too much faith into it due to the probability of rehashed data is higher than the probability of getting the exact same standard deviations in two independent trials
In vitro, Punicic acid appears to have the ability to inhibit breast cancer cell proliferation at 40uM, and did so in both an estrogen responsive and estrogen non-responsive cell line. In the cell lines of MDA-MB-231 and MDA-ERa7, proliferation was inhibited by 92% and 96% while apoptosis via a disrupted mitochondrial membrane potential via PKC was induced in 86% and 91% of these cell lines, respectively. These effects were secondary to Punicic acid's pro-oxidative effects, as these effects were abolished by 20uM Vitamin E tocotrienol incubation. Another study conducted found lower numbers (70-75% inhibition) at 50uM, and noted that the 18:3 conjugated fatty acid known as alpha-eleosteroic acid was more potent, fully inhibiting proliferation at 50uM of MDA-MB-231 and MCF-7 cell lines.
Punicic acid has been demonstrated to be an anti-estrogen on ERa with an IC50 of 7.2uM and on ERb with an IC50 of 8.8uM with slight preference towards the ERa subset. The IC50 values for ERa and ERb were 2.7-fold and 1.36-fold lower relative to resveratrol with similar potencies (Punicic acid being 0.0040-0.0067% as potent as 17β-estradiol on the receptor, Resveratrol being 0.0024-0.0029% as potent).
Punicic acid, at low concentrations (1.8-2uM) is able to activate both of the estrogen receptors while at higher doses (101uM and 80uM for ERa and ERb) antagonized both estrogen receptors. Thus Punicic acid may be a Selective Estrogen Receptor Modulator (SERM) compound.
Xanthigen is a brand name for fucoxanthin, a potential fat burning carotenoid from seaweed, with Pomegranate Seed Oil as a base; thus confering both the bioactivities of Punicic acid and Fucoxanthin. Fucoxanthin itself is implicated in fat loss, and human trials using Xanthigen have shown significant fat loss over time. In vitro, the two molecules show some degree of synergism in pro-fat loss effects.
Mechanisms of synergism, but no real estimate as to how much of fucoxanthin's benefits are enhanced by Punicic acid
- Vroegrijk IO, et al. Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice. Food Chem Toxicol. (2011)
- Schubert SY, Lansky EP, Neeman I. Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids. J Ethnopharmacol. (1999)
- Effect of punicic acid naturally occurring in food on lipid peroxidation in healthy young humans.
- Yuan G, et al. Incorporation and metabolism of punicic acid in healthy young humans. Mol Nutr Food Res. (2009)
- Iwabuchi M, Kohno-Murase J, Imamura J. Delta 12-oleate desaturase-related enzymes associated with formation of conjugated trans-delta 11, cis-delta 13 double bonds. J Biol Chem. (2003)
- Yuan GF, Yuan JQ, Li D. Punicic acid from Trichosanthes kirilowii seed oil is rapidly metabolized to conjugated linoleic acid in rats. J Med Food. (2009)
- Tsuzuki T, et al. Alpha-eleostearic acid (9Z11E13E-18:3) is quickly converted to conjugated linoleic acid (9Z11E-18:2) in rats. J Nutr. (2004)
- Iannone A, et al. Impairment of 8-iso-PGF(2ALPHA) isoprostane metabolism by dietary conjugated linoleic acid (CLA). Prostaglandins Leukot Essent Fatty Acids. (2009)
- Mirmiran P, et al. Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial. Br J Nutr. (2010)
- Coursodon-Boyiddle CF, et al. Pomegranate Seed Oil Reduces Intestinal Damage in a Rat Model of Necrotizing Enterocolitis. Am J Physiol Gastrointest Liver Physiol. (2012)
- Grossmann ME, et al. Punicic acid is an omega-5 fatty acid capable of inhibiting breast cancer proliferation. Int J Oncol. (2010)
- Tran HN, et al. Pomegranate (Punica granatum) seed linolenic acid isomers: concentration-dependent modulation of estrogen receptor activity. Endocr Res. (2010)
- Abidov M, et al. The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat. Diabetes Obes Metab. (2010)
- Lai CS, et al. Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPARγ and C/EBPs and modulation of SIRT-1, AMPK, and FoxO pathways. J Agric Food Chem. (2012)
Via HEM and FAQ:
- Asghari G, et al. Effect of pomegranate seed oil on serum TNF-α level in dyslipidemic patients. Int J Food Sci Nutr. (2012)