Emerging science spotlights pomegranate seed oil’s unique fatty acids as promising allies for heart and metabolic health, if future clinical trials back up the early buzz.
Study: Punicic Acid: A Potential Nutraceutical Compound in Pomegranate Seed Oil and Its Cardiovascular Benefits. Image Credit: SiNeeKan / Shutterstock
Nutraceuticals are foods or food components that offer health benefits, such as preventing or treating disease. Pomegranate seed oil has shown great promise in its beneficial effects on health in multiple preclinical studies. Its potential role as a nutraceutical is the focus of a recent research paper published in the journal Foods.
Introduction
Cardiovascular disease (CVD) remains the leading killer among all diseases worldwide, causing a quarter of all deaths in the UK. It is associated with poor dietary habits, including a high intake of saturated fats, which increases blood cholesterol levels. Approximately 31% of CVD cases and 11% of strokes globally are traceable to diets with a high saturated fat content.
Fats in a healthy diet would come mainly from oily fish and plants rich in polyunsaturated fatty acids (PUFAs), with low amounts of saturated fats and trans fats.
All parts of the pomegranate (Punica granatum L.) are rich in nutrients and medicinal components. After the juice is extracted, the seed waste, which accounts for approximately one-fifth of its weight, becomes a byproduct. The 1.6 million tons of pomegranate seed waste produced annually are a treasure trove of bioactive compounds with enormous therapeutic and economic potential. For instance, pomegranate seed extracts have been shown to possess anti-cancer and anti-osteoporotic properties.
Pomegranate seed oil (PSO) comprises approximately 12% to 20% of the total seed weight, with a high punicic acid content. Punicic acid exhibits anti-inflammatory and anti-cancer properties. It enhances immunity, improves glucose metabolism and insulin sensitivity, while reducing blood lipid levels. Additionally, it protects both the liver and kidneys.
Thus, PSO is an example of a healthy supplement produced from a waste product, largely due to its punicic acid content. The current review examines punicic acid as a potential cardioprotective agent.
What is punicic acid?
Punicic acid is an isomer of conjugated α-linolenic acid, characterized by three conjugated double bonds. It is the most abundant fatty acid in pomegranate seed oil, comprising up to 83% of the total fatty acid content. In addition to pomegranate, this acid is also obtained from various other plant sources, such as Trichosanthes kirilowii seeds.
Once consumed, the liver metabolizes punicic acid to a specific conjugated linoleic acid isomer (9Z,11E-CLA). Increasing punicic acid intake, for example, by eating more T. kirilowii seeds, improves its levels in blood by ~0.47% in plasma and its metabolites in red blood cell membranes by 0.17%. Human trials have shown inconsistent metabolic responses, and optimal dosing remains unclear.
Cardiovascular benefits
PSO induces vasodilation, with a slight, gender-specific (female-only) decrease in blood pressure and heart rate. This effect is mediated by endothelial nitric oxide signaling via the nitric oxide–guanylyl cyclase pathway. It is independent of potassium channels, the renin-angiotensin system, beta-adrenergic receptors, and the prostaglandin pathways.
In preclinical studies, atherosclerosis in rabbits progressed more slowly with PSO treatment; however, other studies report conflicting results due to variations in experimental design. PSO protects cardiac muscle cells against oxidative stress, both by reducing reactive oxygen species (ROS) and by improving antioxidant capacity.
PSO reduces various lipid risk markers in the blood, including low-density lipoprotein (LDL) cholesterol (‘bad’ cholesterol), triglycerides, and total cholesterol, in some animal and hyperlipidemic human studies, though results are inconsistent across trials. It also reduces liver fat accumulation, with marked suppression of apolipoprotein (Apo)B100 secretion – this being an LDL component and a risk marker for coronary heart disease and atherosclerosis.
PSO supplementation also reduces obesity induced by unhealthy or high-fat diets. It increases the expression of the gene uncoupling protein 1 in brown fat. It also promotes beige fat formation in white fat, thus reducing abdominal fat deposition by increasing the metabolic rate of fat tissue. Leptin levels are lower and adiponectin levels higher with PSO consumption.
In hyperlipidemic individuals, PSO intake reduced triglycerides and improved the triglyceride-to-'good' cholesterol ratio. The primary benefit of PSO appears to be its ability to maintain normal lipid metabolism, regardless of fat loss.
Antidiabetic and anti-inflammatory effects
Diabetes is a major CVD risk factor that doubles cardiovascular risk, and PSO may reduce diabetes risk. PSO improves insulin sensitivity and reduces fasting glucose levels in animal models and some diabetic patients, though human data are mixed. It may be a safer alternative to prevent and treat inflammation associated with cardiometabolic disease.
PSO may act by increasing mitochondrial energy metabolism and enhancing glucose absorption into cells that are insulin-resistant. These actions may be mediated by PPAR-γ.
Systemic inflammation underlies these chronic conditions, signaled by pro-inflammatory markers like (NF)-κB, TNF-α, and interleukin (IL)-6. PSO reduces these markers in cell and animal studies while increasing anti-inflammatory cytokines like PPAR-γ and IL-10. This not only reflects its ability to alleviate the inflammation that results in CVD, but also suppresses the inflammatory effects of obesity, diabetes, and the like.
Antioxidant properties
PSO reduces oxidative stress while increasing antioxidant buffer enzymes, such as superoxide dismutase and glutathione peroxidase. It also reduces lipid peroxidation. The antioxidant activity of PSO is attributed to its tocopherol and polyphenolic compound content. These effects have been well-documented in preclinical models but require further clinical validation.
Comparison with omega-3 PUFAs
Omega-3 PUFAs are established cardioprotective, anti-inflammatory, and antioxidant agents. Punicic acid is a PPARγ activator, providing complementary benefits to these compounds by inhibiting lipogenic gene expression. Unlike them, it does not primarily act on eicosanoid pathways but rather inhibits the expression of inflammatory cytokines. It also scavenges ROS while increasing antioxidant activity through its conjugated triene structure.
Limitations and future directions
The greatest limitation to the clinical use of punicic acid is the need for robust clinical evidence from human studies, with the few that have been reported showing highly inconsistent findings. Furthermore, more work is needed to establish its dosing, bioavailability, and metabolism. Significant gaps exist in understanding its long-term safety and efficacy in diverse populations.
Conclusion
PSO is rich in bioactive compounds, which account for both its nutritional content and its multifaceted health benefits. Punicic acid, a major fatty acid component of PSO, appears to help prevent as well as treat cardiometabolic diseases in preclinical models. The activity of punicic acid is similar to that of omega-3 PUFAs but through different mechanisms, offering potential complementary or synergistic benefits.
However, rigorous clinical trials are essential to establish the use of PA as a complementary nutritional agent – a nutraceutical – in the prevention and management of chronic disease. Until then, its therapeutic potential remains promising but unconfirmed in humans.
Journal reference:
- Almoraie, M., Spencer, J., and Wagstaff, C. (2025). Punicic Acid: A Potential Nutraceutical Compound in Pomegranate Seed Oil and Its Cardiovascular Benefits. Foods. DOI: 10.3390/foods14142412, https://www.mdpi.com/2304-8158/14/14/2412