The Overlooked Superfruit Outperforming Most Cardiovascular Supplements
An evidence-based deep dive into the cardiometabolic mechanisms your current stack is probably missing
I need to be honest here.
This research started as justification for my recently developed pomegranate addiction. You know those single-serving aril cups at Costco/Trader Joe’s/most major grocery stores?
Yes - these.
I ignored them for years. Then I tried one late last year. Instantly hooked.
Now they’re in season again (late September to January) and we’re back to spamming 5 or 6/week as a part of my morning pre-workout fuel added on top of Greek yogurt. Quick & fast-digesting carbs prior to a training session.
If you’ve tried these before, you know what I’m talking about. If you haven’t, I’m about to give you every reason why you should start.
What Makes Up a Pomegranate?
Pomegranates are packed with polyphenols giving them their antioxidant properties. The arils contain about 1-2g total polyphenols/100g, but the peel has up to 10x more.
Add on top of that their micronutrient density.
Mechanisms of Action
Pomegranate’s wide-range of proven health benefits are driven by what we’ll group together into five primary mechanisms:
Free Radical-Scavenging & Upregulation of Endogenous Antioxidant Defenses
Pomegranate’s antioxidant defense is two-pronged1 → 1) direct free radical neutralization & 2) upregulation of our natural antioxidant/detox systems.
First, punicalagin & ellagic acid donate electrons to neutralize free radicals before they damage our cells by restoring redox balance at the source.
Other compounds like flavonoids & tannins activate our antioxidant switch Nrf2 turning up production of:
Glutathione → our master antioxidant
SOD & catalase → enzymes breaking down free radicals
HO-1 → a protective cellular enzyme guarding against oxidative stress
Anti-Inflammatory Signaling
Polyphenolic compounds like punicalagin tend to do the heavy lifting in terms of inhibiting the inflammatory cascade2 via a few different pathways. When NF-κB is “turned off”, we produce fewer pro-inflammatory cytokines like TNF-α, IL-1β (via NLRP3) & IL-6 (via MAPK pathways) while downregulating inflammation-producing enzymes like COX-2.
Gut-Microbiome Modulation
Pomegranate’s large polyphenols, known as ellagitannins, aren’t directly absorbed. they break down into ellagic acid in the gut, where specific bacteria convert them into urolithins (A, B, C, D) → metabolites that reach the bloodstream & tissues to impose pomegranate’s systemic effects. Urolithins show strong potential to enhance mitochondrial function and cellular signaling, and they’re now being explored as exogenous compounds3. A tool you’re going to hear much more about in the coming years.
Not everyone produces urolithins equally. Individuals fall into metabotypes (UM-A, UM-B, or UM-0/non-producers), meaning two people consuming the same amount of pomegranate could experience different metabolic &physiological effects….(*emphasizes biochemical individuality*). This kind of variability explains inconsistent clinical trial outcomes.
Pomegranate exerts dual benefits: 1) a postbiotic effect = where urolithins drive systemic health & 2) a prebiotic effect = modulating the microbiome to indirectly influence metabolism and reduce inflammation.
Urolithin-Mediated Mitophagy
Urolithin A activates mitophagy4 → the cellular process that recycles damaged mitochondria. It engages the PINK1/Parkin pathway detecting mitochondrial damage and upregulating genes that produce new mitochondria to enhance oxidative capacity.
Anti-Atherogenic & Vascular Impacts
Pomegranate polyphenols (punicalagin & ellagic acid) reduce the oxidation of LDL cholesterol5. Reduced oxidized LDL decreases inflammatory signals in blood vessels, limiting plaque formation.
Pomegranate excels at balancing redox status. By reducing oxidative stress & enhancing endothelial nitric oxide synthase (eNOS) activity, it boosts NO levels promoting blood vessel relaxation & better blood flow to the peripheral tissues. Another reason pomegranate is an elite pre-workout food.
Health Benefits
Nearly all benefits of pomegranate stem via bettering metabolic health. This makes it a good starting point for us.
Cardiometabolic Health
In the most robust RCT conducted to date on the fruit, Barghchi et al. (2023)6 investigated 1,500mg daily pomegranate peel extract (combined with a 500kcal deficit) in 76 metabolically unhealthy patients for an 8-week trial period. The pomegranate group demonstrated significant improvements across multiple metabolic & body composition parameters:
Weight loss (-5.10 kg) & waist circumference reduction (-7.57 cm)
Triglycerides reduction (-16.02 mg/dL) & HDL-C increase (5.10 mg/dL)
Liver stiffness (-0.72 kPa) & steatosis (−0.30) reduction → markers of fatty liver status
The most recent trial published by Baghdadi et al. (2025)7 confirmed these earlier findings. This double-blind, RCT of 42 NAFLD patients demonstrated that 10 weeks of pomegranate peel extract supplementation (1,000 mg daily) combined with caloric restriction significantly improved liver enzymes (ALT, AST), triglycerides, HDL-C, & inflammatory markers (hs-CRP) compared to placebo.
Blood Pressure
In a 12-week RCT, Farhat et al. (2025)8 studied 740 mg daily pomegranate extract in 86 healthy adults aged 55–70. Compared to placebo, the pomegranate group showed significant reductions in inflammatory markers (IL-6 & IL-1β) and a clinically meaningful 5.2 mmHg decrease in systolic blood pressure.
These findings are also supported by a meta-analysis from Bahari et al. (2024)9 across 22 RCTs & more than 2,300 patients:
“Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced SBP (WMD: -7.87 mmHg; p < 0.001) and DBP (WMD: -3.23 mmHg; p = 0.003).“
Liver Function
In another 21-day randomized, double-blind, placebo-controlled trial with 30 healthy adults, Dormal et al. (2022)10 administered 20g whey protein with 650mg pomegranate extract to the treatment group & protein alone with maltodextrin as the placebo. The pomegranate group demonstrated significant improvements in both liver marker measured: 15.7% decrease in glutamate pyruvate transaminase (GPT) & a 12.1% prealbumin decrease.
Exercise Performance
Resistance Training
A crossover study of nine elite-level weightlifters by Ammar et al. (2016)11 significantly enhanced lifting performance across snatch, clean & jerk, and squat lifts by 8.3% and reduced perceived exertion by 4.3%. Subjects consumed 250 mL of pomegranate juice 6x daily in the 48 hr prior to the sessions.
Aerobic Exercise
A crossover study from Torregrosa-García et al. (2022)12 of 26 male amateur cyclists demonstrated relative to the placebo group, 15 days of 225 mg daily pomegranate extract significantly improved aerobic performance markers: increasing total time to exhaustion by 14% (ranging from 18 to 171 sec) & time to reach ventilatory threshold 2 by 10% (ranging from 27 to 82.5 sec).
Strength Recovery
Trombold et al. (2010)13 demonstrated that 9 days of pomegranate juice (500 mL) was taken 2x daily at 12-h intervals significantly enhanced isometric strength recovery following resistance training with meaningful advantages at 48 hrs (85.4% vs 78.3% of baseline) & 72 hours (88.9% vs 84.0% of baseline).
Cognitive Function
In a one-year RCT, Chatzikostopoulos et al. (2024)14 studied 80 individuals with mild cognitive impairment. They found that 5 drops daily of pomegranate seed oil combined with a Mediterranean diet significantly improved cognitive outcomes compared to the diet alone: global cognition (p=0.004), verbal episodic memory (p=0.009), & processing speed (p<0.001).
Skin Health
A double-blind, placebo-controlled study from Chakkalakal et al. (2022)15 demonstrated that four weeks of 250 mg daily pomegranate extract supplementation significantly reduced wrinkle severity (p<0.01) in healthy adults 25-55 years of age.
The research also revealed strong evidence for gut-skin axis connections with subjects having higher Eggerthellaceae gut bacteria abundance showing significantly greater improvements in facial barrier function (reduced TEWL) & wrinkle reduction.
In a 12-week RCT, Henning et al. (2022)16 studied 74 healthy young women finding that daily consumption of either 1,000 mg pomegranate extract or 8 oz pomegranate juice significantly increased the minimal erythema dose (MED) relative to placebo. A higher MED → greater UV resistance → enhanced skin photoprotection.
Gut Health
As we mentioned in the previous section, pomegranate has a unique ability to modulate the gut microbiota. Hou at al. (2024)17 demonstrated in a 3-week RCT that pomegranate juice with inulin fiber produced progressively greater gut microbiota modifications compared to juice alone or placebo. The juice & inulin treatment significantly enhanced production of beneficial short-chain fatty acids & pomegranate polyphenol metabolites (including urolithins).
Addiction Therapy
One of the newest use cases we’ve seen in the past year. An RCT by Leventlis et al. (2025)18 showed promising results as an adjunctive therapy for opioid use disorder in patients on medication-assisted treatment. Over 4 months, 250 mL of pomegranate juice daily, the pomegranate intervention significantly reduced heroin cravings & increased blood antioxidant capacity.
Canker Sores
In a crossover RCT, Lavaee et al. (2022)19 studied 30 patients with recurrent aphthous stomatitis finding that pomegranate flower tablets (3x daily for 6 days) significantly outperformed Triadent oral paste in pain relief & lesion healing.
Reputable Brands
The preference is to consume pomegranate as either a whole food (seeds + peel) or the arils. However, when pomegranate is out of season or the seeds might not be available, I prefer to consume either juice or the extract alone.
Pomegranate Juice
Pomegranate Arils
Pomegranate Extract
That’s a wrap. I’ve got a few more requests I’m getting around to from you all over the next few weeks. If you want to see a deeper dive on a specific compound, a protocol laid out in detail or any other topic of your choosing in the health space, let me know in the comments below & we’ll make it happen.
And if you haven’t already, reminder to subscribe below. Every little bit makes an impact in the fight against the rampant growth of the reductionist AI/mainstream slop we're seeing. (We’re going to win.) And it’s why we’re running the Anti-Slop Sale™ before we roll out more premium content.
Stay after it & until next time.
Your friend,
Phys
Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways. Nutrients. 2017 Apr 28;9(5):436. doi: 10.3390/nu9050436. PMID: 28452959; PMCID: PMC5452166.
Xu J, Cao K, Liu X, Zhao L, Feng Z, Liu J. Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases. Antioxidants (Basel). 2021 Dec 24;11(1):29. doi: 10.3390/antiox11010029. PMID: 35052533; PMCID: PMC8773334.
Zhao H, Song G, Zhu H, Qian H, Pan X, Song X, Xie Y, Liu C. Pharmacological Effects of Urolithin A and Its Role in Muscle Health and Performance: Current Knowledge and Prospects. Nutrients. 2023 Oct 19;15(20):4441. doi: 10.3390/nu15204441. PMID: 37892516; PMCID: PMC10609777.
Qiu J, Chen Y, Zhuo J, Zhang L, Liu J, Wang B, Sun D, Yu S, Lou H. Urolithin A promotes mitophagy and suppresses NLRP3 inflammasome activation in lipopolysaccharide-induced BV2 microglial cells and MPTP-induced Parkinson’s disease model. Neuropharmacology. 2022 Apr 1;207:108963. doi: 10.1016/j.neuropharm.2022.108963. Epub 2022 Jan 19. PMID: 35065082.
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Baghdadi G, Shidfar F, Mokhtare M, Sarbakhsh P, Agah S. Effect of Pomegranate Peel Consumption on Liver Enzymes, Lipid Profile, Liver Steatosis, and Hs-CRP in Patients With Non-alcoholic Fatty Liver Disease: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Phytother Res. 2025 Feb;39(2):619-629. doi: 10.1002/ptr.8404. Epub 2024 Nov 28. PMID: 39608758.
Farhat G, Malla J, Vadher J, Al-Dujaili EAS. Effects of Pomegranate Extract on Inflammatory Markers and Cardiometabolic Risk Factors in Adults Aged 55-70 Years: A Randomised Controlled Parallel Trial. Nutrients. 2025 Apr 1;17(7):1235. doi: 10.3390/nu17071235. PMID: 40218993; PMCID: PMC11990117.
Bahari H, Omidian K, Goudarzi K, Rafiei H, Asbaghi O, Hosseini Kolbadi KS, Naderian M, Hosseini A. The effects of pomegranate consumption on blood pressure in adults: A systematic review and meta-analysis. Phytother Res. 2024 May;38(5):2234-2248. doi: 10.1002/ptr.8170. Epub 2024 Feb 27. PMID: 38410857.
Dormal V, Pachikian B, Debock E, Buchet M, Copine S, Deldicque L. Evaluation of a Dietary Supplementation Combining Protein and a Pomegranate Extract in Older People: A Safety Study. Nutrients. 2022 Dec 6;14(23):5182. doi: 10.3390/nu14235182. PMID: 36501211; PMCID: PMC9739468.
Ammar A, Turki M, Chtourou H, Hammouda O, Trabelsi K, Kallel C, Abdelkarim O, Hoekelmann A, Bouaziz M, Ayadi F, Driss T, Souissi N. Pomegranate Supplementation Accelerates Recovery of Muscle Damage and Soreness and Inflammatory Markers after a Weightlifting Training Session. PLoS One. 2016 Oct 20;11(10):e0160305. doi: 10.1371/journal.pone.0160305. PMID: 27764091; PMCID: PMC5072630.
Torregrosa-García A, Ávila-Gandía V, Luque-Rubia AJ, Abellán-Ruiz MS, Querol-Calderón M, López-Román FJ. Pomegranate Extract Improves Maximal Performance of Trained Cyclists after an Exhausting Endurance Trial: A Randomised Controlled Trial. Nutrients. 2019 Mar 28;11(4):721. doi: 10.3390/nu11040721. PMID: 30925733; PMCID: PMC6521089.
Trombold JR, Barnes JN, Critchley L, Coyle EF. Ellagitannin consumption improves strength recovery 2-3 d after eccentric exercise. Med Sci Sports Exerc. 2010 Mar;42(3):493-8. doi: 10.1249/MSS.0b013e3181b64edd. PMID: 19952825.
Chatzikostopoulos T, Gialaouzidis M, Koutoupa A, Tsolaki M. The Effects of Pomegranate Seed Oil on Mild Cognitive Impairment. J Alzheimers Dis. 2024;97(4):1961-1970. doi: 10.3233/JAD-231100. PMID: 38306046; PMCID: PMC10977427.
Chakkalakal M, Nadora D, Gahoonia N, Dumont A, Burney W, Pan A, Chambers CJ, Sivamani RK. Prospective Randomized Double-Blind Placebo-Controlled Study of Oral Pomegranate Extract on Skin Wrinkles, Biophysical Features, and the Gut-Skin Axis. J Clin Med. 2022 Nov 14;11(22):6724. doi: 10.3390/jcm11226724. PMID: 36431201; PMCID: PMC9699032.
Henning SM, Yang J, Lee RP, Huang J, Hsu M, Thames G, Gilbuena I, Long J, Xu Y, Park EH, Tseng CH, Kim J, Heber D, Li Z. Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial. Sci Rep. 2019 Oct 10;9(1):14528. doi: 10.1038/s41598-019-50926-2. PMID: 31601842; PMCID: PMC6787198.
Hou C, Shi H, Xiao J, Song X, Luo Z, Ma X, Shi L, Wei H, Li J. Pomegranate Juice Supplemented with Inulin Modulates Gut Microbiota and Promotes the Production of Microbiota-Associated Metabolites in Overweight/Obese Individuals: A Randomized, Double-Blind, Placebo-Controlled Trial. J Agric Food Chem. 2024 Jul 3;72(26):14663-14677. doi: 10.1021/acs.jafc.4c00849. Epub 2024 Jun 18. PMID: 38887904.
Leventelis C, Makri S, Ververi A, Papageorgiou K, Tentolouri A, Mountzouridi E, Tekos F, Barmpas PT, Tasoulis S, Metsios GS, Kouretas D, Veskoukis AS. Pomegranate juice ameliorates craving and oxidative stress on patients under medication for opioid addiction treatment with methadone and buprenorphine: A ranzomised controlled trial. Clin Nutr ESPEN. 2025 Apr;66:34-45. doi: 10.1016/j.clnesp.2025.01.025. Epub 2025 Jan 10. PMID: 39798867.
Lavaee F, Parhizkar E, Tavakoli F, Zarshenas MM, Asmarian N. Evaluation of the Effects of Punica granatum Flower Tablets on Pain and Healing of Minor Recurrent Aphthous Stomatitis: A Randomized Clinical Trial. Clin Exp Dent Res. 2024 Aug;10(4):e920. doi: 10.1002/cre2.920. PMID: 39016077; PMCID: PMC11252825.
Great article. A protocol/deep dive on psyllium would be interesting.
The best thing on planet earth, Pycnogenol plus pomegranate juice = wonders