Table 1. Beneficial effects of pomegranate on human health. The therapeutic properties of pomegranate, number of research studies and references are reported in the table.
3.1. Neuroprotective activity
A study by Siddarth et al. (2020) showed that daily consumption of pomegranate juice over a period of 1 year can exert beneficial effects on visual memory in aging individuals. Another study found that maternal intake of pomegranate juice exhibits neuroprotective effect in newborns with intrauterine growth restriction (IUGR) (Matthews et al., 2019). Bellone and colleagues (2019) showed that pomegranate polyphenol supplements enhance functional and cognitive outcomes in post-stroke rehabilitation.
3.2. Antioxidant activity
A previous study by Urbaniak et al. (2018) found that daily oral intake of pomegranate juice increases total antioxidant capacity (TAC) in athletes (i.e., rowers). Mazani and colleagues (2014) demonstrated that consumption of pomegranate juice limits oxidative damage after exhaustive exercise. Previous research showed that punicalagin present in pomegranate juice has antioxidant activity in human placenta in vivo and in vitro (Chen et al., 2012). Another study demonstrated that consumption of probiotic pomegranate juice improves antioxidant activity in women with polycystic ovary syndrome (PCOS) (Esmaeilinezhad et al., 2019; Esmaeilinezhad et al., 2020). A study by Heber et al. (2007) found that oral consumption of ellagitannin-rich pomegranate extract exerts antioxidant effects in overweight individuals. Another study found that oral intake of pomegranate extract reduces oxidative stress in overweight or obese individuals (Hosseini et al., 2016). Gouda and colleagues (2016) showed improved antioxidant activity in human plasma and urine after daily consumption of polyphenol-rich pomegranate juice. Other two studies showed the antioxidant activity of pomegranate juice in diabetic individuals (Rosenblat et al., 2006; Sohrab et al., 2017). Ghoochani and colleagues (2016) found the antioxidant activity of pomegranate juice in patients with osteoarthritis (OA), while other two studies demonstrated that consumption of pomegranate extract has antioxidant activity in patients with rheumatoid arthritis (RA) (Balbir-Gurman et al., 2011; Ghavipour et al., 2017). Previous studies showed improved oxidative status in individuals undergoing hemodialysis and drinking pomegranate juice three times per week (Barati Boldaji et al., 2020; Shema-Didi et al., 2012) or during a single session (Shema-Didi et al., 2013). Another study demonstrated that pomegranate polyphenol extract has beneficial effects on oxidative stress in hemodialysis patients (Wu et al., 2015). Guo and colleagues (2008) found increased antioxidant activity after daily oral intake of pomegranate juice in elderly individuals and this activity was probably exerted by polyphenols present in the plant. Hamoud et al. (2014) showed an improvement of oxidative status in individuals with hypercholesterolemia after consumption of pomegranate extract pills during statin therapy. A study by Kanlayavattanakul et al. (2020) demonstrated the antioxidant activity of phenolic-enriched pomegranate peel extract in vitro.
3.3. Effects on the reproductive system
Previous studies showed that pomegranate juice consumption ameliorates symptoms and comorbidity of PCOS (e.g., levels of testosterone, metabolic syndrome parameters and cardiovascular risk factors) (Abedini et al., 2021; Esmaeilinezhad et al., 2019; Esmaeilinezhad et al., 2020). Chen and colleagues (2012) found that oral intake of pomegranate juice can prevent placental diseases. Another study demonstrated that pomegranate extract is useful in the treatment of idiopathic central precocious puberty (ICPP) together with gonadotropin-releasing hormone (GnRH) analog terapy (Liu and Tang, 2017).
3.4. Anticolitis activity
Kamali and colleagues (2015) showed that oral intake of pomegranate peels aqueous extract can improve clinical response in patients with ulcerative colitis.
3.5. Anticancer activity
Previous studies demonstrated that consumption of pomegranate juice and extracts can ameliorate clinical outcomes in prostate cancer patients (Paller et al., 2013; Pantuck et al., 2006). Another study found that this activity can be exerted by polyphenol metabolites (i.e., dimethyl ellagic acid and urolithin glucuronides) (González-Sarrías et al., 2010). González-Sarrías and colleagues (2018) showed that oral intake of pomegranate extracts has a beneficial effect in patients with colorectal cancer by decreasing endotoxemia. Other two studies found that pomegranate extracts can regulate microRNAs and gene expression in colorectal cancer tissues (Nuñez-Sánchez et al., 2015; Nuñez-Sánchez et al., 2017). A preliminary study showed that oral intake of pomegranate juice can be effective on the prevention of breast cancer by decreasing serum sex hormone levels (Kapoor et al., 2015).
3.6. Cardiovascular effects
Previous studies demonstrated that oral consumption of pomegranate juice lowers triglycerides and blood pressure and improves high-density lipoprotein cholesterol (HDL-C) (Barati Boldaji et al., 2020; Shema-Didi et al., 2014) and atherosclerosis (Shema-Didi et al., 2012) in patients undergoing hemodialysis. Wu and colleagues (2015) showed that pomegranate polyphenol extract is able to decrease blood pressure in hemodialysis patients, while Jafari et al. (2020) found that consumption of pomegranate peel extract and vitamin E can improve endothelial function in these patients. A previous study demonstrated that oral intake of concentrated pomegranate juice can lead to a reduction of total and low-density lipoprotein cholesterol (LDL-C) in diabetic hyperlipidemia (Esmaillzadeh et al., 2004). Other two studies found that oral intake of pomegranate juice decreases blood pressure in diabetic patients (Sohrab et al., 2019) and in individuals with metabolic syndrome (Moazzen and Alizadeh, 2017). Mirmiran et al. (2010) demonstrated the beneficial activity of pomegranate seed oil on serum lipids in individuals with hyperlipidaemia. Another study found that oral intake of pomegranate extract pills has anti-atherogenic activity in subjects with hypercholesterolemia undergoing statin therapy (Hamoud et al., 2014). Mathew and colleagues (2012) demonstrated that individuals who consumed a drink with ellagitannin-rich pomegranate extract displayed inhibition of postprandial improvement in systolic blood pressure after eating a high fat meal. A previous study showed the cardiovascular protective effect of urolithin present in pomegranate extract in subjects with obesity or overweight (González-Sarrías et al., 2017). Hosseini and colleagues (2016) demonstrated the beneficial effects of pomegranate extract on cardiovascular system in individuals with overweight or obesity. Lynn and colleagues (2012) found that pomegranate juice has a beneficial effect on blood pressure and Razani and colleagues (2017) showed that pomegranate juice has a therapeutic effect in ischemic heart disease. Another study demonstrated that oral consumption of pomegranate juice exerts health benefits on myocardial ischemia in individuals with ischemic coronary heart disease (Sumner et al., 2005). Abedini and colleagues (2021) showed that pomegranate juice can prevent cardiovascular diseases, lowering triglycerides and blood pressure and raising HDL-C in PCOS patients. A study by Esmaeilinezhad et al. (2020) found that consumption of synbiotic pomegranate juice lowers blood pressure, total cholesterol and LDL-C, while improves HDL-C in individuals with PCOS.
3.7. Antidiabetic activity
Previous studies showed the beneficial effects of oral intake of pomegranate juice in diabetic patients, improving cardiovascular parameters (Sohrab et al., 2019), glucose control (Banihani et al., 2014), inflammatory (Sohrab et al., 2018) and oxidative status (Rosenblat et al., 2006; Sohrab et al., 2017). Kerimi and colleagues (2017) demonstrated that pomegranate juice consumption can lower blood glucose levels after a bread meal through α-amilase inhibition by punicalagin and polyphenol metabolites, such as urolithins, can regulate glucose metabolism about 3-6 hours after the meal. A previous study by Hosseini et al. (2016) found that pomegranate extract reduces blood levels of insulin and glucose in individuals with overweight or obesity. Another study showed that pomegranate seed oil can ameliorate diabetic parameters in individuals with obesity and type 2 diabetes mellitus (T2DM) (Khajebishak et al., 2019). Esmaeilinezhad and colleagues (2019) demonstrated that individuals with PCOS who consumed synbiotic pomegranate juice showed improved glycemic control. A study by Banihani et al. (2020) found that oral intake of pomegranate juice exerts beneficial effects in diabetic patients, lowering cortisol levels.
3.8. Effects on metabolic syndrome and obesity
Previous studies showed that pomegranate juice consumption ameliorates metabolic syndrome (Kojadinovic et al., 2017; Moazzen and Alizadeh, 2017). Other two studies found that pomegranate juice (González-Ortiz et al., 2011) or extract (Hosseini et al., 2016) has beneficial effects in overweight or obese individuals. Esmaeilinezhad and colleagues (2019) showed reduced weight, waist circumference and body mass index (BMI) in women with PCOS drinking synbiotic pomegranate juice.
3.9. Antiparasitic activity
A study by El-Sherbini et al. (2010) demonstrated the antiparasitic activity of pomegranate extract against Trichomonas vaginalis in vitro and in vivo. Another study showed the beneficial effects of pomegranate extract against Cryptosporidium parvum in calves (Weyl-Feinstein et al., 2014).
3.10. Antiarthritic activity
Previous studies found that pomegranate juice or extract can be beneficial for OA (Ghoochani et al., 2016) and RA (Balbir-Gurman et al., 2011; Ghavipour et al., 2017) by improving the oxidative status.
3.11. Effects on skin health
Previous studies showed that oral intake of pomegranate juice, extract and extract rich in ellagic acid can protect the skin from ultraviolet (UV) radiation (Henning et al., 2019; Kasai et al., 2006). Kanlayavattanakul and colleagues (2020) demonstrated that phenolic-enriched pomegranate peel extract has beneficial effects against skin hyperpigmentation in vitro through enhanced antioxidant activity.
4. Discussion
In this review, we conducted a literature search to find the therapeutic effects of oral intake of pomegranate. Overall, we show 11 health benefits of this plant, including those on the nervous system, oxidative status, colitis, cancer, the cardiovascular system, diabetes, parasitic infections, arthritis, metabolic syndrome and obesity, the reproductive system and skin health.
Our results show that the most commonly reported therapeutic effect is antioxidant activity, which is described in 20 previous research studies. The beneficial effects of pomegranate on the cardiovascular system is also well reported in the scientific literature and 18 studies showed this plant medicinal property. The antidiabetic activity of pomegranate was examined in 10 studies (Table 1). Diabetes is a risk factor for cardiovascular diseases (Leon and Maddox, 2015) and previous research studies found that oxidative stress is involved in these conditions (Kattoor et al., 2017; Maritim et al., 2003; Sugamura and Keaney, 2011). In this review, we show that oral intake of pomegranate can ameliorate diabetes (Rosenblat et al., 2006; Sohrab et al., 2017) and cardiovascular parameters (Barati Boldaji et al., 2020; Hamoud et al., 2014; Shema-Didi et al., 2012; Shema-Didi et al., 2014) by improving the oxidative status. These therapeutic effects may be mediated by pomegranate phenolic compounds and metabolites (Chen et al., 2012; González-Sarrías et al., 2017; Gouda et al., 2016; Guo et al., 2008; Heber et al., 2007; Kanlayavattanakul et al., 2020; Kerimi et al., 2017; Mathew et al., 2012; Wu et al., 2015). Most of the research studies focused on the medicinal properties of pomegranate juice instead of this plant extracts.
Anticancer activity of pomegranate is found in 7 research studies and this effect may be attributed to pomegranate polyphenol metabolites (González-Sarrías et al., 2010) (Table 1). Previous research has focused on the activity of pomegranate against prostate (González-Sarrías et al., 2010; Paller et al., 2013; Pantuck et al., 2006), colorectal (González-Sarrías et al., 2018; Nuñez-Sánchez et al., 2015; Nuñez-Sánchez et al., 2017) and breast (Kapoor et al., 2015) cancers. The health benefits of pomegranate on the reproductive system and the beneficial effects of this plant on obesity and metabolic syndrome are reported in 5 studies (Table 1). In this review, we show that the therapeutic effects of pomegranate on the reproductive system (Chen et al., 2012; Esmaeilinezhad et al., 2019; Esmaeilinezhad et al., 2020) and obesity or overweight (Heber et al., 2007; Hosseini et al., 2016) can be mediated by improved oxidative status. Polyphenols may exert the beneficial activity on the reproductive system (Chen et al., 2012) and overweight (Heber et al., 2007).
Only few studies reported the therapeutic effects of pomegranate consumption on the nervous system, arthritis and skin health (3 studies), colitis (1 study) and parasitic infections (2 studies) (Table 1). The antiarthritic activity is mediated by the antioxidant effects of pomegranate (Balbir-Gurman et al., 2011; Ghavipour et al., 2017; Ghoochani et al., 2016) and phenolic compounds and metabolites, which are present in this plant, may be beneficial for skin health (Henning et al., 2019; Kanlayavattanakul et al., 2020; Kasai et al., 2006).
Future research is required to define the potential health benefits of pomegranate consumption and the phytochemicals involved in these activities. Limitations of this review are the following: most of the research studies utilise small sample sizes, only published articles are included and personal selection criteria are used.
5. Conclusion
This review describes the main medicinal properties of pomegranate consumption previously reported in the scientific literature. We show 11 health benefits of this plant, which include therapeutic effects on the cardiovascular system, oxidative status, diabetes, the nervous system, colitis, cancer, metabolic syndrome and obesity, parasitic infections, arthritis, the reproductive system and skin health. The most commonly reported effects of oral intake of pomegranate are antioxidant, cardiovascular and antidiabetic activities and polyphenols present in this plant may exert the beneficial effects on human health. Future studies are needed to clarify the medicinal properties of pomegranate and the mechanisms underlying these activities.
Abbreviations
BMI: body mass index
GnRH: gonadotropin-releasing hormone
HDL-C: high-density lipoprotein cholesterol
ICPP: idiopathic central precocious puberty
IUGR: intrauterine growth restriction
LDL-C: low-density lipoprotein cholesterol
OA: osteoarthritis
PCOS: polycystic ovary syndrome
RA: rheumatoid arthritis
T2DM: type 2 diabetes mellitus
TAC: total antioxidant capacity
UV: ultraviolet
 
Statements and Declarations
Acknowledgements
We thank Maurizio Carturan and Lidia Novelli for useful discussions and support.
Funding
No funding was received for conducting this study.
Conflict of interest
The authors declare that there is no conflict of interest.
Authors' contributions
ADN, FG, FP and PZ contributed to the study conception and design. Literature search was performed by ADN. The first draft of the manuscript was written by ADN and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Ethics approval and consent to participate
Not applicable
 Reference list
§   Abedini M, Ghasemi-Tehrani H, Tarrahi MJ, Amani R (2021) The effect of concentrated pomegranate juice consumption on risk factors of cardiovascular diseases in women with polycystic ovary syndrome: a randomized controlled trial. Phytother Res 35(1):442-451.
§   Balbir-Gurman A, Fuhrman B, Braun-Moscovici Y, Markovits D, Aviram M (2011) Consumption of pomegranate decreases serum oxidative stress and reduces disease activity in patients with active rheumatoid arthritis: a pilot study. Isr Med Assoc J 13(8):474-479. 
§   Banihani SA, Makahleh SM, El-Akawi ZJ (2020) Short-term effect of fresh pomegranate juice on serum cortisol and thyroxine in patients with type 2 diabetes. Curr Mol Med 20(5):355-360. 
§    Banihani SA, Makahleh SM, El-Akawi Z, Al-Fashtaki RA, Khabour OF, Gharibeh MY, Saadah NA, Al-Hashimi FH, Al-Khasieb NJ (2014) Fresh pomegranate juice ameliorates insulin resistance, enhances β-cell function, and decreases fasting serum glucose in type 2 diabetic patients. Nutr Res 34(10):862-867. 
§  Barati Boldaji R, Akhlaghi M, Sagheb MM, Esmaeilinezhad Z (2020) Pomegranate juice improves cardiometabolic risk factors, biomarkers of oxidative stress and inflammation in hemodialysis patients: a randomized crossover trial. J Sci Food Agric 100(2):846-854.
§   Bar-Ya’akov I, Tian L, Amir R, Holland D (2019) Primary metabolites, anthocyanins, and hydrolyzable tannins in the pomegranate fruit. Front Plant Sci 10:620.
§   Bellone JA, Murray JR, Jorge P, Fogel TG, Kim M, Wallace DR, Hartman RE (2019) Pomegranate supplementation improves cognitive and functional recovery following ischemic stroke: a randomized trial. Nutr Neurosci 22(10):738-743. 
§   Chen B, Tuuli MG, Longtine MS, Shin JS, Lawrence R, Inder T, Michael Nelson D (2012) Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts. Am J Physiol Endocrinol Metab 302(9):E1142-E1152. 
§   El-Sherbini GM, Ibrahim KM, El Sherbiny ET, Abdel-Hady NM, Morsy TA (2010) Efficacy of Punica granatum extract on in-vitro and in-vivo control of Trichomonas vaginalis. J Egypt Soc Parasitol 40(1):229-244. 
§   Esmaeilinezhad Z, Babajafari S, Sohrabi Z, Eskandari MH, Amooee S, Barati-Boldaji R (2019) Effect of synbiotic pomegranate juice on glycemic, sex hormone profile and anthropometric indices in PCOS: a randomized, triple blind, controlled trial. Nutr Metab Cardiovasc Dis 29(2):201-208. 
§   Esmaeilinezhad Z, Barati-Boldaji R, Brett NR, de Zepetnek JOT, Bellissimo N, Babajafari S, Sohrabi Z (2020) The effect of synbiotics pomegranate juice on cardiovascular risk factors in PCOS patients: a randomized, triple-blinded, controlled trial. J Endocrinol Invest 43(4):539-548.
§   Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L (2004) Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia. J Med Food 7(3):305-308.
§   Ghavipour M, Sotoudeh G, Tavakoli E, Mowla K, Hasanzadeh J, Mazloom Z (2017) Pomegranate extract alleviates disease activity and some blood biomarkers of inflammation and oxidative stress in Rheumatoid Arthritis patients. Eur J Clin Nutr 71(1):92-96. 
§  Ghoochani N, Karandish M, Mowla K, Haghighizadeh MH, Jalali MT (2016) The effect of pomegranate juice on clinical signs, matrix metalloproteinases and antioxidant status in patients with knee osteoarthritis. J Sci Food Agric 96(13):4377-4381. 
§   González-Ortiz M, Martínez-Abundis E, Espinel-Bermúdez MC, Pérez-Rubio KG (2011) Effect of pomegranate juice on insulin secretion and sensitivity in patients with obesity. Ann Nutr Metab 58(3):220-223. 
§   González-Sarrías A, García-Villalba R, Romo-Vaquero M, Alasalvar C, Örem A, Zafrilla P, Tomás-Barberán FA, Selma MV, Espín JC (2017) Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: A randomized clinical trial. Mol Nutr Food Res 61(5). 
§   González-Sarrías A, Giménez-Bastida JA, García-Conesa MT, Gómez-Sánchez MB, García-Talavera NV, Gil-Izquierdo A, Sánchez-Alvarez C, Fontana-Compiano LO, Morga-Egea JP, Pastor-Quirante FA, Martínez-Díaz F, Tomás-Barberán FA, Espín JC (2010) Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice. Mol Nutr Food Res 54(3):311-322. 
§   González-Sarrías A, Núñez-Sánchez MA, Ávila-Gálvez MA, Monedero-Saiz T, Rodríguez-Gil FJ, Martínez-Díaz F, Selma M , Espín JC (2018) Consumption of pomegranate decreases plasma lipopolysaccharide-binding protein levels, a marker of metabolic endotoxemia, in patients with newly diagnosed colorectal cancer: a randomized controlled clinical trial. Food Funct 9(5):2617-2622.
§  Gouda M, Moustafa A, Hussein L, Hamza M (2016) Three week dietary intervention using apricots, pomegranate juice or/and fermented sour sobya and impact on biomarkers of antioxidative activity, oxidative stress and erythrocytic glutathione transferase activity among adults. Nutr J 15(1):52. 
§   Grieve M (1931) A  Modern  Herbal. Dover Publications, New York.
§   Guo C, Wei J, Yang J, Xu J, Pang W, Jiang Y (2008) Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects. Nutr Res 28(2):72-77.
§   Hamoud S, Hayek T, Volkova N, Attias J, Moscoviz D, Rosenblat M, Aviram M (2014) Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study. Atherosclerosis 232(1):204-210. 
§   Heber D, Seeram NP, Wyatt H, Henning SM, Zhang Y, Ogden LG, Dreher M, Hill JO (2007) Safety and antioxidant activity of a pomegranate ellagitannin-enriched polyphenol dietary supplement in overweight individuals with increased waist size. J Agric Food Chem 55(24):10050-10054. 
§   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 (2019) 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 9(1):14528.
§   Hosseini B, Saedisomeolia A, Wood LG, Yaseri M, Tavasoli S (2016) Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: a randomized controlled clinical trial. Complement Ther Clin Pract 22:44-50. 
§   Jafari T, Fallah AA, Reyhanian A, Sarmast E (2020) Effects of pomegranate peel extract and vitamin E on the inflammatory status and endothelial function in hemodialysis patients: a randomized controlled clinical trial. Food Funct 11(9):7987-7993.
§   Jurenka JS (2008) Therapeutic applications of pomegranate (Punica granatum L.): a review. Altern Med Rev 13(2):128-144.
§   Kamali M, Tavakoli H, Khodadoost M, Daghaghzadeh H, Kamalinejad M, Gachkar L, Mansourian M, Adibi P (2015) Efficacy of the Punica granatum peels aqueous extract for symptom management in ulcerative colitis patients. A randomized, placebo-controlled, clinical trial. Complement Ther Clin Pract 21(3):141-146. 
§   Kandylis P, Kokkinomagoulos E (2020) Food applications and potential health benefits of pomegranate and its derivatives. Foods 9(2):122.
§   Kanlayavattanakul M, Chongnativisit W, Chaikul P, Lourith N (2020) Phenolic-rich pomegranate peel extract: in vitro, cellular, and in vivo activities for skin hyperpigmentation treatment. Planta Med 86(11):749-759.
§   Kapoor R, Ronnenberg A, Puleo E, Chatterton RT Jr, Dorgan JF, Seeram NP, Sturgeon SR (2015) Effects of Pomegranate Juice on Hormonal Biomarkers of Breast Cancer Risk. Nutr Cancer 67(7):1113-1119. 
§   Kasai K, Yoshimura M, Koga T, Arii M, Kawasaki S (2006) Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin. J Nutr Sci Vitaminol 52(5):383-388.
§   Kattoor AJ, Pothineni NVK, Palagiri D, Mehta JL (2017) Oxidative Stress in Atherosclerosis. Curr Atheroscler Rep 19(11):42. 
§   Kerimi A, Nyambe-Silavwe H, Gauer JS, Tomás-Barberán FA, Williamson G (2017) Pomegranate juice, but not an extract, confers a lower glycemic response on a high-glycemic index food: randomized, crossover, controlled trials in healthy subjects. Am J Clin Nutr 106(6):1384-1393. 
§   Khajebishak Y, Payahoo L, Alivand M, Hamishehkar H, Mobasseri M, Ebrahimzadeh V, Alipour M, Alipour B (2019) Effect of pomegranate seed oil supplementation on the GLUT-4 gene expression and glycemic control in obese people with type 2 diabetes: A randomized controlled clinical trial. J Cell Physiol 234(11):19621-19628.
§   Kojadinovic MI, Arsic AC, Debeljak-Martacic JD, Konic-Ristic AI, Kardum ND, Popovic TB, Glibetic MD (2017) Consumption of pomegranate juice decreases blood lipid peroxidation and levels of arachidonic acid in women with metabolic syndrome. J Sci Food Agric 97(6):1798-1804. 
§   Leon BM, Maddox TM (2015) Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes 6(13):1246-1258. 
§   Levin GM (2006) Pomegranate. Third Millennium Pubns
§   Liu J, Tang J (2017) Effects of pomegranate extract in supplementing gonadotropin-releasing hormone therapy on idiopathic central precocious puberty in Chinese girls: a randomized, placebo-controlled, double-blind clinical trial. Food Funct 8(2):695-700.
§   Longtin R (2003) The Pomegranate: Nature’s Power Fruit? J Natl Cancer Inst 95(5):346-348.
§   Lynn A, Hamadeh H, Leung WC, Russell JM, Barker ME (2012) Effects of pomegranate juice supplementation on pulse wave velocity and blood pressure in healthy young and middle-aged men and women. Plant Foods Hum Nutr 67(3):309-314. 
§   Magangana TP, Makunga NP, Fawole OA, Opara UL (2020) Processing factors affecting the phytochemical and nutritional properties of pomegranate (Punica granatum L.) peel waste: a review. Molecules 25(20):4690.
§   Maritim AC, Sanders RA, Watkins JB 3rd (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17(1):24-38.
§   Mathew AS, Capel-Williams GM, Berry SE, Hall WL (2012) Acute effects of pomegranate extract on postprandial lipaemia, vascular function and blood pressure. Plant Foods Hum Nutr 67(4):351-357. 
§  Matthews LG, Smyser CD, Cherkerzian S, Alexopoulos D, Kenley J, Tuuli MG, Nelson DM, Inder TE (2019) Maternal pomegranate juice intake and brain structure and function in infants with intrauterine growth restriction: A randomized controlled pilot study. PLoS One 14(8):e0219596.
§  Mazani M, Fard AS, Baghi AN, Nemati A, Mogadam RA (2014) Effect of pomegranate juice supplementation on matrix metalloproteinases 2 and 9 following exhaustive exercise in young healthy males. J Pak Med Assoc 64(7):785-790. 
§   Mirmiran P, Fazeli MR, Asghari G, Shafiee A, Azizi F (2010) Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial. Br J Nutr 104(3):402-406. 
§   Moazzen H, Alizadeh M (2017) Effects of Pomegranate Juice on Cardiovascular Risk Factors in Patients with Metabolic Syndrome: a Double-Blinded, Randomized Crossover Controlled Trial. Plant Foods Hum Nutr 72(2):126-133.
§   Nuñez-Sánchez MA, Dávalos A, González-Sarrías A, Casas-Agustench P, Visioli F, Monedero-Saiz T, García-Talavera NV, Gómez-Sánchez MB, Sánchez-Álvarez C, García-Albert AM, Rodríguez-Gil FJ, Ruiz-Marín M, Pastor-Quirante FA, Martínez-Díaz F, Tomás-Barberán FA, García-Conesa MT, Espín JC (2015) MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts. Mol Nutr Food Res 59(10):1973-1986. 
§   Nuñez-Sánchez MA, González-Sarrías A, García-Villalba R, Monedero-Saiz T, García-Talavera NV, Gómez-Sánchez MB, Sánchez-Álvarez C, García-Albert AM, Rodríguez-Gil FJ, Ruiz-Marín M, Pastor-Quirante FA, Martínez-Díaz F, Tomás-Barberán FA, Espín JC, García-Conesa MT (2017) Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem 42:126-133. 
§   Paller CJ, Ye X, Wozniak PJ, Gillespie BK, Sieber PR, Greengold RH, Stockton BR, Hertzman BL, Efros MD, Roper RP, Liker HR, Carducci MA (2013) A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis 16(1):50-55. 
§   Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L, Belldegrun A (2006) Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res 12(13):4018-4026. 
§   Razani Z, Dastani M, Kazerani HR (2017) Cardioprotective effects of pomegranate (Punica granatum) juice in patients with ischemic heart disease. Phytother Res 31(11):1731-1738.
§   Rosenblat M, Hayek T, Aviram M (2006) Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages. Atherosclerosis 187(2):363-371. 
§   Shabbir MA, Khan MR, Saeed M, Pasha I, Khalil AA, Siraj N (2017) Punicic acid: A striking health substance to combat metabolic syndromes in humans. Lipids Health Dis 16(1):99.
§   Shema-Didi L, Kristal B, Ore L, Shapiro G, Geron R, Sela S (2013) Pomegranate juice intake attenuates the increase in oxidative stress induced by intravenous iron during hemodialysis. Nutr Res 33(6):442-446.
§   Shema-Didi L, Kristal B, Sela S, Geron R, Ore L (2014) Does Pomegranate intake attenuate cardiovascular risk factors in hemodialysis patients? Nutr J 13:18. 
§   Shema-Didi L, Sela S, Ore L, Shapiro G, Geron R, Moshe G, Kristal B (2012) One year of pomegranate juice intake decreases oxidative stress, inflammation, and incidence of infections in hemodialysis patients: a randomized placebo-controlled trial. Free Radic Biol Med 53(2):297-304.
§   Siddarth P, Li Z, Miller KJ, Ercoli LM, Merril DA, Henning SM, Heber D, Small GW (2020) Randomized placebo-controlled study of the memory effects of pomegranate juice in middle-aged and older adults. Am J Clin Nutr 111(1):170-177.
§  Sohrab G, Ebrahimof S, Sotoudeh G, Neyestani TR, Angoorani P, Hedayati M, Siasi F (2017) Effects of pomegranate juice consumption on oxidative stress in patients with type 2 diabetes: a single-blind, randomized clinical trial. Int J Food Sci Nutr 68(2):249-255. 
§   Sohrab G, Nasrollahzadeh J, Tohidi M, Zand H, Nikpayam O (2018) Pomegranate juice increases sirtuin1 protein in peripheral blood mononuclear cell from patients with type 2 diabetes: a randomized placebo controlled clinical trial. Metab Syndr Relat Disord 16(8):446-451.
§   Sohrab G, Roshan H, Ebrahimof S, Nikpayam O, Sotoudeh G, Siasi F (2019) Effects of pomegranate juice consumption on blood pressure and lipid profile in patients with type 2 diabetes: a single-blind randomized clinical trial. Clin Nutr ESPEN 29:30-35.
§   Sreekumar S, Sithul H, Muraleedharan P, Azeez JM, Sreeharshan S (2014) Pomegranate fruit as a rich source of biologically active compounds. Biomed Res Int 2014:686921.
§   Sugamura K, Keaney JF Jr (2011) Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 51(5):978-992. 
§   Sumner MD, Elliott-Eller M, Weidner G, Daubenmier JJ, Chew MH, Marlin R, Raisin CJ, Ornish D (2005) Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. Am J Cardiol 96(6):810-814. 
§  Urbaniak A, Basta P, Ast K, Wołoszyn A, Kuriańska-Wołoszyn J, Latour E, Skarpańska-Stejnborn A (2018) The impact of supplementation with pomegranate fruit (Punica granatum L.) juice on selected antioxidant parameters and markers of iron metabolism in rowers. J Int Soc Sports Nutr 15(1):35. 
§   Viuda-Martos M, Fernández-López J, Pérez-Álvarez J (2010) Pomegranate and its many functional components as related to human health: a review. Compr Rev Food Sci Food Saf 9:635-654.
§   Zarfeshany A, Asgary S, Javanmard SH (2014) Potent health effects of pomegranate. Adv Biomed Res 3:100.
§   Weyl-Feinstein S, Markovics A, Eitam H, Orlov A, Yishay M, Agmon R, Miron J, Izhaki I, Shabtay A (2014) Short communication: effect of pomegranate-residue supplement on Cryptosporidium parvum oocyst shedding in neonatal calves. J Dairy Sci 97(9):5800-5805. 
§   Wu PT, Fitschen PJ, Kistler BM, Jeong JH, Chung HR, Aviram M, Phillips SA, Fernhall B, Wilund KR (2015) Effects of Pomegranate Extract Supplementation on Cardiovascular Risk Factors and Physical Function in Hemodialysis Patients. J Med Food 18(9):941-949.