Pomegranate (Hunter Swindle , University of Mississippi School of Pharmacy

Hunter Swindle Student pharmacist Spring 2022

Pomegranate (Punica granatum)

Background/Common Uses

Pomegranate, Punica granatum, is a fruit-bearing deciduous shrub that bears a round, reddishbrown fruit with a hard outer coating. The fruit has been eaten and used to make juices for thousands of years. The fruit itself can also be referred to as a seeded apple. The fruits, juice, and extracts have been shown to have possible benefits on the cardiovascular system, diabetes, and glucose metabolism, and smaller studies have shown other potential risk lowering benefits. Pomegranate juice provides an excellent source of fructose, sucrose, and glucose; however, the health benefits are believed to be due to the tannins and flavonoids that possess antioxidant and preservative activities.1 Animals studies have been conducted and shown that there may also be benefits in many different forms of cancer.

Pharmacology

Pomegranate exhibits its cardiovascular benefits by reducing oxidative stress, lipid peroxidation, and generation of foam cells. This influences endothelial cell function by increasing nitic oxide levels, lowering glucose levels, and attenuating platelet aggregation. Pomegranate has been shown to provide protection from chemicals and drugs, and therefore it is thought to improve outcomes with some cancers and the cancer drugs. 2 Pomegranate is metabolized by cytochrome P450 enzymes, with one being CYP2D6. This is likely to cause many drug interactions, and genetic testing may be warranted.

Dosing

Pomegranate can exhibit its effects in many different forms including the peel, juice, and leaves. Numerous different formulations of pomegranate have also been studied. Doses of 50 to 750 ml/ day of pomegranate juice has been shown to have potential benefits on cardiovascular disease. Doses of 750 mg/day of pomegranate extract have some potential benefits on exercise endurance performance. Doses of 1-3 grams/day of pomegranate extract have effects at lowering prostate-specific antigen levels.3

Effectiveness Although studies have been conducted to show the benefits of pomegranate in many different disease states, there are currently no FDA approved indications for pomegranate.

Safety and Drug Interactions

Pomegranate is relatively safe and well tolerated by most people. Interactions with CYP P450 enzymes and its effects on other drugs needs to be monitored closely when taking pomegranate. Drug interactions are robust with this metabolism pathway and include drugs such as warfarin, carbamazepine, lisinopril, rosuvastatin, codeine, and many other commonly used prescription medications. Although no evidence suggests that it would be unsafe in pregnancy or while breastfeeding, use during these periods are not recommended until further studies are conducted.3

Adverse Effects and Toxicities

There have been three case reports of priapism lasting up to eight hours while using 50 mg of sildenafil and pomegranate juice concomitantly.4 There have been more than 30 cases of fecal impaction from pomegranate seed bezoars.5 One case of transient hyperphosphatasemia was reported in a 20-month-old who presented to the emergency department with a 2-month history of hyporexia and difficulties with feeding. This was following a daily diet of cereal porridge and pomegranate juice.6

Professional Opinion

Future studies are needed to see the true benefits or this natural product. Although it could benefit some patients, it may interact poorly in others that have predisposing genetic factors. Discussions with healthcare professionals needs to be considered before daily supplementation with this herbal product. ~ H. Swindle

References:

1. Zarfeshany A, Asgary S, Javanmard SH. Potent health effects of pomegranate. Adv Biomed Res. 2014;3:100.

Published 2014 Mar 25. doi:10.4103/2277-9175.129371 2. Wang D, Özen C, Abu-Reidah IM, et al. Vasculoprotective Effects of Pomegranate (Punica granatum L.).

Front Pharmacol. 2018;9:544. Published 2018 May 24. doi:10.3389/fphar.2018.00544 3. https://online.lexi.com/lco/action/doc/retrieve/docid/fc_rnp2/7157521?cesid=8B9aSqKPd Fg&searchUrl=%2Flco%2Faction% 2Fsearch%3Fq%3Dpomegranate%26t%3Dname%26 va%3Dpomegranate#adr-nested. Published October 20, 2021. Accessed March 4, 2022. 4. Senthilkumaran S, Balamurugan N, Suresh P, Thirumalaikolundusubramanian P. Priapism, pomegranate juice, and sildenafil: Is there a connection?. Urol Ann. 2012;4(2):108-110. doi:10.4103/0974-7796.95560 5. El-Majzoub N, Soweid A. Rectal impaction by pomegranate seeds. Ann Saudi Med. 2014;34(6):555. doi:10.5144/0256-4947.2014.555 6. Molina Gutiérrez MA, Alcobendas Rueda RM, Martínez Villar M, de Miguel Cáceres C, Bote Gascón P. Transient

Hyperphosphatasemia Due to Pomegranate Juice. Cureus. 2021;13(4):e14779. Published 2021 Apr 30. doi:10.7759/cureus.14779

Graphics:

7. Make pomegranate your go-to superfood for weight loss and glowing skin. Healthshots. https://www.healthshots.com/healthy-eating/superfoods/ benefits-of-pomegranate-for-weight-loss-and-glowing-skin/. Published September 27, 2021. Accessed March 31, 2022. 8. Make pomegranate your go-to superfood for weight loss and glowing skin. Healthshots. https://www.healthshots.com/healthy-eating/superfoods/ benefits-of-pomegranate-for-weight-loss-and-glowing-skin/. Published September 27, 2021. Accessed March 31, 2022. 9. Make pomegranate your go-to superfood for weight loss and glowing skin. Healthshots. https://www.healthshots.com/healthy-eating/superfoods/ benefits-of-pomegranate-for-weight-loss-and-glowing-skin/. Published September 27, 2021. Accessed March 31, 2022. 10. Home. Recipe, How to make Pomegranate Juice Recipe - Vaya.in. https://vaya.in/recipes/details/pomegranate-juice/. Published July 7, 2021. Accessed March 31, 2022. 11. Kawaguchi-Suzuki M, Anderson A, Suzuki S. Reconsidering sports pharmacists and anti-doping education as the world celebrates the olympic and Paralympic Games. American journal of pharmaceutical education. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499666/. Published August 2021. Accessed March 25, 2022. 106