11 Jul '12

Pomegranate, ProArgi9 Plus and Hypertensive Drugs

by synergy

Recently I received a question concerning Pomegranite which is an ingredient in Proargi9 Plus and its reaction to other hypertensive drugs such as Captopril (Capoten), Enalapril (Vasotec), Lisinopril (Prinivil, Zestril), Ramipril (Altace), calcium blockers like Amlodipine (Norvasc) and statins like Crestor, Lipitor. It seems that numerous health information reports (including pharmacy instructions) cite a reaction between pomegranate juice and these drugs. They indicate that there can be an increase in the effects of the drugs and side effects of the medication. They recommend to not take these drugs if you are taking pomegranate juice. What about the pomegranate juice in Proargi9+? While there may not be any effects from the L-Arginine or the L-Citruline what about the other additives in Proargi9+?

I dutifuly sent an email to Synergy to pose the question and below is their response.

A person taking any of these medications should consult with his health care provider regarding use of ProArgi-9 Plus. Many of the interactions mentioned are based on in vitro data and have not been seen in humans. The potential drug interactions with pomegranate are considered minor to moderate.

The amount of pomegranate fruit concentrate in a serving of ProArgi-9 Plus is small compared to an average serving of pomegrantate fruit juice. For comparison, one serving of ProArgi-9 Plus provides the approximate equivalent of 3 grams of fresh fruit; an average pomegranate fruit weighs 400-500 grams.

Summary of interactions:

ACE INHIBITORS (ACEIs) <> POMEGRANATE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate . Occurrence = Possible . Level of Evidence = B

Pomegranate juice is thought to have ACE inhibitor-like effects. Theoretically, consuming pomegranate juice with other ACE inhibitors might have additive effects (8310). Monitor blood pressure and potassium levels. ACE inhibitors include captopril (Capoten), enalapril (Vasotec), lisinopril (Prinivil, Zestril), ramipril (Altace), and others.

ANTIHYPERTENSIVE DRUGS <> POMEGRANATE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate . Occurrence = Possible . Level of Evidence = B

Consuming pomegranate juice can modestly lower blood pressure. Theoretically, consuming pomegranate juice with antihypertensive drugs might have additive blood pressure lowering effects and increase the chance of hypotension (8310).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES <> POMEGRANATE Interaction Rating = Minor Be watchful with this combination. Severity = Moderate . Occurrence = Unlikely . Level of Evidence = B

Pomegranate contains several polyphenols that have individually been shown to inhibit cytochrome P450 3A4 (CYP3A4). However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme. The inhibitory effect of pomegranate juice appears to be comparable to grapefruit juice (13188,16711,17326). In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times; however, pomegranate does not prolong the elimination half-life. This suggests that pomegranate juice inhibits gastrointestinal CYP3A4, but might not inhibit hepatic CYP3A4 (13188). In human volunteers, drinking a single glass of pomegranate juice 8 ounces does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration (16711). A similar study in healthy Japanese volunteers, drinking 200 mL of pomegranate juice for 2 weeks did not affect levels of midazolam after oral drug administration (17730). Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin (Zocor), which is a CYP3A4 substrate (16712). This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans (17326). Drugs that are substrates of CYP3A4 include some calcium channel blockers (amlodipine, diltiazem, verapamil, and others), some protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), alfentanil (Alfenta), fentanyl (Sublimaze), midazolam (Versed), ondansetron (Zofran), propranolol (Inderal), and numerous others.

ROSUVASTATIN (Crestor) <> POMEGRANATE Interaction Rating = Moderate Be cautious with this combination. Severity = High . Occurrence = Possible . Level of Evidence = D

There is concern that pomegranate juice might inhibit metabolism and increase levels of rosuvastatin, possibly resulting in an increased risk of side effects. In one case, a patient taking rosuvastatin 5 mg every other day in combination with ezetimibe (Zetia) 10 mg daily developed rhabdomyolysis 3 weeks after starting to drink pomegranate juice 200 mL twice weekly. This patient had a history of elevated creatine kinase levels while not receiving any statin treatment. This suggests a possible underlying myopathy and predisposition to rhabdomyolysis (14465).

Best wishes, Synergy WorldWide Ask an Expert team

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