Can You Take L-Citrulline With Daily Tadalafil?

Hello, and thanks so much for using HelloPharmacist!

This is a great question and I'm happy to answer it for you. The combination of L-citrulline and tadalafil is actually fairly common, but there is a theoretical interaction worth understanding here.

Both promote blood vessel relaxation, so taken together they could have an additive blood pressure-lowering effect in some people.

Our database lists this as a moderate, theoretical interaction (L-citrulline and Tadalafil Interaction: Severity & What to Do | HelloPharmacist), meaning it isn't a hard stop, but it does call for some awareness on your part and a quick conversation with your doctor or pharmacist.

Why These Two Overlap in the Body

L-citrulline is an amino acid that your body converts into L-arginine, which is the raw material your cells use to make nitric oxide, a natural compound that relaxes and widens blood vessels.

In fact, oral citrulline raises arginine levels more effectively than taking arginine itself, which is why it's such a popular supplement for exercise performance and circulation.

Tadalafil (the active ingredient in Cialis) works one step further down that same pathway. It's a PDE5 inhibitor, meaning it blocks the enzyme that breaks down the signaling molecule nitric oxide produces, which prolongs and enhances that blood vessel relaxation.

So, citrulline increases the 'supply' side of the nitric oxide pathway while tadalafil amplifies its effects, and that's where the theoretical concern about additive vasodilation and lower blood pressure comes from.

What the Research on Combining Them Shows

The reassuring part is that this pathway overlap hasn't translated into obvious harm in studies.

When L-arginine (which citrulline converts to) was studied in combination with PDE5 inhibitors for erectile dysfunction, a meta-analysis (study) of randomized trials actually found the combination improved erectile function more than either alone, without a signal of dangerous blood pressure drops.

Notably, hypotension was not reported as a problem in those combination studies.

Daily tadalafil combined with L-citrulline has also been used deliberately in penile rehabilitation programs after prostate surgery, which tells you clinicians have been comfortable using the two together under medical supervision.

Precautions With Daily Tadalafil

One thing specific to your situation is that daily 5 mg tadalafil keeps the drug in your system around the clock, so any additive effect from a supplement would apply all day, not just around a dose.

Practically speaking, if you and your doctor decide to go ahead, start citrulline at a modest dose and watch for signs of low blood pressure such as dizziness, lightheadedness (especially when standing up quickly), flushing, or headache. Be extra cautious if you already take blood pressure medications or an alpha-blocker, and remember that nitrates remain strictly off-limits with tadalafil. 

Final words

Overall, L-citrulline and daily tadalafil are often used together and the interaction concern is theoretical rather than well documented, but because both can lower blood pressure, it deserves a mention to your prescriber before you start. If they give the go-ahead, take note of any dizziness or lightheadedness in the first week or two.

Feel free to reach back out if you have any other questions; we're always happy to help!

You may also find these related HelloPharmacist resources helpful: L-citrulline drug interactions and safety information.