I have read citrulline turns into arginine in the body. This is likely an oversimplified description. Many people report arginine is like throwing gasoline on a fire for Herpes outbreaks...
Hi drop247,
Thank you for your question. I agree that it is not good to take pure L-arginine directly. Choosing citrulline malate (an arginine pro-drug) over arginine is very important. Also, I think it is important to only take citrulline malate with a arginase inhibitor like caffeine (see
post). I will explain why the arginase inhibitor matters. The two main enzymes that metabolize arginine are
nitric oxide synthase (NOS) and
arginase.
NOS produces nitric oxide from L-arginine and this NO production is used by the immune system to fight infection and cancer (among other things). NO produced by eNOS also maintains the elasticity of blood vessels and the health of endothelial cells. NO produced by nNOS is important for brain growth and memory development (
Nitric oxide synthases).
One alternative to taking arginine prodrugs is to consume vegetable-based nitrates instead. Nitrates convert to NO in the body. Beet juice and spinach powder are good sources of nitrates (
link), but I'm not sure how much of these vegetables you will have to consume to get the equivalent effect as citrulline.
Arginase produces spermine from L-arginine. Spermine suppresses the immune system and prevents immune cells from killing pathogens. Spermine also increases the rate that viral DNA can be replicated. Some viruses (like herpes) chronically up-regulate arginase through COX-2 and other genetic signaling (
Ref1,
Ref2).
Polyamine = (spermidine, spermine or putrescine)
"Many viruses have been shown to require polyamines for one or more aspects of their replication cycle, including DNA and RNA polymerization, nucleic acid packaging, and protein synthesis...Inhibition of polyamine synthesis with difluoromethylornithine (DFMO) results in a block of both HSV and HCMV replication." -Polyamines and Their Role in Virus Infection
Taking L-arginine causes these infected cells to make more spermine from arginase activity. Since citrulline does not interact arginase, citrulline acts as an arginine-buffer pool to be converted to L-arginine on an as-needed basis. Immune cells like Natural Killer and CD8 T cells require a steady supply of arginine and NO in order to fight viral infection effectively. This citrulline buffer prevents arginine depletion.
NOS is generally anti-viral, while arginase (and spermine) is pro-viral. Now we want to block the arginase (and the production of spermine) so that the available L-arginine is only used to produce the antiviral NO. This is accomplished with an
arginase inhibitor like caffeine.
I actually think tadalafil (Cialis) is a better arginase-1 inhibitor, but caffeine is widely available and cheap. So that is why I would only suggest taking citrulline malate when you are also taking an arginase inhibitor like caffeine. Even if you find a good vegetable based nitrate source (i.e. beet juice or spinach powder) to replace citrulline, I would still take an arginase inhibitor to prevent arginine depletion. My guess though is that you would have to drink a lot of beet juice to get similar NO effects as citrulline. I hope that clarifies things.
Update: Currently, I am not experiencing POIS symptoms except for an itchy feeling on the left side of my face and a compulsion to scratch my beard. This is true even though I have stopped taking daily supplements. For example, last week I had three orgasm within four days and still worked the full days and went to all my social engagements (but my face itched like crazy). I did a lot of experimenting with my immune system around the time when the POIS symptoms started to disappear, but it is not clear to me which one of my experiments (if any) actually made a difference. I started to notice the symptoms disappear slowly around February of this year. I am still trying to figure out why my POIS symptoms disappeared. I also don't know if this is permanent, but the improvement seems very long-term.
