How important is l-arginine?

Perhaps more than any other supplement, l-arginine causes frustration and confusion. It’s difficult to find, sometimes quite expensive, and some preparations cause loose stools.

Just how necessary is it?

L-arginine, you’ll recall, is a source of nitric oxide, or NO. Though it’s the same stuff as in car exhaust, NO provides a critical signaling role in your body’s cells that regulate a multitude of functions. Among the important roles of NO is to powerfully dilate, or relax, arteries. A constant flow of NO is required for health, particularly since each molecule persists only a few seconds.

L-arginine is the body’s source of nitric oxide. In addition, a peculiar but very effective blocker of l-arginine called asymmetric dimethylarginine, or ASDM, has recently been discovered to prevent the production of NO. Varied conditions like hypertension, diabetes, high cholesterol, excessive saturated fat or processed carbohydrate intake all lead to heightened levels of ASDM, often several-fold greater levels, and thereby effectively blocking NO production.

The “Arginine Paradox” is the name that some researchers in this field have given to the unusual property of l-arginine supplementation to “overpower” the blocking effects of ASDM. This is somewhat unusual in biologic systems in that an agent that blocks a receptor cannot usually be outmuscled by providing excess material for a reaction. Kind of like hoping that your car runs faster simply by topping up the gas tank.

Concrete observable benefits have been made for l-arginine in clinical trials, such as arterial relaxation that results in arterial enlargement (which can actually be seen in the cath lab); anti-inflammatory effects; reduction of blood pressure; enhancement of insulin responses, etc. All of these effects can be connected to beneficial properties that may facilitate atherosclerotic plaque regression and, indeed, there are limited data to document that this is true.

Drug companies may be greedy, but they’re not stupid. They’ve been vigorously pursuing this line of research for some years, a research path that led inadvertently to the erectile dysfunction agent, sildenafil (Viagra), and all its subsequent competitors. (Erectile dysfunction is another expression of endothelial dysfunction, since male erections are driven by the ability to dilate penile arteries.) The wonderful properties of NO enhancement continue to occupy research labs around the world.

Wow. So what’s the reluctance? In the early years of the Track Your Plaque program (meaning just a short 7-8 years ago), I was thoroughly convinced that l-arginine was a crucial, necessary part of a plaque regression program. Without it, you would rarely succeed. With it, the odds were tipped in your favor.

However, something curious has emerged recently. I’ve seen more and more people dropping their heart scan scores. Not just a little bit, but a huge amount. Witness our most recent record holder, Neal, who dropped his score 51% in 15 months. Just five years ago, this magnitude of reversal was unimaginable. Granted, Neal is our record holder, but others are obtaining 10, 18, 24, 30% drops in scores all the time. Many have done it without l-arginine.

Now, how about the people who have failed to stop a rising score? Would they do better with l-arginine as part of the mix? I believe so, but sometimes we never quite know except in retrospect. It has been a great dilemma for us trying to predict from the starting gate who will or who won’t drop their heart scan score.

My view from the trenches is that l-arginine packs its greatest atherosclerosis-fighting punch in the first year or two of use, when “endothelial dysfunction” is likely to be present (abnormal artery constriction). But as all other strategies take hold—fish oil, correction of lipid and lipoprotein abnormalities, weight loss (big effect), vitamin D (another very big effect), etc.—endothelial behavior improves over time. Perhaps l-arginine becomes a less necessary component over time.

There’s no doubt that uncertainty still surrounds the use and science surrounding l-arginine. However, if you’re interested in stacking the odds in your favor, particularly during the first year or two of your plaque-reducing efforts, I think that l-arginine is worth considering. It is cumbersome, it can be expensive, some preparations may even be foul. But in the big picture of life, with hospitals trying every possible ploy to get your body on a table for a procedure, doctors perverting their mission by signing employment contracts with hospitals and agreeing to usher you into the hospital as a paying patient whenever possible, and drug companies viewing you and me as a market for medications which may or may not be helpful, l-arginine is surely not that big a burden.

Comments (13) -

  • Anonymous

    4/30/2007 6:39:00 PM |

    Are there any particular formulations of l-arginine that you are familiar enough with to recommend?

    There is such a bewildering array of supplements available; it is sometimes overwhelming to try to make an informed choice.

    Thank you

  • Dr. Davis

    5/1/2007 1:13:00 AM |

    The brand we've used most frequently for its relatively low cost and palatability is the PowerMaker II, available from Life Extension ( and I write articles for Life Extension but have no  interest beyond that with that organization. I have no relationship with Vitacost.

    Please also see my post from yesterday. We've been discussing such a list of recommendations. We resist the idea of selling supplements because of the corrupting effect of doing so, and the erosion of credibility. However, I believe that in future we can recommend/endorse/approve certain supplements without putting our integrity in doubt.

  • Chuck

    10/18/2007 10:44:00 AM |

    Dr D-
    So interesting to read your posts and excellent information! I will be a regular over here, and appreciate on a personal level everything you are commenting on, as I have been one of those *missed by the system* and am still out of range for the great docs that I am working with.

    Just got onto the arginine/endothelial recommendations from a different resource, and appreciate your heads up here on the practical matters of how to turn things around.

    We are on similar missions: over at I discuss a growing awareness of the real advances in neuroscience that often go overlooked in everyday psych care.

    Interestingly, folks think the heart and the brain are two different topics, and so often we see what you are talking about with the heart over here directly effecting brain recovery and brain health - with all of the positive emotional and cognitive benefits arriving right along with good heart scan tracking.

    Thanks again, look forward to talking one day,

  • Mystral

    10/26/2007 6:21:00 PM |

    Dear Dr Davis - was  most interested to read your input on L-Arginine - AAKG (Arginine Alpha-KetoGlutarate).  We have been running a trial on using AAKG on horses with the inflammatory systemic condition, ESPA (Equine Systemic Proteoglycans Accummulation) which is showing considerable success in treating the inflammation that this condition brings with it.  At the same time we also use the Jiaogulan (Gynostemma pentaphyllum) herb.  We are finding that the 'Jia' herb bolsters the effects of the AAKG by supressing the iNOS and supporting the eNOS.

    We have an enormous amount of information on this use on our yahoo groups list.  I should be most happy to direct your footsteps hence.

    I myself take AAKG + 'J' for control of hypertension and for the inflammation due to AS/OA/DDD.  It works very well indeed.

    I enjoy your blog spot, it is most interesting.  Thank you.


  • Rich

    11/25/2007 7:36:00 PM |

    I really have no adverse reaction to any supplement, except for two: magnesium and arginine. Magnesium is known to cause stomach distress, so I take a slow-release kind. As for arginine, I have tried to it several times, in different powder and slow-release formulations, and it eventually causes the following:
    -Stomach distress from powdered arginine
    -An unusual overstimulation from any kind of arginine, which manifests after a couple of days as pounding heartbeat (but not weakness),  slight anxiety, and difficulty sleeping. I know from extensive tests and from my vigorous daily workouts that there is no big problem with my heart that would cause this. It goes away when I stop the arginine. I can't believe that I'm the only person who experiences this effect.

  • Dr. Davis

    11/26/2007 12:53:00 AM |

    That is interesting.

    I suspect that there's an interesting lesson to be learned from your experience, but I'm unsure of what it is.

  • Anonymous

    12/28/2008 6:38:00 AM |

    I too experience the pounding heart from taking arginine- it finally dawned on me tonight that it must be the culprit.  I always notice it most when trying to get to sleep.  Frustrating!

  • Helena

    5/13/2009 4:38:00 PM |

    I just found your blog and it is very interesting! I am an Arginine-lover and truly believe that it can make a big difference in peoples lifes. I have taken Arginine (5 grams a day liquid formula)along with L-Citruline (250mg), omega fatty acids, EDTA, OPCs, vitamins, and other natural supplements since August of 2008 and Love it! I sleep better, have more energy, and can work out much better. I did however notice the heartbeating at bedtime my first few days or week when I started taking the product, like some of you also point out, but that went away by itself and I have not felt anything since then. I actually feel pretty darn good! My allegies have improved like crazy.

    Thank you for a good blog! / Helena

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    11/3/2010 6:53:53 PM |

    The “Arginine Paradox” is the name that some researchers in this field have given to the unusual property of l-arginine supplementation to “overpower” the blocking effects of ASDM. This is somewhat unusual in biologic systems in that an agent that blocks a receptor cannot usually be outmuscled by providing excess material for a reaction. Kind of like hoping that your car runs faster simply by topping up the gas tank.

  • Nick

    1/5/2011 11:36:52 PM |

    Arginine is pretty important. Check

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    5/26/2011 4:45:37 PM |

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  • Bill

    6/3/2011 4:17:10 PM |

    Curious about your thoughts on NEO40. This Nitric Oxide supplement is touted as being Argenine free. I was given a sample this morning after a saliva test showed me slightly low for NO. I am not real sure about this supplement and have a relatively good BP, burn about 3500 calories a week through intense exercise, and eat a paleo style diet. Several years ago my cholesterol was 'high' but is now within clinical guidelines.

    So, will I benefit from this product or one like it?

    Love the blog and the information.


  • zails

    7/15/2014 10:13:53 PM |

    Been on l arginine 2 weeks ,,,my blood pressure is great now ,,,,so glad I found out about this natural supplement ,,blood pressure meds had so many horrible side effects...