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 (LEF.com) and Vitacost.com. 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 www.CorePsychBlog.com 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,
    Chuck

  • 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.

    Mystral

  • 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 |

    Hello!
    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
    www.mi4freedom.blogspot.com

  • buy jeans

    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 http://www.arginineaminoacid.com

  • Richard

    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.

    bill

  • 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...

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My bread contains 900 mg omega-3

My bread contains 900 mg omega-3

Phyllis is the survivor of a large heart attack (an "anterior" myocardial infarction involving the crucial front of the heart) several years ago. Excessive fatigue prompted a stress test, which showed poor blood flow in areas outside the heart attack zone. This prompted a heart catheterization, then a bypass operation one year ago.

FINALLY, Phyllis began to understand that her unhealthy lifestyle played a role in causing her heart disease. But lifestyle alone wasn't to blame. Along with being 70 lbs overweight and overindulging in unhealthy sweets every day, she also had lipoprotein(a), small LDL particles, and high triglycerides. The high triglycerides were also associated with its evil "friends," VLDL and IDL (post-prandial, or after-eating, particles).

When I met her, Phyllis' triglycerides typically ranged from 200-300 mg/dl . Fish oil was the first solution, since it is marvelously effective for reducing triglycerides, as well as VLDL and IDL. Her dose: 6000 mg of a standard 1000 mg capsule (6 capsules) to provide 1800 mg EPA + DHA, the effective omega-3 fatty acids.

But Phyllis is not terribly good at following advice. She likes to wander off and follow her own path. She noticed that the healthy bread sold at the grocery store and containing flaxseed boasted "900 mg of omega-3s per slice!". So she ate two slices of the flaxseed-containing bread per day and dropped the fish oil.

Guess what? Triglycerides promptly rebounded to 290 mg/dl, along with oodles of VLDL and IDL.

A more obvious example occurs in people with a disorder called "familial hypertriglyceridemia," or the inherited inability to clear triglycerides from the blood. These people have triglycerides of 800 mg/dl, 2000 mg/dl, or higher. Fish oil yields dramatic drops of hundreds, or even thousands of mg. Fish oil likely achieves this effect by activating the enzyme, lipoprotein lipase, that is responsible for clearing blood triglycerides. Flaxseed oil and other linolenic acid sources yield . . .nothing.

Don't get me wrong. Flaxseed is a great food. As the ground seed, it reduces LDL cholesterol, reduces blood sugar, provides fiber for colon health, and may even yield anti-cancer benefits. Flaxseed oil is a wonderful oil, rich in monounsaturates, low in saturates, and rich in linolenic acid, an oil fraction that may provides heart benefits a la Mediterranean diet.

But linolenic acid from flaxseed is not the same as EPA + DHA from fish oil. This is most graphically proven by the lack of any triglyceride-reducing effects of flaxseed preparations.

Enjoy your flaxseed oil and ground flaxseed--but don't stop your fish oil because of it. Heart disease and coronary plaque are serious business. You need serious tools to combat and control them. Fish oil is serious business for triglycerides. Flaxseed is not.

Comments (8) -

  • John Townsend

    2/15/2007 6:59:00 PM |

    re: " Her dose: 6000 mg of a standard 1000 mg capsule (6 capsules) to provide 1800 mg EPA + DHA, the effective omega-3 fatty acids."

    Excellent blog entry! On fish oil, this dose seems to be very high. Do you recommend this as a typical regimen?

    On another related topic, your views on common statins (eg lipitor, crestor, zocor, etc) would be appreciated. I'm getting strong warnings from knowledgable friends that statins are dangerous for liver function and can cause irreversiable damage. On the other hand I personally have found them to be very effective in bringing my cholesteral numbers in line, more than anything else I've tried. TIA

  • Dr. Davis

    2/16/2007 2:19:00 AM |

    John--
    No. This dose is for treatment of high triglycerides or postprandial disorders. Our usual starting dose is 4000 mg (1200 mg EPA+DHA).

    Regarding the statin issue. I'd refer you to an article I wrote for Life Extension magazine  archived on their website, www.lef.com. The article, entitled Cholesterol and Statin Drugs: Separating Hype from Reality, can be accessed at http://search.lef.org/cgi-src-bin/MsmGo.exe?grab_id=0&page_id=1044&query=davis%20statin&hiword=DAVI%20DAVID%20DAVIE%20DAVIES%20DAVIN%20DAVIO%20DAVISON%20DAVISS%20DAVIT%20STATI%20STATING%20STATINS%20STATIS%20davis%20statin%20

  • Cindy

    2/16/2007 3:24:00 AM |

    I just read your article that you referred to in your previous comment answer.

    I was on statins several years ago. Not only did I experience muscle and joint pains, I also had serious memory problems, depression and sleep problems. I also found that my long-standing "restless legs syndrome" became much much worse. I've also talked to many people who have experienced serious PND (peripheral nerve disorders).

    What I also experinced was a rather significant drop in HDL cholesterol.

    Thoughts?

  • Mike

    2/16/2007 3:37:00 PM |

    "But Phyllis is not terribly good at following advice. She likes to wander off and follow her own path. She noticed that the healthy bread sold at the grocery store and containing flaxseed boasted "900 mg of omega-3s per slice!". So she ate two slices of the flaxseed-containing bread per day and dropped the fish oil."

    Allow me to defend Phyllis. If all she had been told was to take a given amount of omega-3s, then she was following the prescribed path. She should have been educated as to what the various omega-3s are and which type she needed to consume.

  • John Townsend

    2/16/2007 9:31:00 PM |

    Thank you for passing on your article 'Statin Drugs: Separating Hype from Reality'... very informative I must say! Just a quick heads up on your comment about folic acid (ie “always take folic acid and vitamin B12 with niacin to protect against disruption of healthy methylation patterns”), although studies are not conclusive, apparently folate therapy (taking a combination of folic acid, vitamin B6, and vitamin B12) may be harmful after stent placement and probably should be avoided. For those who have this condition it’s advised instead, to try to get enough vitamin B by eating a balanced diet. [ref: Lange H, et al. (2004). Folate therapy and in-stent restenosis after coronary stenting. New England Journal of Medicine, 350(26): 2673–2681]

  • madcook

    2/17/2007 5:32:00 PM |

    I have to chime in here regarding Cindy's comment on statins:

    I dutifully tried for nearly two years to tolerate the various statins prescribed by my doctor.  The deep muscle aches and spasms were nearly unbearable... getting far worse when my "numbers" still weren't right and he decided to DOUBLE my dosage of Vytorin (Zocor + Zetia) from 10/20 to 10/40.  What resulted was a true nightmare for me.  I terminated this med when I had such severe muscle aching, spasms and dis-coordination that navigating up a flight of stairs was nearly impossible.  Not only that, but my memory was (fortunately temporarily) impaired, and I can remember little from a three month period of time.  Interestingly my CK was never elevated and this all happened while taking 200mgs. daily of a very reputable Co -Q10 formulation.  Cessation of the Vytorin saw the aches subside within 2 or 3 days and full mental clarity resumed within a week.  I was lucky.

    My doctor stated that there were three other statins we hadn't yet tried... fat chance doc!

    What chaps me is that the pharmaceutical companies continue to state that there is only a small percentage of patients who have side effects.  In practice, LOTS of people have problems tolerating statins, BUT these things never are reported, certainly mine wasn't by my doctor.

    Side effects can be reported to the UCSD Statin Study, and to the FDA.  The FDA form is unduly cumbersone and frankly, unless you nearly died, it probably isn't worth the time.  The UCSD Statin Study questionnaire is very thorough... and as soon as I get some time I'm planning to report my experiences with statins to them.

    I am not optimistic that doing either of the above will change the statistical misinformation out there on statin side effects.  The pharmaceutical giants have too many billions at stake to ever allow this information to attain credibility.  Their advertising billions shout otherwise...

    Great meds, IF they work for you without problems.  For me they appear to be deadly, so I think I'll just stick with the other strategies, including niacin, fish oil, etc., etc. that I've learned through TYP.

    madcook

  • madcook

    2/17/2007 5:33:00 PM |

    I have to chime in here regarding Cindy's comment on statins:

    I dutifully tried for nearly two years to tolerate the various statins prescribed by my doctor.  The deep muscle aches and spasms were nearly unbearable... getting far worse when my "numbers" still weren't right and he decided to DOUBLE my dosage of Vytorin (Zocor + Zetia) from 10/20 to 10/40.  What resulted was a true nightmare for me.  I terminated this med when I had such severe muscle aching, spasms and dis-coordination that navigating up a flight of stairs was nearly impossible.  Not only that, but my memory was (fortunately temporarily) impaired, and I can remember little from a three month period of time.  Interestingly my CK was never elevated and this all happened while taking 200mgs. daily of a very reputable Co -Q10 formulation.  Cessation of the Vytorin saw the aches subside within 2 or 3 days and full mental clarity resumed within a week.  I was lucky.

    My doctor stated that there were three other statins we hadn't yet tried... fat chance doc!

    What chaps me is that the pharmaceutical companies continue to state that there is only a small percentage of patients who have side effects.  In practice, LOTS of people have problems tolerating statins, BUT these things never are reported, certainly mine wasn't by my doctor.

    Side effects can be reported to the UCSD Statin Study, and to the FDA.  The FDA form is unduly cumbersone and frankly, unless you nearly died, it probably isn't worth the time.  The UCSD Statin Study questionnaire is very thorough... and as soon as I get some time I'm planning to report my experiences with statins to them.

    I am not optimistic that doing either of the above will change the statistical misinformation out there on statin side effects.  The pharmaceutical giants have too many billions at stake to ever allow this information to attain credibility.  Their advertising billions shout otherwise...

    Great meds, IF they work for you without problems.  For me they appear to be deadly, so I think I'll just stick with the other strategies, including niacin, fish oil, etc., etc. that I've learned through TYP.

    madcook

  • John Townsend

    2/17/2007 8:05:00 PM |

    RE: Madcook's comment "Side effects can be reported to the UCSD Statin Study, and to the FDA. "

    I'm wondering if the 'UCSD Statin Study' provide summary reports on submission findings?

    BTW, his note is a very interesting personal account which echos mine to a certain extent, albeit I'm seemingly in the early stages. I'm starting to have pretty severe shoulder pain coming out of nowhere after six mths on Zocor. I've started taking Q-10 (re: your rec) to see if it helps. Previously my reaction to Lipidor was almost immediate with severe skin rash symptoms.

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