Mended Hearts Open Forum

 View Only
  • 1.  Citrulline and ADMA

    Posted 09-16-2022 10:18
    Hi I am Charles Crow RN FAACVPR   below is information about a new test at Cleveland Clinic for ADMA  a powerful risk factor for CAD   Another risk factor you might need to be checked for is Lp(a)   with a VAP test   both of these risk factors are not on a regular cholesterol test   if you have cardiac questions you may contact me at     

    ADMA Citrulline ..

    Novel Biomarker Test for Cardiovascular Disease Risk Now Available from Cleveland HeartLab


    A novel biomarker called ADMA/SDMA is an independent predictor of heart attack risk and may also identify patients with diabetes, pre-diabetes or kidney disease, according to recent peer-reviewed studies.

    The ADMA/SDMA biomarker blood test, now available through Cleveland HeartLab (CHL), measures levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Elevated levels of these biomarkers can signal damage to the endothelium, the inner lining of blood vessels.

    "Not only does this test help medical practitioners do a better job of assessing the health of the arterial wall, but it can also help identify the cause of problems like high blood pressure and vascular inflammation" says Amy Doneen, DNP, ARNP, medical director of the Heart Attack & Stroke Prevention Center in Spokane, Washington.

    "Very often, as a 2002 study published in JAMA demonstrated, elevated levels of ADMA and SDMA are one of the earliest signs of insulin resistance, the root cause of both type 2 diabetes and about 70 percent of heart attacks," adds Dr. Doneen, coauthor of Beat the Heart Attack Gene.

    new study suggests that insulin resistance may also raise risk for Alzheimer's disease by starving the brain of sugar needed for normal cognition.


    How Does the ADMA/SDMA Test Work?

    Sometimes called the "brain" of the arteries, the endothelium plays a vital role in regulating blood pressure, immunity, and blood clotting. It also acts as a smart barrier between your blood and the walls of your arteries.

    Amazingly, says Dr. Doneen, "the endothelium is only one cell thick, yet is the largest organ in the body; if it was removed from the blood vessels and flattened, it would cover six tennis courts."

    If the endothelium is damaged, LDL (bad) cholesterol particles can invade vessels and form plaque, potentially leading to a heart attack or stroke if the plaque becomes inflamed and ruptures. Endothelial damage also raises risk for kidney failure.

    "When ADMA or SDMA are elevated, the endothelium is robbed of one of the most powerful nutrients it needs to maintain health: nitric oxide," continues Dr. Doneen. Levels of both biomarkers, which are naturally produced as proteins are broken down, may rise in people who smoke, eat a poor diet, or have high cholesterol, high blood pressure or high blood sugar.

    ADMA: One of the Strongest Risk Predictors for Heart Attack

    In a study of 1,908 people with heart disease who were tracked for nearly 3 years, those with the highest levels of ADMA at baseline were 2.5  times more likely to die from heart-related causes or suffer non-fatal heart attacks than participants with the lowest levels, even when such potential confounders as traditional risk factors (such as smoking, high blood pressure, and diabetes) and levels of several biomarkers including C-reactive protein were taken into account.

    The researchers ranked ADMA as one of the "strongest risk predictors," adding that it had "prognostic value beyond traditional risk factors and novel biomarkers and might guide therapeutic strategies." The study was published in the American Heart Association journal Circulation Research.

    Another study of 2,543 people with and 695 people without heart disease, published in Clinical Chemistry found that ADMA levels independently predicted both all-cause and cardiovascular mortality in heart patients "independently of established and emerging risk factors."

    Earlier research shows a strong link between elevated ADMA and high cholesterol, with the researchers also reporting that, "ADMA may be a novel risk factor for endothelial dysfunction in humans."

    ADMA, the Newest and Stronger Predictor of Heart Death


    Now there is a new test that is an even stronger predictor of early heart death, lethal cardiac arrhythmia, and congestive heart failure, as well as vascular problems in other organs, like kidney disease, Alzheimer's, eye diseases, and strokes.


    A main chemical our endothelial cells that line our blood vessels make is a powerful gas, nitric oxide (NO). This causes blood vessels to relax and dilate, allowing more blood flow and precious nutrients with oxygen to the heart muscle and other tissues. Luckily for us, nitric oxide is made through an enzyme nitric oxide synthase. And we can make more of it by adding the simple amino acid l-citrulline.  

     Needless to say we want lots of nitric oxide dilating our vessels. But some folks make too much of a nitric oxide synthase inhibitor called asymmetrical dimethyl arginine. Fortunately we can measure this with a simple blood test called ADMA (asymmetrical dimethyl arginine).

     For when nitric oxide is low because of too much inhibitor, you turn off NO and get high blood pressure, coronary and carotid (heart and neck arteries) arteriosclerosis, diabetes, cancer, kidney problems, brain problems with loss of good mood and memory, arrhythmia, congestive heart failure and much more.

    In fact in one study, when people were just at the top of the normal level of ADMA, they had four times the average amount of heart attacks. And if they were over the top of normal, they had 27-fold increased risk (Valkonen).


    The beauty of this simple blood test is that your doctor can just write on a prescription "ADMA".


    SDMA: A Biomarker of Cardiovascular and Kidney Risk

    In a large 2011 study of patients undergoing coronary angiography to reopen blocked arteries, those with the highest levels of SDMA had a 1.5 times higher rate of death from cardiovascular causes over the next 7.7 years, compared to those with the lowest levels, even adjusting for confounding factors.

    Not only did the researchers report that elevated levels of SDMA are "an independent cardiovascular risk," but they also found that it is "an excellent marker of renal (kidney) function." A meta-analysis of 18 studies involving 2,136 patients suggesting that, "ADMA and SDMA could be used as a combined marker of classical cardiovascular risk and renal function."

    "When used along with other tests of arterial health, such as inflammation testing–which can serve as a 'fire alarm' of heart attack and stroke risk in patients who may seem otherwise healthy–ADMA/SDMA can be helpful in two ways," says Dr. Doneen. "First, it may improve initial identification of at-risk patients, and second, it can be an additional tool to monitor the effectiveness of treatment."

    Therapies to lower ADMA/SDMA levels may include lifestyle changes to boost the health of the endothelium, such as weight loss, eating more fruits and vegetables, limiting or avoiding sugary and salty foods, regular exercise, and drug treatment to lower cholesterol and blood pressure if they are too high.

    Dr. Doneen advises anyone with elevated levels of these biomarkers to be screened for diabetes/prediabetes with a 2-hour oral glucose tolerance test.






    Asymmetric Dimethylarginine Is a Well Established Mediating Risk Factor for Cardiovascular Morbidity and Mortality-Should Patients with Elevated Levels Be Supplemented with Citrulline?

    Mark F McCarty 1

    2016 Jul 8;4(3):40.

     doi: 10.3390/healthcare4030040.

    AbstractThe arginine metabolite asymmetric dimethylarginine (ADMA) is a competitive inhibitor and uncoupler of endothelial nitric oxide synthase (eNOS), an enzyme that acts in multifarious ways to promote cardiovascular health. This phenomenon likely explains, at least in part, why elevated ADMA has been established as an independent risk factor for cardiovascular events, ventricular hypertrophy, and cardiovascular mortality. Fortunately, the suppressive impact of ADMA on eNOS activity can be offset by increasing intracellular arginine levels with supplemental citrulline. Although the long-term impact of supplemental citrulline on cardiovascular health in patients with elevated ADMA has not yet been studied, shorter-term clinical studies of citrulline administration demonstrate effects suggestive of increased NO synthesis, such as reductions in blood pressure and arterial stiffness, improved endothelium-dependent vasodilation, increased erection hardness, and increased ejection fractions in patients with heart failure. Supplemental citrulline could be a practical option for primary or secondary prevention of cardiovascular events and mortality, as it is inexpensive, has a mild flavor, and is well tolerated in doses (3-6 g daily) that can influence eNOS activity. Large and long-term clinical trials, targeting patients at high risk for cardiovascular events in whom ADMA is elevated, are needed to evaluate citrulline's potential for aiding cardiovascular health.

    Br J Clin Pharmacol

    2008 Jan;65(1):51-9.

     doi: 10.1111/j.1365-2125.2007.02990.x. Epub 2007 Jul 27.

    Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism

    Edzard Schwedhelm 1Renke MaasRalf FreeseDonald JungZoltan LukacsAlen JambrecinaWilliam SpicklerFriedrich SchulzeRainer H Böger

    Affiliations expand



    Aims: Oral L-arginine supplementation has been used in several studies to improve endothelium-dependent, nitric oxide (NO)-mediated vasodilation. L-Arginine treatment is hampered by extensive presystemic elimination due to intestinal arginase activity. In contrast, L-citrulline is readily absorbed and at least in part converted to L-arginine. The aim of our study was to assess this metabolic conversion and its subsequent pharmacodynamic effects.

    Methods: In a double-blind, randomized, placebo-controlled cross-over study, 20 healthy volunteers received six different dosing regimes of placebo, citrulline, and arginine. Pharmacokinetic parameters (C(max), T(max), C(min), AUC) were calculated after 1 week of oral supplementation. The ratio of plasma L-arginine over asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase (arginine/ADMA ratio), urinary cyclic guanosine monophosphate (cGMP) and nitrate excretion rates, and flow-mediated vasodilation (FMD) was measured to assess pharmacodynamic effects.

    Results: L-Citrulline dose-dependently increased AUC and C(max) of plasma L-arginine concentration more effectively than L-arginine (P < 0.01). The highest dose of citrulline (3 g bid) increased the C(min) of plasma L-arginine and improved the L-arginine/ADMA ratio from 186 +/- 8 (baseline) to 278 +/- 14 [P < 0.01, 95% confidence interval (CI) 66, 121]. Moreover, urinary nitrate and cGMP were increased from 92 +/- 10 to 125 +/- 15 micromol mmol(-1) creatinine (P = 0.01, 95% CI 8, 58) and from 38 +/- 3.3 to 50 +/- 6.7 nmol mmol(-1) creatinine (P = 0.04, 95% CI 0.4, 24), respectively. No treatment improved FMD over baseline. However, pooled analysis of all FMD data revealed a correlation between the increase of arginine/ADMA ratio and improvement of FMD.

    Conclusion: Our data show for the first time that oral L-citrulline supplementation raises plasma L-arginine concentration and augments NO-dependent signalling in a dose-dependent manner.


    Charles Crow
    cardiac Rehab nurse