L-Arginine, the Prosexual Nutrient

Sexual dysfunction in the United States: prevalence and predictors.

Laumann EO, Paik A, Rosen RC.

Department of Sociology, University of Chicago, Ill 60637, USA. ob01@midway.uchicago.edu

CONTEXT: While recent pharmacological advances have generated increased public interest and demand for clinical services regarding erectile dysfunction, epidemiologic data on sexual dysfunction are relatively scant for both women and men. OBJECTIVE: To assess the prevalence and risk of experiencing sexual dysfunction across various social groups and examine the determinants and health consequences of these disorders. DESIGN: Analysis of data from the National Health and Social Life Survey, a probability sample study of sexual behavior in a demographically representative, 1992 cohort of US adults. PARTICIPANTS: A national probability sample of 1749 women and 1410 men aged 18 to 59 years at the time of the survey. MAIN OUTCOME MEASURES: Risk of experiencing sexual dysfunction as well as negative concomitant outcomes. RESULTS: Sexual dysfunction is more prevalent for women (43%) than men (31%) and is associated with various demographic characteristics, including age and educational attainment. Women of different racial groups demonstrate different patterns of sexual dysfunction. Differences among men are not as marked but generally consistent with women. Experience of sexual dysfunction is more likely among women and men with poor physical and emotional health. Moreover, sexual dysfunction is highly associated with negative experiences in sexual relationships and overall well-being. CONCLUSIONS: The results indicate that sexual dysfunction is an important public health concern, and emotional problems likely contribute to the experience of these problems.

PMID: 10022110 [PubMed - indexed for MEDLINE]

L-Arginine, the Prosexual Nutrient
with Numerous Health Benefits

It's the disorder no one wants to talk about, yet according to a 1999 study published in the Journal of the American Medical Association, 43% of women and 31% of men suffer from sexual dysfunction.1 Sexual dysfunction is broadly defined as the inability to fully enjoy sexual intercourse. Women generally experience it as loss of libido (sexual drive) and/or the inability or difficulty in achieving an orgasm. Men experience it as impotence, known technically as erectile dysfunction.

Based on dozens of studies, Arginine, an essential amino acid and one of the building blocks of proteins in the body, has become known as a safe and effective prosexual nutrient for men and women.

L-Arginine is a precursor of nitric oxide (NO) in the human body. In the 1990s, scientists discovered that not only is NO an essential compound that helps blood circulation, but it is important to normal sexual function in both men and women. Without arginine there would be no NO, and without NO men would not be able to have erections.

Insufficient blood flow is a major cause of incomplete erection in men. L-Arginine has been shown to improve blood flow to the genital area by dilating blood vessels and helping the penis to enlarge to its full capacity, thus increasing the size, hardness and frequency of erections.

Nutritional expert, Dr. Jonathan Wright, explains the mechanism in men: "Molecules of NO are generated when an enzyme called NO synthase (NOS)- which is abundant in the nerve and muscle cells in and around the penis-strips away a nitrogen atom (N) from a passing molecule of the amino acid L-arginine) … and combines it with an atom of oxygen (O)." 2

In other words, in order to produce nitric oxide in the body, a nitrogen atom must combine with an oxygen molecule in the blood. The enzyme called nitric oxide synthase controls this reaction.

Higher blood flow makes clitoral and vaginal tissues more sensitive and responsive to sexual stimulation, and helps increase the possibility of reaching orgasm. Although there haven't been nearly as many studies done on arginine supplementation in women as in men, one study found that postmenopausal women who took a supplement including L-arginine experienced heightened sexual response.3

Another study involving 77 women of all ages found that after four weeks, 73.5% of the women who took a supplement including L-arginine experienced greater sexual satisfaction, including heightened desire and clitoral sensation, frequency of intercourse and orgasm, and less vaginal dryness.4

Both men and women report that L-arginine seems to increase their libido or desire for sex, and some also report that L-arginine gives them greater endurance. Reports also suggest that L-arginine supplements can improve fertility in men who have low sperm counts or poor sperm motility (activity).

The powerful effect of L-arginine was illustrated in a double-blind, placebo-controlled study published in the British Journal of Urology International in which researchers evaluated the nitric oxide levels of 50 men with erectile dysfunction. The men were given either L-arginine or a placebo for six weeks. Nine of the 29 men (31%) given L-arginine reported a significant improvement in their sexual performance. These nine men had low nitric oxide levels at the start of the trial, but their levels doubled by the end of the study.5

It is important to note, however, that erectile dysfunction can be caused by a variety of factors, including aging, diabetes and other endocrine disorders. L-arginine may be effective only in those men whose erectile dysfunction is due to low levels of nitric oxide. In fact, in one study in which the participants suffered from impotence for a variety of reasons, L-arginine was found to be effective in only 17% of the patients.6 However, optimal nitric oxide production will ensure optimum erectile function, and for many people with sexual dysfunction not related to an underlying disease arginine supplements will ensure adequate nitric oxide levels.

Studies done on animals provide some evidence for effectiveness as well. In a laboratory study, two groups of rats were given free access to L-arginine, which was dissolved in their drinking water. Both groups had greater serum and penile concentrations of arginine, and exhibited a significant increase in intra-penile pressure or "hardness."

Serum and penile tissue levels of L-arginine in the treated rats were increased by 64-148% compared to control animals. The penile nitric oxide levels also increased nearly 100% in the L-arginine treated groups compared to the control groups. The researchers concluded that these data support the use of dietary supplements for treatment of erectile dysfunction.7

This remarkable amino acid helps build muscle mass, enhance immune function, improve blood pressure, increase memory, and speed wound healing.8-10 Arginine-derived nitric oxide has also been found to play a supporting role in the cardiovascular, immune, and nervous systems and has been validated by hundreds of studies.

L-Arginine is essential to several systems in the body.
Among its many roles, L-arginine:

Is a precursor of nitric oxide (NO)
Promotes circulation resulting in improved blood flow
Stimulates the release of growth hormone
Improves immune function
Reduces healing time of injuries
Plays a role in the formation of bone and tendons

Increases muscle mass, while reducing body fat
Supports male fertility, improving sperm production and motility
Reduces risk of blood clots and stroke11,12
Supports normal blood pressure13
Improves vascular function for patients with angina14
Helps recovery after heart attack15
Helps prevent and treat cardiovascular disease16
Helps reduce growth of cancerous tumors17
Timing and contra-indications

L-arginine users say they can achieve a prosexual effect by taking it 45 minutes before sex. There are few reported side effects. The most notable are:

People with herpes - L-arginine may increase the severity of attacks, but some reports indicate that it may also enhance your immune function enough so you are less likely to get herpes attacks.
L-arginine is an excellent supplement for anyone wanting to increase his or her sexual arousal, improve performance and overall health. The huge advantage this natural and safe supplement has over Viagra is that men and women can take it, it's considerably less expensive (Viagra, costs as much as $10 a pill!), it's been proven to work in numerous double-blind studies, and it has no side effects.

While L-arginine is an inexpensive way to supplement your dietary arginine and increase nitric oxide production, an even more effective supplement is OKG (Ornithine ketoglutarate). OKG not only is slowly converted to arginine in the body, but is also metabolized to other health promoting amino acids

Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study.

Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

OBJECTIVES: To determine, in a prospective randomized, double-blind placebo-controlled study, the effect of 6 weeks of high-dose (5 g/day) orally administered nitric oxide (NO) donor L-arginine on men with organic erectile dysfunction (ED). PATIENTS AND METHODS: The study included 50 men with confirmed organic ED who were randomized after a 2-week placebo run-in period to receive L-arginine or placebo. A detailed medical and sexual history, O'Leary's questionnaire, a specially designed sexual function questionnaire and a sexual activity diary were obtained for each patient. All participants underwent a complete physical examination including an assessment of bulbocavernosus reflex and penile haemodynamics. Plasma and urine nitrite and nitrate (designated NOx), both stable metabolites of nitric oxide, were determined at the end of the placebo run-in period, and after 3 and 6 weeks. RESULTS: Nine of 29 (31%) patients taking L-arginine and two of 17 controls reported a significant subjective improvement in sexual function. All objective variables assessed remained unchanged. All nine patients treated with L-arginine and who had subjectively improved sexual performance had had an initially low urinary NOx, and this level had doubled at the end of the study. CONCLUSIONS: Oral administration of L-arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production. The haemodynamics of the corpus cavernosum were not affected by oral L-arginine at the dosage used.

Department of Psychology, University of Texas at Austin, 08 E. Dean Keeton, Austin, Texas 78712, USA. meston@psy.utexas.edu

This study examined the effects of the nitric oxide-precursor L-arginine combined with the alpha 2-blocker yohimbine on subjective and physiological sexual arousal in postmenopausal women with Female Sexual Arousal Disorder. Twenty-four women participated in three treatment sessions in which self-report and physiological (vaginal photoplethysmograph) sexual responses to erotic stimuli were measured following treatment with either L-arginine glutamate (6 g) plus yohimbine HCl (6 mg), yohimbine alone (6 mg), or placebo, using a randomized, double-blind, three-way cross-over design. Sexual responses were measured at approximately 30, 60, and 90 min postdrug administration. The combined oral administration of L-arginine glutamate and yohimbine substantially increased vaginal pulse amplitude responses to the erotic film at 60 min postdrug administration compared with placebo. Subjective reports of sexual arousal were significantly increased with exposure to the erotic stimuli but did not differ significantly between treatment groups.

Hypercholesterolemia enhances thromboembolism in arterioles but not venules: complete reversal by L-arginine.

Department of Physiology, CARIM, Maastricht University, Maastricht, the Netherlands.

We investigated in vivo the effect of cholesterol diet-induced hypercholesterolemia (HC) on thromboembolism in nonatherosclerotic rabbit mesenteric arterioles and venules (diameter 21 to 45 micrometer). After mechanical vessel wall injury, the ensuing thromboembolic reaction was studied by intravital videomicroscopy. A dramatic prolongation of embolization duration (median >600 seconds) was observed in the arterioles of the HC group compared with the arterioles of a normal chow-fed (NC) control group (142 seconds, P<0.0001); concomitantly, relative thrombus height increased (thrombus height/vessel diameter was 68% for the HC group and 58% for the NC group; P<0.05). By contrast, in venules, cholesterol did not affect embolization duration (42 seconds for HC group, 34 seconds for NC group) and thrombus height (66% for HC group, 64% for NC group). Furthermore, the role of endothelial NO synthesis was studied. In arterioles, stimulation of endogenous NO synthesis through mesenteric superfusion of L-arginine (1 mmol/L) completely reversed cholesterol-enhanced embolization (152 seconds) but did not influence thrombus height (63%). L-Arginine had no effect in venules of the HC group (51 seconds) and nor in the arterioles and venules of the NC group (177 seconds for arterioles, 43 seconds for venules). This study indicates that hypercholesterolemia selectively enhances thrombus formation and embolization in arterioles but not in venules and that stimulation of endogenous NO production antagonizes this enhancement of arteriolar thromboembolism.

Randomized trial of a medical food for the dietary management of chronic, stable angina.

Division of Research and Development, Cooke Pharma, Inc., Belmont, California, USA. amaxwell@ntgr8.com

OBJECTIVES: We determined the electrocardiographic, vascular and clinical effects of a medical food bar enriched with L-arginine and a combination of other nutrients known to enhance endothelium-derived nitric oxide (NO) in patients with stable angina. BACKGROUND: Enhancement of vascular NO by supplementation with L-arginine and other nutrients has been shown to have clinical benefits in patients with angina secondary to atherosclerotic coronary artery disease (CAD). However, the amounts and combinations of these nutrients required to achieve a clinical effect make traditional delivery by capsules and pills less suitable than alternative delivery methods such as a specially formulated nutrition bar. METHODS: Thirty-six stable outpatients with CAD and class II or III angina participated in a randomized, double-blind, placebo-controlled, crossover trial with two treatment periods each of two weeks' duration (two active bars or two placebo bars per day). Flow-mediated brachial artery dilation was measured by ultrasound. Electrocardiographic measures of ischemia, exercise capacity and angina onset time were measured by treadmill exercise testing and by Holter monitor during routine daily activities. Quality of life was assessed by SF-36 and Seattle Angina Questionnaires and by diary. RESULTS: The medical food improved flow-mediated vasodilation (from 5.5 +/- 4.5 to 8.0 +/- 4.9, p = 0.004), treadmill exercise time (by 20% over placebo, p = 0.05) and quality-of-life scores (SF-36 summary score; 68 +/- 13 vs. 63 +/- 21 after placebo, p = 0.04, Seattle Angina Questionnaire summary score; 67 +/- 10 vs. 62 +/- 18, p = 0.04) without affecting electrocardiographic manifestations of ischemia or angina onset time. CONCLUSIONS: These findings reveal that this arginine-rich medical food, when used as an adjunct to traditional therapy, improves vascular function, exercise capacity and aspects of quality of life in patients with stable angina.

The effect of L-arginine on myocardial recovery after cardioplegic arrest and ischemia under moderate and deep hypothermia.

Heart Science Centre, National Heart and Lung Institute at Harefield Hospital, United Kingdom.

BACKGROUND: Depletion of L-arginine (L-arg), the substrate for nitric oxide (NO) synthesis, could be one of the mechanisms responsible for the reduced production of NO and decreased coronary flow (CF) during reperfusion. This, in turn, may adversely affect mechanical function. We aimed to study the benefits of exogenous administration of L-arg under conditions that mimick preservation of the heart for transplantation and routine cardiac surgery. METHODS AND RESULTS: Isolated working rat hearts perfused with oxygenated Krebs-Henseleit buffer were subjected to one of the two experimental protocols: (1) cardioplegic arrest with St Thomas' No 1 cardioplegic solution and 240 minutes of deep hypothermic (4 degrees C) ischemia, and (2) cardioplegic arrest with St Thomas' No 1 cardioplegic solution and 60 minutes of moderate hypothermic (20 degrees C) ischemia. In each protocol, hearts were divided into four groups (1 to 4 for protocol A and A through D for protocol B; n=6 in each group). In groups 1 and A (controls), hearts were arrested with the St Thomas' No 1 and were reperfused with standard Krebs-Henseleit buffer. In groups 2 and B, L-arg was added to cardioplegic fluid; in groups 3 and C, L-arg was added to reperfusate; and in groups 4 and D, L-arg was added to both cardioplegic fluid and reperfusate. Cardiac output, dP/dt, CF, and NO concentrations in the coronary effluent were evaluated in all groups before and after ischemia. After 4 degrees C ischemia (protocol A), the postischemic recovery of dP/dt for the control hearts in group 1 was 51.0+/-3.4%, which increased significantly to 73.3+/-2.7% and 70.1+/-4.4% in groups 3 and 4, respectively. In group 2, recovery of dP/dt was similar to the control group's and was 56.5+/-4.5%. Increased postischemic cardiac output and CF and increased production of NO correlated with improved functional recovery. After 20 degrees C ischemia (protocol B), the postischemic recovery of dP/dt was 47.2+/-3.5% in control group A and significantly increased to 79.2+/-2.6% in group B, to 82.0+/-3.5 in group C, and to 83.9+/-3.3 in group D. Increased postischemic CF and increased production of NO were closely related to improvement in mechanical function. CONCLUSIONS: Exogenous L-arg considerably improves the postischemic recovery of cardiac mechanical function and CF after cardioplegic arrest and ischemia by stimulation of NO production when given in the reperfusate after both 4 degrees C and 20 degrees C ischemia. However, L-arg as an additive to cardioplegia was only beneficial after 20 degrees C, and not after 4 degrees C ischemia.

OBJECTIVES: To review use of alternative pharmacotherapy (AP) in patients with cardiovascular disease (CVD) and significant drug interactions between AP and traditional CVD medications. STUDY DESIGN: A literature search of MEDLINE and the National Complementary and Alternative Medicine database was done using these search terms: supplements, vitamins, garlic, fish oil, L-arginine, soy, coenzyme Q10, herbs, phytosterols, chelation therapy, alternative medicine, and CVD. PATIENTS AND METHODS: English human clinical trials measuring surrogate and clinical end points. RESULTS: Antioxidants have not been consistently proven beneficial in reducing cardiovascular mortality. Fish oils may be beneficial in patients with hypertension and hypercholesterolemia, but therapeutic doses need to be defined. Use of coenzyme Q10 in patients with heart failure has not demonstrated consistent benefits. Garlic may lower blood pressure and cholesterol levels, but also may increase bleeding, so its use in CVD patients should be monitored. Clinical studies with small sample sizes have demonstrated that L-arginine may be useful to prevent and treat CVD. The Food and Drug Administration recommends 25 g/day of soy protein as part of a diet low in saturated fats for cholesterol reduction. Plant sterols are recommended by the American Heart Association and the National Cholesterol Education Program Expert Panel as adjunct therapy to reduce low-density lipoprotein. No data support use of chelation therapy. Some APs interact with common prescription CVD medications (eg, gingko and ginseng with warfarin, St. John's Wort with digoxin). CONCLUSIONS: The benefits of APs as part of the treatment for CVD are controversial. Routine use is not recommended.

The NO - K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapies.

University of Alberta Hospitals, 2C2 Walker C McKenzie Health Sciences, Centre, Edmonton, Canada.

The prognosis of patients with pulmonary arterial hypertension (PAH) is poor. Available therapies (Ca(++)-channel blockers, epoprostenol, bosentan) have limited efficacy or are expensive and associated with significant complications. PAH is characterized by vasoconstriction, thrombosis in-situ and vascular remodeling. Endothelial-derived nitric oxide (NO) activity is decreased, promoting vasoconstriction and thrombosis. Voltage-gated K+ channels (Kv) are downregulated, causing depolarization, Ca(++)-overload and PA smooth muscle cell (PASMC) contraction and proliferation. Augmenting the NO and Kv pathways should cause pulmonary vasodilatation and regression of PA remodeling. Several inexpensive oral treatments may be able to enhance the NO axis and/or K+ channel expression/function and selectively decrease pulmonary vascular resistance (PVR). Oral L-Arginine, NOS' substrate, improves NO synthesis and functional capacity in humans with PAH. Most of NO's effects are mediated by cyclic guanosine-monophosphate (c-GMP). cGMP causes vasodilatation by activating K+ channels and lowering cytosolic Ca++. Sildenafil elevates c-GMP levels by inhibiting type-5 phosphodiesterase, thereby opening BK(Ca). channels and relaxing PAs. In PAH, sildenafil (50 mg-po) is as effective and selective a pulmonary vasodilator as inhaled NO. These benefits persist after months of therapy leading to improved functional capacity. 3) Oral Dichloroacetate (DCA), a metabolic modulator, increases expression/function of Kv2.1 channels and decreases remodeling and PVR in rats with chronic-hypoxic pulmonary hypertension, partially via a tyrosine-kinase-dependent mechanism. These drugs appear safe in humans and may be useful PAH therapies, alone or in combination.