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Home > Anti-aging Research > Nitric Oxide

Nitric Oxide

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  • Efficacy and Variability in Plasma Nitrite Levels during Long-Term Supplementation with Nitrate Containing Beetroot Juice - J Diet Suppl 2022 Oct 30;1-26 - "Long-term consumption of nitrate containing beetroot juice increased fasting nitrate and nitrite plasma levels compared to baseline" - See beet root capsules at Amazon.com.
    • 5 Ways to Increase Nitric Oxide Naturally - Healthline - "Nitrate is a compound found in beetroot and dark leafy greens like spinach and arugula. When you consume nitrate, your body converts it to nitric oxide, which in turn causes blood vessels to relax and dilate, lowering blood pressure."
  • Quercetin boosts nitric oxide levels and modulates the activities of arginase, acetylcholinesterase and adenosine deaminase in the corpus cavernosum of cyclosporine-treated rats - Andrologia 2022 Feb 25 - "One of the primary causes of erectile dysfunction (ED) in males is cardiovascular disease, such as hypertension (HT). As a result, the goal of this study is to see how quercetin (Q) affects the important biochemical parameters (nitric oxide, endogenous antioxidant enzymes)/specific enzymes (arginase, acetylcholinesterase and adenosine deaminase) linked to be responsible for smooth muscle relaxation in respect to sexual function ... Compared to the control group, Q of both concentrations reduced the activity of these enzymes and improved antioxidant status and NO levels" - See quercetin at Amazon.com.
  • Arginine, an inexpensive oral drug, could enhance radiation therapy for cancer - Science  Daily, 11/6/21 - "Arginine, also called L-arginine, is inexpensive and widely available, generally considered safe, and can get relatively easily from the bloodstream into the brain. The idea of using it to treat cancer arose from observations that tumors often aid their own survival by producing high levels of the related molecule nitric oxide (NO). The latter regulates multiple processes in the body including the flow of blood through blood vessels, and tumors cells often make more NO by upregulating their production of special enzymes called NO synthases, which synthesize NO from arginine ... patients were treated with high-dose arginine or placebo oral suspensions an hour before radiotherapy for their brain metastases -- tumors in the brain that represent the spread from primary tumors elsewhere, such as the lungs ... Six months after their courses of radiotherapy, 82 percent of the arginine group had improvement, or at least no worsening, of their neurological symptoms, compared with 20 percent in the placebo group. Most of the arginine-treated patients who died during the study did so because of their cancers' spread elsewhere in the body ... Moreover, although metastatic cancer usually has a dire prognosis, there were some arginine-treated patients whose tumors in and outside the brain disappeared, suggesting the possibility of cures" - See L-arginine products at Amazon.com and L-arginine at iHerb.
  • Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis - J Int Soc Sports Nutr 2021 Oct 9 - "Acute or chronic dietary NO3- intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance" - [Nutra USA] - See beet root powder at Amazon.com.
  • Effects of L-citrulline supplementation on nitric oxide and antioxidant markers after high-intensity interval exercise in young men: a randomized controlled trial - Br J Nutr 2021 Jun 17 - "L-citrulline (L-Cit) is a nonessential amino acid that stimulates nitric oxide (NO) production and improves exercise performance by reducing muscle damage indices ... nine young men (21 ± 1 years) participated in a double-blind crossover study in which they received 12 g of L-Cit and placebo (PL) an hour prior to high-intensity interval exercise on two occasions, separated by a seven-day washout period ... Our data indicate that L-Cit supplementation (single 12 g dose pre-exercise) induces improvements in antioxidant markers following a session of high-intensity interval exercise in young men" - See l-citrulline at Amazon.com.
  • Changes in mouth bacteria after drinking beetroot juice may promote healthy aging - Science Daily, 3/30/21 - "Beetroot -- and other foods including lettuce, spinach and celery -- are rich in inorganic nitrate, and many oral bacteria play a role in turning nitrate to nitric oxide, which helps to regulate blood vessels and neurotransmission (chemical messages in the brain) ... Older people tend to have lower nitric oxide production, and this is associated with poorer vascular (blood vessel) and cognitive (brain) health ... 26 healthy older people took part in two ten-day supplementation periods: one with nitrate-rich beetroot juice and another with nitrate-free placebo juice, which they drank twice a day ... The results showed higher levels of bacteria associated with good vascular and cognitive health, and lower levels of bacteria linked to disease and inflammation ... Systolic blood pressure dropped on average by five points (mmHg) after drinking the beetroot juice" - See beet root capsules at Amazon.com.
  • The influence of amaranth (Amaranthus hypochondriacus) dietary nitrates on the aerobic capacity of physically active young persons - "J Int Soc Sports Nutr 2020 Jul 13 - "Recent evidence indicates that elevating plasma nitrites through dietary nitrates (NO3-) supplementation is associated with enhanced muscle efficiency, fatigue resistance and performance. Beetroot (in various forms) is the dominant source of dietary NO3- primarily due to its vast availability and the simple form of preparation suitable for final consumption. After a few years of research and experimentation, our scientific team identified alternative source rich with dietary NO3- as possible nitric oxide precursor, amaranth (Amaranthus hypochondriacus) with a standardized concentration 9-11% of NO3-. This study aimed to evaluate the effect of single-dose (±400 mg of dietary NO3-) and long-term (6 days) supplementation of amaranth concentrate derived dietary NO3- on aerobic capacity in physically active young people ... The peak power of the ICE, the maximum oxygen consumption and the first ventilatory threshold were significantly increased after long-term consumption of dietary amaranth (from 4.44 ± 0.50 to 4.55 ± 0.43 W/kg; from 37.7 ± 2.7 to 41.2 ± 5.4 mL/kg/min and from 178.6 ± 30.3 to 188.6 ± 35.2 W, p < 0.05; respectively) in experimental group" - See beet root capsules at Amazon.com and iHerb.
  • Supplementation of L-Arginine, L-Glutamine, Vitamin C, Vitamin E, Folic Acid, and Green Tea Extract Enhances Serum Nitric Oxide Content and Antifatigue Activity in Mice - Evid Based Complement Alternat Med. 2020 Apr 11 - "The purpose of this study was to evaluate the potential beneficial effects of a combined extract comprising L-arginine, L-glutamine, vitamin C, vitamin E, folic acid, and green tea extract (LVFG) on nitric oxide content to decrease exercise fatigue. Male ICR (Institute of Cancer Research) mice were randomly divided into 4 groups and orally administered LVFG for 4 weeks. The 4-week LVFG supplementation significantly increased serum nitric oxide content in the LVFG-1X and LVFG-2X groups. Antifatigue activity and exercise performance were evaluated using forelimb grip strength, exhaustive swimming test, and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after an acute swimming exercise. LVFG supplementation dose-dependently improved exercise performance and nitric oxide content, and it dose-dependently decreased serum ammonia and CK activity after exhaustive swimming test. LVFG's antifatigue properties appear to manifest by preserving energy storage (as blood glucose) and increasing nitric oxide content. Taken together, our results show that LVFG could have the potential for alleviating physical fatigue due to its pharmacological effect of increasing serum nitric oxide content"
  • High-salt diet promotes cognitive impairment through the Alzheimer-linked protein tau - Science Daily, 10/23/19 - "The 2018 study found that a high-salt diet caused dementia in mice. The rodents became unable to complete daily living tasks such as building their nests and had problems passing memory tests. The research team determined that the high-salt diet was causing cells in the small intestine to release the molecule interleukin-17 (IL-17), which promotes inflammation as part of the body's immune response ... IL-17 then entered the bloodstream and prevented the cells in the walls of blood vessels feeding the brain from producing nitric oxide. This compound works by relaxing and widening the blood vessels, allowing blood to flow. Conversely, a shortage of nitric oxide can restrict blood flow ... Based on these findings, Dr. Iadecola, Dr. Faraco and their colleagues theorized that salt likely caused dementia in mice because it contributed to restricted blood flow to the brain, essentially starving it"
  • The effect of omega-3 and vitamin E on oxidative stress and inflammation: Systematic review and meta-analysis of randomized controlled trials - Int J Vitam Nutr Res. 2019 Aug 23:1-1 - "The present meta-analysis found that omega-3 fatty acids and vitamin E co-supplementation significantly decreased hs-CRP and increased NO and TAC" - See omega-3 supplements at Amazon.com and vitamin E products at Amazon.com.
  • Acute Supplementation with Nitrate-Rich Beetroot Juice Causes a Greater Increase in Plasma Nitrite and Reduction in Blood Pressure of Older Compared to Younger Adults - Nutrients 2019, 11(7), 1683 - "Nitrate-rich beetroot juice supplementation has been shown to improve cardiovascular and cognitive function in younger and older adults via increased nitric oxide production ... Older adults showed a greater elevation in plasma nitrite (p = 0.038) and a greater reduction in diastolic BP (p = 0.005) following BR consumption than younger adults. Reaction time was improved in the Stroop test following BR supplementation for both groups (p = 0.045). Acute BR supplementation increased plasma nitrite concentrations and reduced diastolic BP to a greater degree in older adults; whilst systolic BP was reduced in both older and younger adults, suggesting nitrate-rich BR may improve cardiovascular health, particularly in older adults due to the greater benefits from reductions in diastolic BP" - [Nutra USA] - See beet root powder at Amazon.com (I can't imaging trying to down the actual juice.  I remember when I was about six years old in the school cafeteria.  I didn't like anything on the plate.  The teacher said to just eat the beets and I could go.  I barfed trying to eat them.  Every time I think of beet juice, I think of that.).
  • Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-β1 and MMPs Protein Expression - Nutrients. 2018 Oct 19;10(10) - "n-nitro l-arginine methyl ester (l-NAME) ... Male Sprague-Dawley rats were treated with l-NAME (40 mg/kg), l-NAME plus hesperidin (15 mg/kg), hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in l-NAME rats. l-NAME-induced cardiac remodeling, i.e., increases in wall thickness, cross-sectional area (CSA), and fibrosis in the left ventricular and vascular remodeling, i.e., increases in wall thickness, CSA, vascular smooth muscle cells, and collagen deposition in the aorta were attenuated by hesperidin or captopril. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and enhancing plasma nitric oxide metabolite (NOx) in l-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF- β1 protein expression and the overexpression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was suppressed in l-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in l-NAME hypertensive rats" - See hesperidin at Amazon.com.
  • l-Citrulline Supplementation: Impact on Cardiometabolic Health - Nutrients. 2018 Jul 19;10(7) - "Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations" - See l-citrulline at Amazon.com.
  • Vitamin D3 could help heal or prevent cardiovascular damage - Science Daily, 1/30/18 - "A major discovery from these studies is that vitamin D3 is a powerful stimulator of nitric oxide (NO), which is a major signaling molecule in the regulation of blood flow and the prevention of the formation of clots in the cardiovasculature. Additionally, vitamin D3 significantly reduced the level of oxidative stress in the cardiovascular system ... Most importantly, these studies show that treatment with vitamin D3 can significantly restore the damage to the cardiovascular system caused by several diseases, including hypertension, atherosclerosis, and diabetes, while also reducing the risk of heart attack ... "There are not many, if any, known systems which can be used to restore cardiovascular endothelial cells which are already damaged, and Vitamin D3 can do it," Malinski said. "This is a very inexpensive solution to repair the cardiovascular system. We don't have to develop a new drug. We already have it."" - See vitamin D at Amazon.com.
  • A high-salt diet produces dementia in mice - Science Daily, 1/16/18 - "We discovered that mice fed a high-salt diet developed dementia even when blood pressure did not rise ... The scientists discovered that an impaired ability of cells lining blood vessels, called endothelial cells, reduced the production of nitric oxide, a gas normally produced by the endothelial cells to relax blood vessels and increase blood flow. To see if the biological effects of a high-salt diet could be reversed, Dr. Iadecola and colleagues returned some mice to a regular diet for four weeks and found that cerebral blood flow and endothelial function returned to normal"
  • Chocolate Can Boost Your Workout - New York Times, 3/23/16 - "the scientists provided half of the cyclists with 40 grams (1.4 ounces, or about one and a half squares) per day of Dove brand dark chocolate, which has been found in past tests to contain an above-average amount of epicatechin ... The results were beguiling. Each of the cyclists performed better in most of the physical tests after two weeks of supplementing with dark chocolate, compared to baseline results and after they had eaten white chocolate. The riders utilized less oxygen to ride at a moderate pace, a change that would generally allow them to ride longer or harder before tiring; and they covered more distance during a two-minute, all-out time trial, meaning that their anaerobic, sprinting ability had been enhanced ... more than 40 grams is unlikely to be helpful" - See Ghirardelli Chocolate Intense Dark Squares, Midnight Reverie, 4.12 oz., 86% Cacao (Pack of 4) at Amazon.com.  Each individually wrapped square is 10 grams.  Also see Dove Dark Chocolate Candy Bar, Singles (18 Count) which are 40 gram bars which may have been the ones in this study but it doesn't tell you the percentage of cacao.  Some websites show the old packaging and it says 71% cacao.  I doubt if you find anything with a higher percentage of cacao than the Ghirardelli Chocolate Intense Dark Squares, Midnight Reverie  (86%) so my theory is that you're getting the most cacao for the least calories.
  • Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis - J Int Soc Sports Nutr. 2015 Jun 10;12:27 - "Nitric oxide (NO) is endogenously synthesized from L-arginine and L-citrulline. Due to its effects on nitric oxide synthase (NOS), reduced glutathione (GSH) may protect against the oxidative reduction of NO ... plasma NOx with L-citrulline + GSH was significantly greater than control and L-citrulline" - See Stimulin at Amazon.com.  I'm not so sure taking glutathione supplements will raise glutathione.  Some say you need to take NAC.   See:
    • How to Boost Glutathione Levels - Dr. Murray's Newsletter, 7/30/03 - "When healthy subjects were given a single dose of up to 3,000 mg of glutathione researchers found there was no increase in blood glutathione levels.11 ...  In contrast, blood glutathione levels rose nearly 50% in healthy individuals taking 500 mg of vitamin C.12 Vitamin C raises glutathione by helping the body manufacture it. In addition, to vitamin C, dietary sources of glutathione and several other nutritional compounds can help increase glutathione levels including N-acetylcysteine (NAC), alpha-lipoic acid, glutamine, methionine, and whey protein. Also, vitamin B6, riboflavin, and selenium are required in the manufacture of glutathione"
  • Omega-3 fatty acids supplementation improves endothelial function and maximal oxygen uptake in endurance-trained athletes - Eur J Sport Sci. 2015 Jun;15(4):305-14 - "The effects of dietary supplementation (n-3 PUFA at a dose of 1.3 g twice daily for 3 weeks) and placebo administration ... Significant differences between pre- and post-intervention baseline NO levels were observed after n-3 PUFA dietary protocol (13.9 ± 4.2 vs. 23.5 ± 3.6 µmol·l(-1); P < 0.001). Higher post-intervention baseline NO level was observed after n-3 PUFA diet compared with placebo (23.5 ± 3.6 vs. 15.3 ± 3.0 µmol·l (-1); P < 0.01, respectively). The n-3 PUFA increased baseline NO concentration (ΔNO) by 6.7 ± 3.8 µmol·l(-1) and placebo by 1.6 ± 4.4 µmol·l(-1). The positive correlation was observed between baseline post-intervention NO concentration and maximal oxygen uptake (r = 0.72; P < 0.01) and also between ΔNO and [Formula: see text] (r = 0.54; P < 0.05) in response to omega-3 fatty acids supplementation. There was an association between a 5.25% higher FMD (P < 0.05) and higher [Formula: see text] (P < 0.001) after n-3 PUFA diet compared with lower values of placebo" - [Nutra USA] - See fish oil supplements at Amazon.com.
  • Resveratrol Decrease Fructose-Induced Oxidative Stress Mediated by NADPH Oxidase via an AMPK-Dependent Mechanism - Br J Pharmacol. 2014 Feb 18 - "Resveratrol, an important antioxidant in red wine, improves NO bioavailability to prevent cardiovascular disease ... Collectively, resveratrol decreased BP through the phosphorylation of AMPK, AKT, and nNOS in fructose-fed rats. These novel findings suggest that the resveratrol may be a potential pharmacological candidate for the treatment of hypertension" - See resveratrol products at Amazon.com.
  • Thiamine deficiency leads to reduced nitric oxide production and vascular dysfunction in rats - Nutr Metab Cardiovasc Dis. 2013 Oct 5 - "Thiamine deficiency is a condition that is known to cause damage to the nervous and cardiovascular systems because it interferes with cellular metabolism. It is well known that the control of vascular function is highly dependent on the production of nitric oxide (NO) by NO synthases ... Thiamine deficiency modulates eNOS-dependent NO production, leading to a decreased vasorelaxation and an increased contractile response in the rat aorta"
  • Arginine Therapy Shows Promise for Sickle Cell Pain - Science Daily, 9/16/13 - "A deficiency of nitric oxide, a potent vasodilator, has been identified in sickle cell disease and may contribute to episodes of blocked vessels and pain. Since arginine is a building block of nitric oxide, researchers hypothesized that arginine could be a beneficial treatment for pain related to sickle cell disease ... a randomized, double blind placebo control clinical trial of 38 children with sickle cell disease hospitalized for 56 episodes of pain. The research team discovered a 54 percent reduction in the use of opioid pain medication and significantly lower pain scores at hospital discharge in those treated with arginine over those receiving placebo" - See L-arginine products at Amazon.com.
  • Quercetin Protects Mouse Brain against Lead-induced Neurotoxicity - J Agric Food Chem. 2013 Jul 15 - "QE markedly increased NO production (39.1%, 61.1%) and PKA activity (51.0%, 57.8%)" - See quercetin at Amazon.com.
  • Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase - Int J Impot Res. 2013 Jan 17 - "This study aimed at comparing the effects of atorvastatin and vitamin E on erectile dysfunction in patients initially irresponsive to sildenafil, with investigation into the underlying possible mechanisms. Sixty patients were randomly divided into three groups: the atorvastatin group received 80 mg daily, the vitamin E group received 400 IU daily and the control group received placebo capsules ... glutathione peroxidase (GPO) ... nitric oxide (NO) ... Both atorvastatin and vitamin E showed a statistically significant GPO increase (P<0.05) and a statistically significant IL-6 decrease (P<0.05). Only atorvastatin showed a statistically significant increase in NO (15.19%, P<0.05), eNOS (20.58%, P<0.01), IIEF-5 score (53.1%, P<0.001) and Rigiscan rigidity parameters (P<0.01), in addition to a statistically significant decrease in CRP (57.9%, P<0.01). However, SOD showed a statistically significant increase only after vitamin E intake (23.1%, P<0.05). Both atorvatstain and vitamin E had antioxidant and anti-inflammatory activities. Although activating eNOS by atorvastatin was the real difference, and expected to be the main mechanism for NO increase and for improving erectile dysfunction" - See Jarrow FamilE (contains all eight members of the vitamin E family, includes Tocomin) at Amazon.com.
  • Folate intake and incidence of hypertension among American young adults: a 20-y follow-up study - Am J Clin Nutr. 2012 Apr 4 - "Laboratory studies suggest that folate intake may decrease blood pressure (BP) through increasing nitric oxide synthesis in endothelial cells and/or reducing plasma homocysteine concentrations ... participants in the highest quintile of total folate intake had a significantly lower incidence of hypertension (HR: 0.48; 95% CI: 0.38, 0.62; P-trend < 0.01) than did those in the lowest quintile. The multivariable HRs for the same comparison were 0.33 (95% CI: 0.22, 0.51; P-trend < 0.01) in whites and 0.54 (95% CI: 0.40, 0.75; P-trend < 0.01) in African Americans (P-interaction = 0.047)" - See folic acid products at Amazon.com.
  • Cardiovascular effects of flavanol-rich chocolate in patients with heart failure - Eur Heart J. 2011 Dec 15 - "Flavanol-rich chocolate (FRC) is beneficial for vascular and platelet function by increasing nitric oxide bioavailability and decreasing oxidative stress. Congestive heart failure (CHF) is characterized by impaired endothelial and increased platelet reactivity ... Twenty patients with CHF were enrolled in a double-blind, randomized placebo-controlled trial, comparing the effect of commercially available FRC with cocoa-liquor-free control chocolate (CC) on endothelial and platelet function in the short term (2 h after ingestion of a chocolate bar) and long term (4 weeks, two chocolate bars/day) ... Flow-mediated vasodilatation significantly improved from 4.98 +/- 1.95 to 5.98 +/- 2.32% (P = 0.045 and 0.02 for between-group changes) 2h after intake of FRC to 6.86 +/- 1.76% after 4 weeks of daily intake (P = 0.03 and 0.004 for between groups). No effect on endothelial-independent vasodilatation was observed. Platelet adhesion significantly decreased from 3.9 +/- 1.3 to 3.0 +/- 1.3% (P = 0.03 and 0.05 for between groups) 2 h after FRC, an effect that was not sustained at 2 and 4 weeks. Cocoa-liquor-free CC had no effect, either on endothelial function or on platelet function. Blood pressure and heart rate did not change in either group"
  • Hydroxytyrosol is key anti-inflammatory compound in olive: DSM study - Nutra USA, 8/25/11 - "Hydroxytyrosol, an ingredient to watch, has been identified as the main anti-inflammatory compound in olives ... hydroxytyrosol was found to inhibit both nitric oxide (NO) and prostaglandin E2 (PGE2), both are pro-inflammatory compounds ... The effects of hydroxytyrosol on NO and chemokine production point to their impact on chronic inflammatory processes in endothelium or arthritis ... Hydroxytyrosol is thought to be the main antioxidant compound in olives, and believed to play a significant role in the many health benefits attributed to olive oil ... Data has also suggested the compound may boost eye health and reduce the risk of against macular degeneration ... Several companies already offer the compound for nutraceutical applications ... Results showed that hydroxytyrosol inhibited the production of both NO and PGE2 in mouse cells, "reflecting strong anti-inflammatory activity"" - [Abstract] - Note:  Trouble is, you usually don't want to inhibit nitric oxide.
  • Repeated and long-term treatment with physiological concentrations of resveratrol promotes NO production in vascular endothelial cells - Br J Nutr. 2011 Jul 27:1-7 - "Repeated treatment with resveratrol for 5 d resulted in an increase in endothelial NO synthase (eNOS) protein content and NO production in human umbilical vein endothelial cell (HUVEC) in a concentration-dependent manner. A significant increase in functional eNOS protein content was observed with resveratrol, even at 50 nm. In contrast, eNOS phosphorylation was not stimulated and inducible NO synthase (iNOS) was not detected after resveratrol treatment. Both eNOS protein and mRNA expression were promoted by 50 nm-resveratrol in a time-dependent manner. Increased eNOS mRNA expression in response to resveratrol was not decreased by an oestrogen receptor (ER) antagonist ICI182780, a PPARα inhibitor MK886 or a sirtuin inhibitor Salermide. However, a combination of ICI182780 and MK886 significantly inhibited resveratrol-induced eNOS mRNA expression. Salermide had no effect even in the presence of ICI182780 or MK886. These results demonstrate that resveratrol within the physiological range increases eNOS mRNA and protein expression through ER and PPARα activation, thereby promoting NO production in endothelial cells. eNOS induction might result from the accumulative effect of nanomolar concentrations of resveratrol. The present study results can account in part for the observation that cardiovascular benefits of red wine are experienced with routine consumption, but not with acute consumption" - See resveratrol products at Amazon.com.
  • Exercise protects the heart via nitric oxide, researchers discover - Science Daily, 5/4/11 - "Nitric oxide, a short-lived gas generated within the body, turns on chemical pathways that relax blood vessels to increase blood flow and activate survival pathways. Both the chemical nitrite and nitrosothiols, where nitric oxide is attached to proteins via sulfur, appear to act as convertible reservoirs for nitric oxide in situations where the body needs it, such as a lack of blood flow or oxygen ... Our study provides new evidence that nitric oxide generated during physical exercise is actually stored in the bloodstream and heart in the form of nitrite and nitrosothiols. These more stable nitric oxide intermediates appear to be critical for the cardioprotection against a subsequent heart attack ... voluntary exercise boosted levels of an enzyme that produces nitric oxide (eNOS, endothelial nitric oxide synthase). Moreover, the levels of eNOS in heart tissue, and nitrite and nitrosothiols in the blood as well as heart tissue, stayed high for a week after exercise ceased, unlike other heart enzymes stimulated by exercise. The protective effects of exercise did not extend beyond four weeks after the exercise period was over, when nitrite and nitrosothiols in the heart returned to baseline"
  • High levels of dietary nitrate might in part explain the vascular benefits of diets rich in leafy greens - Science Daily, 3/23/11 - "Nitric oxide (NO) is an important molecule that helps maintain the contractility and health of vascular smooth muscle cells, and multiple studies have linked vascular pathology to a decreased level of NO ... NO is synthesized from arginine by an enzyme called nitric oxide synthase (NOS) ... after vessel injury in the rat, the NOS pathway is disrupted, but a secondary pathway that generates NO from nitrate is activated. Furthermore, supplementing rats with nitrate before inducing vessel injury markedly limited the extent of the damage, while a diet low in nitrate exacerbated it ... high levels of dietary nitrate might in part explain the vascular benefits of diets rich in leafy greens, but warn that high dose supplementation could lead to the generation of carcinogenic molecules"
  • Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome - J Clin Endocrinol Metab. 2011 Feb 23 - "Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits ... Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H(2)O(2). Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 +/- 1.19 vs. 7.78 +/- 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption" - See hesperidin at Amazon.com.
  • Want more efficient muscles? Eat your spinach - Science Daily, 2/1/11 - "dietary nitrate feeds into a pathway that produces nitric oxide with the help of friendly bacteria found in our mouths. Nitric oxide has been known for two decades as a physiologically important molecule. It opens up our blood vessels to lower blood pressure, for instance ... Among the more consistent findings from nutritional research are the beneficial effects of a high intake of fruit and vegetables in protection against major disorders such as cardiovascular disease and diabetes ... the underlying mechanism(s) responsible for these effects is still unclear, and trials with single nutrients have generally failed. It is tempting to speculate that boosting of the nitrate-nitrite-NO pathway may be one mechanism by which vegetables exert their protective effects"
  • Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction - Urology. 2011 Jan;77(1):119-22 - "L-arginine supplementation improves nitric oxide-mediated vasodilation and endothelial function; however, oral administration has been hampered by extensive presystemic metabolism. In contrast, L-citrulline escapes presystemic metabolism and is converted to L-arginine, thus setting the rationale for oral L-citrulline supplementation as a donor for the L-arginine/nitric oxide pathway of penile erection ... A total of 24 patients, mean age 56.5 +/- 9.8 years, were entered and concluded the study without adverse events. The improvement in the erection hardness score from 3 (mild ED) to 4 (normal erectile function) occurred in 2 (8.3%) of the 24 men when taking placebo and 12 (50%) of the 24 men when taking L-citrulline (P < .01). The mean number of intercourses per month increased from 1.37 +/- 0.93 at baseline to 1.53 +/- 1.00 at the end of the placebo phase (P = .57) and 2.3 +/- 1.37 at the end of the treatment phase (P < .01). All patients reporting an erection hardness score improvement from 3 to 4 reported being very satisfied" - See citrulline malate at Amazon.com.
  • Blueberries linked to improved blood vessel health: Rat study - Nutra USA, 11/18/10 - "Our data provide clear evidence that the 8 week dietary treatment with 8 percent wild blueberry in the adult SHR with established endothelial dysfunction results in a significant moderation of the increased aortic vascular tone ... The berries were proposed to act via the NO pathway – nitric oxide is a potent vasodilator, or compound that promotes the dilation or relaxation of blood vessels, thereby easing blood pressure" - [Abstract] - See blueberry extract at Amazon.com.
  • A Wild Blueberry-Enriched Diet ( Vaccinium angustifolium ) Improves Vascular Tone in the Adult Spontaneously Hypertensive Rat - J Agric Food Chem. 2010 Nov 24 - "The vasoconstriction elicited by Phe was reduced in the WB group, attributed to the NO pathway, favoring a lower vascular tone under basal conditions. Acetylcholine-induced vasorelaxation in the WB group was possibly mediated through the COX, but not the NO pathway. These findings document the potential of wild blueberries to modify major pathways of vasomotor control and improve the vascular tone in the adult SHR with endothelial dysfunction" - See blueberry extract at Amazon.com.
  • Chocolate eaters may have healthier hearts: study - MSNBC, 11/8/10 - "The authors found that women older than 70 who ate chocolate at least once per week were 35 percent less likely to be hospitalized or die from heart disease over the course of the study, and nearly 60 percent less likely to be hospitalized or die from heart failure ... The danger is that many people will start eating more of it than is necessary, without cutting back in calories from other snacks, which will result in weight gain and will counteract any beneficial effects of chocolate ... Flavonoids are thought to reduce the risk of heart disease, the leading cause of death in many industrialized countries, by helping to increase nitric oxide, which in turn helps boost the functioning of blood vessels and lower blood pressure"
  • Dark chocolate lowers blood pressure, research finds - Science Daily, 6/28/10 - "Flavanols have been shown to increase the formation of endothelial nitric oxide, which promotes vasodilation and consequently may lower blood pressure. There have, however, been conflicting results as to the real-life effects of eating chocolate. We've found that consumption can significantly, albeit modestly, reduce blood pressure for people with high blood pressure but not for people with normal blood pressure ... The pressure reduction seen in the combined results for people with hypertension, 5mm Hg systolic, may be clinically relevant -- it is comparable to the known effects of 30 daily minutes of physical activity (4-9mm Hg) and could theoretically reduce the risk of a cardiovascular event by about 20% over five years" - See flavonoids at Amazon.com.
  • Glycine Propionyl-L-carnitine Modulates Lipid Peroxidation and Nitric Oxide in Human Subjects - Int J Vitam Nutr Res. 2009 May;79(3):131-141 - "Nitric oxide was increased (p<0.05) from pre- to post-intervention with 3 g GPLC (21.34+/-2.27 vs. 29.46+/-3.61 micromol.L (-1))" - Note:  (29.46 - 21.34) / 21.34 = 38% increase in nitric oxide. See GPLC at Amazon.com.
  • Endothelial-Vasoprotective Effects of High-Density Lipoprotein Are Impaired in Patients With Type 2 Diabetes Mellitus but Are Improved After Extended-Release Niacin Therapy - Circulation. 2009 Dec 21 - "Patients with diabetes were randomized to a 3-month therapy with ER niacin (1500 mg/d) or placebo ... HDL from healthy subjects stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell-mediated endothelial repair. In contrast, these beneficial endothelial effects of HDL were not observed in HDL from diabetic patients, which suggests markedly impaired endothelial-protective properties of HDL. ER niacin therapy improved the capacity of HDL to stimulate endothelial nitric oxide, to reduce superoxide production, and to promote endothelial progenitor cell-mediated endothelial repair. Further measurements suggested increased lipid oxidation of HDL in diabetic patients, and a reduction after ER niacin therapy ... HDL from patients with type 2 diabetes mellitus and metabolic syndrome has substantially impaired endothelial-protective effects compared with HDL from healthy subjects. ER niacin therapy not only increases HDL plasma levels but markedly improves endothelial-protective functions of HDL in these patients, which is potentially more important" - See niacin at Amazon.com.
  • Sea of science deepens for fish heart benefits - Nutra USA, 12/16/09 - "left ventricular systolic dysfunction (LVSD) ... moderate fish consumption, defined as , was associated with 53 per cent reduction in the risk of developing LVSD compared to no/rare consumption of fish ... In addition, moderate fish consumption was associated with a lower inhibition of the nitric oxide synthase, an enzyme which produces nitric oxide – a potent vasodilator that relaxes blood vessels and improves blood flow" - See Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com and glucosamine products at Amazon.com.
  • Carnosine facilitates nitric oxide production in endothelial f-2 cells - Biol Pharm Bull. 2009 Nov;32(11):1836-9 - "These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca2+, which might be released from intracellular Ca2+ stores in response to carnosine" - See carnosine products at Amazon.com.
  • Regulation of nitric oxide production in health and disease Curr Opin Clin Nutr Metab Care. 2009 Oct 16 - "The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency" - See L-arginine products at Amazon.com and l-citrulline products at iHerb.
  • Scientists Help Explain Effects Of Ancient Chinese Herbal Formulas On Heart Health - Science Daily, 8/19/09 - "Nitric oxide is crucial to the cardiovascular system because it signals the inner walls of blood vessels to relax, which facilitates the flow of blood through the heart and circulatory system. The messenger molecule also eliminates dangerous clots, lowers high blood pressure and reduces artery-clogging plaque formation ... In the study, researchers performed laboratory tests on DanShen, GuaLou and other herbs purchased at a Houston store to assess their ability to produce nitric oxide"
  • Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men - Am J Clin Nutr. 2008 Oct;88(4):1018-25 - "Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function"
  • Pycnogenol((R)), French maritime pine bark extract, augments endothelium-dependent vasodilation in humans - Hypertens Res. 2007 Sep;30(9):775-80 - "These findings suggest that Pycnogenol((R)) augments endothelium-dependent vasodilation by increasing in NO production. Pycnogenol((R)) would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction" - Some say that grape seed extract is the same as Pycnogenol((R)) without the patent markup.  See Pycnogenol at Amazon.com and grape seed extract at Amazon.com.
  • Pine bark extract boost for blood flow and heart health - Nutra USA, 10/18/07 - "Acetylcholine stimulates the cells of arteries to produce NO from L-arginine faster ... In turn, the NO causes the muscle surrounding arteries to relax, which results in an increase of blood vessel diameters. When subjects had taken Pycnogenol the relaxation of arteries was increased by 42 per cent as compared to the group taking placebo tablets" - See Pycnogenol at Amazon.com and citicholine at Amazon.com.
  • Why Cocoa May Help Heart Health - WebMD, 1/18/06 - "cocoa's antioxidants -- called flavonoids -- coax the body into making more nitric oxide, which relaxes the blood vessels"
  • Jarrow Formulas’, Inc. Introduces ALCA 500(TM) (Acetyl-L-Carnitine Arginate Dihydrochloride) - NPI Center, 3/8/05 - "Acetyl-l-carnitine arginate (ALCA) represents an advancement in the carnitine and arginine fields as this new dietary supplement offers potential benefits in affecting levels of nitric oxide over and above the traditional benefits of carnitine" - See acetyl l-carnitine at Amazon.com.
  • Vitamins enhance benefits of exercise for heart - Nutra USA, 5/25/04 - "Exercise alone has been shown to increase nitric oxide in the body ... But adding the amino acid L-arginine and the antioxidants vitamins C and E to the mix significantly magnified the effect" [WebMD]
  • Nitric Oxide Now -- Ask Me How -  WashingtonPost.com, 10/6/03 - "In the arteries, the innermost layer of cells releases nitric oxide to signal smooth muscle cells to dilate (increase the diameter of) the arteries. This allows blood to flow more freely, particularly during exercise ... By the 1990s, many scientists saw nitric oxide as the next great weapon for treating heart disease, impotence and even bacterial infections ... Niteworks has L-arginine and also L-citrulline, which recycles spent L-arginine by resupplying it with atoms it lost producing nitric oxide ... "Ninety dollars a month? That's obscene," Murad said. "You can probably get [vitamin] C and E for pennies a day. You can probably get arginine for about a dollar a day"" - See L-citrulline at Amazon.com.
  • N-acetylcysteine Improves Blood Vessels - Nutrition Science News, 5/01 - "Researchers suspect this is because NAC enhances the bioavailability of the relaxing substance nitric oxide, but because nitric oxide has a short half-life and cannot be measured by current methodology, they were unable to determine this directly. In addition, NAC may act as an antioxidant that protects nitric oxide destruction"
  • A Fish Story - Nutrition Science News, 4/01 - "daily consumption of very low daily doses of EPA/DHA (120 mg/180 mg, about one standard fish oil capsule) in an enriched milk led to a 19 percent decrease in blood triglycerides and a 19 percent increase in HDL cholesterol after six weeks ... It is unclear whether EPA is superior to DHA, although EPA has proven more potent in relaxing cow coronary arteries and producing the vasodilator gas, nitric oxide, in vitro"
  • Want a love potion? What to know before you try - CNN, 6/15/00 - "Tissue and animal studies of one form of ginseng, called panax, give some credence to the root's sexy reputation. A study published in the May 1995 issue of the journal British Pharmacology, for instance, concluded that substances in ginseng extract known as ginsenosides may work in a similar way to Viagra. Viagra enhances the effects of nitric oxide, which helps relax artery walls, allowing more blood flow into the penis. Ginsenosides may encourage the release of more nitric oxide."

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