LONGECITY

A nice, albeit with a very positive inclination, review article about arginine.

http://www.sciencedi...090123210000573

Abstract l-Arginine is one of the most metabolically versatile amino acids. In addition to its role in the synthesis of nitric oxide, l-arginine serves as a precursor for the synthesis of polyamines, proline, glutamate, creatine, agmatine and urea. Several human and experimental animal studies have indicated that exogenous l-arginine intake has multiple beneficial pharmacological effects when taken in doses larger than normal dietary consumption. Such effects include reduction in the risk of vascular and heart diseases, reduction in erectile dysfunction, improvement in immune response and inhibition of gastric hyperacidity. This review summarises several positive studies and personal experiences of l-arginine. The demonstrated anti-aging benefits of l-arginine show greater potential than any pharmaceutical or nutraceutical agent ever previously discovered.

© 2010 Cairo University. All rights reserved.

(maybe it is a good idea to have some topics that group information about specific supplements)
Edited by Brainbox, 28 August 2011 - 10:55 AM.

Arginine is terrible. It's the only supplement I've ever taken where I threw the entire bottle in the garbage after taking it for two weeks, because I knew I would never take the stuff again. A study a few years ago suggested it increased the risk of heart attack in people with congestive heart failure. When I started taking it I thought, no problem, I don't have congestive heart failure. After taking it a week and a half, I noticed that my heart had been beating way too hard in the afternoon for the past several days. I wondered what was wrong with me, then I suspected the arginine. I reduced the arginine dose from the recommended 4 pills (I don't remember the mg, may have been 500 per pill), to a single pill. The problem was greatly reduced. After I stopped taking it completely, the problem resolved and I tossed the stuff.

"The demonstrated anti-aging benefits of l-arginine show greater potential than any pharmaceutical or nutraceutical agent ever previously discovered."

Whoa, that's a strong claim.

Arginine is terrible. It's the only supplement I've ever taken where I threw the entire bottle in the garbage after taking it for two weeks, because I knew I would never take the stuff again. A study a few years ago suggested it increased the risk of heart attack in people with congestive heart failure. When I started taking it I thought, no problem, I don't have congestive heart failure. After taking it a week and a half, I noticed that my heart had been beating way too hard in the afternoon for the past several days. I wondered what was wrong with me, then I suspected the arginine. I reduced the arginine dose from the recommended 4 pills (I don't remember the mg, may have been 500 per pill), to a single pill. The problem was greatly reduced. After I stopped taking it completely, the problem resolved and I tossed the stuff.

You might be sensitive to increases in nitric oxide(if arginine truly does increase NO). Just because it's bad for you, doesn't mean it's bad.

I've been taking 500 mg a day at bedtime for a few weeks now to help with blood pressure and leg pain/arthritis issues. In addition to Gotu Kola that I take in the morning. Seems to be working for me. There are some cautions, however. Reported to react with nitrates and viagra causing dizziness. Also reported that it may make allergies, asthma, and herpes worse if you have any of those. Also saw warnings to avoid 2 weeks before surgery or if you've had a recent heart attack. None of which apply to my situation. I think many of the blood-flow related cautions would apply equally to Gotu Kola but not the allergies, asthma, and herpes interaction, so that might be a limited alternative if you want the nitric oxide blood-flow effects. As I understand it, however, they are slightly different in how they work; arginine is an amino acid that metabolizes into niitric oxide while Gotu Kola is an herb that stimulates the body to do its own nitric oxide production in the blood vessel walls. I've been taking gotu about 4 months now but avoided taking it in the evenings when I take my cholesterol medication but arginine doesn't have any effect on statin absorption so adding that in the evening has really worked out well for me as indicated by my latest blood work.

Howard
Edited by hav, 28 August 2011 - 07:02 PM.

I've not had a problem with L-arginine but then again I only take 1 gram prior to bedtime.

More articles on L-arginine:

http://www.life-enha...=16&search.y=15

Would AAKG be a better choice due to it's much longer half life compared to l Arginine?

Don't know if this will work in humans but i have read that GFR slowly declines with age. I can't find a link to the full article only the abstract. I have also read that caloric restriction can slow the rate of GFR decline.
https://www.ncbi.nlm.../pubmed/9227589

Long-term dietary supplementation with L-arginine prevents age-related reduction in renal function.

Reckelhoff JF, Kellum JA Jr, Racusen LC, Hildebrandt DA.

Source

Department of Physiology, University of Mississippi Medical Center, Jackson 39216, USA.

Abstract

Aging is associated with loss of nephron function and reductions in serum L-arginine and excretion of nitric oxide (NO) metabolites. The present study was performed to determine if long-term dietary treatment with L-arginine, the NO synthase substrate, could prevent age-related renal injury. Studies were performed in four groups of rats, aged 12-13 mo, for 8 mo: group 1 received L-arginine (2% in 2.5% corn syrup, n = 5); group 2 received sodium nitrite, an NO donor (0.1%, in 2.5% syrup, n = 7); group 3 was an untreated control group (n = 7); group 4 was treated with 2.5% corn syrup (n = 5). Urinary protein increased and urinary nitrate/nitrite decreased with age in controls, but, during L-arginine treatment, urinary protein decreased and nitrate/nitrite increased. Two weeks after L-arginine was stopped, urinary protein had increased and nitrate/nitrite had decreased to the same level as in controls. L-Arginine treatment increased glomerular filtration rate (GFR) by 50% compared with untreated controls. In contrast, nitrite had no effect on GFR. Morphologically, L-arginine protected against aging injury by reducing the number of sclerotic glomeruli. In summary, we found that L-arginine prevented the age-related glomerular injury and reduction in GFR. The mechanism of protection, however, may be independent of NO.

Anybody have an idea why these two studies conflict with each other?

In the first study it suggest that arginine fed to rats at 2% in diet induces renal failure but the second study says no adverse effect in rats fed up to 5% arginine in diet. 

 

http://www.ncbi.nlm....pubmed/12670191

 

 

influence of green tea polyphenol in rats with arginine-induced renal failure.

Yokozawa T1, Cho EJ, Nakagawa T.

Author information

 

Abstract

To determine whether green tea polyphenol ameliorates the pathological conditions induced by excessive dietary arginine, green tea polyphenol was administered to rats at a daily dose of 50 or 100 mg/kg body weight for 30 days with a 2% w/w arginine diet. In arginine-fed control rats, urinary and/or serum levels of guanidino compounds, nitric oxide (NO), urea, protein, and glucose increased significantly, while the renal activities of the oxygen species-scavenging enzymes superoxide dismutase (SOD) and catalase decreased, compared with casein-fed rats. However, rats given green tea polyphenol showed significant and dose-dependent decreases in serum levels of creatinine (Cr) and urea nitrogen and urinary excretion of Cr, and they exerted a slight reduction of nitrite plus nitrate, indicating that green tea polyphenol reduced the production of uremic toxins and NO. In addition, in arginine-fed rats the urinary urea, protein, and glucose level increases were reversed by the administration of green tea polyphenol. Moreover, in rats given green tea polyphenol the SOD and catalase activities suppressed by excessive arginine administration increased dose-dependently, implying the biological defense system was augmented as a result of free radical scavenging. These results suggest that green tea polyphenol would ameliorate renal failure induced by excessive dietary arginine by decreasing uremic toxin, and NO production and increasing radical-scavenging enzyme activity.

 

http://www.ncbi.nlm....pubmed/15204729

 

 

Thirteen-week oral toxicity study of L-arginine in rats.

Tsubuku S1, Hatayama K, Mawatari K, Smriga M, Kimura T.

Author information

 

Abstract

The amino acid L-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% (w/w) for both genders (males, 3.3 +/- 0.1 g/kg/day; females, 3.9 +/- 0.2 g/kg/day).

 

Anybody have an idea why these two studies conflict with each other?

In the first study it suggest that arginine fed to rats at 2% in diet induces renal failure but the second study says no adverse effect in rats fed up to 5% arginine in diet. 

 

http://www.ncbi.nlm....pubmed/12670191

 

 

influence of green tea polyphenol in rats with arginine-induced renal failure.

Yokozawa T1, Cho EJ, Nakagawa T.

Author information

 

Abstract

To determine whether green tea polyphenol ameliorates the pathological conditions induced by excessive dietary arginine, green tea polyphenol was administered to rats at a daily dose of 50 or 100 mg/kg body weight for 30 days with a 2% w/w arginine diet. In arginine-fed control rats, urinary and/or serum levels of guanidino compounds, nitric oxide (NO), urea, protein, and glucose increased significantly, while the renal activities of the oxygen species-scavenging enzymes superoxide dismutase (SOD) and catalase decreased, compared with casein-fed rats. However, rats given green tea polyphenol showed significant and dose-dependent decreases in serum levels of creatinine (Cr) and urea nitrogen and urinary excretion of Cr, and they exerted a slight reduction of nitrite plus nitrate, indicating that green tea polyphenol reduced the production of uremic toxins and NO. In addition, in arginine-fed rats the urinary urea, protein, and glucose level increases were reversed by the administration of green tea polyphenol. Moreover, in rats given green tea polyphenol the SOD and catalase activities suppressed by excessive arginine administration increased dose-dependently, implying the biological defense system was augmented as a result of free radical scavenging. These results suggest that green tea polyphenol would ameliorate renal failure induced by excessive dietary arginine by decreasing uremic toxin, and NO production and increasing radical-scavenging enzyme activity.

 

http://www.ncbi.nlm....pubmed/15204729

 

 

Thirteen-week oral toxicity study of L-arginine in rats.

Tsubuku S1, Hatayama K, Mawatari K, Smriga M, Kimura T.

Author information

 

Abstract

The amino acid L-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% (w/w) for both genders (males, 3.3 +/- 0.1 g/kg/day; females, 3.9 +/- 0.2 g/kg/day).

 

 

They didn't say they actually induced any renal failures in the 1st study.  They only talk about measuring increased nitric oxide (NO), urea, protein, and glucose, which are believed to be markers associated with renal failure, and note a decline in those levels when polyphenols are also taken.  They therefore inferred a lower risk of renal failure.  Also, the 1st study's abstract doesn't specify when they took their measurements... my guess is they did it right at the end of the 30 day test period.  In the 2nd study they focused on marker recovery and measured 5 weeks after 13 weeks of test dosages ended.  So the studies would not contradict each other unless they also waited 5 weeks in 1st study to take measurements.  Which I doubt is the case.
 

It is curious that they did not measure blood pressure, which is probably the biggest risk factor for renal failure.  Increased NO production lowers high blood pressure.  I assume the green tea polyphenol plus arginine test group would have had increased blood pressure compared to the arginine-only group.  Which would undercut the inference drawn in the 1st study.

 

The biggest thing I get from the 1st study is that green tea polyphenols probably neutralize the effects of arginine so it would probably be a waste to take them together.  What I do is cycle my arginine and polyphenols (with antioxidants)  on alternate weeks.  Also note the arginine dosage they used for the 5% case translates to 3.3 g/kg of rat body weight daily suggesting the 2% case translates to about 1.32 g/kg rats or 220 mg/kg humans assuming a 6:1 rat to human conversion ratio.  Which would be over 15 grams per day for a 70 kg human male. 

 

Howard

Great response!

Do you feel it would be beneficial to supplement Pycnogenol/grape seed extract along with arginine?  I have read that they work synergistically together to increase nitric oxide.

 

I avoid Arginine because for those that have herpes, it can cause outbreaks. I also believe that it's use a year ago caused me to have a shingles outbreak, which is also a herpes virus.

Do you feel it would be beneficial to supplement Pycnogenol/grape seed extract along with arginine?  I have read that they work synergistically together to increase nitric oxide.

 

I take both gse and arginine, but on alternate weeks.  Lets me cycle supplements without any roller coaster effect on my blood pressure.  My situation is that my olmesartan medication has difficulty fully controlling my blood pressure all by itself.  My doctor tried adding an HTC diuretic which did the trick well enough but unfortunately triggered a gout-like side effect reaction so I had to drop it.  I've had better luck with Arginine and herbal supplements.

 

My current dosage is 500 mg of l-arginine with 500 mg of l-cysteine 3x daily.  On the off weeks I do a 50/50 mix of 500 mg of gse/ pine bark 3x daily in my antioxidant stack.

 

I've always been prone to occasional fever blisters, which I think are a kind of herpes, like once every couple of years, but have not noticed any change in frequency or level of occurrence since I started my current regimen over two years ago.  Perhaps the resveratrol or other antioxidants I also take inhibit any herpes aggravation by arginine.

 

Howard