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pu12en12g · #1 04-08-2006, 05:38 AM

If this thread bores you I apologize in advance. My goal is to consolidate the pros and cons of Nitric Oxide in a organized manner instead of a thread filled with confusing opinions because let's face it... like any supplement.. RESULTS WILL VARY... so let's start off with a bang... the science.

Quote:

Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males.

Elam RP, Hardin DH, Sutton RA, Hagen L.

"Twenty-two adult males participated in a 5 week progressive strength training program. One half the subjects received the amino acids L-arginine and L-ornithine and the other half, a placebo. The study used a double blind protocol so that subjects as well as investigators had no knowledge of which substances were being administered. Dosages amounted to 2 grams or 1 gram each of L-arginine and L-ornithine, and 600 mg of calcium and 1 gram of Vitamin C as placebos. These supplements were taken orally for a total of 25 administrations. Following the short term strength program using progressively high intensities, tests were taken for total strength (TS), lean body mass (LBM) and urinary hydroxyproline (UH).

The results from ANOVA showed that subjects who were taking the arginine-ornithine combination scored significantly higher in TS and LBM (p less than .05), and significantly lower in UH (p less than .05), than subjects on placebos.

It was concluded that arginine and ornithine taken in prescribed doses can, in conjunction with a high intensity strength training program, increase TS (Total Strength) and LBM (Lean Body Mass) in a relatively short period of time. Arginine and ornithine also aid in recovery from chronic stress by quelling tissue breakdown as evidenced by lower UH levels."

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pu12en12g · #2 04-08-2006, 07:26 AM

Nitric Oxide / Arginine and Creatine:

Quote:

The more muscle you gain, the greater the demand on creatine-synthesizing pathways to supply extra creatine to the newly added tissue. Arginine is required for the synthesis of creatine. Almost 2.5 grams of arginine are required to match the daily loss of creatine (as creatinine) in a 70-kg (~154-lb) male. By combining arginine with creatine, more arginine is free to promote nitrogen retention (essential for building muscle) and enhance sodium and water excretion (so-called 'muscle hardening' effects).

"[O]rally administered arginine hydrochloride certainly has anabolic effects by increasing insulin secretion. This molecule has been often used for its anti-asthenic effects in convalescent patients. Weight gain often occurs in patients receiving this therapy. This weight gain is often considered to be a side effect but is to be taking into account when arginine is consumed."

- Arginine researcher Dr. Adrien Schaefer

pu12en12g · #3 04-08-2006, 07:27 AM

When is the best time to take l-arginine ?

Quote:

Following ingestion, L-arginine is absorbed from the lumen of the small intestine into the enterocytes. Absorption is efficient and occurs by an active transport mechanism. Some metabolism of L-arginine takes place in the enterocytes. L-arginine not metabolized in the enterocytes enters the portal circulation from whence it is transported to the liver, where again some portion of the amino acid is metabolized. L-arginine not metabolized in the liver enters the systemic circulation, where it is distributed to the various tissues of the body. L-arginine participates in various metabolic activities, including the production of proteins, D-glucose, glycogen, L-ornithine, urea, nitric oxide, L-glutamate, creatine, polyamines, L-proline, agmatin and tuftsin. L-arginine is eliminated by glomerular filtration and is almost completely reabsorbed by the renal tubules. L-arginine produces peak plasma levels approximately one to two hours after oral administration.

pu12en12g · #4 04-08-2006, 07:28 AM

Arginine and Growth Hormone:

Quote:

Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults.

Marcell TJ, Taaffe DR, Hawkins SA, Tarpenning KM, Pyka G, Kohlmeier L, Wiswell RA, Marcus R.

Department of Exercise Science, University of Southern California, Los Angeles, USA. marcellt@grc.nia.nih.gov

BACKGROUND: Growth hormone (GH) helps maintain body composition and metabolism in adults. However, basal and peak GH decline with age. Exercise produces a physiologic GH response that is subnormal in elderly people. Arginine (Arg) infusion can augment GH secretion, but the efficacy of oral Arg to improve GH response to exercise has not been explored. We investigated whether oral Arg increases GH secretion in young and old people at rest and during exercise.

METHODS: Twenty young (Y: 22.1 +/- 0.9 y; SEM) and 8 old (O: 68.5 +/- 2.1 y) male and female subjects underwent three different trials following determination of their one-repetition maximum strength (1-RM); exercise only (EO; 3 sets, 8-10 reps at 85% of 1-RM; on 12 separate resistive lifts), Arg only (5.0 g), or Arg + exercise. Blood samples were collected between successive lifts, and GH (ng x ml(-1)) was determined via RIA.

RESULTS: In Y vs O: Basal GH secreted (area under the curve) was 543.6 +/- 84.0 vs 211.5 +/- 63.0. During EO, values were 986.6 +/- 156.6 and 517.8 +/- 85.5. Both were significantly lower in the older individuals (p < .05). Oral Arg alone did not result in any increase in GH secretion at rest (310.8 +/- 73.2 vs 262.9 +/- 141.2). When Arg was coadministered during exercise, GH release was not affected in either the young or old and appeared to be blunted in the young compared to the exercise only trial in the young.

CONCLUSION: Based upon these findings, we concluded that oral Arg does not stimulate GH secretion and may impair GH release during resistive exercise.

J Gerontol A Biol Sci Med Sci. 1999 Aug;54(8):M395-9.

pu12en12g · #5 04-08-2006, 07:30 AM

Arginine and IGF-1:

Quote:

Arginine increases insulin-like growth factor-I production and collagen synthesis in osteoblast-like cells.

Chevalley T, Rizzoli R, Manen D, Caverzasio J, Bonjour JP.

WHO Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland. chevalle@cmu.unige.ch

Protein-energy malnutrition, which is common in elderly patients with osteoporotic hip fractures, is associated with reduced plasma levels of insulin-like growth factor-I (IGF-I). IGF-I is an important regulator of bone metabolism, particularly of osteoblastic bone formation both in vivo and in vitro. Pharmacological doses of arginine (Arg) increase growth hormone (GH) and IGF-I serum levels. Whether amino acids, particularly Arg, can directly modulate the production of IGF-I by osteoblasts is not known. We investigated the effects of increasing concentrations of Arg on IGF-I expression and production, alpha1(I) collagen expression and collagen synthesis, and cell proliferation and cell differentiation, as assessed by alkaline phosphatase (ALP) activity and osteocalcin (OC) release, in confluent mouse osteoblast-like MC3T3-E1 cells. The addition of Arg (7.5-7500 micromol/L, equivalent to 0.1- to 100-fold human plasma concentration) for 48 h increased IGF-I production (adjusted for cell number) in a concentration-dependent manner with a maximum of 2.3 +/- 0.3-fold at 7500 micromol/L Arg [x +/- standard error of the mean (SEM), n = 3 experiments, p < 0.01]. Arg (7.5-7500 micromol/L) increased the percentage of de novo collagen synthesis in a concentration-dependent manner (2.1 +/- 0.4-fold with 7500 micromol/L Arg, p < 0.001) and ALP activity with a maximal stimulation of 144% +/- 13% plateauing at 750 micromol/l Arg (p = 0.002). The steady state level of IGF-I messenger ribonucleic acid (mRNA) and alpha1(I) collagen mRNA (both normalized to cyclophilin mRNA) of cells incubated with Arg at high (100-fold) or low (0.1-fold) human plasma concentrations, was 1.4 +/- 0.2, 1.2 +/- 0.2, and 1.1 +/- 0.2 after 24 h for the 7.5, 1.8, and 0.9 kb IGF-I mRNA transcripts, respectively (n = 3 experiments) and 1.5 +/- 0.2 and 3.1 +/- 0.7 after 24 and 48 h, respectively, for the combined analysis of the 5.6 and 4.7 kb alpha1(I) collagen mRNA transcripts (n = 3 experiments). A maximal mitogenic effect (cell number) of +21% +/- 3% (p < 0.01) was obtained with 1000 micromol/L Arg. In contrast, Arg (7.5-7500 micromol/L) induced a reduction of OC production, which reached 30% +/- 3% with 7500 micromol/L Arg (p = 0.02). In conclusion, Arg stimulated IGF-I production and collagen synthesis in osteoblast-like cells. Thus, Arg may influence bone formation by enhancing local IGF-I production.

Influence of dietary arginine on the anabolic effects of androgens.

Cremades A, Ruzafa C, Monserrat F, Lopez-Contreras AJ, Penafiel R.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Murcia, Spain.

Feeding mice an arginine-deficient diet decreased plasma concentrations of arginine, citrulline and ornithine in the females and arginine in the males, abolishing the sexual dimorphic pattern of these amino acids found in mice fed the standard diet. In addition, the restriction of dietary arginine produced a marked decrease in body and renal weights as well as in the activity of renal ornithine decarboxylase, decreases that were gender dependent since they were observed exclusively in males. The fact that these changes were not associated with the decrease in the circulating levels of testosterone and that the dietary arginine restriction prevented the body weight gain induced by testosterone treatment of female mice fed the standard diet indicates that dietary arginine is required for the anabolic action of androgens. Moreover, under certain conditions that could compromise the renal synthesis of arginine, as in the compensatory renal hypertrophy that follows unilateral nephrectomy, the myotrophic effect of testosterone was transiently impaired. The results also revealed that arginine deficiency produced an opposite effect in the expression of IGF-I and IGF-binding protein 1 in the liver and kidney. Taken together, our results indicate that dietary arginine may be relevant to the anabolic action of testosterone, and suggest that this effect may be mediated by changes in the insulin-like growth factor system.

pu12en12g · #6 04-08-2006, 07:32 AM

Arginine and Insulin / Growth Hormone:

Quote:

Dietary Arginine Supplementation Enhances the Growth of Milk-Fed Young Pigs

ABSTRACT

This study was conducted to determine the effect of dietary arginine supplementation on the growth of artificially reared piglets. The pigs were removed from sows to a nursery facility and assigned randomly to 1 of the 3 treatments representing diets supplemented with 0, 0.2, or 0.4% L-arginine (on the basis of milk replacer powder). Each milk feeder was assigned to 1 dietary treatment. Fresh liquid milk replacer (18.6% dry matter) was provided daily (0800 h) to piglets. Body weights of piglets were measured and jugular venous blood samples were obtained for metabolite analysis at d 7, 14, and 21 of age. Food intake did not differ between control and arginine-supplemented piglets [66.7 vs. 69.5 g dry matter/(kg body wt d)]. Compared with control piglets, dietary supplementation with 0.2 and 0.4% L-arginine dose dependently increased (P 0.05) plasma concentrations of arginine by 30 and 61%, and decreased (P 0.05) plasma concentrations of ammonia by 20 and 35%, and those of urea by 19 and 33%, respectively. Dietary supplementation with 0.4% L-arginine also increased plasma concentrations of insulin and growth hormone by 24–27% in piglets, compared with controls.

Between 7 and 21 d of age, the supplementation of 0.2 and 0.4% L-arginine to piglets enhanced (P 0.05) average daily weight gain by 28 and 66%, and body weight by 15 and 32%, respectively, compared with control piglets.

Plasma concentrations of orotate and glucose did not differ between control and arginine-supplemented piglets.

Compared with control pigs, dietary supplementation with 0.4% L-arginine increased plasma concentrations of insulin and growth hormone by 24–27%. Dietary supplementation with 0.2% L-arginine did not affect plasma concentrations of insulin and growth hormone during the 2-wk experimental period.

Arginine serves as the most abundant nitrogen carrier in body proteins (17) and takes part in multiple metabolic pathways (18). In addition, as the physiologic nitrogenous precursor for the synthesis of nitric oxide (the endothelium-derived relaxing factor, a neurotransmitter, a mediator of immune response, and a signaling molecule), arginine plays an important role in whole-body homeostasis (21).

Paradoxically, in neonatal pigs, intestinal synthesis of citrulline and arginine from glutamine/glutamate and proline (abundant amino acids in sow’s milk) decreases markedly within the first 3 wk of life via unknown mechanisms (8,14).

Intriguingly, a substantial decrease in arginine availability occurs around the time (d 8 of life) (9) when suckling piglets start to exhibit submaximal growth (1).

Plasma concentrations of arginine and ammonia are sensitive indicators of arginine nutritional status in neonatal pigs (22) and human infants (23,24). As an allosteric activator of N-acetylglutamate synthase, which synthesizes N-acetylglutamate, an activator of carbamoylphosphate synthase I, arginine
plays a crucial role in ammonia detoxification via the hepatic urea cycle (25). Thus, a hallmark of arginine deficiency is an elevated concentration of plasma ammonia in mammals (22– 24). Consistent with this, plasma concentrations of ammonia were greater in 14- and 21-d-old control pigs than in 7-d-old
pigs, but were decreased by dietary supplementation with 0.2 and 0.4% L-arginine.

Although milk-fed piglets continue to grow, this does not necessarily mean that their growth is maximal, as exemplified by submaximal growth and impaired nitric oxide synthesis in arginine-deficient young rats (28).

There is experimental evidence supporting the view that a decrease in arginine availability may limit maximal growth in young pigs. For example, Leibholz (11) reported that in early weaned piglets, supplementing 0.2 and 0.4% L-arginine to a milk-protein–based powder diet (containing 19.2% crude protein) numerically improved weight gain between d 7 and 14 of life compared with control piglets. However, that study involved a small number of piglets (n 4/treatment group) and the data were not subjected to statistical analysis (11).

Importantly, dietary supplementation with 0.2 and 0.4% L-arginine dose dependently increased plasma concentrations of arginine and the body weight gain of piglets. It is noteworthy that plasma concentrations of lysine and histidine were not affected by dietary supplementation with 0.2 and 0.4% L-arginine, suggesting a lack of either an antagonism or an imbalance among the basic amino acids.

The ratios of lysine:arginine:histidine (g:g:g) in the milk replacer diets supplemented with 0, 0.2 and 0.4% L-arginine were:

1:0.346:0.221
1:0.449:0.221
1:0.552:0.221

which would not be expected to impair intestinal absorption of lysine or histidine (30). Thus, supplementing the liquid milk replacer with 0.2 and 0.4% L-arginine ensured its continuous availability to piglets without affecting lysine and histidine utilization. Because dietary intake of all nutrients (including protein, fat, carbohydrates, vitamins, and minerals), except for arginine, did not differ between control and arginine-supplemented piglets, the enhanced growth of piglets in response to arginine supplementation was attributed to the increase in arginine availability.

Arginine is a potent stimulator of the secretion of insulin by pancreatic -cells and of growth hormone by the anterior pituitary gland in mammals (33), including young pigs (34).

Through an increase in arginine availability as well as the concurrent increases in plasma concentrations of anabolic hormones, dietary arginine supplementation improved the efficiency of nutrient utilization for enhancing tissue protein synthesis and growth performance.

Although arginine was identified 50 years ago as an essential amino acid for young pigs (35), and it displays remarkable metabolic and regulatory versatility (36,37), it is surprising that little is known about its quantitative requirements in neonates (including milk-fed piglets) (38).

In conclusion, dietary supplementation with 0.2 and 0.4% L-arginine to milk-fed young piglets dose dependently increases plasma concentration of arginine, decreases plasma concentration of ammonia, and promotes growth performance. Importantly, increasing arginine availability holds great promise as a potent method for enhancing neonatal piglet growth.

pu12en12g · #7 04-08-2006, 07:33 AM

Arginine and IGF-1 and Growth Hormone:

Quote:

http://www.blackwell-synergy.com/lin....11605.x/full/

"Arginine is a basic amino acid that plays several pivotal roles in cellular physiology. Like any amino acid, it is involved with protein synthesis, but it is also intimately involved with cell signaling through the production of nitric oxide and cell proliferation through its metabolism to ornithine and the other polyamines. Because of these multiple functions, arginine is an essential substrate for wound healing processes. Numerous studies have shown that arginine supplementation can lead to normalization or improvement of healing. This article reviews the basic biochemistry and cell signaling within which arginine performs its functions. In particular, the requirement for this amino acid in tissue repair is highlighted."

"Arginine is a dibasic amino acid. It is a constituent of several proteins in the body, and its metabolism is intimately tied to several metabolic pathways involved in the synthesis of urea, NO, polyamines, agmatine, and creatine phosphate. Arginine can be provided via nutritional intake or via new synthesis. Citrulline, generated from glutamine in the small intestine, is the major precursor for arginine. 4 About 50% of the ingested arginine is released into the portal circulation. The other part is directly utilized in the small bowel. The physiological uptake of arginine and citrulline by the liver is low because the liver does not express large amounts of the cationic transporter for the basic amino acid arginine (system y+). Therefore, most of the portal venous arginine and citrulline enters the systemic circulation and serves as substrate for extrahepatic tissues."

"...Although iNOS gene deletion delays, and arginine and NO administration improve healing, the exact mechanisms of action of NO on wound healing parameters are still unknown."

"One of the well-known biological effects of arginine is its very potent secretagogue activity on the pituitary 4547 and pancreatic glands. 48,49 The beneficial effects of supplemental arginine on wound healing are similar to the effects noted when growth hormone is administered to wounded animals or burned children."

"The response of healthy elderly human volunteers given 2 weeks of dietary supplementation with 30 g of arginine aspartate is enhanced wound collagen accumulation together with a significant elevation in circulating IGF-1. 39 This suggests that arginine does stimulate pituitary activity in the doses used and that this may be one of the mechanisms of action underlying its beneficial effect on wound healing."

pu12en12g · #8 04-08-2006, 07:35 AM

Arginine / Nitric Oxide and Recovery / Growth:

Quote:

"Nitric oxide generation from L-arginine is required for optimal human peripheral blood lymphocyte DNA synthesis."- Efron DT, Kirk SJ, Regan MC, Wasserkrug HL, Barbul A. Department of Surgery, Sinai Hospital of Baltimore, MD 21215.

"These data suggest that nitric oxide synthesis is critical to wound collagen accumulation and acquisition of mechanical strength".

Nitric oxide regulates wound healing - J Surg Res. 1996 Jun;63(1):237-40. Schaffer MR, Tantry U, Gross SS, Wasserburg HL, Barbul A.

"NO has been shown to be cytostatic to multiple cell types including endothelial cells, smooth muscle cells, hepatocytes, and fibroblasts [37, 38 and 39]. Depending on the cell type this effect can be cGMP dependent [40] or independent [41]. Target enzymes include complexes I and II of the respiratory chain [42] and ribonucleotide reductase [43], a rate-limiting enzyme in the DNA synthetic pathway. NO is cytostatic in large doses. However, several studies have shown that NO can stimulate cell proliferation when added in low concentrations [44 and 45]. Recent evidence suggests that NO can also reduce cell proliferation by inhibiting ornithine-decarboxylase activity, the rate limiting enzyme for polyamine formation [46].

NO also regulates gene expression [47 and 48] and cellular differentiation [49 and 50]. Regulation of gene expression by NO probably occurs indirectly, through amplification of other regulatory mechanisms [51]. For example, although NO is critical for wound collagen deposition, clear-cut enhancement of collagen synthesis or gene expression has not been found (see the following). Collagen metabolism and accumulation are tightly regulated through the activity of collagenases and their inhibitors, tissue inhibitors of metalloproteinases (TIMP). Inhibiting the collagenolytic pathway can enhance collagen accumulation. Addition of the NO donor SNAP to rat mesangial cells increases gelatinase A activity [52] whereas rat fibroblasts collagenase activity is unaffected by SNAP [41]. Another potential mechanism of posttranslational collagen regulation by NO is regulation of protein kinase C (PKC) activity [53 and 54]. By inhibiting PKC activity, NO could down-regulate PKC-related collagen synthesis in fibroblasts.

when humans and animals are fed an arginine-enriched diet there is improved healing as measured by collagen deposition and breaking strength"

"We also review the evidence that in certain nutritional or disease states or in certain stages of development otherwise dispensable amino acids may become indispensable. Arginine, citrulline, ornithine, cysteine, and tyrosine thus may be considered as acquired indispensable amino acids. Evidence for the indispensability of taurine is also considered. We propose a classification of the indispensability of amino acids based on clinical and therapeutic considerations."

- Newer concepts of the indispensable amino acids. Laidlaw SA, Kopple JD. Am J Clin Nutr. 1987 Oct;46(4):593-605.

"Some stress conditions that put an increased demand on the body for the synthesis of L-arginine include trauma (including surgical trauma), sepsis and burns. Under these conditions, L-arginine becomes essential, and it is then very important to ensure adequate dietary intake of the amino acid to meet the increased physiological demands created by these situations.

L-arginine, even when it is not an essential amino acid as defined above, is a vital one. In addition to participating in protein synthesis, it plays a number of other roles in the body. These include the detoxification of ammonia formed during the nitrogen catabolism of amino acids via the formation of urea. In addition, L-arginine is a precursor in the formation of nitric oxide, creatine, polyamines, L-glutamate, L-proline, agmatin (a possible neurotransmitter in the brain) and the arginine-containing tetrapeptide tuftsin, believed to be an immunomodulator. L-arginine is a glycogenic amino acid; it can be converted to D-glucose and glycogen if needed by the body or it can be catabolized to produce biological energy.

L-arginine, when administered in high doses, stimulates pituitary release of growth hormone and prolactin and pancreatic release of glucagon and insulin. Intravenous L-arginine may be used as an aid in the evaluation of problems with growth and stature that may be due to growth hormone deficiency. Intravenous arginine hydrochloride may be used as a fourth-line agent in the treatment of severe metabolic alkalosis. L-arginine is also used as an immunonutrient in enteral and parenteral nutrition to help improve the immune status in those suffering from sepsis, burns and trauma."

"L-arginine supplements theoretically may potentiate the effects of organic nitrates if taken concomitantly."

pu12en12g · #9 04-08-2006, 07:36 AM

Arginine and Prolactin:

Quote:

More on Prolactin (see above):

Prolactin is a hormone produced by the anterior pituitary gland in both men and women. It is known as a gonadotrophic hormone as it affects the gonads (testes and ovaries). It also has an effect on other organs in the body. However, only the effects on the reproductive organs will be discussed here.

In males, prolactin influences the production of testosterone and affects sperm production. In conditions where prolactin secretion is increased (hyperprolactinaemia), testosterone levels drop and sperm production is reduced or absent, resulting in male infertility.

pu12en12g · #10 04-08-2006, 07:37 AM

Arginine as a anti-oxidant:

Quote:

The influence of two different doses of L-arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in atherosclerotic patients.

Jablecka A, Checinski P, Krauss H, Micker M, Ast J.

Department of Clinical Pharmacology, Karol Marcinkowski Medical University, Poznan, Poland.

BACKGROUND: The purpose of this study was to assess the effect of two different doses in 28-day L-arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in patients with atherosclerotic peripheral arterial disease at Fontaine's stages II and III.

MATERIAL/METHODS: 32 patients were divided into 2 groups receiving L-arginine at 3i2 g/day (group A) or 3i4 g/day (group B). Nitric oxide concentration was determined with the testing set provided by Oxis using a Hyperion Micro Reader. Total antioxidant status (TAS) in mmol/l was established in serum with the RANDOX NX2332 test.

RESULTS: Group A showed substantially higher NO levels after 14 and 28 days of therapy. In group B, the NO level increase was substantial after 28 days. Noticeably higher total antioxidant statuses were noted in both groups: group A showed this only after 28 days of treatment, while group B exhibited substantial increase in TAS after 7, 14 and 28 days of L-arginine supplementation.

CONCLUSIONS: Oral supplementation of L-arginine for 28 days leads to substantial increases in NO and TAS levels (comparable in both groups of patients) in the blood of patients with atherosclerotic peripheral arterial disease at Fontaine's stages II and III. The TAS concentration rise points to an antioxidative effect of L-arginine oral supplementation.

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