Arginine and Viruses

Lotus97

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What's the deal with arginine and viruses? I've heard that it's not good to take arginine (and precursors citrulline and ornithine) if you have viruses, but I don't know why. Part of the reason I'm starting this thread is because I have Lyme and I want to know if people with Lyme (and accompanying coinfections) also need to avoid arginine.
 

Seven7

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I read also the same but related to Herpes viruses. Like it helps them replicate or something like that?!?!?
 

Lotus97

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There were a lot of customer reviews on iHerb for lysine where people said it helped them with their herpes. I don't know the details, but there's also something about a lysine/arginine balance.
 

Creekee

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My doctor believes arginine is used by the critters to create biofilm. Along with magnesium, calcium and maybe some others.
 

jeffrez

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Yeah, you should avoid arginine if you have viral load. Conventional wisdom is to take C and lysine.
 

Lotus97

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Do people with Lyme have viral loads? I stopped taking arginine, ornithine, and citrulline and I'm not sure I feel any better. I want to play it safe, but I'm kind of confused as to what's considered a virus and what's an infection or coinfection or viral infection.
 

jeffrez

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Lyme's a bacteria - or more correctly, I guess, a spirochete. You might want to check with a Lyme expert to be sure, but I don't think it's stimulated by arginine. Probably a non-issue, unless of course you *also* had viruses and the arginine was making those worse, possibly weakening your immunity.
 

heapsreal

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there is conflicting info out there saying arginine is good for the immune system which u would think would help us fight herpes virus?? but arginine supposedly feeds herpes viruses and lysine is used as it competes with arginine and can reduce arginine available to herpes viruses. But this is just what i have read and i have only tried lysine which didnt do anything for me but it has helped others with herpes 1.
 

Lotus97

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I've heard some Lyme doctors say not to take arginine, but I'm not sure why or if it's necessary. I partially asked because of coinfections, but it seems I might of misread the Wikipedia entry on coinfections. It does mention viruses in the wiki, but it seems the Lyme coinfection Bartonella is bacterial and Babesia is protozoan. There are some Lyme coinfections that are viral though:
http://www.niaid.nih.gov/topics/lymedisease/research/pages/co-infection.aspx
In Europe and Asia,Ixodes ticks also are known to transmit tickborne encephalitis viruses. Fortunately, this tickborne viral infection has not yet been reported in the United States, although in rare instances, ticks have been found to be co-infected with B. burgdorferi and Powassan virus.
 

Lotus97

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I was mainly taking arginine, citrulline, and ornithine because they were supposed to be good for dealing with ammonia and since I eat at least 100 grams of protein a day I probably have an ammonia problem. Right now I'm taking carnitine, AKG, lysine, and yucca for ammonia.

Actually, I initially bought them because they're supposed to increase human growth hormone, but I'm a little skeptical now of that claim. I'd like to see more research on that subject.

I'm not sure if the nitric oxide from arginine/citrulline/ornithine is a good thing or a bad thing. The information on that is confusing. For relatively healthy people, increasing NO is usually recommended. It seems Dr. Pall says too much NO is bad for CFS/ME/MCS/Fibromyalgia
http://chronicfatigue.about.com/od/treatmentprotocols/a/Pall_Protocol.htm
 

jeffrez

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I don't think there's much scientific doubt that arginine increases growth hormone secretion. Not sure of the doses needed to get any therapeutic increase, though - a few grams, at least, probably. If you want GH increase without the arginine problem, you might want to try glutamine.
 

heapsreal

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I don't think there's much scientific doubt that arginine increases growth hormone secretion. Not sure of the doses needed to get any therapeutic increase, though - a few grams, at least, probably. If you want GH increase without the arginine problem, you might want to try glutamine.
i think arginine has to be given IV to stimulate GH.
 

jeffrez

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Growth Horm IGF Res. 2005 Apr;15(2):136-9. Epub 2005 Jan 26.
Growth hormone responses to varying doses of oral arginine.

Collier SR, Casey DP, Kanaley JA.
Source

Department of Exercise Science, Syracuse University, 820 Comstock Avenue, Room 201, Syracuse, NY 13244, USA.
Abstract

Intravenous (IV) arginine invokes an increase in growth hormone (GH) concentrations, however, little is known about the impact of oral arginine ingestion on the GH response.
OBJECTIVE:

The purpose of this study was to determine the dose of oral arginine that elicits an optimal GH response and to determine the time course of the response.
DESIGN:

Eight healthy males (18-33 years - 24.8+/-1.2 years) were studied on 4 separate occasions. Following an overnight fast at 0700 h, a catheter was placed in a forearm vein. Blood samples were taken every 10 min for 5 h. Thirty minutes after sampling was initiated, the subject ingested a dose of arginine (5, 9 or 13 g) or placebo (randomly assigned).
RESULTS:

Mean resting GH values for the placebo, 5, 9 and 13 g day were 0.76, 0.67, 2.0 and 0.79 microg/L (n=6), respectively. Integrated area under the curve was not different with 13 g (197.8+/-65.7 min microg/L), yet it increased with 5 and 9 g compared with the placebo (301.5+/-74.6, 524.28+/-82.9 and 186.04+/-47.8 min microg/L, respectively, P<0.05). Mean peak GH levels were 2.9+/-0.69, 3.9+/-0.85, 6.4+/-1.3 and 4.73+/-1.27 microg/L on each day for the placebo, 5, 9 and 13 g days.
CONCLUSION:

In conclusion, 5 and 9 g of oral arginine caused a significant GH response. A 13 g dose of arginine resulted in considerable gastrointestinal distress in most subjects without augmentation in the GH response. The rise in GH concentration started approximately 30 min after ingestion and peaked approximately 60 min post ingestion.
 

Lotus97

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I've found doses higher than a couple grams of arginine too stimulating, but maybe some people would like the extra energy. Interestingly, Hip said arginine helped him with anxiety (not sure what doses though). It might have been arginine pyroglutamate specifically, but that kind also was too stimulating at higher doses. It definitely wouldn't be something I'd want to take too much of before bed which is when you're supposed to take HGH supplements (or before a workout). When I was able to work out, citrulline malate seemed to help, but part of that could have been from the malic acid. I forget if I took ornithine AKG and arginine pyroglutamate with it.
 

Hip

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The effects of arginine supplementation in promoting viral replication I believe only relate to herpes simplex virus, though even for herpes simplex, it seems that there is no simple answer as to whether arginine does or does not boost viral replication. A very good article entitled "Should Herpes Patients Avoid Arginine?" by Richard S. Lord — which I have copied and quoted below — summarizes the evidence for and against arginine boosting herpes replication.

The article basically says that arginine can boost herpes simplex virus replication, but in order to do so, it requires that the arginine is methylated. If it is not sufficiently methylated, then arginine may in fact inhibit herpes simplex virus replication.

Thus one might assume that if you are a good methylator, arginine may promote herpes simplex virus replication; whereas if you are a bad methylator, arginine may inhibit herpes simplex virus replication.

I have found myself that high doses of arginine (10 grams or more) can sometimes cause a cold sore outbreak (cold sores being a herpes simplex virus eruption), but I find this is no big deal anyway.


Note that in the case of enteroviruses, arginine has been shown to be antiviral:

Oral L-arginine prevents murine coxsackievirus B3 myocarditis.

This antiviral effect of arginine is probably due to its ability to promote nitric oxide, which is a potent antiviral/antibacterial.


Should Herpes Patients Avoid Arginine?
BY RICHARD S. LORD, PHD. OCTOBER 2011

Ever since the free love movement of the '60s, stories about managing herpes lesions with arginine and lysine have circulated. We were recently chided for not being on-board with recommending low arginine diets for patients with chronic Herpes simplex lesions. So I decided to probe related literature for scientific evidence that clarifies this relationship.

The science is briefly summarized below. Dates of the references show a period of high activity in the '70s and '80s, followed by a hiatus of about 20 years, and then another foray on the molecular details of viral replication, including Herpes simplex virus type 1 (HSV-1).

The early data from in-vitro studies tended to suggest that HSV replication was arginine dependent. Those studies culminated in the sweeping conclusion of Griffith, DeLong and Nelson, “that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.” This attitude became widely adopted for a while, followed by a period of diminished enthusiasm when dietary restriction of arginine was found to be ineffective at reducing lesions for many people.

Later studies throw some light on the molecular mechanisms, accompanied by evidence of contradictory clinical effects. Studies of people with herpes virus infection showed no differences in lysine and arginine intake, and cell culture studies led to conclusions of arginine being antiherpetic. It turns out that there is a key protein involved in herpes replication that contains arginine-rich regions. Interpretation of this finding might suggest that arginine restriction would help. However, the arginine residues found in the protein must become methylated in order to stimulate replication. Otherwise, replication can be inhibited. Thus, effects of dietary arginine restriction seem to be overridden by the multiple factors that govern rates of arginine residue methylation..

So, once again, we find that the devil is in the details, and that it can be dangerous to jump from cell culture experimental evidence to human therapeutic conclusions. This literature review did not include studies on lysine use as anti-herpetic, as that conclusion is more consistently supported by the evidence, thus far. But, restricting dietary arginine is no longer considered to be an effective way to manage herpes. And, it may be deleterious for anyone with problems concerning nitric oxide production pathways (esp. those with hypertension).

~ Richard S. Lord, Ph.D. • Chief Science Officer



Herpes Simplex Infection and Effects of Dietary Arginine

Herpetic-stimulating evidence
  • In arginine-deficient medium, the synthesis of herpes simplex viral peptides in the cytoplasm of virus-infected cells is reduced.[1]
  • Reduction of arginine by addition of arginase to rabbit tears results in the cure of the herpetic process.[2]
  • Arginine deficiency suppressed herpes simplex virus replication in tissue culture. Lysine, an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. The in vitro data may be the basis for the observation that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.[3]
  • The mean daily intakes of lysine and arginine for the 16 subjects studied were 8.11 gm +/- 2.28 and 6.32 gm +/- 1.74, respectively. The standard deviations of the mean intakes indicate that there was a large variability in the intake of both amino acids and the ratios of the two amino acids in individual diets. This information is important, considering the conflicting results obtained previously by researchers investigating the efficacy of lysine therapy for herpes infections.[4]
  • Arginine-rich regions are required for efficient nuclear localization and for the regulatory activity of immediate-early protein ICP27 involved in herpes simplex virus type 1late gene expression.[5]
Anti-herpetic evidence
  • Arginine-free media promotes viral infection in cell culture. Replenishment of arginine reduced the virus-enhancing activity of preincubated media.[6]
  • Dietary intake of the amino acids lysine and arginine did not differ significantly between normal controls and patients with herpes virus.[4]
  • Addition of arginine reduced the multiplication of herpes simplex virus type 1 (HSV-1) and demonstrated the potential of arginine as an antiherpetic agent.[7]
  • Critically ill patients fed a high-protein diet enriched with arginine, fiber, and antioxidants showed no increase in incidences of infections, including ventilator-associated pneumonia, surgical infection, bacteremia, or urinary tract infections.[8]
  • Arginine methylation of the ICP27 RGG box regulates its export activity and that early export of ICP27 interferes with the performance of its nuclear functions. [Thus, excess arginine in growth media in absence of methylation capacity may inhibit viral replication.][9]
  • Arginine and NaCl in conjunction with elevated temperature enhances inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus type A.[10]
  • HSV-1 replication is inhibited by hypomethylation of the ICP27 RGG-box resulting from the use of general PRMT inhibitors or arginine mutations.[11]


References
1. Olshevsky U, Becker Y. Synthesis and transport of herpes simplex virus proteins in arginine-deprived BSC-1 cells. Isr J Med Sci 1976;12:1298-307.

2. Kahan IL, Hajas K, Halasz A. The significance of the arginine and arginase of tears in experimentally-induced herpes simplex corneae. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1979;209:219-24.

3. Griffith RS, DeLong DC, Nelson JD. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture. Chemotherapy 1981;27:209-13.

4. Algert SJ, Stubblefield NE, Grasse BJ, Shragg GP, Connor JD. Assessment of dietary intake of lysine and arginine in patients with herpes simplex. Journal of the American Dietetic Association 1987;87:1560-1.

5. Hibbard MK, Sandri-Goldin RM. Arginine-rich regions succeeding the nuclear localization region of the herpes simplex virus type 1 regulatory protein ICP27 are required for efficient nuclear localization and late gene expression. J Virol 1995;69:4656-67.

6. Henle W, Henle G. Effect of arginine-deficient media on the herpes-type virus associated with cultured Burkitt tumor cells. J Virol 1968;2:182-91.

7. Naito T, Irie H, Tsujimoto K, Ikeda K, Arakawa T, Koyama AH. Antiviral effect of arginine against herpes simplex virus type 1. Int J Mol Med 2009;23:495-9.

8. Caparros T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr 2001;25:299-308; discussion -9.

9. Souki SK, Gershon PD, Sandri-Goldin RM. Arginine methylation of the ICP27 RGG box regulates ICP27 export and is required for efficient herpes simplex virus 1 replication. J Virol 2009;83:5309-20.

10. Utsunomiya H, Ichinose M, Tsujimoto K, et al. Co-operative thermal inactivation of herpes simplex virus and influenza virus by arginine and NaCl. Int J Pharm 2009;366:99-102.

11. Yu J, Shin B, Park ES, et al. Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation. Biochemical and biophysical research communications 2010;391:322-8.

Source: here.
 
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Lotus97

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Stephen Buhner, author of Healing Lyme (and a new book devoted to Lyme disease coinfections bartonella and mycoplasma), recommends arginine for his bartonella protocol (unless you have cetain illnesses).
http://buhnerhealinglyme.com/herbs/lyme-with-bartonella/
If you have bartonella, then you will have to treat it as well as the lyme. The best easy protocol for bartonella is:

Sida acuta tincture (from woodlandessence.com or julie@gaianstudies.org) ¼ tsp 3x day for 30 days
Hawthorn tincture, same
Japanese knotweed, (tincture, same dose as above, fromwoodlandessence.com or julie@gaianstudies.org, or capsules fromgreendragonbotanicals.com 2 capsules 3x daily)
ECGC 400mg +- daily
Houttuyina (Yu Xing Cao – 1st Chinese Herbs, powder) 1 tbl daily
L-arginine 5000 mg daily in divided doses
Milk thistle seed, standardized, 1200 mg daily
All for 30 days.
PLEASE NOTE: If you have active herpes, chicken pox, or shingles DO NOT USE L-arginine.
In general, the most important thing is to decrease the inflammation dynamics that are occurring in the lyme (knotweed), increase immune strength (cat’s claw, rhodiola tincture – ¼ tsp 3x daily, eleuthero tincture, same), and work on the bartonella. Plus addressing specific symptoms.
 

Lotus97

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He also has a response on the question of arginine feeding mycoplasma
http://buhnerhealinglyme.com/uncategorized/okay-to-supplement-l-arginine-with-mycoplasma/
Dear Stephen,
I read an article on the Rain-Tree website about supplementing l-arginine with mycoplasma, saying: “upplementing back the depleted amino acids has been reported to be helpful in some recovering from these infections. These include L-cysteine, L-tyrosine, L-glutamine, L-carnitine, and malic acid. Remember, however, that mycoplasmas thrive on arginine! Avoid L-arginine supplements and multi-amino acid formulas containing L-arginine, as well as foods rich in arginine to avoid feeding the mycoplasmas. The richest food sources of arginine (to avoid) are nuts and seeds, including the oils derived from seeds and nuts which should be eliminated or drastically reduced in the diet.” Under these circumstances, is the use of L-arginine when treating mycoplasma still okay? Also, would it be okay to take milk thistle, which is a seed?

Stephen’s response:
Here is the skinny on mycoplasmas and arginine: many mycoplasmas take arginine from the body to grow. THINK ABOUT IT: many mycoplasmas take arginine from the body to grow. WE, their human hosts, NEED arginine to be healthy. The mycoplasmas are going to get arginine no matter what. In fact what they do is scavenge if from your body’s tissues. That depletes your body of that substance and believe me, it is a crucial substance that you really do need. Some websites share horror stories About FEEDING the mycoplasmas if you take L-arginine. No matter what they will get it one way or another, so it matters not, for them, if you take a supplement or not. However FOR YOU, it is rather crucial to keep your arginine levels high since it is essential to your healthy functioning. Further, a number of mycoplasmas are actually sensitive to arginine, it can reduce their numbers in the body. So no matter what, you should be taking an L-arginine supplement or else eating foods high in arginine. Several score peer reviewed journal papers have noted that the only way to resolve cellular problems in infected mycoplasma cells is TO REPLACE THE ARGININE. So, yes, take the arginine. And the milk thistle is good to take as well.
 
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Hey,
I just found another article on arginine and its antiviral properties:

"
We investigated the effects of arginine on the multiplication of herpes simplex virus type 1 (HSV-1) and the potential of arginine as an antiherpetic agent. Arginine suppressed the growth of HSV-1 concentration-dependently. "
source: http://www.ncbi.nlm.nih.gov/pubmed/19288025
 

Dufresne

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Stephen Buhner, author of Healing Lyme (and a new book devoted to Lyme disease coinfections bartonella and mycoplasma), recommends arginine for his bartonella protocol (unless you have cetain illnesses).
http://buhnerhealinglyme.com/herbs/lyme-with-bartonella/

He also says it's essential for babesia treatment. He explains that the pathogen infects endothelial cells along blood vessels, thereby compromising their functioning. Arginine is apparently the fastest way to restore normal functioning and protect these cells from infection.

Perhaps babesia infection of endothelial cells is why I've often needed to take norepinephrine re-uptake inhibitors for circulatory problems, why my ADH was 20-50 times what it should have been, and why I've elevated ACE.

I've just started taking arginine.
 
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