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 (read further re: ADMA [185.96 kb PDF], Laboratory Evaluations for Integrative and Functional Medicine; Lord, Bralley).
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
- In arginine-deficient medium, the synthesis of herpes simplex viral peptides in the cytoplasm of virus-infected cells is reduced.
- Reduction of arginine by addition of arginase to rabbit tears results in the cure of the herpetic process.
- 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.
- 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.
- 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.
- Arginine-free media promotes viral infection in cell culture. Replenishment of arginine reduced the virus-enhancing activity of preincubated media.
- Dietary intake of the amino acids lysine and arginine did not differ significantly between normal controls and patients with herpes virus.
- Addition of arginine reduced the multiplication of herpes simplex virus type 1 (HSV-1) and demonstrated the potential of arginine as an antiherpetic agent.
- 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.
- 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.]
- Arginine and NaCl in conjunction with elevated temperature enhances inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus type A.
- HSV-1 replication is inhibited by hypomethylation of the ICP27 RGG-box resulting from the use of general PRMT inhibitors or arginine mutations.
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