L-lysine is an essential amino acid. That means that the body cannot make it and must instead get it from outside sources: namely dietary intake of protein foods—although dietary supplements with L-lysine can also serve as a source. The best dietary sources of L-lysine are animal proteins, such as meats, poultry, and milk. Proteins from grains, such as wheat and corn, generally tend to be low in lysine.1 This article will address the clinical research that has been conducted on supplementation with L-lysine—with a focus on its anti-Herpes virus effects. But first, let's quickly review L-lysine's biological functions in our bodies.

The Biological Functions Of Lysine
L-lysine serves various important roles in human biology. One of these is its requirement for collagen synthesis.2,3 which in turn makes it important for connective tissues found in bone and skin, among other tissues. In addition, L-lysine is necessary for the synthesis of carnitine and the resultant conversion of fatty acids to energy, as well its playing roles in supporting healthy growth and development in children, and maintaining healthy immune function.4 In particular, L-lysine plays a critical role in the management of Herpes simplex virus (HSV) infections, via its antagonistic relationship with L-arginine.

Lysine And Herpes Virus Infections
Lysine appears to have an antagonistic relationship with the amino acid arginine, which is required for the replication of HSV. Lysine competes with arginine for absorption in the intestine, reabsorption in the renal tubules, and transport across the plasma membrane into cells. in vitro, lysine inhibits the growth-promoting action of arginine on HSV. Increasing over all lysine intake or influencing the lysine-to-arginine ratio is the basis for lysine's potential benefit in managing an HSV outbreak,5,6 as demonstrated in various studies.

Lysine and herpes study 1
This study7 examined the efficacy of long-term preventive effect of lysine supplementation. Twenty-six volunteers with a history of frequently recurring HSV on their lips (HSV labialis), completed a 12-month double-blind crossover study. The frequency of Herpes recurrences ranged from four to sixteen per year (with many occurring twelve times in the past year). The participants included in the statistical analysis were randomly divided into two groups at the beginning of the study. Group A, consisting of fifteen members, began with lysine tablets. Group B, comprising eleven members, started with a placebo. The experimental group received daily oral supplements of 1,000 mg L-lysine. They were instructed to take two tablets every morning before breakfast. A crossover took place at sixmonths (where the L-lysine group switched to a placebo, and vice versa). At this time, a new 6-month supply of tablets was issued, and the participants were instructed to continue the daily regimen without interruption. At the end of the second 6-month period the study was terminated. Serum samples were analyzed at scheduled intervals.

Results showed that at the end of the first 6-month period, the frequency of lesions in those subjects given lysine did not differ significantly from the frequency in those given the placebo. Although this was surprising, it was even more surprising that the subjects who began taking lysine during the second 6-month test period reported significantly fewer lesions than those who had reverted to placebo (p < 0.05). In this group, the frequency of herpetic lesion episodes over a 6-month period was 1.18 times versus 4.05 compared to baseline. Similarly, during the second 6-month test period, when Group A was taken off the lysine supplementation, there was a significant increase in the frequency of lesions (p < 0.01). Conversely, patients in Group B, in which lysine was now added, reported a significant decrease in lesion recurrence (p < 0.01).

In light of the significant differences found between the groups at 12 months, a further examination of the data was conducted to determine if there was any correlation between a patient's serum levels of lysine and the number of lesion recurrences. Results for this sample population indicated that when a person's serum lysine concentration exceeded 165 nmol/ml, there was also a corresponding significant decrease in recurrent lesions (p < 0.05). The results obtained herein tended to corroborate previous in vitro data indicating that lysine is a herpes virus inhibitor. If, 1,000 mg of L-lysine is taken daily over a 6-months period, and if the blood levels exceed 165 nmol/ ml, the number of lesion recurrences is significantly reduced in most cases. When lysine supplements are discontinued, lesion frequency significantly increases again if serum levels fall below 165 nmol/ml. In conclusion, prophylactic lysine may be useful in managing selected cases of recurrent HSV labialis if serum lysine levels can be maintained at adequate concentrations.

Hence, this study explains why some reports indicate that oral L-lysine administration is effective in the treatment/ recurrence of herpes viral infections, while other reports have not found a benefit. Namely, it's not enough to consume a specific dose of lysine. Rather it is necessary that blood levels of lysine be made to exceed 165 nmol/ml in order to see clinical benefits. Consequently, for some individuals, 1,000 mg of lysine daily may provide the desired prophylactic effect, while others may require a higher dose such as 3,000 mg daily.

Lysine and herpes study 2
In this study, researchers also evaluated the preventive effect of L-lysine monohydrochloride 1000 mg daily on recurrent HSV labialis in 65 patients in a double-blind, placebo-controlled, crossover study.8 After 12 weeks of lysine treatment the patients shifted to placebo treatment for a similar period. On the whole, lysine had no effect on the recurrence rate of herpes simplex. However, significantly more patients were recurrence-free during lysine than during placebo treatment (p = 0.05), suggesting that certain patients may benefit from prophylactic lysine administration.

Lysine And Herpes Study 3
In another double-blind, placebo-controlled, multicenter trial,9 subjects were given oral L-lysine monohydrochloride—this time with 3,000 mg—for the prevention and treatment of recurrent HSV infection. The treatment group was given L-lysine monohydrochloride tablets (1,000 mg L-lysine per dose) three times a day for six months. A total of 27 (six male and 21 female) subjects on L-lysine and 25 (6 male and 19 female) subjects on placebo completed the trial. The L-lysine treatment group had an average of 2.4 (p < 0.05) less HSV infections, symptoms were significantly (p < 0.05) diminished in severity and healing time was significantly reduced (p < 0.05). The researchers concluded that L-lysine appears to be an effective agent for reduction of occurrence, severity and healing time for recurrent HSV infection.

Lysine and herpes study 4
In a prospective, randomized, double-blind, placebo-controlled, cross-over study10 of forty-one patients, researchers found that oral ingestion of 1,248 mg a day of L-lysine monohydrochloride shows evidence of decreasing the recurrence rate of herpes simplex attacks in non-immunocompromised hosts. A dose of 624 mg a day was not effective. L-lysine may also be capable of decreasing the severity of symptoms associated with recurrences.

Lysine and herpes study 5
In a fifth clinical study,11 45 patients with frequently recurring herpes infection were given 312–1,200 mg of lysine daily in single or multiple doses. The clinical results demonstrated a beneficial effect from supplementary lysine in accelerating recovery from herpes simplex infection and suppressing recurrence. Tissue culture studies have demonstrated an enhancing effect on viral replication when the amino acid ratio of arginine to lysine favors arginine. The opposite, preponderance of lysine to arginine, suppresses viral replication and inhibits cytopathogenicity of herpes simplex virus.

Lysine and herpes study 6
To test the effect of lysine supplementation on herpes infection, 1543 subjects were surveyed12 by questionnaire after a sixmonth trial period. The study included subjects with cold sores, canker sores, and genital herpes. Of these, 54 percent had been diagnosed and treated by a physician. The results showed that the average dosage used was 936 mg of lysine daily. Eighty-four per cent of those surveyed said that lysine supplementation prevented recurrence or decreased the frequency of herpes infection. Whereas 79 percent described their symptoms as severe or intolerable without lysine, only 8 percent used these terms when taking lysine. Without lysine, 90 percent indicated that healing took six to 15 days, but with lysine 83 percent stated that lesions healed in five days or less. Overall, 88 percent considered supplemental lysine an effective form of treatment for herpes infection.

L-lysine, an essential amino acid, has important roles to play in human biology. With regard to human clinical research with supplemental L-lysine, perhaps the most significant contribution that this amino acid has made is in managing HSV outbreaks. Multiple studies have indicated that L-lysine supplementation is effective in reducing the frequency of HSV outbreaks and speeding up their healing time when an outbreak does occur. For most people with the HSV, supplementation with 1,000 mg/day is recommended for preventive purposes. Once an outbreak occurs, however, intake should be increased to 3,000 mg/day.


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Gene Bruno, MS, MHS

Gene Bruno is the Dean of Academics and Professor of Dietary Supplement Science for Huntington College of Health Sciences (a nationally accredited distance learning college offering diplomas and degrees in nutrition and other health science related subjects. Gene has two undergraduate Diplomas in Nutrition, a Bachelor’s in Nutrition, a Master’s in Nutrition, a Graduate Diploma in Herbal Medicine, and a Master’s in Herbal Medicine. As a 32 year veteran of the Dietary Supplement industry, Gene has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines, and peer-reviewed publications. Gene's latest book, A Guide to Complimentary Treatments for Diabetes, is available on Amazon.com, and other fine retailers.

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