Introduction
Herpes simplex is a common viral infection of the skin or mucous membranes. The lesions caused by this infection are often painful, burning, or pruritic, and tend to recur in most patients.
Shortterm treatment with acyclovir can accelerate the healing of an acute outbreak, and continuous acyclovir therapy is often prescribed for people with frequent recurrences.
While this drug can reduce the recurrence rate by 60-90 percent, it can also cause a wide array of side effects, including renal failure, hepatitis, and anaphylaxis. Safe and effective alternatives are therefore needed.
There is evidence that certain dietary modifications and natural substances may be useful for treating active Herpes simplex lesions or preventing recurrences.
Herpes simplex virus (HSV) infections of the skin are caused by one of two viruses (HSV-1 or HSV-2). Cutaneous Herpes simplex is characterized by painful, burning, or pruritic clusters of vesicles on the lips, oral mucous membranes, genital region, or other areas of the body. HSV infection of the eye results in keratoconjunctivitis, a serious condition that sometimes leads to corneal blindness. HSV may also cause encephalitis or other systemic infections, particularly in immunocompromised patients.
HSV
Herpes simplex 1 and 2 are members of the herpes virus family, Herpesviridae, that infect humans.
Both HSV-1 and HSV-2 (which produces most genital herpes) are ubiquitous and contagious.
Symptoms of herpes simplex virus infection include watery blisters in the skin or mucous membranes of the mouth, lips or genitals.
As neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by becoming latent and hiding from the immune system in the cell bodies of neurons.
After a primary infection, the virus travels to a nerve cell ganglion where it persists in a dormant phase. Various factors such as sun exposure, abrasion of the skin, fever, stress, fatigue, or menstruation can reactivate the virus, resulting in a recurrence at the site of the original infection. Recurrences are common, particularly in the case of genital infections.
Animal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large double-stranded, linear DNA genome encased within an icosahedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument.
While Herpes simplex can occur in seemingly healthy people, patients with cancer, acquired immunodeficiency syndrome (AIDS), and other diseases associated with impaired immune function are especially prone to such infections. Immune system deficiencies that are more subtle, but not necessarily associated with a serious disease, might also increase the risk of experiencing Herpes simplex infections.
For that reason, a comprehensive prevention and treatment plan should include measures designed to enhance immune function.
Lysine
Lysine is an amino-acid with the chemical formula HO2CCH(CH2)4NH2. It is an essential amino acid for humans.
Lysine is a base, as are arginine and histidine. The ε-amino group often participates in hydrogen bonding and as a general base in catalysis. (The ε-amino group (NH 3 +) is attached to the fifth carbon beginning from the α-carbon, which is attached to the carboxyl (C=OOH) group.)
As an essential amino-acid, lysine is not synthesized in animals, hence it must be ingested as lysine or lysine-containing proteins. In plants and bacteria, it is synthesized from aspartic acid.
L-Lysine is a necessary building block for all protein in the body. L-Lysine plays a major role in calcium absorption; building muscle protein; recovering from surgery or sports injuries; and the body's production of hormones, enzymes, and antibodies.
The nutritional requirement per day, in milligrams of lysine per kilogram of body weight, is: infants (3–4 months) 103, children (2 years) 64, older children (10–12 years) 60 to 44. For a 70 kg adult, 12 milligrams of lysine per kilogram of body weight.
Good sources of lysine are high-protein foods such as eggs, meat (specifically red meat, lamb, pork).
Foods containing significant amounts of lysine include:
- Catfish, channel, farmed, raw: 9.19% of the protein is lysine.
- Chicken, roasting, meat and skin, cooked, roasted: 8.11% of the protein is lysine.
- Beef, ground, 90% lean/10% fat, cooked: 8.31% of the protein is lysine.
- Soybean, mature seeds, raw: 7.42% of the protein is lysine.
- Soybean, mature seeds, sprouts: 5.74% of the protein is lysine (sprouting decreases the lysine content).
- Winged Bean (aka Goa Bean or Asparagus Pea), mature seeds, raw: 7.20% of the protein is lysine.
- Lentil, pink, raw: 6.97% of the protein is lysine.
- Lentil, sprouts, raw: 7.95% of the protein is lysine (sprouting increases the lysine content).
- Parmesan cheese, grated: 7.75% of the protein is lysine.
- Azuki bean (adzuki beans), mature seeds, raw: 7.53% of the protein is lysine.
- Milk, non-fat: 7.48% of the protein is lysine.
- Egg (food), whole, raw: 7.27% of the protein is lysine.
- Pea, split, mature seeds, raw: 7.22% of the protein is lysine.
- Kidney Bean, mature seeds, raw: 6.87% of the protein is lysine.
- Chickpea, (garbanzo beans, Bengal gram), mature seeds, raw: 6.69% of the protein is lysine.
- Navy Bean, mature seeds, raw: 5.73% of the protein is lysine.
- Amaranth, grain, uncooked: 5.17% of the protein is lysine.
- Quinoa: 5% of the protein is lysine
Lysine and Arginine role in HSV replication
The proteins synthesized by HSV contain more arginine and less lysine than proteins synthesized by host cells, and arginine is required for HSV replication.
Arginine is essential for the replication of herpes simplex virus.
The absence of arginine prevent the formation of virions.
The synthesis of enzymes necessary for the synthesis of viral DNA is not affected in the absence of arginine. Thus, the inhibition of virus formation does not occur at the level of viral DNA.
Arginine is incorporated in the coat proteins of mature herpes virions. This indicates that arginine is essential for the synthesis of the viral coat proteins and is incorporated into them. When arginine is absent, the viral messenger RNA is present in the cytoplasm, probably in association with the cytoplasmic ribosomes, but lacks the ability to continue protein synthesis. Arginine is needed for the synthesis of coat proteins of herpes simplex viruses.
Genetic information required for the early enzymes necessary for the synthesis of DNA polymerase, as well as the inhibitors of cellular nucleic acid synthesis, are not affected in the absence of arginine. Arginine is necessary for the expression of the late viral functions concerned with the synthesis of viral coat proteins.
Thus in the absence of arginine, the viral DNA molecules remain in the infected nuclei.
Lysine's role
Lysine appears to antagonize arginine by several mechanisms: it functions as an antimetabolite of arginine; it competes with arginine for reabsorption at the renal tubule, thereby increasing arginine excretion; it competes with arginine for intestinal absorption; it induces the enzyme arginase, resulting in degradation of arginine; and it competes with arginine for transport into cells.
In tissue culture, lysine antagonize the growth-promoting action of arginine on HSV.
These observations raise the possibility that increasing either absolute lysine intake or the ratio of lysine-to-arginine intake would be of value for the prevention and treatment of Herpes simplex infections.
Lysine and Arginine Food Chart
Forty-five patients with frequently recurring Herpes simplex infections received lysine (usually 312-1,200 mg per day) for periods of two months to three years. Foods high in arginine were restricted. Lysine treatment appeared to reduce the frequency of recurrences. When lysine was discontinued, lesions usually recurred within 1-4 weeks.
Nine patients with recurrent Herpes simplex infections received 500 mg per day lysine hydrochloride and reduced their intake of high-arginine foods. In comparison with past experiences, recurrences were less frequent, less severe, and of shorter duration. Lesion formation was invariably associated with high arginine intake 12-36 hours previously.
Forty-one patients with recurrent Herpes simplex infections were randomly assigned to receive, in double-blind fashion, lysine hydrochloride (624 or 1,248 mg per day) or placebo for 24 weeks, and then the alternate treatment for an additional 24 weeks. All patients were prescribed a diet high in lysine and low in arginine. In the high-dose group, there were significantly fewer recurrences during the lysine period than during the placebo period. The lower dose of lysine was ineffective.
One hundred-fourteen patients with recurrent orofacial or genital herpes, or both, were randomly assigned to receive, in double-blind fashion, 1 g lysine hydrochloride three times daily or placebo for six months; 52 patients completed the trial. Among those who completed the trial, the proportion of patients who reported the treatment to be effective or very effective was 74 percent in the lysine group and 28 percent in the placebo group (p<0.01). Lysine was significantly more effective than placebo in terms of frequency and severity of lesions and healing time.
These studies suggest that lysine supplementation reduces the recurrence rate of Herpes simplex infections.
The effectiveness of lysine may vary according to the dosage used, the lysine and arginine content of the diet, and the efficiency of lysine absorption, which appears to vary from person to person.
The optimal lysine dose for Herpes simplex prophylaxis is not known, but a reasonable dosage range is 500-3,000 mg daily.
Doses up to 6 g per day are said to be safe, but long-term toxicity studies have not been conducted in humans.
By comparison, the estimated dietary lysine requirement for a 70 kg human is in the range of 800-3,000 mg per day.
Lysine intake can be increased by increasing consumption of lysine-rich foods, such as legumes and animal proteins, and reducing intake of lysine-poor foods such as grains and refined sugars.
Food preparation methods that reduce the amount of bioavailable lysine include heating of protein-containing foods in the presence of a reducing sugar (e.g., fructose, glucose,or lactose), heating protein-containing foods in the presence of sucrose and yeast, or cooking at high temperatures.
Short-term administration of 1-3 g lysine daily has been found to reduce the duration of attacks, with higher doses being more effective than lower doses.
Some patients report that eating arginine-rich foods such as chocolate, nuts, and seeds causes them to experience herpes outbreaks, but the importance of dietary arginine as a causative factor has not been investigated scientifically.
Conclusions
In summary, these studies suggest that lysine supplementation may be helpful in reducing the rate of recurrence for HSV infections, especially when accompanied by a high-lysine, low-arginine diet.
