Treating Cat Flu – Lysine 100

Lysine 100 is a nutritional supplement for cats which has been specifically developed and formulated for cats infected with or at risk from infection with feline herpes virus, the causative agent for feline rhinotracheitis (cat flu). Lysine 100 impairs the replication of feline herpes virus and contains components which help to boost the innate and acquired immune system.

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Feline Herpes Virus

Feline herpes virus 1 (FHV-1) is one of the most common infectious diseases amongst cats and causes the clinical symptoms associated with feline rhinotracheitis or cat flu. FHV-1 infection is widespread and it is estimated that up to 97% of the feline population are exposed to FHV-1 (Maggs, 1999). Spread between cats is by direct contact and virus is shed from ocular and nasal secretions. Following the acute phase of infection up to 80% of cats may become persistently or latently infected. The virus frequently remains latent in the nerve tissue in the head (trigeminal ganglia), from where it can reactivate. Of the persistently/latently infected cats, 45% will shed FHV-1 virus spontaneously or following stressful periods and 70% will shed FHV-1 virus following corticosteroid administration (Gaskell, 1977). Consequently, control of FHV-1 infection in multi-cat households and cat shelters can be extremely challenging.

Clinical signs associated with FHV-1 infection can be considered in two broad categories:

Primary infection – often affecting young immunologically naïve kittens is characterised by coughing, sneezing and nasal discharge. Cats may develop a very high fever and many are anorexic, in part because they are unable to smell their food through nasal discharges and therefore food is not palatable. FHV-1 has a predilection for the corneal epithelium and ocular signs include, blepharospasm (squinting), reddened and swollen conjunctiva (often with ulcers) and serous ocular discharge that becomes purulent after 5-7 days of infection. Dendritic corneal ulcers are pathognomonic for a diagnosis of FHV-1 infection. Morbidity is high and mortality generally low, however kittens can become very depressed and anorexic.

Recrudescent infections –aren’t very common despite the frequency with which latently infected cats undergo viral reactivation following stress or corticosteroid administration. Signs of recrudescent infection include low grade chronic conjunctivitis and chronic inflammatory changes in the cornea resulting from viral replication. In many cases latently infected cats in which FHV-1 is re-activated and being shed may be asymptomatic which makes control of viral spread extremely challenging.

Given the various clinical syndromes associated with FHV-1 infection that can be seen, the greatest challenge in managing FHV-1 infection is identifying clinically asymptomatic cats that are actively shedding FHV-1 virus.  In practical terms, screening cats to test for viral shedding is not very practical or economically feasible, therefore it is usually assumed that any cat experiencing stressful circumstances can be shedding FHV-1 and act as a source of infection to others. Cats in close contact, such as those in shelters and unvaccinated cats are most at risk from infection. Therefore any nutritional support that can help to reduce viral shedding during periods of stress if extremely valuable in reducing in the incidence and severity of disease.

Treatment of FHV-1 infection is primarily based around good nursing, provision of highly palatable food (often warmed) and intravenous fluids if cats and kittens become dehydrated. Antibiotics are required in the presence of secondary bacterial infection. There are no specific FHV-1 treatments licensed for use in cats however, some human antivirals such as famciclovir and triflourothymidine have been used with reasonable success in cats but the cost and availability of such treatments is often prohibitive (Gould, 2011).

Vaccines are available that are very effective at reducing the duration and severity of clinical signs associated with FHV-1 infection, however vaccination does not stop infection if a cat is exposed to the FHV-1 virus. Young kittens are extremely susceptible to FHV-1 infection. Passive protection against FHV-1 is provided by maternal antibodies in the first few weeks of life. However as maternal antibodies start to decline kittens are at risk of developing severe clinical signs associated with infection, especially if the kitten has not commenced a vaccination programme against FHV-1. The decline in passive immunity is usually greatest in kittens 2-4 months of age, often prior to vaccination but during the period of re-homing, therefore kittens are stressed and extremely vulnerable to infection and clinical disease. Consequently kittens of 2-6 months of age and unvaccinated naïve cats are most frequently presented with feline rhinotracheitis.

LYSINE 100 is a nutritional supplement specifically developed and formulated by Mervue Laboratories to support cats experiencing FHV-1 infection (rhinotracheitis) and to reduce shedding from cats with latent FHV-1 infection.

LYSINE 100 contains the lysine, Echinacea angustifolia and seaweed Laminaria hyperborea.

L-lysine

Lysine inhibits the replication of many viruses including FHV-1. The mechanism of action is not entirely clear however it is believed that lysine exerts its antiviral effect by the antagonism of arginine. Arginine exerts a substantial growth promoting effect on FHV-1. In the presence of small amounts of arginine, lysine supplementation reduced viral replication by about 50% (Maggs, 2011; Maggs, 2000).

One study evaluated the effects of L-lysine supplementation on conjunctivitis caused by feline herpes virus (Stiles, 2002). Four cats were administered lysine twice daily and compared with four cats that were administered placebo (lactulose). Lysine/placebo administration commenced six hours prior to the inoculation of the left conjunctival sac with FHV-1. Cats were evaluated and given clinical scores once daily for 21 days following inoculation. Plasma lysine concentration was measured prior to the study and on days 3, 14 and 22.

Lysine supplementation was well tolerated in cats. Cats that received lysine had less severe conjunctivitis than those that received placebo. Plasma lysine concentrations were significantly higher in cats receiving lysine compared with controls and plasma arginine concentrations did not differ between groups.

In another study (Maggs, 2003) reported the effect of orally administered L-lysine on clinical signs of feline herpes virus type 1 (FHV-1) infection and ocular shedding of FHV-1 in latently infected cats. Fourteen FHV-1 naïve adult cats were inoculated with FHV-1 and five months later, when they were assumed to be latently infected, they were rehoused and assigned to receive either lysine supplementation in food once daily for 30 days or no lysine supplementation in food. Viral shedding following the stress of rehousing was monitored for 30 days. Fifteen days following rehousing cats were administered corticosteroids also to reactivate latent infection. As expected these cats were normal latently infected cats so little or no clinical disease was seen during the month long study.  Lysine administration was associated with a significant reduction in viral shedding compared with cats that received placebo after rehousing but not following corticosteroid administration. Cats that received lysine supplementation had significantly greater plasma lysine concentrations than unsupplemented cats. Arginine levels remained unaltered and no adverse clinical signs were observed.  This study concluded that lysine supplementation could reduce ocular shedding in latently infected cats following rehousing.

In another study (Maggs, 2007) cats with enzootic upper respiratory tract disease were fed a diet supplemented with lysine for 52 days while being subjected to rehousing stress, which is known to cause viral reactivation. Food (and therefore lysine intake) decreased coincident with the peak viral shedding and disease. Consequently supplemented cats had more severe signs and shedding was greatest in supplemented cats. These differences were most notable among groups of entire male cats where fighting and aggression was associated with rehousing. Opinion leaders in the field of FHV-1 agree that more research needs to be performed and clinical trials need to be undertaken to evaluate the efficacy of lysine in the management of upper respiratory tract disease in cats, specifically FHV-1. However authors (Maggs, 2011) recommend the administration of lysine to cats at the time of high stress that may lead to reactivation of latent infection, recrudescent disease resulting from viral reactivation, and to cats with active disease and those with frequent recurrence of symptoms.

Cats are exquisitely sensitive to arginine deficiency (Morris, 1978) consequently supplementation with L-lysine must not antagonise or reduce arginine levels. In one study (Fascetti, 2004) cats were supplemented with 11, 36, 61 86, 111 or 131g of lysine/kg of diet for 14 days. There was a significant effect of treatment on mean plasma lysine concentrations (P< 0.05) but not on arginine concentrations.  A decreased feed intake was noted for cats receiving 111 or 131g lysine/kg feed and this was attributed to lysine toxicity. On the basis that a cat would eat about 100g of food per/day 131g of lysine/kg food equates to 13,100mg/100g feed. Decreased feed intake was not noticed in cats receiving concentrations of 86g lysine/kg feed or less. This study demonstrated that lysine supplementation did not cause arginine depletion or deficiency and that supplementation of lysine at 111 or 136g/kg feed resulted in toxicity.

In the study conducted by Maggs 2007, he observed that mean plasma arginine concentration was lower and plasma lysine concentration was higher in supplemented cats. Mean plasma arginine concentration declined throughout the study in both dietary groups. Clinical signs of arginine deficiency were not observed. On this basis the author recommends supplementation with a bolus twice daily in order to control the amount of lysine administered and advises that unlike the situation in humans, arginine intake should not be restricted in cats.

LYSINE 100 contains L-lysine at a concentration of 250mg/ml which is well below levels which may cause toxicity.

Echinacea angustifolia

Echinacea is a plant native to the USA and has been used for centuries as an anti-inflammatory and immune stimulant. There are three species of echinacea that are of interest E. angustifolia, E. purpurea and E.  pallida. The spectrum of activity varies from one species to the other. The active components of echinacea vary slightly according to species and include caffeic acid derivatives (primarily echinocoside), flavonoids, essential oils, polyacetylenes, alkylamides, and polysaccharides (derived from the root). No single component has been found to be primarily responsible for echinacea’s effects but rather a combination of components.

Alcohol extracts of echinacea have been demonstrated to stimulate the immune system though increased white cell production and phagocytic activity, increased NK cell activity, and increased antibody-dependent cellular cytotoxicity, mediated by tumour necrosis factor-alpha (TNF- α). (Melchart, 1995; Morazzoni, 2005).

Echinacea angustifolia also appears to have a mild antibiotic effect, probably attributable to its caffeic acid constituent, which is capable of directly inhibiting Staphylococcus aureus. In addition, certain polyacetylene constituents of Echinacea have been found to be bacteriostatic against E.coli and Pseudomonas aeruginosa (Schar,1999). Caffeic acid derivatives, high molecular weight polysaccharides, flavonoids, and essential oils found in echinacea all possess anti-inflammatory properties. Animal studies using E.  angustifolia have indicated the polysaccharide constituents of the extracts possess significant anti-inflammatory activity in attenuating paw and ear oedema when applied topically to the skin of mice and rats (Tragni, 1985; Tubaro, 1987; Tragni, 1988).

Echinacea has been used in people with the common cold for many years. Shah (2007) performed a meta-analysis of 14 randomised, placebo controlled studies that evaluated the use of echinacea in reducing the incidence of the cold (n=7), reducing the duration of the cold (n=5) and reducing the incidence and duration of the common cold (n=2) in humans. Five studies used E. angustifolia alone or in combination with E. pupurea, six studies used E. pupurea, one study used E. pallida and in one study the echinacea species evaluated was not specified. 1356 study participants were evaluated for the incidence of cold and 1630 for the duration. Meta-analysis showed that echinacea decreased the odds of a patient contracting a cold by 58% (p < 0.001) and decreased the duration of a cold by 1.4 days (p = 0.01).

Few masked placebo control studies have been conducted in animals, however those that have indicate that Echinacea angustifolia has a similar immune modulating effects in animals (O’Neill, 2002; Zhai, 2007; Hua, 2010). The use of echinacea as an immune modulator in cats is widely reported (Wynn, 2007’ Zucker, 2010); however, no masked placebo controlled studies have been published in cats.

Seaweed – Laminaria hyperborea

L. hyperborea is large brown seaweed native to north east Atlantic coasts. The rods are typically used for the manufacture of high grade alginates used as emulsifiers and gelling agents in the food industry (www.seaweedindustry.com).  L. hyperborea is also rich in laminarins and mannitol which play important roles as immune modulators in many species. Laminarins are composed of beta 1-3,beta 1-6-glucan (a sulphated polysaccharide) which in addition to demonstrating probiotic activity, b-glucans from laminarins also have the ability to  increase host immune defence by activating complement system, enhancing macrophages and natural killer cell function (Vetvicka, 2004; Vetvicka, 2007, Vetvicka, 2011). The relatively recent discovery of the immune modulating effects of β-glucans means that the precise mechanism by which they exert their effect on the immune system is unclear and clinical evidence of their use in cats is lacking.  The potential use of L. hyperboea as a functional food and the extent of the bioactivity this seaweed, have not been fully evaluated, however reports on work to date show enormous potential for their use in modulating immunity and as anti-oxidants (Holdt, 2011; Demais , 2013). Recent studies have shown that the bioactive components of brown seaweed such as L. hyperborea can positively affect the health and wellbeing improving intestinal mucosa metabolism, and have anti-microbial, anti-inflammatory and immunomodulatory effect in pigs. Additionally, in pigs laminarin exerts an anti-inflammatory activity, reducing the pro-inflammatory cytokine response and might positively affect immune system, enhancing immunoglobulin production. (Reilly, 2008; Leonard, 2010; Mukhopadhya, 2012; Maghin, 2014).

LYSINE 100 has been specifically developed by Mervue Laboratories to address the nutritional requirements of suffering from cat flu and cats exposed to or at risk of exposure to feline herpes virus (FHV-1) and the development of cat flu. LYSINE 100 is the only nutritional supplement which contains Echinacea angustifolia and the seaweed Laminaria hyperborean, specifically harvested from north Atlantic coasts, in addition to lysine. The addition of Echinacea and seaweed provides support to the immune system through the addition of Echinacea and seaweed.

Dosage and Administration

Lysine 100 should be administered to cats and kittens during stressful periods such a rehoming, placement in a cattery or animal shelter, or when introducing new animals or family members to the house hold. Lysine 100 should be administered to all cats with signs of active infection with FHV-1 or cat flu.

For adult cats 1-2ml should be administered orally twice daily and for kittens 1ml should be administered orally twice daily.

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References

Demais, (2013) http://www.allaboutfeed.net/Nutrition/Research/2013/9/Seaweed-A-new-option-for-immune-stimulation-1363529W/)

Fascetti, A.J., Maggs, D.J.,  Kanchuk, M.L.,  Clarke, H.E. and Rogers, Q.R. (2004) Excess Dietary Lysine Does Not Cause Lysine-Arginine Antagonism in Adult Cats J. Nutr. 134: 2042S–2045S.

Leonard, S.G., Sweeney, T., Bahar, B., Lynch, B.P. and  O’Doherty, J.V. (2010) The effects of maternal dietary supplementation with seaweed extract and fish oil on the humoral immune response and performance of suckling piglets. Livestock Science 134(1-3): 211-214.

Gaskell, R.M. and Povey, R.C. (1977). Experimental induction of feline viral rhinotracheitis virus re-excretion in FVR-recovered cats. The Veterinary Record 100(7):128-133

Gould, D. (2011). Feline Herpes Virus -1 Ocular manifestations, diagnosis and treatment options. Journal of Feline Medicine and Surgery 13, 333-346

Holdt, S.L. and Kraan, S (2011) Bioactive compounds in seaweed: functional food applications and legislation. J. Appl Phycol 23:543–597

Hua, W.U., Nardone,  A. and Lacetera, N  (2010) Effects of the standardized purified dry extract Polinacea~(TM) from Echinacea angustifolia on immunity function of peripheral blood mononuclear cells of dairy heifers Chinese Veterinary Science 2010-05

Maggs, D.J., Lappin, M.R., Reif, J.S., Collins J.K., Carman, J., Dawson D.A. and Bruns, C. (1999) Evaluation of serologic and viral detection methods for diagnosing feline herpesvirus-1 infection in cats with acute respiratory tract or chronic ocular disease. Journal of the American Veterinary Medical Association 214(4):502-507.

Maggs, D.J., Collins, B.K., Thorne, J.G. and Nasisse, M.P. (2000) Effects of L-lysine and l-arginine on in vitro replication of feline herpes virus type – 1. American Journal of veterinary research 61; 1474-1478.

Maggs, D.J., Nasisse, M.P. and Kass, P.H. (2003) Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus. American Journal of Veterinary Research 64, 37- 42.

Maggs, D.J. (2011) Proceedings from International Society Feline Medicine, Vienna, 2011 p 43-46.

Maghin, F., Ratti, S. and Corino, C. (2014). Biological Functions and Health Promoting Effects of Brown Seaweeds in Swine Nutrition. J Dairy Vet Anim Res 1(1): 00005

Melchart, D., Linde, K., Worku, F., Sarkady, L., Holzmann, M.,  Jurcic, K.  and Wagner, H.( 1995) Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. J Altern Complement Med 1:145-160.

Morazzoni, P., Cristoni, A., Di Pierro, F., Avanzini, C., Ravarino, D., Stornello, S., Zucca, M. and  Musso, T. (2005)  In vitro and in vivo immune stimulating effects of a new standardized Echinacea angustifolia root extract (Polinacea) Fitoterapia. 76:401–411

Morris, J. G. & Rogers, Q. R. (1978) Ammonia intoxication in the near adult cat as a result of dietary deficiency of arginine. Science 199: 431–432

Mukhopadhya, A., O’Doherty, J.V., Smith, A., Bahar, B. and Sweeney, T. (2012).The microbiological and immunomodulatory effects of spray-dried versus wet dietary supplementation of seaweed extract in the pig gastrointestinal tract. J Anim Sci 90(4): 28-30.

O’Neill, W., McKee, S. and Clarke, A.F. (2002) Immunological and haematinic consequences of feeding a standardised Echinacea (Echinacea angustifolia) extract to healthy horses. Equine Vet J. 34:222–227

Reilly, P., Sweeney, T., Pierce, K.M., Callan, J.J. and Julka, A. (2008) The effect of seaweed extract inclusion on gut health and immune status of the weaned pig. Animal 2(10): 1465-1473.

Schar, D. (1999) Echinacea, The Plant That Boosts Your Immune System. London: Souvenir Press Ltd.

Shah, S.A., Sander, S., White C.M., Rinaldi, M. and Coleman, C.I. (2007) Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis. Lancet Infect Dis 7:473–80

Stiles, J., Townsend, W.M., Rogers, Q. R. and Krohne, S.G. (2002) Effect of oral administration of L-lysine on conjunctivitis caused by feline herpes virus in cats. American Journal of Veterinary Research 63; 99-103

Tragni, E., Tubaro, A., Melis, S. and Galli, C.L. (1985) Evidence from two classic irritation tests for an anti-inflammatory action of a natural extract, Echinacina B. Food Chem Toxicol 23:317-319.

Tragni, E., Galli, C.L., Tubaro, A., Del Negro, P. and Della Loggia, R.( 1988)  Anti-inflammatory activity of Echinacea angustifolia fractions separated on the basis of molecular weight. Pharmacol Res Commun 20:S87-S90.

Tubaro, A., Tragni, E., Del Negro, P., Galli, C.L. and Della Loggia, R.  (1987) Anti-inflammatory activity of a polysaccharide fraction of Echinacea angustifolia. J Pharm Pharmacol 39:567-569.

Vetvicka, V. and Yvin, J-C.  (2004) Effects of marine β−1,3 glucan on immune reactions International Immunopharmacology Volume 4, Issue 6, Pages 721–730

Vetvicka, V., Dvorak, B., Vetvickova, J., Richter, J., Krizan, J., Sima, P. and  Yvin, J.C.( 2007) Orally administered marine (1–>3)-beta-D-glucan Phycarine stimulates both humoral and cellular immunity. Int J Biol Macromol. 40(4):291-8.

Vetvicka, V. (2011) Glucan-immunostimulant, adjuvant, potential drug. World J Clin Oncol. 2(2): 115–119.

Wynn, S.G. and Fougère, B.J.  (2007) Eds Veterinary Herbal Medicine: A Systems-Based Approach (Mosby Elsevier, 2007) p 375,

Zhai, Z., Liu, Y., Wu, L., Senchina, D.S., Wurtele, E.S.,  Murphy, P.A.,  Kohut, M.L. and Cunnick, J.E. (2007). Enhancement of Innate and Adaptive Immune Functions by Multiple Echinacea Species. J Med Food. 10(3): 423–434.

Zucker, M. (2010) The Veterinarians’ Guide to Natural Remedies for Cats: Safe and Effective Alternative Treatments and Healing Techniques from the Nations Top Holistic Veterinarians Crown Publishing Group, 11 Aug 2010