Originally published in the January 2016 issue of Veterinary Practice News. Two virologists are urging veterinarians to immediately stop lysine supplementation in cats suffering from feline herpesvirus-1 because they say the therapy is ineffective. Their conclusion, published Nov. 16 in the online journal BMC Veterinary Research, drew a measured response from two experts in the field who said anecdotal reports of successful lysine use leave open the possibility that the therapy does work. Husband-and-wife virologists Sebastiaan Bol, MS, Ph.D., and Evelien M. Bunnik, MS, Ph.D., reached the conclusion after conducting a systematic review—essentially a study of previous lysine studies. Bol, who like his wife is employed at the University of California, Riverside, began the review after their 8-year-old cat, Aguereberry, was diagnosed with FHV-1, a highly contagious infection of the upper respiratory system. Their veterinarian recommended lysine nutritional supplements to treat and manage the disease. “With my background in biology and nutrition, I was very suspicious, and I started clicking—doing some searches online—and I was not very convinced,” Bol said. “So I started looking into more and more of the publications, and it was really shocking to see that there’s absolutely no evidence [that lysine is effective in cats].” Bol and Bunnik’s research article looked at seven studies of lysine and FHV-1—two in vitro studies and five involving cats—as well as 10 studies of human herpesvirus-1. Examining papers dating to the 1970s, Bol found that the lysine recommendation originated with a human study. The veterinary studies offered no scientific proof of lysine’s efficacy in cats, he said. Those papers, he discovered, all stopped short of advocating an end to lysine supplementation in FHV-1 cases. What Bol didn’t know at first was how often veterinarians prescribed lysine to FHV-1 cats. Did Aguereberry’s doctor follow the crowd or was she an exception? “So I did a survey and found that over 90 percent of the veterinarians are recommending it,” Bol said. He asked 68 cat hospitals spread across the United States, Australia and the United Kingdom whether they prescribed lysine. Of the 23 hospitals that replied, 21 of them, or 91 percent, did. FHV researcher David Maggs, BVSc, Dipl. ACVO, a professor of veterinary ophthalmology at the University of California, Davis, School of Veterinary Medicine, complimented Bol for that additional research and for Bol and Bunnik’s overall work. “The authors have done a tremendous review of the literature,” Dr. Maggs said. “It seems to be very comprehensive, very complete. They turned up one or two articles that I wasn’t aware of, and then they certainly turned up all the articles that I am aware of.” Five of the seven veterinary studies were co-authored by Maggs. But none of Maggs’ studies reached the same conclusion as Bol’s: a recommended “immediate stop of lysine supplementation because of the complete lack of any scientific evidence for its efficacy.” “I was surprised by the conclusion,” Maggs said. “The conclusion seems to be, at least for science, very boldly stated. Scientists are well known for not really stating things very boldly, and that’s one of the criticisms we get. “To say that there was no evidence strikes me as a little bit odd because they point out in their own manuscript that there has been at least one study that suggested a benefit.” Bol responded that of the clinical feline studies he examined, “maybe one study” found something, “but that was only after they very narrowly looked at one specific thing.” He also noted that the clinical studies had small sample sizes and that one study showing some effectiveness “only compared four cats to four other cats.” Anecdotal evidence should not be discarded, Maggs said. “I have clients who tell me that every time they take the cat off lysine the problem returns,” he said. “Now that’s totally anecdotal evidence, but … I’m using it as an example that we should not recommend a blanket immediate cessation of therapy in all cats. “There are clearly some cats who respond well in a disease that sometimes has very subtle signs,” he added. “Maybe it’s just as well to leave those cats on lysine if the clients genuinely feel that it’s making a difference.” Maggs’ comment was supported by Texas feline practitioner Gary D. Norsworthy, DVM, Dipl. ABVP, who co-edited “The Feline Patient, 4th Edition.” “[Lysine] is used frequently by many of my clients at the recommendation of Dr. Google,” Dr. Norsworthy said. “Some cats have a very convincing response in spite of what the science says. “I do not recommend it as a first-line treatment for feline herpesvirus-1,” he said, “but I also do not discourage it. Cats are not very conversant with the literature. Its use should be based on response, whether scientific or not.” The textbook “The Feline Patient” acknowledges some uncertainty about lysine. One part states: “For several years, lysine (250-500 mg/cat q12h PO) has been thought to have activity against the acute and chronic phases of FHV-1 infection. However, two recent studies failed to demonstrate efficacy of lysine against upper respiratory infections in groups of shelter cats. In one of these studies, lysine therapy was associated with worsening of clinical signs and increased detection of FHV-1 viral DNA in oropharyngeal and conjunctiva mucosal samples. As such, use of lysine for treating FVH-1 must be reconsidered.” Bol suggested that practitioners swayed by anecdotal evidence should consider another possible reason for improvements in FHV cats: the passage of time. “When people bring their cats to the clinic … the symptoms are pretty severe and [veterinarians] prescribe the lysine,” Bol said. “Over time, with or without treatment, symptoms will improve. When you give the cat lysine, symptoms will improve. Is it because of the lysine? “They have absolutely no way to say that it is because of the lysine,” he added. “They have no way to say that the same improvement would occur if they would not have treated the cat with lysine. That’s why you need a control group [in studies]. Anecdotal evidence is no evidence. … Anecdotal evidence is a contradiction in terms.” Bol and Bunnik’s paper, available at http://bit.ly/1O666oi, noted that scientists believe lysine does not possess antiviral properties. Rather, some researchers propose that lysine works by lowering arginine levels. And therein lies another issue, Bol stated. “Lowering arginine levels is highly undesirable since cats cannot synthesize this amino acid themselves,” he and Bunnik wrote. “Arginine deficiency will result in hyperammonemia, which may be fatal.” Having studied FHV himself and after reading the virologists’ systematic review, Maggs remained wary. “[I] recommend perhaps a moderation of the final conclusion because I don’t think we can say that this drug should be stopped in all cats with herpesvirus,” Maggs said. “I think they’ve introduced a useful cautionary note of whether it should be initiated in every cat, but recommending an immediate cessation is probably a stronger conclusion that I would have drawn from the same data.” Going by the Book An industry authority, The Merck Veterinary Manual, has backed away from endorsing lysine therapy in feline herpesvirus cases. The most recent print edition, published in 2010, suggested lysine’s use. The online version has since been updated to read: “Previously, lifelong oral L-lysine (250-500 mg/day) was recommended to help prevent or reduce the severity of recurrent feline herpesvirus infections. However, recent work has shown that oral L-lysine can actually exacerbate feline herpesvirus infections.” The 11th edition of the manual, due out in February, will reflect the change, an editor told virologist Sebastiaan Bol in an email.
