My daughter, Catherine, has several autoimmune conditions, and has been treated with biologics—specific antibody treatment—which have knocked off her immune system. She is now extremely vulnerable to infections. One of the infections is recurrent shingles.
Shingles is due to reactivation of the human herpes virus (HHV), more commonly known as the chicken pox virus or varicella zoster, or simply zoster.
The first time Catherine developed shingles she had an itchy, painful rash. She thought she had been bitten by a mosquito, but then the pain developed, and it became obvious that it wasn’t an insect bite after all. Shingles affects an area of skin served by a single nerve. This area is called a dermatome and there are online maps showing the distribution of dermatomes.
She started acyclovir and, as with most cases of shingles, managing the pain was the most difficult thing.
We figured that the reason she had developed shingles was that she was stressed – it was the end of her first year at university, she had exams, she had been sent home from university urgently as there were cases of coronavirus in the residences and she was deemed high risk, or extremely clinically vulnerable, as we have now learnt to call it.
She told me she had recently started drinking coffee again, and could this have anything to do with the shingles and I laughed, dismissing the notion as, quite frankly, ridiculous. How can coffee cause shingles!
Skip forward a year. Catherine has had shingles recurrently requiring higher than usual maintenance doses of acyclovir. I read that increased doses are sometimes required to prevent recurrence in immunosuppressed and immunocompromised patients, such as those with HIV. Interestingly, the shingles is now atypical. The prodromal sore throat, headache, fever, fatigue (which Catherine describes as feeling ‘hit by a bus’) is the worst part, the rash may be a single lesion, with a change in the skin sensation on that dermatome.
Each time the shingles recurs she has to increase her dose of steroids for her body to cope with the stress of an infection—something the endocrinologists call ‘sick day rules’. Unfortunately it often takes longer that the 2 days of sick day rules to control the symptoms and for the fever to resolve, and hence this leads to higher steroid requirement, when she is desperate to reduce the dose have already suffered the consequences of long term steroids.
She joined various groups to connect with other sufferers. One such forum suggested lysine supplementation. She read up on it, ordered it online, told me it was probably nonsense, but unlikely harmful and that she might as well give it a go.
She took the lysine, stopped drinking coffee, and managed to reduce her dose of steroids and even felt confident about reducing the maintenance dose of acyclovir.
Catherine is committed to reducing her impact on the planet wherever possible. Acyclovir packaging is not planet-friendly, another motivation for reducing the dose. Many of the drug packets involve wasteful packaging. She also takes dispersible aspirin. Boots recently changed their packaging from a small plastic bottle to blister packs. She has been collecting blister packs ready to recycle when the facilities are available. Catherine chooses to be vegan as she recognizes that this is the best way she can reduce her impact on our planet.
For the past few weeks Catherine has felt unwell. She had a chest infection, non-Covid related, requiring a course of antibiotics, which helped with the productive cough, but the fever and exhaustion persisted. A couple of days ago she found a small flat blister-like lesion on her arm with abnormal sensation and, it became obvious, she had developed shingles again. She had run out of lysine a month ago, and had been drinking coffee regularly.
I found this curious and wondered whether there was any scientific support for lysine to suppress viral reactivation.
Lysine is an amino acid—one of the basic building blocks for protein. Lysine is in fact ‘essential’, meaning that humans cannot make it so they have to take it in their diet. Lysine is found in highest quantities in dairy produce and meat.
Arginine, another amino acid, structurally similar to lysine, promotes viral growth. Arginine is essential for viruses enabling them to replicate. Arginine is found in nuts, seeds and many fruits and vegetables—a vegan diet.
Arginine can be synthesised by humans but synthesis is limited for example, during severe infections. When the body is deficient in arginine it starts making more from another amino acid called citrulline, which is found in squash and chickpeas—the vegan diet again.
When there is ample lysine in the diet lysine is taken up from the diet instead of arginine. It is the same transporter that controls the uptake of both amino acids.
Studies in tissue culture (in vitro—using petri dishes to grow the viruses in the lab) have shown that arginine deficiency can suppress replication of herpes simplex virus—the caus e of cold sores when it reactivates. Lysine slows down the viral growth-promoting effects of arginine.1 Arginine is necessary for the virus to produce protein to make virus particles.2
Hence there is some scientific proof to support reducing foods high in arginine (nuts and seeds) and taking lysine supplements.
A similar experiment was carried out with another herpes virus—cytomegalovirus. Removing arginine in the feed slowed the virus production, the virus became inactive—dormant, but then could be activated by adding arginine again.3 This is like activation of a latent virus, as seemed to be happening with Catherine.
It seems that lysine-rich foods or lysine supplements mean that lysine is absorbed in preference to arginine and this results is arginine depletion in the body.
Not all viruses are sensitive to arginine depletion, but it is possible that SARS-CoV2 is suppressed by lysine, particularly as MERS-CoV (another coronavirus) activity was reduced in a petri dish using a lysine-aspirin drug.4 There are studies underway to investigate whether taking an enzyme that destroys arginine could be beneficial in acute Covid.5
Another study showed that 80% of sufferers had a 70% reduction in symptoms of acute Covid whilst taking lysine.6 This article by Kagan actually gives very helpful advice on how to take lysine (not with food) and the dose (usually 2g per day, up to 3g), avoiding zinc and calcium supplements at the same time, and starting on a low dose (500mg) if you have medical conditions. There are also cautions against taking single amino acid supplements long term, particularly in children, although I wonder whether it may be beneficial in vegan diets.
There was an explanation for how coffee might make Catherine more prone to shingles. Coffee or caffeine causes an increase in arginine; it somehow displaces lysine, which presumably means that the lysine is excreted faster resulting in lower levels.
Another interesting comment seems to refer to long-Covid. It stated that ‘coffee/high caffeine consumption was the most common behavior of long-term symptomatic sufferers’, presumably referring to long-Covid sufferers. The other common traits were being a vegetarian. If lysine has a part to play here, then a vegan diet might cause further problems given that dairy provides a good source of lysine. Exercise was also linked to the development of long-term symptoms.
Could this help people with long-Covid? Would they benefit from Lysine supplementation, or avoiding coffee and arginine-rich foods? However vegans and pescatarians are reportedly less likely to get severely ill from coronavirus.7 Are they more likely to get long-Covid though?
I suspect long-Covid is, like many syndromes, due to a diverse combination of causes. Even though the original trigger is acute Covid infection, the body’s response is extremely varied and the subsequent long-Covid syndrome is likely to be different in each individual. I couldn’t find any specific reports on using lysine to recover from long-Covid.
Finally, scientists have reported that Covid-19 virus particles have been found in the brainstem and the vagus nerve.8 Disruption of the vagus nerve function might explain some of the dysautonomic symptoms experienced after Covid infections. Brainstem involvement affecting the breathing centre could be the reason acute Covid sufferers aren’t aware when the blood oxygen level is dangerously low—rather tragically called ‘happy hypoxia.’
I was more concerned that the virus might lie dormant in the nerves in some individuals, just like zoster virus, able to reactivate when conditions are right.
If this is the case lysine might help individuals with persistent, dormant coronavirus, patients who are experiencing flares, as though they are getting recurring infections.
Sensible advice would then be to stop coffee and caffeinated drinks, reduce high arginine-containing foods and consider trying lysine supplements.
References
- Griffith RS, DeLong DC and Nelson JD. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture. Chemotherapy. 1981; 27: 209-213.
- Becker Y. Olshevsky U and Levitt J. The role of arginine in the replication of herpes simplex virus. J Gen Virol. 1967; 1(4): 471-8.
- Garnett HM. The effect of arginine deprivation on the cytopathic effect and replication of human cytomegalovirus. Arch Virol. 1975; 48(2): 131-45.
- Müller C, Karl N, Ziebuhr J and Pleschka S. D, L-lysine acetylsalicylate + glycine impairs coronavirus replication. J Antivir Antiretrovir. 2016: 8;4.
- Grimes JM, Khan S, Badeaux M, Rao RM, Rowlinson SW and Carvajal RD. Arginine depletion as a therapeutic approach for patients with COVID-19. Int J Infect Dis. 2021; 102: 566-70.
- Kagan C, Chaihorsky A, Tal R and Karlicki B. Lysine therapy for SARS-Cov-2. https://www.researchgate.net/publication/344210822
- COVID-19: Vegans and pescatarians less likely to get severely ill from coronavirus, study suggests. Sky News. 08/06/21
- Bulfamante G, Bocci T, Falleni M, Campiglio L, Coppola S, Tosi D, Chiumello D and PrioriA. Brainstem neuropathology in two cases of Covid-19: SARS-CoV-2 traficking between brain and lung. J Neurol. 2021. https://doi.org/10.1007/s00415-021-10604-8.
Questions, quibbles and quandaries 