What are the commonly available immune modulators?

[Jonathan Edwards]

What you seem to fail to understand, is that many of us don't care about reliable evidence. Until you are so sick that you can't function, you will never understand that.

I actually think this is an important point for PR as a community and it should not be flavoured by personal feelings. I do understand what it is like to be faced with an incurable illness for which there seems to be no treatment. It was not myself but it was on two occasions my wife and in some ways I think that may be worse. Madness is worse than anything I ever imagined. And I think its only fair that you appreciate that as much as I appreciate your point of view.

I have no problem with people believing in things but as a community we have to be careful.

If someone has tried something and it has benefited them, then we have nothing to lose to try it.

This is simply not the case. In the 1950s and 1960s huge numbers of adults and children 'benefitted' from steroids. By 1970 we realised that many had died unnecessarily as a result. This sort of thing is still happening on a regular basis. If a drug is potent enough to make a big positive difference it is more or less by definition potent enough to make a big negative difference. Each individual is entitled to abandon reliable evidence, and I would too, but encouraging other people to do the same is a very different issue. You will probably not be familiar with the experience that you have caused somebody's death. I live with that (maybe a dozen deaths) permanently. I hope that I made no more mistakes than others, but that never quite solves the problem. You don't need that.

Nobody regular on PR has a bad agenda or is lazy in thinking as far as I can see. But we do have to understand each other's point of view, because we all have dark places we want to keep away from.

 

[Gingergrrl]

@Jonathan Edwards I feel I need to respond since I am the one who started this thread in order to broaden my understanding of immune modulators. It is a term that I hear frequently but felt silly to admit that I didn't understand it (but am now very glad that I asked.)

What frustrates me is that when I first came to PR, there was a lot of hope and excitement about different treatments and it seemed like an open and safe place to discuss them with others who had actually suffered from the same illness as me AND had actually tried the treatment AND in most cases had tried the treatment with the consent of their treating doctor.

I find in many threads that I ask a question (like I did in Leo Kittens thread) re: blood volume re: how a virus or pathogen can affect the autonomic nervous system of the brain. This idea is commonly accepted by the CFS specialists that I see and is something I am living with every day.

You immediately jumped in that viruses or pathogens do not cause autonomic dysfunction and I was stunned. When I tried to question this, you implied it was fantasy or folly on behalf of those doctors and used the word "imaginative" re: those doctors as if it were a bad thing.

I am confused why you are so quick to discount meds or research theories that may help us in the long run and each time you do, it takes away a little bit of my hope.

I do not mean any disrespect in saying this but I understand where Heapsreal and Minkeygirl are coming from. When you are this ill, you are willing to try things that have not been proven in a double blind study. I am happily on my fourth month of Famvir and it may or may not work for me but I will never regret trying it.

I am a cautious person and do not blindly try a med b/c someone told me to on a forum but I want to be able to discuss these ideas freely. I debated posting this but it was really bothering me.

 

[Gingergrrl]

@Ema you mentioned that Inosine had helped you and I was wondering what you noticed from it?

Also I agree with you and everyone else who said immune mods may be wrong for me due to Hashimotos and all I am trying to do is gather information from others who have tried them. I discuss everything I take with my CFS dr first.

 

[adreno]

I find in many threads that I ask a question (like I did in Leo Kittens thread) re: blood volume re: how a virus or pathogen can affect the autonomic nervous system of the brain. This idea is commonly accepted by the CFS specialists that I see and is something I am living with every day.

You immediately jumped in that viruses or pathogens do not cause autonomic dysfunction and I was stunned. When I tried to question this, you implied it was fantasy or folly on behalf of those doctors and used the word "imaginative" re: those doctors as if it were a bad thing.

I was confused about this, too. That's why I quoted research that showed autonomic dysfunction (POTS) as a result of a virus, through autoantibodies blocking adrenergic receptors. I never got any comment on that, though.

 

[Jonathan Edwards]

@Jonathan Edwards I feel I need to respond since I am the one who started this thread in order to broaden my understanding of immune modulators. It is a term that I hear frequently but felt silly to admit that I didn't understand it (but am now very glad that I asked.)

What frustrates me is that when I first came to PR, there was a lot of hope and excitement about different treatments and it seemed like an open and safe place to discuss them with others who had actually suffered from the same illness as me AND had actually tried the treatment AND in most cases had tried the treatment with the consent of their treating doctor.

I find in many threads that I ask a question (like I did in Leo Kittens thread) re: blood volume re: how a virus or pathogen can affect the autonomic nervous system of the brain. This idea is commonly accepted by the CFS specialists that I see and is something I am living with every day.

You immediately jumped in that viruses or pathogens do not cause autonomic dysfunction and I was stunned. When I tried to question this, you implied it was fantasy or folly on behalf of those doctors and used the word "imaginative" re: those doctors as if it were a bad thing.

I am confused why you are so quick to discount meds or research theories that may help us in the long run and each time you do, it takes away a little bit of my hope.

I do not mean any disrespect in saying this but I understand where Heapsreal and Minkeygirl are coming from. When you are this ill, you are willing to try things that have not been proven in a double blind study. I am happily on my fourth month of Famvir and it may or may not work for me but I will never regret trying it.

I am a cautious person and do not blindly try a med b/c someone told me to on a forum but I want to be able to discuss these ideas freely. I debated posting this but it was really bothering me.

Thanks Gingergrrl,
I am glad you did post because I am acutely aware of the effect of my posts in this regard. I often spend a long time pondering before I hit the 'reply' button. I have discussed it with the board and with the moderators. I am not doing this to upset people but I knew from the start that sometimes it would.

All I can say is that after thirty years in research mostly surrounded by junk ideas, but with a few really worthwhile breakthroughs coming in between from colleagues around the world I think I have got a fair idea of what is solid and what is not. I was asked to the IiME meeting and I got hooked on trying to understand ME, partly because I have a friend who has it. And looking at the research it seemed to me that almost all of it was the sort of stuff I was used to that would turn out to be nothing but wishful thinking.

So that seems negative. But on the other side I also saw a few researchers like Mady Hornig really doing solid work. And doing solid work often means saying 95% of the time - 'we found nothing after all'. But maybe there was a clue to follow up. And what is more I seemed to be part of a sudden rush of new people taking interest. The Norwegians were taking interest, the UK MRC had set up new projects, Dr Angela Vincent was taking interest, new things were opening up in the US. The consensus at the last IiME researchers' workshop in May was that there was still nothing really proven in the way of biomarkers but there was a new commitment to working together to get biomarkers sorted out. And that sort of atmosphere seemed to me to be the atmosphere you get at the point where people are really committed and informed enough to make the breakthroughs. It all seems to me very positive because despite the poor funding there is a will to get things sorted.

So I do not want to discourage anybody. But in order to get the solid research done that will get the right answers we need to question a lot more the stuff that has been done so far. This is not being anti-ME as you know. I did exactly the same thing for my own disease - RA - and only when I had been hypercritical did I see how to make progress.

The issue I keep coming back to is that there is an awful lot of sharing ideas here which seems harmless and only reasonable but unwittingly it may often be a way of advertising for practitioners who are not backing up their clinical work with adequate evidence. And there is every point on the spectrum from real snake oil merchants to practitioners with the very best of intentions but maybe just not quite rigorous enough testing.

And if we have no criticism of all this then to be honest there is a slippery slope down to things going very badly wrong indeed. I think we need people to be sceptical all the time. I also think that PR needs to move away from it being acceptable to call people 'narrow minded' simply because they voice such scepticism. Nobody who knows me has ever considered me to be narrow minded. I am fairly sure that I have never made an ad hominem criticism of this (usually veiled) sort of anyone on the site. If I think ideas are junk I say so, but I do try not to criticise people's motives. OK, it is easy for me. I know that and I can take the gripes. But I genuinely want to help people with ME find out the truth about their illness and I think that is going to need a bit more scepticism until we find the answer and in the meantime we all want to get on with each other.

 

[Ema]

@Ema you mentioned that Inosine had helped you and I was wondering what you noticed from it?

Also I agree with you and everyone else who said immune mods may be wrong for me due to Hashimotos and all I am trying to do is gather information from others who have tried them. I discuss everything I take with my CFS dr first.

I can't say that I noticed anything dramatic physically but I think having in range uric acid levels is beneficial regardless. I keep hoping things are happening "behind the scenes". Uric acid is an important antioxidant.

Check out this article on Medscape (I would link it except it always shows me logged in!):

Hypotheses on Evolutionary Advantages of the Loss of Uricase

It also helped me narrow down the portion of the purine pathway that is malfunctioning. Adenosine should ultimately end up at uric acid with inosine as a midpoint. I have over range adenosine and under range uric acid. But when I take inosine, my uric acid comes right up. So I know that my problem is more likely in the breakdown of adenosine, rather than the breakdown of inosine, which makes sense considering adenosine induces hibernation effects in mammals. Now I just have to figure out how to clear excess adenosine!

 

[Jonathan Edwards]

I was confused about this, too. That's why I quoted research that showed autonomic dysfunction (POTS) as a result of a virus, through autoantibodies blocking adrenergic receptors. I never got any comment on that, though.

I realised that we had not really teased out all the arguments on this one and that some people would feel things were not answered. I have got a bit behind in trying to keep up with all these discussions! The point about a link between virus and autonomic dysfunction I was trying to make was that there does not seem to be any very obvious direct mechanism from virus to autonomic change. OK a vagus theory would do it but I think there are problems with that. The paper on autoantibodies to adrenergic receptors is fascinating but I am not sure that has any connection to viruses. As I have said many times, we do not have much evidence that viruses cause autoantibodies to form, even if it is a popular theory that people often put in the introduction to a paper.

Does that help?

 

[minkeygirl]

Not everything has to be a teaching moment. There are too many other's I'd go to about the truth of my disease than someone who knows zero about me.

Sometimes those of us that are sick just want to talk without having to defend everything we say or have everything we say questioned. Maybe there should be a forum for medical professionals so people who are interested can talk there.

 

[Gingergrrl]

I also think that PR needs to move away from it being acceptable to call people 'narrow minded' simply because they voice such scepticism.

I am not sure if this was addressed to me but if it was, I have NEVER since joining PR in June called anyone on this board narrow minded and I never would. I try to ask scientific questions in order to understand potential treatments and when I don't understand (which is often the case) then I try to ask follow-up questions. Prior to starting Famvir, I composed a thread which was a survey about anti-virals and this thread is still in action five months later. The moderators participated in this thread and everyone gave me their experiences (good and bad) with anti-virals and I made an informed choice with my doctor.

I realised that we had not really teased out all the arguments on this one and that some people would feel things were not answered. The point about a link between virus and autonomic dysfunction I was trying to make was that there does not seem to be any very obvious direct mechanism from virus to autonomic change. OK a vagus theory would do it but I think there are problems with that. The paper on autoantibodies to adrenergic receptors is fascinating but I am not sure that has any connection to viruses. As I have said many times, we do not have much evidence that viruses cause autoantibodies to form, even if it is a popular theory that people often put in the introduction to a paper.

Does that help?

To be honest, it does not help me b/c I have a top cfs dr and cardiologist (he is the head of his dept at two hospitals) and they have spoken with each other re: my case twice and BOTH feel that I have significant autonomic dysfunction which has affected my heart rate, angina, breathing, blood pressure and blood volume. I am still being tested for cardiac issues but thus far, the issues are being found as autonomic.

My understanding is that autonomic issues stem from the central nervous system or brain (unless this is incorrect?) I did not have any autonomic issues prior to having mono from EBV in 2012. For you to outright dismiss what is happening to me is confusing and hurtful. You have not seen my lab tests or examined me in person. When I get feedback from peers on the board, I know they are not doctors so I take the feedback to learn what their experience has been as a fellow patient.

But you are giving feedback as an actual doctor when you do not know all the details of my situation. It is using up so much of my energy having to defend this and will have to stop soon but even if there is no proven link between a virus/pathogen and autonomic dysfunction, I'd bet that 90% of us on PR have experienced this link and I don't think you know what it feels like to be dismissed by a doctor on PR when we have all been dismissed by doctors in real life (which thank God my current doctors are not doing or I really would have no hope.)

And again I mean no disrespect and if it seems that way, I will stop posting here.

 

[Seven7]

I am confused, I thought in the medical community the fact that infection does cause dysautonomia is not even questioned.
1) CFS at least a subgroup has low NK cell. Not all but In my case I had low NK cell like so many others.
2) If you google Natural killer cell dysfunction, is very accepted that you get virus reactivation.
3)There is a known fact that infection is cause of dysautomia:

-Infections such as Mononucleosis, Epstein Barr Virus, Lyme Disease, extra-pulmonary Mycoplasma pneumonia and Hepatitis C1,2,3,4,10,11
http://www.dysautonomiainternational.org/page.php?ID=30


1) One would infer then CFS can cause dysautonomia. At least in a subgroup.

 

[Gingergrrl]

@lnester7 Thank you for posting that and I wish I could have explained it as well as you just did! Everything I have ever read about POTS and dysautonomia lists a virus as one of the #1 triggers.

Even my cardio who knows nothing about ME/CFS, but is an autonomic specialist, believes in a viral cause behind dysautonomia in many patients including myself.

 

[Seven7]

Ahhh back to topic I use imunovir and I had great results, I do not experience flue like symptoms, I do not how explain it, you have a CFS side where you feel sick. I do not get that anymore, I do get tired and have symptoms but not immune fluish like related.

Another natural modulator is Acai.

My advise is to be careful because some people need boosters, some suppressors, some modulators, It will be based on your unique immune profile.

Now by the time I went to the Specialist I had tried suppresors, boosters and modulator, and I could always tell immediately what I could or could not do.
Example: If you wanna send me to bed have equinacea tea. Is flue like right there.
Booster: I used something called thyamus A or something like that. Again direct to bed,
W modulators I always felt a bit better. So I figure it out myself.

When you try immune stuff just try one group at a time (booster Vs suppressors Vs mods) and separate by weeks. You will see what helps and what doesn't.

 

[SDSue]

Also I agree with you and everyone else who said immune mods may be wrong for me due to Hashimotos and all I am trying to do is gather information from others who have tried them. I discuss everything I take with my CFS dr first.

I have Hashimoto's, and have been on both LDN and inosine for nearly five months, under the care of a well-known ME/CFS specialist. Overall, I have seen improvements in several areas, but most importantly my PEM is less severe and shorter in duration. With each increase in inosine dose, I experience 4 or 5 days of flu-like symptoms.

At the six month mark, labs will be ordered to retest my NK cell number and function, as well as my cytokines and viral reactivation levels (EBV and HH6). If my labs aren't improved, I will be very surprised. I'm glad my doctor recognizes the seriousness of this illness and refuses to wait for large scale studies while we patients lose our lives year after year.

Just as my husband, in spite of standing by my side, cannot comprehend childbirth, I don't believe we can understand any particular illness unless we live it. I also believe this is particularly true of ME/CFS as it defies all logic and everything patients and doctors thought we knew about illness to this point.

Not until I was bed bound with this horrifically misunderstood and disrespected illness did I understand ME/CFS and the desperation it brings. Because death is not imminent in ME/CFS, it's unlikely that the FDA will ever recognize that our illness constitutes a legitimate need for compassionate drug use.

Therefore, because I own my brain, my genes, my blood, and all else that constitutes my body, I will continue to take calculated and educated risks as I attempt to climb out of the cesspool that is ME/CFS. And I will support others who do the same.

 

[Gingergrrl]

Ahhh back to topic I use imunovir and I had great results, I do not experience flue like symptoms, I do not how explain it, you have a CFS side where you feel sick. I do not get that anymore, I do get tired and have symptoms but not immune fluish like related.

Another natural modulator is Acai.

My advise is to be careful because some people need boosters, some suppressors, some modulators, It will be based on your unique immune profile.

Now by the time I went to the Specialist I had tried suppresors, boosters and modulator, and I could always tell immediately what I could or could not do.
Example: If you wanna send me to bed have equinacea tea. Is flue like right there.
Booster: I used something called thyamus A or something like that. Again direct to bed,
W modulators I always felt a bit better. So I figure it out myself.

When you try immune stuff just try one group at a time (booster Vs suppressors Vs mods) and separate by weeks. You will see what helps and what doesn't.

@lnester7 Thank you for letting me know about your experiences and I know you suffer a lot from dysautonomia so the info is helpful to me. I can relate to your first paragraph a lot b/c prior to Famvir I used to have what I would call a "sickly fatigue" in which I not only had fatigue and dysautonomia but I also constantly felt feverish, alternate freezing/hot, and just felt sick as if I had mono. With the Famvir, the sick and feverish feeling has completely disappeared. Unfortunately though it has not yet changed the autonomic stuff.

It is also interesting that you mentioned that Acai was an immune modulator b/c I did not know that and have been taking Acai (from NOW brand) 2x/day for about six months. I don't notice any benefit from it but also have not noticed anything bad from it. ETA: I wonder how many other supplements that I take are immune mods but I just don't know it?

How does a lay person like me know if something like Acai (or any other supplement) is in the immune mod category? This is part of what I was curious about when I started the thread. How would someone know if something is an immune booster, suppressor or modulator (or does that differ greatly from person to person?)

 

[Gingergrrl]

@SDSue, I wish I could triple like your post and it really made me feel a lot better after a difficult day today.

I have Hashimoto's, and have been on both LDN and inosine for nearly five months, under the care of a well-known ME/CFS specialist. Overall, I have seen improvements in several areas, but most importantly my PEM is less severe and shorter in duration. With each increase in inosine dose, I experience 4 or 5 days of flu-like symptoms.

Even though we have been talking this whole time, I did not realize that you had Hashimotos! I also did not realize that LDN was an immune modulator. I tried LDN very briefly with my former ND but had a horrible reaction to it and was awake the entire night (didn't even sleep for five min) whereas I normally sleep pretty well. She and my Endo had made a plan to check my thyroid labs every seven days while on LDN and now I understand why. I never got that far but it seems like certain immune mods can be safe if you have doctors monitoring your thyroid at the same time.

Do you take Immunovir (from Europe?) or the Inosine that you can buy in the U.S.? The Monolaurin that I've been taking since Feb has a very small amount of Inosine in it 7.5 mg per pill (and I take four pills per day) which is 30 mg per day. I know this is a micro amount but I tolerate it with no problems which makes me wonder how I would do with a bigger amount?

In another thread a few days ago, someone mentioned to me that I need to try things that get at the underlying cause of my symptoms toward long-term improvement (not just symptom management like Atenolol and Midodrine) and in addition to the anti-viral, the only other thing I could think of which might be in this category are immune modulators which is partially why I started this thread.

At the six month mark, labs will be ordered to retest my NK cell number and function, as well as my cytokines and viral reactivation levels (EBV and HH6). If my labs aren't improved, I will be very surprised. I'm glad my doctor recognizes the seriousness of this illness and refuses to wait for large scale studies while we patients lose our lives year after year.

I am so excited to hear what your labs will be and my NK function is only 5 and will be re-tested around the six month mark on Famvir (around January.) My doctors are at a major research center as well (although they do not do the cytokine tests) but they are at the heart of a major current ME/CFS research project.

Just as my husband, in spite of standing by my side, cannot comprehend childbirth, I don't believe we can understand any particular illness unless we live it. I also believe this is particularly true of ME/CFS as it defies all logic and everything patients and doctors thought we knew about illness to this point.

Agreed and I would never have understood this illness if I had not lived it.

Not until I was bed bound with this horrifically misunderstood and disrespected illness did I understand ME/CFS and the desperation it brings. Because death is not imminent in ME/CFS, it's unlikely that the FDA will ever recognize that our illness constitutes a legitimate need for compassionate drug use.

I also agree and when death is not imminent it makes the illness seem less severe even though my doctors have told me that I am functioning at the level of a patient with congestive heart failure.

Therefore, because I own my brain, my genes, my blood, and all else that constitutes my body, I will continue to take calculated and educated risks as I attempt to climb out of the cesspool that is ME/CFS. And I will support others who do the same.

Thank you and I will do the same and support others who do the same. The irony is that I actually run everything by my doctor and don't feel that I have made any extreme risks. The biggest medical injury I have ever experienced was from Levaquin which was given to me by a doctor and if I had the benefit of a discussion board like this at the time, I never, ever would have taken it and made an alternate more informed choice.

 

[Sushi]

Speaking of having the results of rigorous medical trials before trying treatments...personally I don't have time. To get positive results from such studies will take many (if not many, many) years. (And where will the funding come from?) I've already waited 30 years since the onset of my symptoms. I'd guess that my risk of dying of old age would be greater than the risk of trying protocols which, though they have good science behind them and significant clinical success, lack rigorous studies.

My doctor is cautious but willing to try new approaches if the risks are low. He has extensive clinical experience with this illness and puts together individual protocols based on history, symptoms and lab testing.

This approach has taken me from not being able to walk across a room eight years ago to being able to lead a life that passes for normal (if you don't look too closely...and ignore the handicapped placard on my car).

Sushi

 

[SDSue]

Do you take Immunovir (from Europe?) or the Inosine that you can buy in the U.S.? The Monolaurin that I've been taking since Feb has a very small amount of Inosine in it 7.5 mg per pill (and I take four pills per day) which is 30 mg per day. I know this is a micro amount but I tolerate it with no problems which makes me wonder how I would do with a bigger amount?

Yes, that is a small dose compared to mine. I started on OTC inosine (not Immunovir) 250 mg per day and am up to 2,000 mg daily, always with weekends off. Once I can tolerate 3,000 mg daily we will being an every-other-week pulsing regimen.

@Sushi probably knows more, but it is my understanding that LDN has (not well understood) immune modulating ability.

In another thread a few days ago, someone mentioned to me that I need to try things that get at the underlying cause of my symptoms toward long-term improvement (not just symptom management like Atenolol and Midodrine) and in addition to the anti-viral, the only other thing I could think of which might be in this category are immune modulators which is partially why I started this thread.

Agreed. I keep asking "why" until there are no more answers. Then I know I'm as close to the cause as I can get. (Even the, I keep asking lol).

Glad you liked my post.

Speaking of having the results of rigorous medical trials before trying treatments...personally I don't have time. To get positive results from such studies will take many (if not many, many) years. I've already waited 30 years since the onset of my symptoms. I'd guess that my risk of dying of old age would be greater than the risk of trying protocols which, though they have good science behind them and significant clinical success, lack rigorous studies.

Ditto!

 

[Gingergrrl]

This approach has taken me from not being able to walk across a room eight years ago to being able to lead a life that passes for normal (if you don't look too closely...and ignore the handicapped placard on my car).

That is all I want and literally if I could breathe and walk normally again, I will never ask for anything else.

Yes, that is a small dose compared to mine. I started on OTC inosine (not Immunovir) 250 mg per day and am up to 2,000 mg daily, always with weekends off. Once I can tolerate 3,000 mg daily we will being an every-other-week pulsing regimen.

Wow, that is a high dose! I do very well with micro doses of meds so if my dr ever agreed to Inosine, I suspect my final dosage would be much lower than this. When you said that you started on OTC Inosine, did you mean that you ultimately switched to Immunovir or you stayed with Inosine to this day?

Agreed. I keep asking "why" until there are no more answers

Me, too, and I feel like I have not even begun to scratch the surface. I have gotten so many messages from different people with ideas to try and I intend to respond and research every single one and then discuss with my dr. I am also reading the book by Dr. Jay Goldstein (which may not be popular on PR?) and in the process of researching his treatments, too.

My biggest struggle right now is just to eat and drink something every day or I am afraid of ending up with a feeding tube. So any medications or supplements that can make this easier for me, I am open to learning about them. Like Sue, I will never stop asking the questions and like Sushi, I don't have time to sit around and wait for the official research studies.

 

[Sushi]

@Sushi probably knows more, but it is my understanding that LDN has (not well understood) immune modulating ability.

From the Home Page of the Low dose naltrexone site.

FDA-approved naltrexone, in a low dose, can normalize the immune system — helping those with HIV/AIDS, cancer, autoimmune diseases, and central nervous system disorders.

 

[SDSue]

Wow, that is a high dose! I do very well with micro doses of meds so if my dr ever agreed to Inosine, I suspect my final dosage would be much lower than this. When you said that you started on OTC Inosine, did you mean that you ultimately switched to Immunovir or you stayed with Inosine to this day?

I, too, normally tolerate only tiny doses of meds. It apparently took me longer to increase my dose than it does most patients. Also, I was never on Immunovir, only Inosine from the get-go.

I am also reading the book by Dr. Jay Goldstein

Not familiar with this one.

My biggest struggle right now is just to eat and drink something every day or I am afraid of ending up with a feeding tube. So any medications or supplements that can make this easier for me, I am open to learning about them. Like Sue, I will never stop asking the questions and like Sushi, I don't have time to sit around and wait for the official research studies.

Sorry to hear this! I hope it ends soon and you're back to eating well. Those are the days I drink Muscle Milk - low sugar, high protein. It's the best I've found to keep me hydrated and nourished on the days I can't swallow or tolerate food.