Post COVID Migraine in a Six Day Cycle

After COVID infections and three vaccinations (AZx2 + Modx1), I now have a cycle of inflammation causing migraines which lasts six days. The inflammatory episode lasts three days so that means three days on and three days off. With ME CFIDS related PEM (post exertion malaise) all the time. 

Previously my ME CFIDS involved a recurring virus cycle which started at about 30 days long in 1986 and either caused or was a result of whatever was causing ME CFS. 

Subsequently I caught other viruses and some appeared to become recurrent e.g. recurring swine flu after 2009 whenever my head got cold. In about 2017 I caught something I cant identify but may be an enterovirus like echovirus as it caused rib cramps (Bornholm symptoms) and headaches recurring every two weeks odd. 

Every time I caught a new recurring virus the cycle got shorter. My best guess is its like a ratchet because whichever virus is quickest to recur triggers my immune response first. The others are held at bay by the immune response to the quickest repeater, but some are still there and show themselves from time to time.

The new six day cycle has been accompanied by a new degree of intolerance for some foods, especially maize, in addition to all my other intolerances, which make the headaches much worse. This started to be a problem around the swine flu epidemic in 2009. I found eating tortilla chips, which I used to love, gave me an intolerable headache.

This new phase of 6 day cycle began after a dose of suspected COVID-19 and caught me off guard. At first the migraine was very intense and I honestly feared for my health and wellbeing. 

I noticed it varied in intensity and tried to work out why. After much observing, thinking and experimenting on myself, I have found several factors which all reduce the severity a little. Primarily, during an inflammatory episode my migraine is much worse if I eat any protein, animal or vegetable and also any food high in manganese or vitamin K. 

I can now usually survive the entire cycle with minimum migraine pain as long as I stick to what helps. I score my headaches 1-10 and the worst I got to was 8, which I felt was approaching life threatening due to the sensation of compression inside my head and the fear of aneurism. 10 I think would be very dangerous, probably coma. Right now I can usually manage to keep it below 1, with the worst being 2. This is a big improvement and relief for me so I wanted to share.

Details below, in the hope it might help others in a similar situation and save them some pain.

During the three day migraine phase ...

• I need a low protein diet excluding both animal and plant protein. i.e. no meat, no eggs, no rice, no lentils or other legumes as these all have more than 5g protein per 100g. I live on assorted vegetables, spices, oils and fats and (not too much) white cassava gari. - I use eatthismuch.com for looking up food data. https://www.eatthismuch.com/food/browse/?q=&type=food
• I have to avoid foods or supplements rich in vitamin K or manganese (Mn) or the pain increases significantly. (Implicated in blood clotting.)
• Taking moderate amounts of magnesium (Mg) supplements helps to reduce head pain as well as heart arrhythmia.
• Head pain is also reduced by taking linseed oil for omega 3 lipids, vitamin D and turmeric extract (Solgar), which are commonly recommended as anti-inflammatory supplements and turmeric is a blood thinner.
• I have to restrict sugars or the pain can get worse, sugars are considered proinflammatory.
• I need to relax and avoid using my brain too much or it starts to hurt. I drink hop tea herb tea to help as it is mildly tranquilising. I usually add marigold and bucchu to this, sometimes lavender. (UPDATE I have to be careful with any green plants like hops as they tend to have VitK which can exacerbate migraine, possibly via microclotting.) 
• I often feel sleepy in the inflammatory phase and do better if I sleep when I feel the need. It feels like there is inflammation in my brain affecting my cognition and in my experience it is best not to fight it. Best to sleep, somewhere warm and let one's body heal.
• Heat treatment for the neck and back can promote vasodilation which helps reduce head pain. Likewise hot showers or short hot baths.
• I have to avoid getting exhausted by activity and my ability is even less than usual. Otherwise I get post exertion malaise (PEM) which makes the migraine worse.
• It helps to drink plenty of fluid.
• Sometimes the inflammatory phase is accompanied by a symptom which causes my mind to race, involuntarily and to an excessive degree, which feels like a vicious spiral, as though my brain is on fire. This is exacerbated by too much onion (quercetin). At these times, when hop tea does not work but Mg usually helps a little, I have also found a wee medicinal dram of alcohol and I mean wee, about a quarter measure, damps this down, which I ascribe to the way alcohol acts as a depressant of brain activity, hence its effect when taken in larger quantities. In this situation the benefits significantly outweigh the mild proinflammatory drawbacks. 

Outside a migraine phase...

I cannot tolerate any maize corn as this always causes a migraine.

It looks like I cannot tolerate eating any meat from an animal which has been fed maize either. I have tested this and now order regeneratively farmed meat, like 100% pasture fed beef and lamb which I can eat outside a migraine phase without ill effect. If I buy meat from a supermarket from animals which have been fed standard animal feeds containing maize then it sets off a food intolerance headache lasting 12-18 hours which occurs even when not in a migraine phase and can significantly exacerbate a migraine phase.

I am not eating any nuts now. Anything with hazelnuts in causes headache and other nuts like walnuts or pecans seem to cause itching skin around my fingers.

When eating high protein food like meat, at any time, it is helpful to take digestive enzymes including proteases and also DAO (diamine-oxidase) which reduces histamine absorbtion by oxidising it in the digestive system. These reduce the likelihood and severity of any headaches arising from eating protein.

It helps to take B vits complex, B12, also minerals excluding manganese. Also I have beetroot juice in my omega 3 heavy salad dressing every morning (helps vasodilation).

I still have to avoid even very light exertion causing PEM.

My other preexisting dietary constraints.

I am avoiding wheat gluten all the time based on doctors advice. It does seem to exacerbate headachey patches.

I do not eat any dairy, palm oil or coconut oil as they contain high levels of MCTs (medium chain triglycerides) which are proinflammatory as I addressed in a previous blog.

I do not eat any nightshade vegetables as they cause me mouth ulcers along with inflammation of the skin inside my mouth causing me to bite my cheeks (I get the ulcers even if I don't bite myself accidentally) and it also causes a body wide malaise of ache and weakness. This means no potato, tomato, aubergine (egg plant), chili peppers (paprika), sweet peppers, blueberries. I dont know if that is just me but its what I need to do to avoid getting iller.

Good news is... 

By avoiding these common but problematic foods and taking anti-inflammatory supplements, I can turn three days of excruciating headache into three days of being an airhead, which believe me is much better. 

Discussion.

To recap: I get headaches if I eat the wrong foods (anything with maize in or which has been fed maize, any supplement with manganese in). I also get headaches in a regular cycle and these are exacerbated by high protein foods and anything with high levels of vitamin K or manganese in.

Outside the migraine phase of the inflammatory cycle I can eat limited portions of protein without getting headaches and low levels of vitamin K and manganese containing foods, (not supplements though) without getting headaches. 

My method for reaching this conclusion was based on applying scientific logic to personal experience. 

Observations of my condition were recorded in my diary, alongside foods I eat. I tried to make sense of these to see if there was anything I could do to reduce my pain, by painstakingly tabulating them in spreadsheets.

I ran experiments to test foods which seemed to cause problems at one time to see if they caused a problem at different times.

It was confusing at first because there were too many things going on at the same time. I could not tell the inflammatory cycle headaches from the food triggered headaches and just seemed to be getting headaches all the time whatever I did but with inconsistent triggers.

I learned to avoid a lot of foods and ended up only able to tolerate stewed beef short ribs from among supermarket meats and good quality eggs as long as I only ate one per serving and only one serving of protein per day. One serving of short rib stew for example contained half a short rib worth of beef at around the 100g mark and I could not have more protein like an egg on the same day without getting a headache.

I also realised that whatever I ate or didn't eat, there was also an underlying cycle of inflammatory episodes, three days on and three days off and that during the migraine phase, foods which would not normally cause a headache could cause one or compound a migraine making it more severe. 

That meant any protein at all was out in the inflammatory phase, even from vegetable sources like rice or lentils. Though I could eat these and either short rib stew or an egg (but not both) on the other three days in the less inflammatory phase.

I also noticed that supplements containing manganese caused headaches and so did very green vegetables, both of which I thought would be healthy for me but were making my headaches worse.

Deductions.

The key observation though, was realising that if I took a hot shower it helped relieve my migraine.

It took a while to twig but the implication was that vasodilation was helping to reduce the head pain, as heat causes vasodilation, i.e. the blood vessels relax and get wider.

I tried it out several times and it usually worked unless I had one of those headaches brought on by onions where my mind was racing and which responded  well to medicinal alcohol. 

I then began to experiment with supplements which could assist vasodilation including magnesium, which also helped. I also noticed that taking calcium supplements sometimes triggered a migraine. 

Calcium (Ca) is an antagonist for magnesium (Mg), to be clear we need them both but they need to be balanced. My deduction was that too much calcium was lowering magnesium and impairing vasodilation and possibly encouraging vasoconstriction during headaches. 

My conclusion was I needed more magnesium in headachey patches, which did help a little. The problem then was that sometimes I would get muscle cramps from taking too much Mg all the time and it occurred to me the inflammatory cycle seemed to cause Ca/Mg balance to change quite dramatically at one point  in the cycle (which coincided with the onset of the headache) and then change back. So I had to dose the Mg to coincide with the point where my body was acting as if it had just had a dose of Ca, then ease off the Mg dose, which worked. 

Other vasodilation promoters include Coenzyme Q10 and B12 which is also anti-inflammatory. I also find Kirkman B complex and zinc (Zn) supportive. 

(UPDATE 9/8/23 the above struck through are not always helpful actually, depending on timing and I think it is because CoQ10 has a structure similar to VitK which promotes microthrombosis, while B12 interacts in complex ways with the nitric oxide based control of vasodilation/constriction and may not be particularly influential on its own, while Zn is implicated in clotting and may not always be helpful. B vits complex I still consider moderately supportive though containing B12 as these include niacin aka vitamin B3 which is known to cause vasodilation.) 

Manganese and VitK cause headaches or make them worse and since they are known to be implicated in blood clotting it seems possible that my headaches result from vasoconstriction exacerbated with a tendency to blood thickening or even microthrombotic tendency, as these have been recorded in conjunction with longCOVID. 

Its possible my 6 day cycle is caused by recurring COVID just like the other recurring viruses I have. I had an aching right kidney after initial infection which lasted over two years and may have been acting as a refugium for the virus and may still be though the ache is less obvious now, as it is a site for the expression of ACE2 receptor, as is the endothelium of blood vessels and many other locations in the body.

The fact that reducing protein intake reduces the severity of headaches is consistent with this scenario as protein is the type of molecule involved in blood clotting mechanisms (fibrin) and when being digested can contribute to the levels of proteins and amino acids in the blood plasma adding to viscosity and perhaps reacting to increase the size and or frequency of microclots and protein agglomerations.

ME patients have long been known for having slower ESR (erythrocyte sedimentation rates) than normal and lower blood volumes.

It stands to reason that thicker blood in thinner, possibly vasoconstricted and possibly inflamed, blood vessels will not flow as well.

So IMHO that is the long and the short of it and the key facts I managed to untangle to save myself from the worst effects of an ongoing migraine cycle.

This is a WIP (work in progress) which I am publishing while working on it to get the facts out for others to read. Will try to polish it up and add links etc later. 

Hope it helps.

UPDATE 9/8/23 I have seen a pattern in the 3 day migraine which can be described as M shaped, appropriately enough, the migraine pain is worst (peaks) on the first and third day and is almost not detectable on the second day as long as I dont eat any protein. 

UPDATE DISCUSSION 9/8/23 Regarding protein, it strikes me as a possible hypothesis that the symptoms of headache due to vasoconstriction might be explained by the periodic blocking of ACE2 receptors by SARS-2-COV spike protein, leading to vasoconstriction due to the inhibition of angiotensin conversion to the vasodilatory form. 

The M shaped curve of migraine intensity might be a result of my immune system interacting with the spike protein itself and whatever is producing spike protein. There are more than one candidates for this but first among them must be the virus variants themselves and given my experience with other recurring viruses this is likely. 

Given my predisposition for one day migraines before COVID and after a recurring infection resembling enterovirus since 2015-7, it may be that the post COVID M shaped curve is composed of two types of migraine with different but interrelated causes. These one day migraines used to occur predictably after any recurring infection bout as my immune system was clearing up the aftermath, the timing of which was most evident with bouts of HSV2 as the symptoms are so marked. 

So it seems possible that the second phase or hump of the M shaped 3 day migraine is immunological mop up inflammation migraine, following on from a viral infection recurrence which causes the first hump of migraine directly by releasing spike protein which blocks ACE2 and vasodilation causing vasoconstriction headaches. 

That is my current working hypothesis for management, it follows that each phase of the migraine needs appropriate treatments. The first phase needs vasodilation therapy like heat treatment and possibly B3 (niacin) though this is not good for your liver in large amounts. The second phase needs anti-inflammatory treatments like Vitamin D, Turmeric and Linseed oil for Omega 3 lipids. This approach seems to help.

Will update again if there are further changes to my condition or perspective.

No more potatos. Nightshade alkaloid intolerance and exclusion in ME CFIDS in relation to calcium, apoptosis and the mitochondrial pore.

I have heard of more than a few people with ME who suffer food intolerance and for some it can become dangerous. This is a facet of my condition too and I have to avoid dairy and soy for example as well as high amine foods, MAOi foods and other foods which I know from experience repeatedly cause symptoms.

I also now avoid nightshade vegetables; i.e. potatos, tomatoes, chili and sweet peppers, aubergines etc and get iller if I don't. Though stopping eating them was not straightforward and had unexpected consequences, so I thought I should let people know what happened and what I learned from it so that anyone else who is obliged to go down this route can be a step ahead.

I have had ME CFIDS since 1986 but my intolerance to nightshades has been getting worse since about 2010 and I excluded them from 2012 onwards.

Nightshades.

It took a while for me to realise it was nightshades. I kept biting the inside of my own mouth and getting mouth ulcers. At first I thought I was being clumsy but then realised the lining on the inside of my mouth was swelling which is why I was biting it by accident. When I took care not to bite my mouth, I still got ulcers anyway and I realised there was some kind of immune reaction involved.

I eventually decided to use the food diary I always keep now after consulting an expert in food intolerance, Prof Jonathan Brostoff who raised my awareness of food intolerance in general, after which I learned how to test for food intolerance with an elimination diet.

So I began to log ulcer incidents and correlate them with foods and after a couple of years found they were happening regularly after eating curry, potato and tomato plus other random looking incidences. I was puzzled but googled these three foods plus mouth ulcers and it spat out nightshades. Once I had familiarised myself with the other foods in this family, a lot of the seemingly random incidences suddenly made sense. So I decided to try excluding all nightshades from my diet and as a result the ulcers reduced in frequency.

It was a bit more complicated as I still got ulcers after eating olives and other foods with alkaloids in them which are not nightshades. I am still unsure about why this is. As a working hypothesis I assumed I had a general alkaloid intolerance and it was causing a hypersensitivity reaction of some kind. It may be more complicated than that, but the point is excluding the high alkaloid foods prevented ulcers and inflammation. However things then got even more complicated.

It took a couple of years for the ulcer frequency to reduce to near normal levels, partly because I was still learning which foods were a problem, but much to my relief the ulcers eventually stopped. However during that time I began to experience changes as follows.

Changes after stopping nightshades.

• excruciating muscle pain
• mitochondrial (ATP translocase) blood tests for white blood cells normalised
• cell free DNA blood test improved
• viral recurrence frequency increased

I lived with a cricked back on both sides under the shoulder blades and terrible muscle cramp pain restricting my movement for the best part of a year before I finally realised it wasn't going to fix itself and that I needed to try something new. Considering the problem was muscular I decided to try a basic sports science approach and boost mineral supplements to see if I could fix it. Thankfully super-doses of extra calcium over a few weeks did the trick and made the cramps manageable again, though I had to balance calcium with magnesium to keep my heart rhythm stable. (I later found extra sodium salt helped with muscle pain as well FYI.) At the time I had no idea why calcium fixed it or why it had become so severe in the first place though it did occur to me that being on a dairy free diet probably didn't help.

Blood tests on the mitochondrial function of my white blood cells (neutrophils) showed that it was returning to normal from a previous pathologically low state, yet I still had ME. Also my cell free DNA, which measures rate of cell death, was reducing from extremely high to just high.

Both these improvements bode well on the face of it, the only problem was I still felt lousy and still had post exertion malaise and still had regular recurring viruses which are a hallmark of my CFIDS. I recently reevaluated the rate of virus recurrence and found it had increased from 8/yr in 2006 to 13/yr ten years later in 2016. It was a perplexing pattern of observations and painful experiences that made little sense. 

It was several years after giving up nightshades that I chanced upon a research paper which seemed to offer a potential explanation. I hasten to add this paper is proper science but the connection to my own symptoms is not proven scientifically but is highly circumstantial and food for thought, to coin a phrase.

Effect of solanine on the membrane potential of mitochondria in HepG2 cells and [Ca2+]i in the cells.By Shi-Yong Gao, Qiu-Juan Wang, Yu-Bin Ji.

Solanine is the name given to one of the toxic alkaloids present in nightshades (another is chaconine which is thought to be similar in action but I only have research on solanine to draw on). The paper above showed that solanine has important toxic affects on human cells.

• It opens the inner mitochondrial membrane permeability transition pore,
• this depolarises the inner mitochondrial membrane,
• releases calcium,
• this also increases likelihood of cell death (apoptosis).

All of these affects match the changes after I stopped eating nightshades.

• My suddenly increased muscle pain was remedied by calcium, perhaps because the calcium previously released by solanines was no longer being released, which meant I needed more calcium.
• ATP translocase and other mitochondrial activity scores in white blood cells improved, perhaps because solanines were no longer depolarising the inner mitochondrial membrane enabling the membrane potential to drive the ATP translocator enzyme normally.
• Cell free DNA tests improved, perhaps because cells were not being killed by apoptosis induced by solanines opening the inner mitochondrial membrane pore and so were no longer releasing so much of their DNA into my blood.
• Viral recurrence due to my ME CFIDS condition got worse and increased in frequency, perhaps because infected cells were not dying as easily due to the lower rate of apoptosis as above.

In addition I have read that nightshades contain an active form of vitamin D called calcitriol which may have been raising my internal calcium levels by taking it from my bones, which isn't so good and makes you wonder about cases of severe ME where people get osteoporosis.

Questions?

It raises questions, such as why solanines would be toxic to me but not other people. The truth is they are toxic to everyone but most people can deal with them. I don't have a clear answer about my own difficulty but my guess is my body is not eliminating them effectively for some reason. I am now exquisitely sensitive to even tiny quantities of nightshade and they make me far iller than when I was eating them regularly and habituated to them having eaten them all my life.

Another question is why my ME didn't get better when the mitochondrial activity of white blood cells improved. I don't know but recent research suggests there are other metabolic bottlenecks in ME and it may be that just because one metabolic bottleneck due to nightshade toxin improved, did not mean the other bottlenecks or adverse reactions due to ME CFIDS were improved, so these would still cause a fatigue syndrome. Plus my immune dysfunction definitely got worse as the nightshades were no longer helping my white cells out by inducing apoptosis of infected cells. So swings and roundabouts.

My conclusion is that my intolerance of nightshades is a secondary illness brought about by primary ME CFIDS reducing my digestive and other defences. I talked it over with a friendly sceptic who suggested I should check whether the dosage from eating these foods is comparable with the doses in the research paper, before jumping to any conclusions.

Quantitative Analysis.

So I looked for quantitative data for a back of envelope type calculation and found the following report online of an investigation for the Bureau of Chemical Safety of Health and Welfare Canada, presumably sometime before 1993 and sometime after the latest 1990 reference used in the report.

SOLANINE AND CHACONINE Dr T. Kuiper-Goodman and Dr P.S. Nawrot, Bureau of Chemical Safety, Health and Welfare Canada, Ottawa, Ontario, Canada.

I was interested to note that potato flesh does contain significant amounts of solanine. So I made a back of an envelope calculation, as below, using empirical experimental data for quantity, absorption and excretion half-life from human and animal experiments summarised in Kuiper-Goodman, to get a rough idea.

Unless I messed up the maths or missed something important (not impossible considering how befuddled I get sometimes) the figures suggest normal portions of nightshades could provide enough solanines to create concentrations in some human tissues comparable to the Shi-Yong Gao paper, sufficient to have an effect on mitochondrial membrane potential, calcium release and apoptosis rates.

Calculation of approximate magnitude of solanine concentrations in the body from consuming potato.

Using an upper bound figure of 5mg / 100g for potato flesh TGA (total glycoalkaloid) from the Kuiper-Goodman article (table 1), then each 100g serving of potato flesh adds a putative maximum of 5mg which works out at 5,000 µg per 70,000* mL i.e. potentially up to 0.0714 µg/mL, if it is all absorbed, which it isn’t but this is addressed below. This compares to the Shi-Yong Gao paper value of 0.016 µg/mL to produce depolarisation of the inner mitochondrial membrane. *(Assuming about 70L human body volume.) 

The experiments summarised in Kuiper-Goodman (para 2.1.1.2) show figures for rats absorbing 10-22% of total dose with 90-78% excreted within 24 hours in faeces and urine.

Human experiments (para 2.1.1.4) indicate tritiated I.V. solanine is rapidly removed from blood plasma and sequestered in blood cells then transferred to major organs, suggesting measured low levels in blood serum during dietary experiments are misleading.

Excretion had a measured half life of 34-68 days, on which basis 1mg per day regular absorption was calculated to give a 50mg load i.e. 50x the daily dose but this experiment does not take into account biotransformation of the tritiated molecules and the real value for glykoalkaloid load ratio is certainly less than 50x.

So if we guess using the lowest value of 10% absorption for solanine 5mg/100g dose food i.e. absorbtion of 0.5mg/100g; it should result in a single dose of 0.0071 µg/mL for a 70 L adult (a tenth of the dose content) and a putative maximum loading up to 50x i.e. very approx 0.3571 µg/mL. The real load is certainly lower due to biotransformation but since the tritium evidence suggests solanines are rapidly concentrated in erythrocytes and then major organs (leukocytes not mentioned), local concentrations may nevertheless rise considerably higher than the estimate for a whole human body volume, due to sequestration.

The Shi-Yong Gao et all study used treatments with 2, 0.4, 0.08, 0.016 and 0.0032 µg/mL and reported significant lowering of mitochondrial membrane potential (P<0.01) at levels of 0.016 µg/mL and above (p 3363). So the putative average concentration from a single dose of 100g potato is 0.0071 µg/mL, just under half the Shi-Yong Gao lower bound for a single dose. It seems feasible that sequestration could take the local concentration significantly higher in some tissues (eg definitely erythrocytes, liver, kidneys and spleen but I saw no info on neutrophils,) for a single dose and that loading could increase this to values potentially exceeding an order of magnitude higher than the Shi-Yong Gao lower bound. Suggesting a range of TGA concentrations which could account for low function mitochondria and also a raised rates of apoptosis in some tissues.

In the real world the case is strengthened by the reality that portion sizes were often considerably larger than 100g eg a 150g bag of kettle chips or a bag of chips from a fish and chip shop or large baked potato. Also Kettle chips and baked potato can include potato skin which has a much higher value for TGA. A greater sensitivity to processed foods containing potato than to potato flesh could likewise be explained by the likelihood that processed potato probably has higher levels of TGA per dose than the potato flesh value of 5mg/100g because in the food industry solanine levels are apparently considered safe at 20mg/100g ie four times higher, so processed mass produced food is able to reach these levels when skin and green potato (TGA up to 11x more at 220mg/100g) can be accidentally incorporated in bleached potato flour for example or a delay between peeling and processing can raise TGA due to time sensitive injury response in the tuber, especially if TGA is regulated per product mass rather than the incorporated potato mass which could explain my sensitivity to apparently small quantities of potato. So a “safe” 20mg dose of TGA would give 0.0286 µg/mL, exceeding the lower bound of the Gao study even without considering sequestration and half life / load.

PS Allegedly similar values for aubergines and sweet peppers btw. http://www.safespectrum.com/articles/potato-toxicity-solanine.php

Soil degradation of glycoalkaloids takes 21- 42 days. https://www.ncbi.nlm.nih.gov/pubmed/19290452