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