A new approach to find biomarkers in (CFS/ME) by single-cell Raman micro-spectroscopy, 2018, Morten et al

[adambeyoncelowe]

I wondered the same. If phenylalanine is being diverted to other uses then that might imply difficulty in producing its normal downstream products including dopamine, noradrenaline and adrenaline - which would imply some pretty systemic symptoms like we see in ME/CFS.

Xu et al do reference other studies that indicate a reduction in 'amino acids including phenylalanine' in blood and serum:

• Armstrong et al, 2012 - found reduced glutamine and orthinine. Phenylalanine was not significantly reduced (p=0.35) on an absolute basis. However, it was correlated with the overall (reduced) level of orthinine;
  
• Armstrong et al, 2015 - phenylalanine was decreased in ME/CFS patients (p=0.003)
• Fluge et al, 2016 - the famous pyruvate paper - the only mention I can find of phenylalanine, using my highly scientific Ctrl+F approach, is a reference back to the 2015 Armstrong paper above. This paper did find lots of other reduced amino acids though
• Niblett et al 2007- lower excretion of phenylalanine in urine (p<0.003) alongside a number of other compounds. Also references an earlier study (Jones et al, 2005) that found that urinary excreta differed between CFS and depressed patients

Now, this all needs to come with a pinch of salt given the fact Xu et al is a small pilot study, but - with that caveat applied - it does seem to give additional credence to a range of studies that indicate something is up with phenylalanine in at least a subset of patients. As with all metabolic studies, whether that is a cause of ME/CFS or caused by ME/CFS (i.e. does the fact that patients move less than healthy controls cause their metabolite pattern to differ?) is still to be seen. Additionally, this finding was with PBMCs and so we don't know if any metabolic shift is replicated in other tissues, which might indicate a primarily metabolic problem, or just PBMCs, which might indicate some form of immune system activation. Still, caveats aside, it is encouraging to see findings that seem to support each other - i.e. increase phenylalanine in cells = lowered elsewhere.

This might also be why drugs like amitriptyline work for a minority of patients (it increases noradrenaline, as do the SNRIs used in FM).

So is this a good study, in general? Do we think this is an important finding?

 

[Mij]

Wouldn't low tyrosine also lead to low dopamine, which is implicated in central fatigue in some other illnesses?

My amino acid (in plasma) tyrosine was the lowest of all my amino acids at 28 (24-115).

Report states, low values might stem from the low status of phenylalanine and could lead into thyroid hormone deficiency, which would be noticeable in low values with the energy production panel in (UOA).

Report states, "And sure enough the UOA analysis shows most values rather low within the energy production panel!"

 

[Mij]

Obviously it will be great if this works as an objective biomarker.

To convert phenylalanine into tyrosine you use an enzyme that is dependent on BH4. From memory we are low in BH4 or thought to be. So at first glance this does not seem a great surprise.

I was very low in BH4 so yes, no surprise.

 

[adambeyoncelowe]

My amino acid (in plasma) tyrosine was the lowest of all my amino acids at 28 (24-115).

Report states, low values might stem from the low status of phenylalanine and could lead into thyroid hormone deficiency, which would be noticeable in low values with the energy production panel in (UOA).

Report states, "And sure enough the UOA analysis shows most values rather low within the energy production panel!"

And could this knock-on effect be responsible for rt3 issues too?

 

[Mij]

This was not an issue for me personally, but my free t3 did dip below ref range at times.

 

[Inara]

But if this is all correct and central, shouldn't many of us improve? Many are taking or have taken supplements, including amino acids, and I suppose many avoid aspartam and so on (I don't honestly, although I'm not kern on taking it). I took tyrosin and taurine and so on a pretty while, but since it didn't change anything, I stopped it.

 

[adambeyoncelowe]

But if this is all correct and central, shouldn't many of us improve? Many are taking or have taken supplements, including amino acids, and I suppose many avoid aspartam and so on (I don't honestly, although I'm not kern on taking it). I took tyrosin and taurine and so on a pretty while, but since it didn't change anything, I stopped it.

It could be another downstream effect of something else. Just because it's diagnostic for a condition doesn't mean it's causative, if that makes sense?

 

[Mij]

But if this is all correct and central, shouldn't many of us improve? Many are taking or have taken supplements, including amino acids, and I suppose many avoid aspartam and so on (I don't honestly, although I'm not kern on taking it). I took tyrosin and taurine and so on a pretty while, but since it didn't change anything, I stopped it.

When I had my consult it was advised I take a whole bunch of 'custom formulas' to correct the deficiencies, including all the co-factors. He told me it was a malabsorption issue but that there was another underlying root cause for the low citric acid cycle, possibly viral.

The supplements did nothing for me.

 

[Mij]

Re: single-cell Raman micro-spectroscopy

This experiment was conducted on CFS pts and healthy controls. They need to conduct this experiment with other medical conditions before applying it as a possible biomarker for CFS.

 

[Colleen Steckel]

The BH4 angle might tie this into Rich von K ' s theory re folate availability. If folate availability is poor , homocysteine can form methionine via BH4 , this may compromise its availability for other reactions ?

Would probably be important to verify which of those in the study have the MTHFR gene mutation if this is affected by folate availability. If it is then the diet of the person could affect the outcome of the study.

 

[adambeyoncelowe]

Re: single-cell Raman micro-spectroscopy

This experiment was conducted on CFS pts and healthy controls. They need to conduct this experiment with other medical conditions before applying it as a possible biomarker for CFS.

It sounds like it'd be a downstream metabolic issue (like the hit-and-miss findings about glucose metabolism) that are a result, rather a cause, and so it might be prevalent in other illnesses where fatigue or metabolic issues are present.

 

[Colleen Steckel]

Patient selection for this study? Does anyone have access to see how they chose those 5 patients?

 

[Mij]

It sounds like it'd be a downstream metabolic issue (like the hit-and-miss findings about glucose metabolism) that are a result, rather a cause, and so it might be prevalent in other illnesses where fatigue or metabolic issues are present.

Me too re hit and run.

I had RNA/DNA viral testing up the ying and nothing was found.

 

[Londinium]

Patient selection for this study? Does anyone have access to see how they chose those 5 patients?

I can't see it noted in this paper. The study carried out by Tomas around the same time that also looked at PBMCs used Fukuda criteria.

 

[JaimeS]

But if this is all correct and central, shouldn't many of us improve? Many are taking or have taken supplements, including amino acids, and I suppose many avoid aspartam and so on (I don't honestly, although I'm not kern on taking it). I took tyrosin and taurine and so on a pretty while, but since it didn't change anything, I stopped it.

I take quite a lot of tyrosine, and it has improved my symptoms. I looked up what was considered the right dose, though, and it's a lot more than one, average-sized pill for dysfunction, as it almost always is. Supplement companies don't want to get into trouble; and most who take these supplements are essentially healthy people who want to feel that little bit better. They're not dosed for people like us.

The tyrosine pills I have amount to 1/3 of the tyrosine in a nice salmon filet. Not exactly at huge physiological impact levels.

Patient selection for this study? Does anyone have access to see how they chose those 5 patients?

Yeah, Fukuda (writing this months Research Roundup again, in case you've been seeing me lurking in all these study pages). [Edit: that's a world of nope -- been reading too much and started to mix them up. Not only can I not tell how pts were diagnosed, but this is the weirdest citation system I've ever seen. I see no mention of Fukuda or Carruthers, though, in citations?!]

So far, I think this study was the most interesting one of the lot, because I know a handful of researchers quite possibly onto the same thing. That makes it extra-special interesting to me.

Can't help but feel we're getting closer to AN answer if not THE answer.

Also can't help but wonder if chronically fatigued people tend to drink a lot of diet cola (phenylalanine!) as a rule. I sure hope a broader sample still shows these numbers.

I'm with whoever said we're looking at a biomarker for fatigue. This has been shown in mito disorders as well, and cancer-related fatigue. But hey -- a biomarker for fatigue is still remarkable, if it turns out that's what we're looking at. Especially if it points to potential therapies.

 

[Inara]

I take quite a lot of tyrosine, and it has improved my symptoms. I looked up what was considered the right dose, though, and it's a lot more than one, average-sized pill for dysfunction, as it almost always is. Supplement companies don't want to get into trouble; and most who take these supplements are essentially healthy people who want to feel that little bit better. They're not dosed for people like us.

I think I took 1g or so, over the day. That wouldn't be enough? So what range would be a dose, do you know?

 

[Inara]

Also can't help but wonder if chronically fatigued people tend to drink a lot of diet cola (phenylalanine!) as a rule. I sure hope a broader sample still shows these numbers.

I do, but not a lot. So if this theory should be correct and if I have ME, then skipping the cola alone should make it a bit better?

Are people here who've made the experience besides @JaimeS?

 

[arewenearlythereyet]

Also can't help but wonder if chronically fatigued people tend to drink a lot of diet cola (phenylalanine!) as a rule. I sure hope a broader sample still shows these numbers.

I think I read that in the UK, diet cola now has overtaken full sugar in terms of consumption ...so in general a lot of people will be drinking it anyway.

Personally I find aspartame quite bitter and I prefer water to flavoured drinks (unless it’s gin and tonic or a cocktail). I read an interesting article the other day showing the limiting effect of switching to artificial sweeteners based on a significant proportion of people who taste the bitterness. This appears to be genetic, a bit like how 25% of people can’t taste the TCP molecule (slightly weird example ...but it’s the one example I can remember right now...point is we don’t all taste the same)

I suspect taste will trump any perceived benefits of the phenylalanine in terms of diet cola consumption ...particularly when it is quite readily available in loads of other things and people generally have a diverse choice of things to eat/drink to get it. (Eggs, meat, fish, dairy, soy, nuts and seeds etc etc).

 

[ukxmrv]

I do, but not a lot. So if this theory should be correct and if I have ME, then skipping the cola alone should make it a bit better?

Are people here who've made the experience besides @JaimeS?

We asked around at our early ME groups but no one drank diet cola

A few did drink a lot of ordinary cola and said that they fainted less. This was before we knew about pots.

It comes up as a question whenever one of those aspartame emails does the rounds in the (relatively) newer groups.

Some people feel less faint on coke and coffee they said. I do. Always assumed the caffeine and blood vessels or something?

 

[Mij]

I feel caffeine decrease blood flow to my brain, but it occurs several hours later.