.... been a while since I gave them a poke. Have always regretted it. Just wanted to see if things are changing in my profession. Posted in the......
Nutrition Forum
A Philosophical Observation on the ICC Criteria for diagnosing ME
A Philosophical Observation on the ICC Criteria for diagnosing ME and its similarities with the Symptom-scape of multiple nutritional deficiencies.
Sometime this month Dr Ron Davis of Stanford University, of Human Genome Project fame and standing, is expected to present his next instalment of insight, drawn from computationally dissected and analysed mega-data from hundreds of different clinical tests performed on each of hundreds of individuals deemed to be suffering from pure, unadulterated ME of a severe degree. He has hinted that he believes he has identified a ‘metabolic trap’ of such a fundamental nature that there may even be a simple, one off (involving several days therapy as an inpatient) treatment to rescue and restore sufferers to ‘normal’. He has also hinted that the metabolism involved is so fundamental that inexpert and/or unmeasured intervention may prove harmful, even fatal, if embarked upon recklessly. This has raised hopes that there may be a set of simple measurements that could be taken to clinically confirm the metabolic dysfunction, and the diagnosis, qualitatively and quantitively, with tailored treatment resulting in not just relief, but cure and prevention! Crucial to this has been the ICC Criteria for sifting out those with co-morbid conditions, physical and mental, and those with less severe illness. The ICC Criteria were designed to improve the quality of research sampling and as such were designed to be highly specific while lacking in sensitivity. They are not designed to be clinically diagnostic but are very useful as a reference clinically and in teaching the more ‘psychiatrically challenged’ clinician that the cult of believing that ME is a psychosomatic disorder with ‘deconditioning’ consequences has really had its day and that if they cling on to the beliefs of this deluded cult, it says far more about them as a person, and as a doctor, than their cult ever did about the patients who were ever diagnosed, or misdiagnosed, with ME.
If we assume that the 5 (compulsory) very specific ways of describing and defining the nature and severity of fatigue, as described in the International Concensus Criteria for defining ME for research purposes, as possibly being met by each vitamin and mineral deficiency that is associated with the symptom of ‘fatigue’ then:-
Symptoms of B3, Niacin (Nicotinic acid and Nicotinamide) deficiency can, on their own, fulfil the ICC research criteria for a diagnosis of severe ME/CFS. Its utilization by transformation into Nicotinamide Adenosyl Dinucleotide (NAD), requiring the incorporation of ribosyl components, is therefore zinc and magnesium dependent and for the production of the adenosyl component is therefore B9 (folates), zinc, magnesium, B2 (riboflavin, (and therefore possibly PQQ)), B12 (Cobalamin) and B6 (Pyridoxine/Pyridoxal-5-phosphate) dependent . Niacin deficiency symptoms secondary to dietary inadequacy (of Niacin and Tryptophan) alone could therefore fulfil the ICC diagnostic criteria. Production of endogenous Niacin (so, strictly speaking not a vitamin) from Tryptophan is Iron (?PQQ), FAD(B2,Zinc,?PQQ) dependent in it’s own right to the metabolic intermediate Quinolinate through the kynurenine pathway and therefore (through the need for the adenosyl component of FAD) doubly B9 (folates), zinc, magnesium, B2 (riboflavin, (and therefore possibly PQQ)), B12 (Cobalamin) and B6 (Pyridoxine/Pyridoxal-5-phosphate) dependent .
B9 (folates) deficiency falls one symptom category short of the 3 of 5 required in Group C impairments (namely lacking “susceptibility to viral infections with prolonged recovery periods, genitourinary symptoms (specified) and chemical, food, medication or odour sensitivities) although B9 deficiency is generally accepted to be associated with immune deficiency with recurrent infection or chronic infection. If this is accepted as equal to the ICC definition of “susceptibility to viral infections with prolonged recovery periods”, then symptoms of B9 deficiency could also fulfil the criteria for the ICC on the definition of ME for research purposes. B6, B12, Zinc and Iron deficiency are all associated with immune deficiency and recurrent infections but would even then still fall short of the ICC criteria by one, in the case of B12 and Zinc, and two in the case of B6 and Iron, symptom category of the 3 of 5 required in Group C impairments. B6 and Zinc also fail to qualify on the Group D impairments (Energy production/transportation impairments) of the ICC criteria.
It is interesting to note that a combination of Zinc and B2 deficiency symptoms can equate to the “one short” of the criteria in exactly the same way as B9 (folates) and that Zinc deficiency, like B9 (folates), is associated with immune deficiency with recurrent infection or chronic infection and so, if co-existing with B2 deficiency, might be considered to be capable of fulfilling the ICC criteria, like B9 (folates).
The ICC criteria allows for a definition of “Atypical ME” if the individual falls short of up to no more than 2 symptom categories, adding that ME without pain or sleep problems is rare. Individually, with a full set of symptoms, B12 (Cobalamin), Magnesium, B1 (Thiamine), Carnitine, Copper, B5 (Pantothenate), Mobydenum, Selenium and Vitamin E deficiency could all meet the criteria for ICC “Atypical ME”. So could an excess of Vit D (Calcitriol).
This last example of a solo explanation for a form of ICC positive diagnosis of ‘Atypical ME’ is of some interest. It has been hypothesised that thyroid hormone resistance, secondary to raised Vit D(Calcitriol)/proVit D(Calcidiol) ratios, may account for much of ME symptomatology. In chronic inflammation provit D (Calcidiol) levels drop [the vitamin D that is measured ‘clinically’] and Vit D (Calcitriol) levels increase way beyond normal [these are not measured clinically] the ‘toxic’ levels of Vit D (Calcitriol) have been suggested to be compensating for pathogen produced vitamin D receptor antagonists. Unfortunately, at these levels, the Vit D (Calcitriol) begins to antagonise/displace T3’s effect on its T3 (alpha, + possibly beta) receptors. If a doctor has measured the provit D (Calcidiol) levels, found them low, and presumed this represents low Vit D levels, rather than the toxic levels, prescribing (pro)Vit D may actually make the symptoms of Vit D toxicity and thyroid hormone resistance worse?
Of the remaining symptoms commonly accepted as being associated with ME/CFS, by such organisations as; the NHS, Open Medical Foundation, ME Association and CFS unravelled(.com), that are not included in the intentionally specific, but not as sensitive ICC criteria, deficiencies of B3, B9, Zinc, B2, B6, Iron, B12 or Magnesium could between them account for 15 of the 28 remaining symptoms, 49 times. The remaining 13 of these 28 symptoms that deficiencies in any of these vitamins and minerals were not associated with were; seeing spots, double vision, loss of speech, loss of swallowing, weight change, muscle wasting, inflammation, allergies, skin test/IgE negative allergies, morning stiffness, alcohol intolerance, cardiac syndrome X and thirst.
At a glance of tabulated symptom lists versus: individual vitamin, mineral, pseudovitamin, essential nutrient and conditionally essential nutrient deficiencies, it would appear that many more pairs, triplets or larger groups of commonly co-existing nutrient deficiencies could ‘blag’ their way into the ICC criteria for a ‘full set’ symptom match for ME/Atypical ME diagnosis.
I do not think that these observations need be perceived as any criticism of the ICC Criteria. Indeed, the assumption in my first paragraph is more philosophical than observational and it must be remembered that the fatigue of ME has been consistently characterised, described and measured objectively for so long, to such a degree and in such a way that no fatigue/lethargy/cognitive decline of nutrient deficiency origin has ever been. However, it does raise questions as to whether, by taking ten steps back and squinting our eyes to blur the picture, that this panoramic ‘symptom-scape’, with key features, could perhaps resemble a familiar picture to those with familiarity with nutrition. Perhaps, such individuals with such a familiarity, might be able to offer insights and observations to those who are now making headway with the metabolic pathogenesis of ME symptoms. Whether any such nutritional deficiencies can be judged primarily due to our modern, agriculturally leeched, industrialised, globalised diet in combination with unnaturally relocated geo-specialised metabolisms and/or secondary to an increase in increased frequency of acute and increased volume of chronic immunological challenge and metabolic/nutritional load on our immune systems is probably well over the horizon of discovery.
In examining nutrition in the context of searching for explanations for the patho-physiology of the symptoms of fatigue/exhaustion and neurological deficits in ME there have already been correlations drawn with similar, recent insights into the patho-physiology of Type 2 DM, Alzheimer’s, Parkinson’s, Multiple Sclerosis, HIV, Congestive Heart Disease, certain cancers, atherosclerosis and many more illnesses begging for faster advancement in understanding and treatment.
Nutrition Forum
A Philosophical Observation on the ICC Criteria for diagnosing ME
A Philosophical Observation on the ICC Criteria for diagnosing ME and its similarities with the Symptom-scape of multiple nutritional deficiencies.
Sometime this month Dr Ron Davis of Stanford University, of Human Genome Project fame and standing, is expected to present his next instalment of insight, drawn from computationally dissected and analysed mega-data from hundreds of different clinical tests performed on each of hundreds of individuals deemed to be suffering from pure, unadulterated ME of a severe degree. He has hinted that he believes he has identified a ‘metabolic trap’ of such a fundamental nature that there may even be a simple, one off (involving several days therapy as an inpatient) treatment to rescue and restore sufferers to ‘normal’. He has also hinted that the metabolism involved is so fundamental that inexpert and/or unmeasured intervention may prove harmful, even fatal, if embarked upon recklessly. This has raised hopes that there may be a set of simple measurements that could be taken to clinically confirm the metabolic dysfunction, and the diagnosis, qualitatively and quantitively, with tailored treatment resulting in not just relief, but cure and prevention! Crucial to this has been the ICC Criteria for sifting out those with co-morbid conditions, physical and mental, and those with less severe illness. The ICC Criteria were designed to improve the quality of research sampling and as such were designed to be highly specific while lacking in sensitivity. They are not designed to be clinically diagnostic but are very useful as a reference clinically and in teaching the more ‘psychiatrically challenged’ clinician that the cult of believing that ME is a psychosomatic disorder with ‘deconditioning’ consequences has really had its day and that if they cling on to the beliefs of this deluded cult, it says far more about them as a person, and as a doctor, than their cult ever did about the patients who were ever diagnosed, or misdiagnosed, with ME.
If we assume that the 5 (compulsory) very specific ways of describing and defining the nature and severity of fatigue, as described in the International Concensus Criteria for defining ME for research purposes, as possibly being met by each vitamin and mineral deficiency that is associated with the symptom of ‘fatigue’ then:-
Symptoms of B3, Niacin (Nicotinic acid and Nicotinamide) deficiency can, on their own, fulfil the ICC research criteria for a diagnosis of severe ME/CFS. Its utilization by transformation into Nicotinamide Adenosyl Dinucleotide (NAD), requiring the incorporation of ribosyl components, is therefore zinc and magnesium dependent and for the production of the adenosyl component is therefore B9 (folates), zinc, magnesium, B2 (riboflavin, (and therefore possibly PQQ)), B12 (Cobalamin) and B6 (Pyridoxine/Pyridoxal-5-phosphate) dependent . Niacin deficiency symptoms secondary to dietary inadequacy (of Niacin and Tryptophan) alone could therefore fulfil the ICC diagnostic criteria. Production of endogenous Niacin (so, strictly speaking not a vitamin) from Tryptophan is Iron (?PQQ), FAD(B2,Zinc,?PQQ) dependent in it’s own right to the metabolic intermediate Quinolinate through the kynurenine pathway and therefore (through the need for the adenosyl component of FAD) doubly B9 (folates), zinc, magnesium, B2 (riboflavin, (and therefore possibly PQQ)), B12 (Cobalamin) and B6 (Pyridoxine/Pyridoxal-5-phosphate) dependent .
B9 (folates) deficiency falls one symptom category short of the 3 of 5 required in Group C impairments (namely lacking “susceptibility to viral infections with prolonged recovery periods, genitourinary symptoms (specified) and chemical, food, medication or odour sensitivities) although B9 deficiency is generally accepted to be associated with immune deficiency with recurrent infection or chronic infection. If this is accepted as equal to the ICC definition of “susceptibility to viral infections with prolonged recovery periods”, then symptoms of B9 deficiency could also fulfil the criteria for the ICC on the definition of ME for research purposes. B6, B12, Zinc and Iron deficiency are all associated with immune deficiency and recurrent infections but would even then still fall short of the ICC criteria by one, in the case of B12 and Zinc, and two in the case of B6 and Iron, symptom category of the 3 of 5 required in Group C impairments. B6 and Zinc also fail to qualify on the Group D impairments (Energy production/transportation impairments) of the ICC criteria.
It is interesting to note that a combination of Zinc and B2 deficiency symptoms can equate to the “one short” of the criteria in exactly the same way as B9 (folates) and that Zinc deficiency, like B9 (folates), is associated with immune deficiency with recurrent infection or chronic infection and so, if co-existing with B2 deficiency, might be considered to be capable of fulfilling the ICC criteria, like B9 (folates).
The ICC criteria allows for a definition of “Atypical ME” if the individual falls short of up to no more than 2 symptom categories, adding that ME without pain or sleep problems is rare. Individually, with a full set of symptoms, B12 (Cobalamin), Magnesium, B1 (Thiamine), Carnitine, Copper, B5 (Pantothenate), Mobydenum, Selenium and Vitamin E deficiency could all meet the criteria for ICC “Atypical ME”. So could an excess of Vit D (Calcitriol).
This last example of a solo explanation for a form of ICC positive diagnosis of ‘Atypical ME’ is of some interest. It has been hypothesised that thyroid hormone resistance, secondary to raised Vit D(Calcitriol)/proVit D(Calcidiol) ratios, may account for much of ME symptomatology. In chronic inflammation provit D (Calcidiol) levels drop [the vitamin D that is measured ‘clinically’] and Vit D (Calcitriol) levels increase way beyond normal [these are not measured clinically] the ‘toxic’ levels of Vit D (Calcitriol) have been suggested to be compensating for pathogen produced vitamin D receptor antagonists. Unfortunately, at these levels, the Vit D (Calcitriol) begins to antagonise/displace T3’s effect on its T3 (alpha, + possibly beta) receptors. If a doctor has measured the provit D (Calcidiol) levels, found them low, and presumed this represents low Vit D levels, rather than the toxic levels, prescribing (pro)Vit D may actually make the symptoms of Vit D toxicity and thyroid hormone resistance worse?
Of the remaining symptoms commonly accepted as being associated with ME/CFS, by such organisations as; the NHS, Open Medical Foundation, ME Association and CFS unravelled(.com), that are not included in the intentionally specific, but not as sensitive ICC criteria, deficiencies of B3, B9, Zinc, B2, B6, Iron, B12 or Magnesium could between them account for 15 of the 28 remaining symptoms, 49 times. The remaining 13 of these 28 symptoms that deficiencies in any of these vitamins and minerals were not associated with were; seeing spots, double vision, loss of speech, loss of swallowing, weight change, muscle wasting, inflammation, allergies, skin test/IgE negative allergies, morning stiffness, alcohol intolerance, cardiac syndrome X and thirst.
At a glance of tabulated symptom lists versus: individual vitamin, mineral, pseudovitamin, essential nutrient and conditionally essential nutrient deficiencies, it would appear that many more pairs, triplets or larger groups of commonly co-existing nutrient deficiencies could ‘blag’ their way into the ICC criteria for a ‘full set’ symptom match for ME/Atypical ME diagnosis.
I do not think that these observations need be perceived as any criticism of the ICC Criteria. Indeed, the assumption in my first paragraph is more philosophical than observational and it must be remembered that the fatigue of ME has been consistently characterised, described and measured objectively for so long, to such a degree and in such a way that no fatigue/lethargy/cognitive decline of nutrient deficiency origin has ever been. However, it does raise questions as to whether, by taking ten steps back and squinting our eyes to blur the picture, that this panoramic ‘symptom-scape’, with key features, could perhaps resemble a familiar picture to those with familiarity with nutrition. Perhaps, such individuals with such a familiarity, might be able to offer insights and observations to those who are now making headway with the metabolic pathogenesis of ME symptoms. Whether any such nutritional deficiencies can be judged primarily due to our modern, agriculturally leeched, industrialised, globalised diet in combination with unnaturally relocated geo-specialised metabolisms and/or secondary to an increase in increased frequency of acute and increased volume of chronic immunological challenge and metabolic/nutritional load on our immune systems is probably well over the horizon of discovery.
In examining nutrition in the context of searching for explanations for the patho-physiology of the symptoms of fatigue/exhaustion and neurological deficits in ME there have already been correlations drawn with similar, recent insights into the patho-physiology of Type 2 DM, Alzheimer’s, Parkinson’s, Multiple Sclerosis, HIV, Congestive Heart Disease, certain cancers, atherosclerosis and many more illnesses begging for faster advancement in understanding and treatment.