Chronic Fatigue Syndrome: NICE and CDC miss the boat
The recent "NICE" guidelines in the UK like their sister guidelines
from the U.S. Center of Disease Control (CDC) on this side of the Atlantic
both miss the boat.
I have seen and analysed hundreds of cases of chronic fatigue over
the past decade without ever having to use the term Chronic Fatigue
The problem with these guidelines is that they either omit major causes of
fatigue or make flagrant misguided mistakes such as the following “NICE”
“Vitamin B12 deficiency and folate levels should not be carried out
unless a full blood count and mean cell volume show a macrocytosis”.
Vitamin B12 deficiency (or insufficiency) is extremely common even without
Macrocytosis is a very late sign of this vitamin deficiency.
Furthermore, a concomitant iron deficiency, such as in celiac disease,
would cancel out macrocytosis and the resultant mean corpuscular volume of
the RBC would be normal.
The reference range of vitamin B12, at least in the USA is outdated
and new reference ranges should be implemented (300-1000 pg/ml).
It is very common to miss mild vitamin B12 deficiency without checking
either homocysteine or methylmalonic acid or both. The latter 2
metabolites would be both elevated when serum B12 is insufficient. Even if
B12 level is 300 pg/ml but homocysteine or methylmalonic acid are elevate,
a diagnosis of B12 insufficiency should be made and the fatigued patient
must be treated.
Vitamin B12 is a very common cause of fatigue, malaise, dizziness and
vertigo in people labeled with the diagnosis of CFS.
Vitamin D deficiency is extremely common above the latitude 0f 36 in
the USA. It is even more common in Europe where milk is not widely
fortified with vitamin D.
The daily requirement of vitamin D of 400 IU a day is a thing of the past
but still promoted as if written in stone.
The recent research-supported daily requirement of vitamin D is at least
1000-4000 IU a day.
25 Hydroxy vitamin D should be between 32-100 ng/ml (see a recent NEJM
review on vitamin D by Michael Holick).
25% of the US population have metabolic syndrome. Many of these have
impaired fasting glucose or impaired glucose tolerance (IGT). These pre-
diabetic conditions cause fatigue via glycosuria. Fasting glucose
measurement is not nearly sufficient to detect early glucose intolerance.
A 2-hr glucose tolerance test (OGTT) is abosoluitely necessary to detect
IGT defined as plasma glucose of > 130 from 30 minute- 120 minute
Many patients with CFS have benign positional vertigo and they don’t
They are basically unable to describe their symptoms and for lack of
expression they say they are fatigued. In one such case the Romberg test was abnormal and symptoms resolved within 7 minutes of application of the Epley maneuver. I have yet to see a guideline on CFS that is complete.
It is a good point that NICE mentions ferritin level, although I prefer
iron saturation since ferritin is an acute phase reactant and could be
falsely elevated during periods of acute illnesses due to any cause such
Screening for celiac disease was also a good addition since this disease
is relatively common in Caucasians (1% of populations with an average of a
decade of late diagnosis due to lack of awareness). Addition of sleep
apnea is also a step in the right direction.
I also recommend addition of free T4 to TSH (at least once) so you don’t
miss central hypothyroidism. Serum early morning cortisol should be
measured in every patient with CFS.
If a male person has sexual dysfunction such as poor libido and erectile
dysfunction, muscle weakness and infrequent shaving of beard, a free
testosterone by dialysis method plus LH measurement are necessary
In summary, for me a patient with CFS is a patient who has not been
adequately investigated despite adherence to big- name guidelines of NICE
A thorough and guided investigation would yield the diagnosis in almost
> 90% of patients.
By adherence to my own time-honoured investigation, I have succeeded
in abolishing chronic fatigue syndrome from my medical vocabulary.
Vitamin D deficiency.
N Engl J Med. 2007 Jul 19;357(3):266-81