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Chronic Fatigue and Vitamin C

by E. Cheraskin, M.D., D.M.D.

 

(Reprinted with permission from the Journal of Orthomolecular

 

Medicine, 9:1, p 39-45, First Quarter, 1994)

 

Fatigue: Its Meaning

 

Generally speaking, the dictionary defines fatigue with equally incomplete

substitutes such as tiredness, lassitude, weakness, exhaustion, ennui, burnout

and/or boredom. Some few larger lexicons go beyond this synonym chanting. When

they do, fatigue and energy are somehow related. As energy goes down ... fatigue

goes up!

 

Interestingly, one of the highly innovative health questionnaires developed by

the Human Population Laboratory (HPL) in California utilizes energy reserve as

the ultimate demarcating denominator. (1)

Apropos, according to the International Classification of Diseases, (2)

fatigability is now recognized as a sovereign syndrome with its own distinctive

designation (Chronic Fatigue Syndrome), its abbreviation (CFS) and its own

number (780.7).

 

This new-found diagnosis must be viewed in the light of history. For a long

time, every standard medical textbook (3-7) makes the point that one of the most

consistent prodromal findings of practically all disease states is tiredness. It

is recognized as one of the early findings in malignancies (e.g. leukemia),

infectious conditions (i.e. mononucleosis), and even hormonal syndromes

(diabetes mellitus, hypothyrodism). Hence, implied, if not stated, is that CFS

is arrived at by exclusion. 

 

The Measurement of Tiredness

 

Viewed in broad strokes, there are two approaches. The first is simple,

inexpensive, but unfortunately highly qualitative. It consists of

questionnaires. There are many, as one might expect, some more sophisticated

than others. (8) The other option is more complex, costly, but surely more

quantitative. Actually, it takes two forms. The direct includes gadgets such as

hand ergometry, exercycles, treadmills, etc. The other, the indirect, centers

about measures of oxygen consumption. This physiologic phenomenon will be

addressed later in this report.

 

How Big a Problem is Fatigue?

 

According to a recent Department of Health and Human Services report entitled

Reasons for Visiting Physicians, a staggering 14 million Americans go to the

doctor complaining of exhaustion.(9) It is a report that presents a detailed

tabular analysis of data collected in the National Ambulatory Medical Care

Survey (NAMCS) of the National Center for Health Statistics. It is based on

patients' reasons for visiting office-based physicians, determined from a

classification system developed in 1977 for use in this survey.

 

Data collection and processing for the 1977 and 1978 NAMCS were the

responsibility of the National Opinion Research Center at the University of

Chicago. Sample selection was accomplished with the assistance of the American

Medical (AMA) and the American Osteopathic (AOA) Associations.

 

Add to that uncounted millions who seek medical advice for other reasons but

also mention significant exhaustion. And plus the fact there are millions more

who never seek help but are nonetheless tired all the time. It becomes clear

that fatigue is one of the major problems in America!

 

But, it may even be bigger. The HPL study (earlier mentioned) eventuated in

several publications, one of which presented a unique approach to the

measurement of health.(1) In a survey of a sample of the adult population of

Alameda County in 1965, respondents were asked a number of questions regarding

disability, chronic conditions, symptoms and energy status. From their answers,

they have been categorized along a physical health spectrum ranging from a

minimum condition defined by inability to work and/or care for personal needs

(Level I), to an optimal state expressed by no complaints and high energy (Level

VII).

 

Believe it or not, by this diagnostic system, only 6% qualify as energetic and

healthy!

 

However viewed, it is safe to conclude that fatigue is one of the, or the most,

common signal in the health/sickness spectrum. 

 

The Incidence and Prevalence of Vitamin C

 

How many people suffer with hypoascorbemia?

C. J. Schorah of Leeds, England provides us with some exciting answers.(10)

Table 1 summarizes the approximate frequency of classical scurvy in different

samples as judged by the buffy coat layer. It is obvious that some- where

between zero percent of healthy young subjects (line 1) to one out of two

institutionalized elderly (line 6) may possibly demonstrate biochemically

full-blown classical scurvy. With regard to the shades of gray (Table 2), the

evidence suggests that somewhere between three percent of young and healthy

subjects (line 1) and 100 percent of institutionalized young (line 6) suffer

from marginal hypovitaminosis C. Whatever the figures, what seems unquestioned

is that a significant segment of the population shows biochemical evidence of

ascorbate deficiency.

 

Summary of Table 1:

Percentage of Population Groups With Unequivocally Low Leukocyte Vitamin C

Reserves (Classical Scurvy)

young, healthy  0

elderly, healthy  3

elderly, outpatients  20

institutionalized young  30

patients with cancer  46

institutionalized elderly  50

 

 

Summary of Table 2:

Percentage of Population Groups With Marginal Leukocyte Vitamin C Reserves

young, healthy  3

elderly, healthy 20

elderly, outpatients 68

patients with cancer 76

institutionalized elderly 95

institutionalized young 100

 

 

We too have been studying this problem in our clinic at the University of

Alabama Medical Center for a number of years in five unique populations with

over 4,000 subjects including: 1: a dental school patient population (11)  2:

participants in a dental prepayment program,'(12) 3: orthodontic candidates,

(13) 4: selected groups of Floridian dentists and their staffs, (14) and 5:

dental students.(15). Depending upon the tests and the criteria for optimality,

we have concluded that somewhere between 17 and 72 percent of the subjects

studied by us demonstrated suboptimal to clearcut ascorbic acid deficiency

levels.

 

If indeed the figures summarized by Schorah and those cited by us reflect the

true epidemiologic status of ascorbic acid deficiency, then hypovitaminosis C is

a very real and common, probably epidemic, problem which clearly has not been

properly viewed and surely not adequately reported.

 

So, What is the Connection Between C and Fatigue?

 

The correlations are abundant beginning with the earliest medical writings and

still appear in the most recent professional literature.

A Look Back Into the Future

 

There is the old adage, variously described that, those who have not read

history are destined to repeat it. At the end of the Middle Ages, sailors began

to make ever more daring voyages out from western Europe. This could be

explained, in part, by technical developments in the design of the ships that

allowed sailing at a greater angle from the direction of the wind, and in

methods of navigation with a more reliable compass. There were also strong

commercial inducements to find a more profitable sea route in lieu of the

overland trade of silk and spices between Europe and the Far East.

We know that Portuguese sailors began to explore Africa in the 1400s finally

rounding the Cape in 1487. It soon became obvious, though, that on such voyages

the men at sea became quite ill. Their hands and feet swelled and their gums

grew over their teeth, which made eating difficult if not impossible. One of the

earliest, most impressive and relevant findings was inordinate tiredness. As a

matter of fact, many a sailor was asked to walk the gangplank because the

captain accused him of malingering. The truth of the matter was the poor soul

was too tired to perform his duties.

 

For our purposes, we can skip the subsequent experiences with the French,

English and the Dutch. There is ample documentation that their navies suffered

the same fate.

 

Back to the Portuguese who quite by accident encountered Moors who were carrying

oranges which seemed to provide a magical cure.

One naval surgeon who became particularly interested in the devastation of

scurvy at sea was James Lind, now the most celebrated name in the history of

this subject. It was during one such outbreak of scurvy that this British

physician carried out his now famous experiment, probably the first controlled

trial in clinical nutrition, or even in any branch of clinical science. He

studied a group of sailors all with scurvy under what today would be viewed as

an acceptable double-blind experience. Without delving into all the particulars,

it became evident that this terrible syndrome responded almost magically to the

consumption of oranges and lemons.

The Now and New Scurvy

As we have just learned, the vitamin C connection was established with the

recognition that an absence of what later became known as vitamin C led to a

fatal disease identified as scurvy. When the correlation was finally and firmly

established, the scientific community rested with the happy thought that here

was a specific substance associated with a specific syndrome. From this time on

until the middle of the 1900s, not much occurred clinically. True, there were

some isolated brilliant discoveries like the identification of vitamin C by

Albert Szent-Gyorgyi. However, from a practical clinical standpoint, the two

centuries from 1750 to the early 1900s could be viewed as the dark ages.

 

In October 1939, John Crandon(16), a resident surgeon attached to Harvard

Medical School placed himself on a diet of bread, crackers, eggs, cheese, beer,

pure chocolate, and sugar with supplements of yeast and all the then known

vitamins other than C. At the beginning of the trial, chemical analysis of his

blood plasma for ascorbic acid gave a value of 1.0 mg%. (Incidentally, in our

judgement, this is probably the " ideal " plasma concentration.) After 21 days,

the value had fallen to 0.1 mg%, and from six weeks on, none could be detected.

The buffy coat concentration was 28 mg% (which is viewed as marginal) when early

measured and crashed to a non-detectable value only after eight weeks without

vitamin C.

 

Crandon had continued his surgical work all this time. And most important to

point out, before he demonstrated any physical signs, there was an obvious

feeling of tiredness. After 26 weeks, Crandon was given a fatigue test. He could

run at seven miles per hour for only 16 seconds and showed rapid exhaustion in

other measurements. One gram of C was given intravenously each day for a week. A

subjective improvement was noticed in the first 24 hours.

 

There are a number of other reasonably well-designed observations on the

possible connection between tiredness and the ascorbates. To set the scene, one

must recall for most of us, health/sickness is a black and white, either/or

concept. By this definition, making healthy kids healthier is a contradiction in

terms. Even our health experts, by act if not by word, assume that the majority

of children are healthy. Unless the youngster has brittle diabetes, the swollen

joints of classical rheumatic fever, or a glaring congenital defect, we take it

for granted that there is health.

 

But, for the purists, health/sickness represents a spectrum ranging from the

untimate in health (white) to disease and death (black) with an infinite number

of intermediate gradations. There is, in fact, average health versus optimal,

ideal, and possibly the perfect state. With this in mind, it now becomes

conceivable for healthy kids to be made healthier.

Five investigators from Zagreb, in the former Republic of Yugoslavia (17) looked

beyond this traditional concept. They sought the acme (the ultimate in

well-being) through a continuing series of vitamin studies extending over a

number of years. One phase emphasized the effect of ascorbic acid

supplementation on physical working capacity in adolescent boys. After daily

administration for two months of 70 mg ascorbic acid, the mean plasma vitamin C

in the 49 subjects in the experimental group rose four and one-half fold. There

was a bonus of improved oxygen utilization. Conversely, no convincing changes in

biochemical state or in oxygen consumption could be shown in the 42

placebo-supplemented children. Hence, according to Suboticanec-Buzina and his

Yugoslavian coIleagues from the Department of Nutrition at the Institute of

Public Health, it is clear that overall performance can be heightened even in

seemingly healthy kids.

 

There is much more to the story. One vitamin C expert (Doctor C.A.B. Clemetson,

author of a monumental three-volume review of the subject, (18)) best described

the picture: Clearly about half the boys in the supplemented group showed a very

marked increase in working capacity, such as would likely make the difference

between losing and winning their next soccer game. Moreover, their improved

ascorbate status could lift their spirits and would most probably improve their

resistance to infection.

 

We here at the University of Alabama Medical Center have also looked at this

connection. (19) The vitamin C intake of 411 dentists and their spouses was

determined from data on daily vitamin C consumption in a food-frequency

questionnaire. The mean number of fatigue symptoms listed in answers to the

seven questions comprising Section I of the Cornell Medical Index Health

Questionnaire (CMI) was designated the fatigability score. The relationship

between the two variables was determined by calculating the tiredness grade for

different levels of vitamin C intake.

 

The 81 subjects who consumed less than 100 mg of ascorbic acid per day reported

a fatigability mark averaging 0.81. Conversely, the 330 participants ingesting

more than 400 mg of the ascorbates per day reported an exhaustion index of 0.41.

The mean difference was statistically significant. Phrased another way, these

limited data suggest that individuals consuming the generally accepted RDA for

vitamin C report approximately twice the fatigue symptomatology as those taking

about sevenfold the RDA. 

 

Quite apart, it is well-known that, with advancing age, there is increasing

weariness. Old people get more tired than young folks. With that in mind, these

same data were reexamined in terms of the aging process (20).  Figure 1 shows

that, with time, there is a rise in fatigability in those individuals consuming

approximately 41 mg of C. In contrast, it is equally evident from this figure

that persons ingesting an average of 318 mg of the ascorbates do not display

this increment. What  is particularly noteworthy is that the average 57 year

old utilizing about seven times the RDA showed a mean score (0.4) which is less

than the average 33 year old (0.7) demonstrating the RDA for vitamin C.

 

(Figure 1. in the original paper shows the relationship of reported relatively

low daily (mean 41 mg/day) and high (mean 318 mg/day) vitamin C consumption

versus fatigability symptoms and signs. The low vitamin C group showed

significantly more fatigue symptoms with a confidence level of p<0.05.)

 

Fashions in Fatigue in the 90s

 

In the last few years, there has appeared what now seems to be the gospel (21),

official pamphlets for the layman (22) and the physician (23) several

international symposia, a plethora of books (24-32) and even a video proporting

a " new†disorder, Chronic Fatigue Syndrome (CFS).

 

(Figure 2. shows a timeline from 1800 to the present of diseases with symptoms

very similar  to CFS, including (oldest first): febricula, vapors,

neurasthenia, Dad Costa's (effort) syndrome, chronic brucellosis, hypoglycemia,

myalgic encephalomyolitis, epidemic neuromyasthenia, total allergy syndrome,

chronic mononucleosis, chronic EBV, chronic candidiasis, and postvlral fatigue

syndrome.)

Two points are worthy of special mention. Figure 2 shows the timeline graph from

1800 to the present of diseases with symptomatology very similar to CFS. (23)

From this figure, it is clear that CFS is likely not new. Secondly, the

information cited here suggests that Chronic Fatigue Syndrome is viewed by many

as an infectious disorder, by others as a psychiatric/psychologic problem and

finally classified neither of the above. For purposes of this report, it is safe

to conclude that not one of the above cited references recognizes the potential

role of vitamin C in fatigue. As a matter of fact, we have communicated with

experts in CFS. (33-34) From their correspondence, it appears that in their

studies vitamin C was not even considered as a possible factor in the syndrome.

 

Summary and Conclusions

 

There is the proverbial good/bad news. On the positive side, it is comforting

that the ubiquity and devastation associated with fatigue is now being

recognized. This is borne out by the fact that the problem has been ordained as

Chronic Fatigue Syndrome with its own abbreviation (CFS) and even a special

number (780.7) in the International Classification of Diseases. Unfortunately,

having pigeonholed the problem has not added to our general body of fact.

The ecology of disease in general (and this clearly applies here) has been

ignored. Some of the evidence for multifactoriality are cited in the three

forthcoming experiments.

 

In a study in Glasgow " muscular strength was measured by grip pressure and was

found to decrease with lower potassium consumption. Approximately half of the

participants showed low blood potassium. Twenty-eight subjects (36) complaining

of tiredness completed a double-blind cross-over trial of injections of

(vitamin) B-12 (5 mg twice weekly for two weeks) followed by a fortnightly rest

period and then a similar course of matching placebo injections. Appetite, mood,

energy, sleep and general feeling of well-being were assessed. Conclusion:

significant reduction in tiredness with vitamin B,2 administration.

Approximately 45% of adult male workers (37) on a rubber plantation in West Java

(Indonesia) were anemic. Hemoglobin values and performance as measured by the

Harvard Step Test (HST) were significantly correlated. Treatment with 100 mg of

elemental iron for 60 days resulted in a significant improvement in their

performance, work output and morbidity.

 

Because of its history and subsequent course, we have been particularly

concerned with the role of the ascorbates in fatigue. Strangely, in a very

recent book on CFS (38) absolutely no mention is made of vitamin C. The evidence

presented here suggests that increased efforts in this area might help clarify

this seemingly sovereign syndrome.

 

 

References

 

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Andrew Saul, PhD