EN - Here is the translated version of my
Finnish Thyroid-CVD essay.
I
got the original inspiration to write about this topic after reading some nice
blog posts by Matt
Stone and Chris
Masterjohn. There just were some studies these guys didn't mention about, so
I decided to try to write a larger article on this
topic.Thyroid Hormones
and Heart Disease1. Introduction
This essay is about the possibility of using traditional thyroid
medication, desiccated thyroid, as a strategy for an efficient prophylaxis for
heart disease. There is a considerable amount of studies carried out on this
subject that, for some reason, aren't very well-known despite their notable
results.
In addition to describing these studies conducted mostly in the
middle of the 20th century, some parts regarding diagnosis, causes and treatment
of hypothyroidism are included.
2. Regarding the current CVD
treatments
In the last
decades, a large part of the discussion related to heart disease (CVD) has been
about cholesterol levels. According to the modern knowledge, some of the LDL
cholesterol in the blood causes atheroma plaques to the intima part of blood
vessels.
This is also the reason why low-fat or low-SFA diets are
recommended for the prevention of heart disease. Saturated fat is supposed to
cause CVD by increasing the serum concentration of LDL cholesterol. It's also
the reason why a large amount of the western human population uses
cholesterol-lowering drugs, statins.
These two methods, however, haven't
proved very effective. Especially, if we look at the recent meta-analyses
compiling evidence from a large amount of fat-modification trials, they don't
support the view that saturated fat is an important cause of CVD. (
Hooper 2011,
Ramsden 2010,
Skeaff&Miller
2009)
Statins, on the other hand, have proved effective.
Meta-analysis published in 2012 revealed that in the context of secondary
prevention, statins can decrease total mortality by 20 per cent in men, though
no significant benefit was seen in women. Also, Cochrane review published in
2011 showed that in primary prevention statins can decrease total mortality by
16 per cent, and heart attacks by a few dozen per cent. (
Gutierrez et al. 2012,
Taylor et al.
2011)
These results are quite good, but of course we want to maximize
the effectiveness of medications and even statins do leave a majority of people
vulnerable to CVD deaths. That's the reason why we should consider if some other
treatment could give better results than the statins.
3. Desiccated
thyroid and CVD, part I: William B. Kountz
In 1951, physician
William
B. Kountz published his monograph
Thyroid
function and its possible role in vascular degeneration, in which he
introduced his 5-year study with 268 subjects.
As study subjects, Kountz
had specifically chosen people with low
basal metabolic rate
(BMR). For the intervention groups he prescribed
desiccated
thyroid to raise their metabolic rate to the normal level. The control group
did not get thyroid. Both groups got some B vitamins as well.
There were
three intervention groups plus their corresponding control groups. Group 1
consisted of middle-aged businessmen, Group 2 consisted of middle-aged office
workers and Group 3 consisted of elderly infirmary patients.
The study
results were promising. The rates of heart attacks were 85, 76 and 44 per cent
lower in the intervention groups (group 1, 2 and 3). The reductions in mortality
were similar, and are shown below.
|
The absolute values are shown
here: Figure
6 |
4. Desiccated thyroid and CVD, part II: James
C. Wren
Two decades after Kountz' research, physician
James Wren conducted two studies which gave additional support to Kountz'
results.
The first study,
Thyroid function and coronary
atherosclerosis, was published in 1968. During the two years, 74 CVD
patients were given desiccated thyroid plus some vitamins. Forty-six controls
were matched for the same number of intervention subjects.
The results were positive. The thyroid treatment
decreased subjects' pains, improved their ECGs and lowered their cholesterol
levels 17 per cent on average. 95 per cent of the subjects reported subjective
benefit from the treatment. The difference in the mortality rates between the
intervention and control group was six-fold (2 vs 12).
In this five-year study there were 347 CVD
patients (1/3 of them were symptomatic), all of which were put on desiccated
thyroid medication even though only 9 per cent of them had hypothyroidism based
on the blood tests.
There was no control group, but during the five
years of study, there were half as much deaths as the statistics would have
predicted for the people of the same age. When a rough adjustment for the risk
factors (heart disease, hypertension etc) was made, it was clear that the
subjects had a fortunate survival rate. Their mortality was only one fifth of
the expected number (11 vs. 53).
|
Did
they prevent ~40 unnecessary deaths in this study? (Kountz
1971) |
5. Desiccated thyroid and CVD, part III:
Broda Barnes
Physician
Broda Otto Barnes'
dissertation was
related to the function of thyroid gland. In the beginning of his medical
practice, he noticed that many of his patients had symptoms that were similar to
mild hypothyroidism. After noticing this, he began prescribing desiccated
thyroid to a large part of his patients.
Barnes didn't diagnose hypothyroidism based on
his patients' blood tests or basal metabolism (BMR), but instead he claimed that
basal temperature is a more accurate marker of thyroid hormone function and
health. His essay on that subject,
Basal
temperature versus basal metabolism, was published in 1942 in The Journal of
the American Medical Association. In that article, Barnes wrote that he told his
patients to measure their axillary temperature immediately after waking up.
Temperature lower than 36.5 celcius (98.6F) was an important indicator of
hypothyroidism and thus, a need for prescription of desiccated thyroid.
Thirty years later, in 1973, Barnes published
some of his patient data in his article
On the genesis of
atherosclerosis. The occurrence of CVD in his 1500+ patients was
94%
lower than Framingham statistics would have predicted. This is a remarkable
results considering that Barnes didn't advocate his patients to quit smoking or
change their other habits.
I think it's wise to mention one of Barnes'
other papers too,
Prophylaxis of ischaemic
heart-disease by thyroid therapy (1959), published in Lancet. The paper
shows that thyroid treatment lowers high cholesterol levels very
reliably.
For his study, Barnes chose 80 persons who had high
cholesteroli (>200mg/dl). Usually the cholesterol levels fell to the range of
170-200mg/dl or 4.4-5.2 mmol/l after the patients had been on their thyroid
medication for a sufficient duration.
6. Desiccated thyroid
and CVD, part IV: Mark Starr, Lerman&White and Henry Russek
Physician
Mark Starr (who has written a book Hypothyroidism Type 2: The Epidemic) has
treated his patients according to Broda Barnes' recommendations. In his book, he
mentions that despite having treated over 1600 patients, only two have had a
heart attack.
"I have treated over 1,600 patients during my 14 years
of private practice and only two have had a heart attack while under my
care." - Mark Starr, MD
In 1946, Jacob Lerman and Paul D. White
described how of 27 young CVD patients 21 had BMR less than 10 per cent below
normal. Desiccated thyroid raised their BMR and lowered their cholesterol
levels. According to Lerman ja White, they couldn't make any clear conclusions
from their observations, but in all except two patients with angina pectoris a
little amount of thyroid extract decreased or cured the pain. And the patients
without previous angina pectoris symptoms didn't suffer any adverse effects from
thyroid extract either. (J Clin Invest 1946; 25:914)
In 1959, Henry I.
Russek wrote in Circulation the following: "To access the effects of thyroid
therapy in patients with coronary artery disease, this hormone, or an identical
placebo, was administered to 58 clinically proven cases of angina pectoris. All
patients studied were determined to be euthyroid by appropriate tests (BMR, PBI,
and cholesterol). [...] Although all patients have been taking maximum doses
[180mg] of thyroid extract for 6 to 15 months, no complications from therapy
have been observed. Exercise-electrocardiographic tests have not demonstrated
diminution in exercise tolerance and, in fact, have shown improved response in 6
patients. Forty-six patients reported subjective benefit as evidenced by an
improved sense of well being, greater motivation, alertness and increased
exercise tolerance. These observations are not only contrary to the traditional
view that thyroid extract is dangerous in the presence of coronary heart
disease, but also establish a rationale for its use in selected euthyroid
patients with this disorder." (Circulation 20: 761, 1959)
7. Desiccated
thyroid and CVD, part V: Other human and animal studies.So, that was
all the clinical data regarding prevention of heart disease with thyroid. Now we
are going to look at some indirect evidence from other kinds of
studies.
1) Clinical hypothyroidism causes heart disease, and
thyroxine prevents this effectIn clinical hypothyroidism, LDL levels
do increase and LDL also oxidizes much faster than usually (lag time 29min), but
thyroxine (T4) restores LDL levels and oxidation rate to normal (lag time
77min). (
Diekman et al.
1998) This phenomena is at least partially related to the physiological fact
that triiodothyronine (T3) increases hepatic LDL receptor activity, which causes
LDL to stay less time in the blood because of the increased uptake*. (
Lopez et al. 2007,
Bakker et al. 1998,
Scarabottolo et al.
1986)
Clinically and subclinically hypothyroid people have increased
intima-media thickness (IMT), and thyroxine resolves this problem. (
Nagasaki et al. 2003,
Duman et al. 2007,
Monzani et al. 2004,
Adrees et al. 2009)
2) Quite often, people with heart disease have also problems with their
thyroids
István Gáspár studies patients who died from
atherosclerosis (n=55). Seventy-one per cent of them had abnormally small
thyroid glands. Twenty-four patients also had signs of thyroid inflammation,
fibrosis and other kinds of thyroid degeneration. (
Gaspar 1968)
Gordon
J. Azar noticed that in his group of 73 heart attack survivors, approximately
half of the subjects had marginal or submarginal thyroid function according to
the protein-bound iodine PBI test. (
Azar 1965)
Unto
Uotila's group, here in Finland in the '50s, noticed that 58% of men and 50% of
women dying of CVD had goiter, while amongst people dying because of other
cause, 28% of men and 22% of women had goiter. (
Uotila et al. 1958)
3) Higher TSH levels are correlated with raised
cholesterol and heart disease even within normal rangeSubclinical
hypothyroidism is correlated with increased risk of myocardial infarction in
elderly women (OR 2.3). (
Hak et al.
2000)
HUNT study included more than 25 000 Norwegians. Those with TSH
in the range of 1.5-2.4, had 41 per cent higher CVD mortality than those with
TSH in the range of 0.5-1.4. TSH of 2.5-3.5 was correlated with 69 per cent
increased heart mortality. (
Asvold et al.
2008)
HUNT also revealed that higher TSH was correlated with worse
serum lipids even in the normal TSH range. (
Asvold et al. 2007) We
also know from the 30's that cholesterol levels higher than 7mmol/L is strongly
correlated with hypothyroidism, and usually thyroid extract lowers the
cholesterol levels sufficiently. (
Hurxthal
1934,
Gildea
et al. 1939 etc...)
|
(Hurxthal,
1934) |
|
(Gildea,
1939) |
4) The classic "herbivore cholesterol feeding"
studiesPathologist Nikolai Anichkov is considered a very important
person in the history of cholesterol theory. He showed that "without cholesterol
there's no atherosclerosis". In 1912, he fed rabbits with cholesterol in
vegetable oil medium, and because of this, rabbits developed atherosclerosis. In
1933 Anichkow stated that this rabbits' atherosclerosis is similar to human
atherosclerosis.
In the same year, Kenneth B. Turner and I.B. Friedland
published their own studies on the same topic. Turner noticed that cholesterol
feeding raised rabbits' cholesterol levels to very high levels (13.45mmol/L),
and feeding thyroid extract prevented this (4.60mmol/L). Iodine had a similar
effect, but thyroxine prevented the rise in cholesterol levels only slightly.
Friedland noticed the same thing: thyroid extract prevented cholesterol-induced
rise in the serum cholesterol and atherosclerosis. (
Turner
1933,
Friedland
1933,
Hoption Cann
2006)
In 1964, L.V. Malysheva noticed that feeding rabbits with
cholesterol lowered their metabolic rate even in the important tissues such as
liver and brain, and in the long term during the development of atherosclerosis
this effect became even larger. The magnitude of this decrease in metabolism has
been compared to the post-thyroidectomy decrease in metabolism. (
Malysheva 1964,
Duntas&Wartofsky
2007)
5) HypertensionHypertension is an
important risk factor of CVD. Desiccated thyroid seems to be a quite potent
medication for hypertension.
In 1952, Pericles Menof published his treatment results based on the
data of 334 patients in South African Medical Journal. He had begun to treat
essential hypertension with sole thyroid. Based on his 4-year experience, he
reported that 69 per cent of his hypertensive patients benefitted from the
treatment, and that the lack of results in some patients can be explained by
their renal hypertension which couldn't be cured by thyroid. (
Menof
1952)
Fifteen years later Menof had the same thoughts regarding
hypertension and thyroid, and in the conclusions of his paper he stated that
"relative thyroid insufficiency is the basic factor in the causation of
essential hypertension". (
Menof
1967)
In 1971, Broda Barnes wrote in the Federation Proceedings, that
during 20+ years and 1000+ patients, only twelve patients developed hypertension
and of 127 hypertensive patients, 102 benefited from thyroid. He also stated
that the reductions in blood pressure happen quite slowly and might take up to
three years. (Fed Proc. Vol 31, Issue 2, s. A214)
Moreover, Fang and
Reyes have also studied the usage of desiccated thyroid in the treatment of
hypertension, but I haven't managed to obtain the full text. According to a
secondary source,
"they were the first to report a coincident fall in the
pulse rate in the majority of the cases successfully treated (68%)". (
Fang&Reyes 1953,
Menof
1967)
8. Regarding the diagnostics: Is the incidence of
hypothyroidism underestimated?One important thing to remember now is
that none of the above physicians (Kountz, Wren, Barnes, Starr) diagnosed their
patients according to the typical guidelines, but instead they based their
diagnoses on other markers such as basal metabolic rate, basal metabolism and
heart disease. Still they had excellent treatment results.
Here in Finland, it's generally accepted that no more than
half
a million Finns suffer from thyroid symptoms. That would equal nine percent
of Finnish population.
However, some doctors such as Broda Barnes have
stated that there are probably a lot more people who would benefit from thyroid
treatment. According to Barnes, in 1976 approximately 40% of Americans had
symptoms of hypothyroidism. In 1989, Jacques Hertoghe estimated that in Belgium,
up to 80 per cent of population suffer from hypothyroid symptoms.
In
common language, "hypothyroidism" refers mainly to primary hypothyroidism, in
which the thyroid gland doesn't produce thyroid hormones normally, and because
of that TSH levels are high and T4 and/or T3 levels are low. The most common
reason for primary hypothyroidism is Hashimoto's thyroiditis. Especially in men,
it's quite rare. Despite this, many people seem to suffer from low metabolism
and various symptoms which seem to be alleviated or cured by thyroid
extract.
It's probable that Barnes' results can't be explained by primary
hypothyroidism. I think that some other thing than low thyroid hormone blood
concentration would explain why some people are susceptible to CVD if they are
not given thyroid extract. I think that the mechanism is more likely related to
function of receptors and target tissues (liver etc). Maybe many people have
some other underlying metabolic problems caused by deficiencies, infections or
other causes, that inhibit thyroid hormone function and aerobic metabolism on
the cellular level. This could be reason why some people need some extra thyroid
hormones, which often leads to extremely low TSH
levels.**
9. Synthetic Hormones VS Natural Desiccated
ThyroidNowadays the medication of thyroid patients is almost
completely based on the synthetic hormones, most usual prescription being
Synthroid (levothyroxine, T4). However, all of those positive results of Barnes
and others were achieved with
natural
desiccated thyroid (NDT).
As a medication, NDT became popular in the '30s, but after the sixties
the synthetic hormones have replaced them almost completely. So nowadays most
hypothyroid patients receive T4 monotherapy. Sometimes but still quite rarely
patients are treated by synthetic combination therapy (T4+T3), sole
triiodothyronine (T3) or desiccated thyroid (NDT; Armour Thyroid being the most
popular trademark).
T4 treatment has often been compared to the
combination therapy. I haven't compiled the research on the subject, but from
what I have seen, it seems to me that for many people the combination therapy
works better than the monotherapy.
Baisier et al. have compared T4 and
NDT treatments, and according to their results, NDT is utterly superior to the
T4 treatment (see the diagram below). They also state that urine free T3 is a
more worthy marker than the typical blood tests. NDT-treated patients had much
higher urine free T3 than those who received synthetic treatment. (
Baisier et
al. 2001,
pdf)
|
T4 got really PWNT by NDT
:) |
I think that no relevant studies on the
efficacy of
levothyroxine on prevention of CVD, but in the seventies one
very large study was conducted, in which they used
dextrothyroxine. Those
who received the synthetic hormone, had a slightly elevated total mortality. (
The Coronary Drug Project
1972)
In the social media there are a lot of discussions regarding
thyroid medications, and I think that very many people on various health forums
also believe that the natural thyroid treatment is often better than the
synthetic treatment.
10. Possible causes of
inadequate thyroid hormone function
The
function of thyroid hormones is related to a large amount of metabolic
processes, so it wouldn't be very illogical to think that in some people, the
inadequate metabolic rate (or thyroid function) could be related to their diet
or lifestyle. Below I demonstrate some of the possible associations between
diet, lifestyle, thyroid hormone function and CVD.
Nutritional
deficiencies - Iodine deficiency is obviously the most well-known cause
of hypothyroidism and goiter. Here in Finland, a large percentage of the
population suffered from iodine deficiency goiter in the '50s. However, salt and
some other foods have been fortified with iodine since those times and therefore
the deficiency is quite rare nowadays. (
Lamberg 1986,
Lamberg 2003)
Selenium is another trace
mineral which is closely related to the thyroid function. In Finland, soils were
quite depleted of selenium until the beginning of 1980s. (
Arthur 2003,
Hoption Cann 2006)
I have been thinking
that he additions of iodine and selenium to the Finnish food supply might have
been one of the main contributors to the decline in coronary heart disease
during the North Karelia project. The common view is that the project decreased
CVD mortality by advocating people to eat less saturated fat (SFA) and to start
exercising.
However, I think it's quite probable that decreased SFA
intake didn't affect the mortality as much as the changes in iodine and selenium
consumption. Paavo Roine's research group stated in 1958, that while there was
higher CVD mortality in the eastern Finland, North Karelia in particular, fat
consumption didn't differ in the east, compared to the western Finland. However,
iodine intake was a little bit lower in the eastern Fnland.*** So maybe we
shouldn't blame fat, but iodine deficiency instead. (
Roine et al. 1958)
Another mineral that
seems to be related to thyroid hormone function and atherosclerosis is copper,
whose deficiency
seems to cause cardiovascular disease. Copper
and zinc can attenuate the damage that cholesterol feeding causes to rabbits.
(
Alissa et al. 2004)
Iron deficiency can also be problem for some
people, but on the other hand, excessive iron can also be a problem, as can be
seen from the people with genes causing haemochromatosis (iron overload). (
Edwards et al. 1983)
Obviously, there
are plenty of associations between nutrients and thyroid
function.
Stress - Those who have read Robert Sapolsky's
popular book
Why
Zebras Don't Get Ulcers or any other similar work, are aware of the fact
that chronic stress can make one more susceptible to a large amount of diseases.
A popular health-blogger Chris Kresser has written about some mechanisms of
stress-induced
hypothyroid symptoms.
Endotoxemia and infections - When the lipopolysaccharides
(LPS) of gram-negative gut bacteria end up in your bloodstream, the condition is
called "endotoxemia". Robert McLeod on has written an interesting blog post
about how
endotoxemia
can disturb the function of thyroid hormones. Endotoxemia does also
correlate with CVD. (
Wiedermann et al.
1999)
11. Other potential targets of desiccated
thyroid therapy
In 1976, Broda Barnes published his book Hypothyroidism: The Unsuspected
Illness. In the book he claims that there are numerous diseases which often
can be cured or relieved with desiccated thyroid. The list includes health
problems such as fatigue, migraine, mental health issues, frequent respiratory
infections, hypoglycemia, acne and the vasculary complications of
diabetes.
12. ConclusionsDesiccated thyroid, as a
medication, has been studied a few times for prophylaxis of heart disease on
clinically euthyroid (no hypothyroidism) people. Without exception, the results
have been very favourable: In the studies, the cardiovascular mortality in
thyroid-treated patients has been less than a fifth of normal. The best effect
was seen in people with no background of heart disease.
These studies
also raise some questions concerning the diagnosis and treatment of
hypothyroidism. Modern blood tests seem to leave a significant amount of people
with hypothyroid symptoms undiagnosed, so maybe some other tests such as basal
temperature, symptoms, basal metabolic rate and total cholesterol, could be
useful in the diagnosis of thyroid hormone insufficiency. We should also
consider that desiccated thyroid could be a more useful medication than
thyroxine monotherapy.
I see that the professionals do not talk much
about the studies I've been talking about here. I'm not really sure what are the
reasons. One could be that these studies do not follow the current RCT gold
standard, but on the other hand lack of adequate data doesn't imply lack of
efficacy, and we are faced with the problem that to this date every clinical
trial on this subject seems to point to the direction that desiccated thyroid
could be a very valuable tool in the prevention of the heart disease.
Endnotes*
Oxidized LDL (ox-LDL) seems to be an especially good marker for CVD, and better
than the traditional markers such as age, total cholesterol HDL, blood pressure,
diabetes and smoking. This seems to be quite logical, because immune cells
degrade specifically ox-LDL, not unoxidized LDL. (
Holvoet et al.
2011,
Meisinger et al.
2005,
Chris
Masterjohn's presentation,
Chris
Masterjohn's cholesterol article,
Sata&Walsh 1998,
Henriksen et al. 1983,
Steinbrecher et al.
1984,
Watson et al.
1997,
Nagy et al.
1998)
** In many people, successful thyroid treatment does lower
their TSH levels to almost zero.
*** The absolute difference was just
11-16µg depending on the time of the year, but even these minor amounts might
have physiological effect because the total intake of iodine by Finns was as
little as 51-71µg per day.
Appendix I: Extra citations
from articles related to thyroid function or heart disease
1916: Bailey CH: Atheroma and other
lesions produced in rabbits by cholesterol feeding. "Enlargement
of the adrenals has been noted by several of the previously mentioned
investigators and also by Rothschild (25), who reports experiments on the
relationship of the adrenals to cholesterol metabolism and hypercholesterinemia.
Enlargement of the adrenals appears to be a consistent finding, having been
present in all rabbits except Nos. 2 and 3. In Rabbits 5 and 14 these organs
were about four times the normal size."
1929: Swaim LT:
Chronic arthritis: Further metabolism studies "In
200 cases of chronic arthritis there was an abnormal metabolic rate in 39 per
cent; 20 per cent were minus and 19 per cent plus. [...] An interesting drop in
metabolic rate was noted in some cases after the administration of thyroid
extract, with an improvement in the stability and regularity of the graphic
metabolic chart."
1935: Turner&Bidwell: Further
observations on the blood cholesterol of rabbits in relation to
atherosclerosis. "In
thyroidectomized rabbits fed cholesterol and potassium iodide, both thyroid and
thyroxin delayed but did not prevent a rise in blood cholesterol. Even with the
hypercholesterolemia in these animals, however, the incidence of atherosclerosis
was low." "Page and Bernhard (4) also found that rabbits fed cholesterol and an
organic iodide developed an average plasma cholesterol higher than those fed
cholesterol alone. The animals given iodide, however, were largely protected
from atherosclerosis"
1937: Litzenberg JC:
The endocrines in relation to sterility and abortion "Since
1922 I have studied the relation of the basal metabolic rate to sterility,
abortions and menstrual disturbances. In our first small series of sixty-nine
consecutive women, in whom no other evidence of myxedema was present, 50 per
cent had a low basal rate; adding those who had conceived but aborted, the
figure was 56 per cent. Carefully supervised thyroid medication resulted in 33.3
per cent conception, 14 per cent of whom aborted. [...] Haines and Mussey of the
Mayo Clinic confirmed our thyroid treatment of functional menstrual
disturbances, saying: "Because of a desire to determine the effectiveness of
thyroid medication alone, in the treatment of certain menstrual disturbances, no
patient received any other treatment. All were definitely improved; amenorrhea,
72 per cent; oligomenorrhea, 55 per cent; menorrhagia, 73 per cent, and general
health, 75 per cent.""
1938: Turner et al: The
role of the thyroid in the regulation of the cholesterol of rabbits.
1942: Barnes BO:
Basal temperature versus basal metabolism. "The
blood cholesterol has been extensively used by some investigators but has been
found useless in the present study. Since most of the present observations were
carried out on college students, the failure of a correlation between metabolic
rate and cholesterol content of the blood may be due to the age of the patient.
Further work would be necessary to prove this point. The pulse rate has been
suggested by some authors, but in college students many rapid pulses have slowed
down on thyroid therapy."
"The
therapeutic results would leave no doubt in the mind of the physician or the
patient that what had appeared to be a classic hyperthyroid syndrome was in
reality hypothyroid in causation. The body temperature was the only criterion on
which a correct diagnosis might have been made. That such cases are not rare is
indicated by 6 additional cases that I have observed during the past twelve
months. In 5 of these an operation had been performed, and the subsequent
history left no doubt of a mistaken diagnosis."
1946: Popják G: The effect of
feeding cholesterol without fat on the plasma-lipids of the rabbit. The role of
cholesterol in fat metabolism. "During
prolonged cholesterol feeding all plasma-lipids show a progressive increase."
"During the administration of cholesterol the iodine value of the phospholipid
fatty acids decreased markedly, i.e. these phospholipids contained more
saturated fatty acids than before the experiment.[...] There appears to be a
selective 'secretion' into the blood by the liver of the phospholipids
containing the more saturated fatty acids."
1947: Barnes BO: Headache; etiology
and treatment. "Practically
all cases presented evidence of thyroid deficiency, and hence, were treated with
thyroid extract. Within thirty days after medication was started, a marked
decrease in both frequency and severity has been the rule. Many cases of
migraine have been completely relieved"1949: Kirk et al. The correlation
between thyroid function and the incidence of
arteriosclerosis.1950: Kountz WB: Vascular
degeneration in hypothyroidism. "This work
reveals that hypothyroidism and its associated metabolic deficiency in man may
lead to advanced degeneration of the blood vessels when present over an extended
period"]1951: Herbut et al: The effect of
hepbisul (heptyl aldehyde-sodium bisulfite addition compound) and thyroxin on
Walker rat carcinoma 256. "Hepbisul
and natural [levo]thyroxin were administered subcutaneously to
Sprague-Dawley rats bearing the Walker rat carcinoma 256. Of the 108 animals
treated, 27 showed complete regression of the tumors and 12 others showed a
favorable histologic response." "Hepbisul and synthetic [dextro]thyroxin
resulted in a favorable response in 2 of 50 animals treated or a total of 4 per
cent. The cause of this discrepancy is unknown."
1952: Menof P: The thyroid
treatment of essential hypertension; report on 334 cases. (pdf) "On
the assumption that thyroid insufficiency is the basic factor in the causation
of essential hypertension, 334 cases of hypertension were treated with thyroid
extract. About 70% responded favourably" "Renal hypertension does not respond to
thyroid treatment."1953: Fang&Reyes: Thyroid
extract in the management of hypertension. ["Fang
and Reyes reported successful results in the treatment of 50 cases of
hypertension. All received a uniform dose of thyroid gr.3 [180mg]. They were the
first to report a coincident fall in the pulse rate in the majority of the cases
successfully treated (68%)."]
Barnes
BO: Etiology and treatment of lowered resistance to upper respiratory
infections. "During
the past 11 years over 150 patients susceptible to respiratory infections have
been treated with thyroid, with gratifying results. In addition to feeling
better, their incidence of colds and sore throats has been reduced to
normal."1954: J. G. C. Spencer:
The Influence of the Thyroid in Malignant Disease "A
higher death rate from cancer was shown to exist in two Swedish counties,
Kopparberg and Gefleborg[...] Those two counties (...) were found to have a
higher incidence of goitre as compared with the rest of the
country."
"The
association of goitre and malignant disease in the post-mortem room was
strikingly illustrated by analysis of 1000 post mortems at the Middlesex
Hospital (Stocks, 1924) [...] The final result of the survey showed that thyroid
anomalities occurred in 18.7 per cent of 500 persons dying of cancer and only in
3.9 per cent of 500 persons dying of conditions other than cancer." "The
presence of excess of thyroxine in the tissues appears to be prejudicial to the
successful grafting of tumours from one mouse to another."
"In
an attempt to explain how this change in tissue is effective we are left with
several possibilities : (a) That thyroxine encourages normal physiological
tissue respiration rather than the so-called anaerobic type which appears to be
the one demonstrable biochemical difference between normal and neoplastic tissue
(Greenstein, 1947)"
Eaton CD: Co-existence of
hypothyroidism with diabetes mellitus. [I
couldn't find this paper so the citation is from a secundary
source]
"[...]when
he sought to determine the incidence of hypothyroidism in diabetic patients by
means of the basal metabolic rate, he found that even though that test is not
very sensitive and may miss many cases of low thyroid function, it established
that hypothyroidism was frequent in diabetics, more so than in the nondiabetic
population. When he then began administration of thyroid in small, physiological
doses to his hypothyroid diabetic patients, he found that the thyroid had no
influence on the diabetes. [...] But there were other marked changes in his
patients [...] They lost their fatigue, their skin problems, and other symptoms
of thyroid deficiency which had not been controlled by the control of the
diabetes. Their susceptibility to infections decreased greatly.Dr.
Eaton also noted that there were fewer problems with thromboses, or blood clots,
in the arteries, which he correctly interpreted as being due to improved
circulation and less pooling and stagnation of blood. And he also noted that, as
the result of increased circulation in the extremeties, there was less gangrene
even in those with arteriosclerosis."]
1955: Feinblatt et al: Treatment of
arteriosclerosis and vague abdominal distress with niacinamide hydroiodide,
without side-effects. [Feinblatt
et al. [83], in a series of 59 arteriosclerosis patients, reported a reduction
in dizziness (71%), headache (61%), disturbed orientation (50%), and fatigue
(41%). Subjects were given both iodine and niacinamide.]1958: Wallach et al: Cardiac
disease and hypothyroidism; complications induced by initial thyroid
therapy.1961: Keating et al. Treatment of
heart disease associated with myxedema. ["Keating
et al. (68) reported a series of 1503 patients with hypothyroidism seen at the
Mayo Clinic, 55 (3%) of whom had angina at the time of diagnosis. Among these
patients with preexisting angina, improvement or no change in symptoms occurred
in 84% after thyroid hormone replacement, with worsening of angina in only 16%.
Thirty-five patients (2%) without preceding angina developed it after initiation
of thyroid hormone therapy. The 1-yr cardiovascular mortality in those with
preexisting angina and treated hypothyroidism was 3%, which is actually less
than the 9–15% 1-yr cardiac mortality reported for angina patients during the
same era (64)."]1964: Dupertuis
CW: The thyroid-vitamin approach to cholesterol atheromatosis and chronic
disease. A ten year study. By Murray Israel, M.D. VIII & 132 pp. The George
Press, Inc., New York, 1960 [book
review] "According
to this concept, hypofunction of the thyroid gland is fundamentally related to
the deposition of cholesterol in the intima as well as to a chain of other
commonly associated symptoms such as nervousness, irritability, depression and
fatique." Treatment for the alleviation of these conditions was based on the
administration of a combination of thyroid extract in varying dosages with
standaradized amounts of Vitamin Complex. [...] According to him, of the
original 714, 443 remain under active treatment from seven months to more than
30 years later, but 202 are lost to follow-up for various reasons, especially
economic. Others have died or moved away. The improvement rate of 92 per cent,
however, is given on 655 patients. [...] As one reads this account of the
results of the thyroid-vitamin therapy, one is impressed with the generally good
results obtained. There seems to be no question that sluggish thyroids do
contribute to a large number of clinical disorders and that these conditions can
be improved by the thyroid-vitamin treatment." [Huom. arvostelija kuitenkin
moittii Israelia puutteellisesta datan antamisesta.]1967: Menof P: High blood pressure
and thyroid insufficiency--recent developments. (pdf) "The
clinical and experimental evidence in support of the view that a relative
thyroid insufficiency is the basic factor in the causation of essential
hypertension is summarized."
1971: Barnes BO:
Physical Fitness in Military Personnel "Heart
attacks have been always infrequent in Graz. In 1930, there were only 0.8% of
the deaths from this cause. At the height of World War II, this fell to 0.3%.
This drop was not the result of less atherosclerosis due to changes in the diet,
since the coronary vessels showed approximately a fourfold increase in sclerosis
in 1944. A marked rise in tuberculosis during the war was responsible for
killing adult males with advancing coronary sclerosis before heart attacks could
occur. The introduction of antibiotics at the end of the war curtailed deaths
from infectious diseases; myocardial infarctions rose year by year until the
incidence in 1966 was 7% of the total deaths."Barnes BO: The
Coronary Drug Project "[...]
the directors should be censored for selecting dextrothyroxine sodium, a
synthetic preparation of variable activity, which has been listed as
contraindicated in coronary disease by the Physicians Desk Reference.
[...] The use of 6 mg of dextrothyroxine sodium by the Coronary Drug Project
represented the calorigenic equivalent of 0.45 mg of levothyroxine sodium or 4.5
grains of desiccated thyroid. Since 1925 it has been repeatedly demonstrated
that such dosages may be fatal in patients with coronary
disease."
Barnes
BO: The role of hypothyroidism in hypertension "A
20-year follow-up on over 1000 patients receiving thyroid therapy reveals that
new cases of hypertension are rare; only 12 new cases appeared in the interval.
In 127 patients the blood pressure was elevated before thyroid was started. In
102 of these a marked reduction in pressure occurred; only a few required any
other medication. In 19 others there was no change in the blood pressures, while
6 showed a mild further elevation over the years. [...] The reduction is very
gradual, and in some cases may require as long as 3 years. [..] Basal
Temperatures have been found more reliable than customary thyroid-function tests
in selecting patients likely to respond to thyroid administration. [...] The
improvement may be due to diuresis, increased renal blood flow and less
atherosclerosis."1974: Dencla WD: Role of
the pituitary and thyroid glands in the decline of minimal O2 consumption with
age. "All
the major endocrine ablations were performed in this and earlier work, and only
pituitary ablation (a) restored in adults part of the responsiveness to
thyroxine found in immature rats and (b) arrested the normal age-associated
decrease in responsiveness to thyroxine in immature rats. Bovine pituitary
extracts were found that decreased the responsiveness of immature rats to
thyroxine."
1976: Barnes BO:
Thyroid Supplements and Breast Cancer "[...]they
state that "a definite relationship between breast cancer and hypothyroidism has
been established." This is certainly true, and the most convincing evidence for
it are some personal, unpublished observations on the routine autopsies
performed in Graz, Austria. Graz is a goiter area; the entire population suffers
from a relative thyroid deficiency. Thyroid replacement is rarely employed
there. Yet the incidence of breast cancer is as high as ten times that seen in
the United States."1981: Lamberg et al. Further
decrease in thyroidal uptake and disappearance of endemic goitre in children
after 30 years of iodine prophylaxis in the east of Finland. "Endemic
goitre of moderate severity was mainly found in the east of Finland in the
1930's. Studies in the 1950's showed an average daily iodine intake of 65-70
micrograms in the west and 50-65 micrograms in the east of the country. The use
of iodized salt was introduced in the late 1940's but added only 15 micrograms
of iodine to the daily intake. In the late 1950's iodine prophylaxis was
intensified and the use of salt containing 25 mg KI/kg was recommended. In 1978
about 95% of all household salt used in the Savonlinna area was iodized. This
region in the east of Finland has been used as an area of surveillance and
studies have been carried out there in 1959, 1969 and 1979. During this period
the thyroidal uptake decreased from 67 to 23% in non-goitrous subjects and from
62 to 28% in goitre patients the difference between the two last figures being
statistically significant. The goitre patients also had significantly higher
serum thyroxine and triiodothyronine levels. During the same period the urinary
excretion of stable 127I increased from 45 micrograms to about 250 micrograms a
day. Concomitantly the goitre prevalence among school children has decreased.
Having been in the early 1950's in most parts 15-30% it is generally now 1-4%.
It seems that the iodine intake is now adequate and that the endemia is
gradually subsiding."
Estes NC: Mastodynia due to
fibrocystic disease of the breast controlled with thyroid hormone. "Nineteen
patients were evaluated for breast pain and nodularity associated with
fibrocystic disease. Rapid pain relief occurred in 73% of patients, with total
relief in 47 percent after daily treatment with 0.1 mg of levothyroxine.
Softening of breast tissue and decreased nodularity occurred within 3 months in
many patients. Three patients had elevated levels of serum prolactin before
treatment, with dramatic pain relief and normalization of prolactin levels after
treatment."1983: Saito et al. Hypothyroidism as
a cause of hypertension. "Adequate
thyroid hormone replacement therapy for an average 14.8 months in 14 patients
resulted in a normalization of thyroid function and a reduction of blood
pressure (p less than 0.01). In four who showed no change in thyroid function
due to inadequate replacement therapy, blood pressure remained elevated. These
results suggest a close association between hypertension and
hypothyroidism."1989: Escobar del Rey et al.:
Generalized deficiency of 3,5,3'-triiodo-L-thyronine (T3) in tissues from rats
on a low iodine intake, despite normal circulating T3 levels. "The
present results show that, despite normal plasma T3, a deficiency of T3 occurs
in more tissues of rats on a low iodine intake than previously
assumed."
Lindberg et al. The impact of
25 years of iodine prophylaxis on the adult thyroid weight in Finland. "In
the 1950's the iodine intake calculated both from urinary excretion of stable
iodine and from food analysis data was 50-70 micrograms per day the intake being
lower in the main endemic area in the eastern part of the country. [...] At the
beginning of the 1980's the iodine intake calculated in the same way was around
300 micrograms per day all over the country. [...] A significant decrease in
thyroid weight from a mean of 44 to a mean of 34 g was
observed."
1990: Oster&Prellwitz: Selenium
and cardiovascular disease. "For
humans, ecological and epidemiological results are reported that show a
relationship between the serum selenium concentration and cardiovascular disease
in populations where low serum selenium concentrations are found, e.g., in
Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland,
and Sweden, subnormal serum selenium and partially whole blood selenium
concentrations are reported in patients with acute myocardial
infarction."
1991: abdel Khalek et al: Effect of
triiodothyronine on cyclic AMP and pulmonary function tests in bronchial
asthma. "Twenty-three
children clinically euthyroid and complaining of chronic bronchial asthma were
given a triiodothyronine (T3) supply for a period of 30 days. [...] All
patients tolerated well the T3 regimen without any adverse effect. They all
reported at the end of the 30 days an obvious subjective improvement of their
asthmatic conditions with a decrease in the number of exacerbations. Seven
patients stopped their usual antiasthmatic medicines, being maintained on T3
only and 3 have decreased the amount of bronchodilators needed."
Witztum&Steinberg: Role of
exodized low density lipoprotein in atherogenesis. "The
nature of the substrate for lipid peroxidation, mainly the polyunsaturated fatty
acids in lipid esters and cholesterol, is a dominant influence in determining
susceptibility. As noted by Esterbauer et al. (52), there is a vast excess of
polyunsaturated fatty acids in LDL, in relationship to the content ofnatural,
endogenous antioxidants. The importance ofthe fatty acid composition was
impressively demonstrated by our recent studies of rabbits fed a diet high in
linoleic acid (18:2) or in oleic acid (18:1) for a period of 10 wk. LDL isolated
from the animals on oleic acid-rich diet were greatly enriched in oleate and low
in linoleate. This LDL was remarkably resistant to oxidative modification,
measured either by direct parameters oflipid peroxidation (i.e., TBARS and
conjugated dienes) or by the indirect criterion of uptake by macrophages
(53)."1995: Escobar-Morreale et al.
Replacement therapy for hypothyroidism with thyroxine alone does not ensure
euthyroidism in all tissues, as studied in thyroidectomized rats. "No
single dose of T4 was able to restore normal plasma thyrotropin, T4 and T3, as
well as T4 and T3 in all tissues, or at least to restore T3 simultaneously in
plasma and all tissues. Moreover, in most tissues, the dose of T4 needed to
ensure normal T3 levels resulted in supraphysiological T4 concentrations.
Notable exceptions were the cortex, brown adipose tissue, and cerebellum, which
maintained T3 homeostasis over a wide range of plasma T4 and T3
levels."
1996: Escobar-Morreale et al. Only
the combined treatment with thyroxine and triiodothyronine ensures euthyroidism
in all tissues of the thyroidectomized rat.1998: Vine et al. Dietary oxysterols
are incorporated in plasma triglyceride-rich lipoproteins, increase their
susceptibility to oxidation and increase aortic cholesterol concentration of
rabbits. "Seven
animals received rabbit chow supplemented with 1.0% auto-oxidized cholesterol
(containing 6% oxysterols), 8 rabbits received 1.0% purified cholesterol
supplemented chow (control diet), and 5 rabbits received standard rabbit
chow."
"Oxidized cholesterol feeding increased total plasma cholesterol
8-fold, reflecting a greater proportion of apolipoprotein B containing
lipoproteins [...] However, the increase in plasma cholesterol after
supplementation with pure cholesterol was more than double that seen with the
oxidized cholesterol-fed rabbits."
"[...]the concentration of aortic
total cholesterol in rabbits fed oxidized cholesterol was increased more than
2-fold (653 ± 131 μg/g versus 278 ± 39 μg/g aorta, respectively) compared to
unsupplemented and purified cholesterol-fed rabbits (Fig. 6). Supplementation of
the diet with pure cholesterol caused no significant increase in arterial
cholesterol concentration (398 ± 41 μg/g aorta) compared to the unsupplemented
group."
"In addition, it has been suggested that arterial fatty lesions
in cholesterol-fed rabbits are due to oxysterols associated with USP-grade
cholesterol (16) [...] It
is possible that the atherogenic basis of cholesterol-fed diets is positively
related to the level of oxidized sterol products."
2000: Downing D:
Hypothyroidism: Treating the Patient not the Laboratory (pdf)Taylor-Robinson&Thomas:
Chlamydia pneumoniae in atherosclerotic tissue. "71%
of atheromatous arteries taken at autopsy from white South African subjects were
C. pneumoniae positive compared with 9% of nonatheromatous
arteries."2002: Espinola-Klein et al: Impact
of infectious burden on progression of carotid atherosclerosis. "Infectious
burden, divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities, was
significantly associated with progression of atherosclerosis, with odds ratios
of 1.8 (95% confidence interval, 1.1 to 2.9) for 4 to 5 and 3.8 (95% CI, 1.6 to
8.8) for 6 to 8 compared with 0 to 3 seropositivities after
adjustment."
Umans-Eckenhausen et al:
Low-density lipoprotein receptor gene mutations and cardiovascular risk in a
large genetic cascade screening population. "Patients
with FH had CVD 8.5 times more often compared with their unaffected relatives
(RR, 8.54; 95% CI, 5.29 to 13.80)."
2004: Gaby AR: Sub-laboratory
hypothyroidism and the empirical use of Armour thyroid. "Research
supporting the existence of sub-laboratory hypothyroidism is reviewed, and the
author's clinical approach to the diagnosis and treatment of this condition is
described."2006: Watanabe et al. Bile acids
induce energy expenditure by promoting intracellular thyroid hormone
activation. ["In
this study, mice that were fed a high-fat diet supplemented with bile acids were
noted to be resistant to diet-induced obesity, but this protective effect of
bile acids was lost in D2-knockout mice."]
Lowe et al. Female
fibromyalgia patients: lower resting metabolic rates than matched healthy
controls.Cohen et al: Sequence
variations in PCSK9, low LDL, and protection against coronary heart
disease. "Of
the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9;
these mutations were associated with a 28 percent reduction in mean LDL
cholesterol and an 88 percent reduction in the risk of CHD" ""Of the 9524 white
subjects examined, 3.2 percent had a sequence variation in PCSK9 that was
associated with a 15 percent reduction in LDL cholesterol and a 47 percent
reduction in the risk of CHD"2007: Roos et al. Thyroid function
is associated with components of the metabolic syndrome in euthyroid
subjects. "A
total of 2703 adult inhabitants of a middle-sized city in The Netherlands
participated in this cross-sectional study. Subjects who were not euthyroid were
excluded, as were subjects taking thyroid medication, medication for diabetes,
and subjects for whom medication data were not available (n = 1122). [...] After
adjustment for age and sex, free T4 (FT4) was significantly associated with
total cholesterol [standardized beta (beta) = -0.059; P = 0.014], low-density
lipoprotein cholesterol (beta = -0.068; P = 0.004), high-density lipoprotein
cholesterol (beta = 0.100; P < 0.001), and triglycerides (beta = -0.102;
P < 0.001). Both FT4 and TSH were significantly associated with HOMA-IR
(beta = -0.133; P < 0.001 and beta = 0.055; P = 0.024, respectively).
Median HOMA-IR increased from 1.42 in the highest tertile of FT4 to 1.66 in the
lowest tertile of FT4."
2008: Taubes G: Diabetes.
Paradoxical effects of tightly controlled blood sugar. "The
obvious explanation for why the three studies came up negative is that the
hypothesis that high blood sugar causes macrovascular complications in type 2
diabetes is simply wrong." [At this point we ought to remember that Barnes and
Eaton could prevent the complications of diabetes with desiccated
thyroid.]
Lowe
JC: Inadequate Thyroid Hormone Regulation as the Main Mechanism of Fibromyalgia:
A Review of the Evidence
"Low
resting metabolic rates of FMS patients. In the first study, patients’ mean
resting metabolic rate was 29% below their predicted rate [...] The mean of the
healthy control subjects’ metabolic rates was only 8% below their predicted
rates. [...] In the second study, the mean resting metabolic rate for patients
was 30% below the predicted rate. The mean metabolic rate of healthy controls
was, again, 8% below the predicted rate."
"Low
basal body temperatures of FMS patients. In the first study, patients’ average
basal temperature was 96.95/F. The average for healthy women was 97.54/F. In the
second study, the average temperature of patients was 96.38/F. The average for
healthy controls was 97.54/F. Statistically, the patients’ temperatures in both
studies were significantly lower than those of controls."
Wikland
B: Redefining Hypothyroidism—A Paradigm Shift "A
direct approach to demonstrate thyroid autoimmunity is to examine the gland by
means of fineneedle aspiration cytology (FNA). For many years, this has been a
routine procedure in our centre in Stockholm, Sweden. The diagnostic and
therapeutic potential of FNA as a complement to conventional first-line tests is
remarkable. In summary, we [1][2] found that no less than 40% of unselected
patients with chronic fatigue (90% women) had definite evidence of lymphocytic
invasion of the thyroid—the gold standard criterion of thyroid
autoimmunity.
What
about TSH in patients with FNA-documented evidence of thyroid autoimmunity? We
found that TSH values were scattered, ranging from less than 1 mU/L to over 30;
the median TSH value was 3.8. (These were baseline values, and none of [1] the
patients were on thyroid medication.) In patients with
cytologically-demonstrated thyroid autoimmunity, the clinical response to
thyroid medication was equally favourable, regardless of the presenting TSH
value."
2009: Georgopoulos et al. Basal
metabolic rate is decreased in women with polycystic ovary syndrome and
biochemical hyperandrogenemia and is associated with insulin
resistance. "Adjusted
BMR was 1,868 +/- 41 kcal/day in the control group, 1,445.57 +/- 76 in all PCOS
women, 1,590 +/- 130 in PCOS women without IR and 1,116 +/- 106 in PCOS women
with IR."
Lowe
JC: Stability, Effectiveness, and Safety of Desiccated Thyroid vs Levothyroxine:
A Rebuttal to the British Thyroid Association2010: Kuppens et al. Maternal
thyroid function during gestation is related to breech presentation at
term. 2011: Yarur et al. Inflammatory
bowel disease is associated with an increased incidence of cardiovascular
events. "The
unadjusted hazard ratio (HR) for developing CAD in the IBD group was 2.85 [...]
IBD patients had significantly lower rates of selected traditional CAD risk
factors (hypertension, diabetes, dyslipidemia, and obesity [...] Adjusting for
these factors, the HR for developing CAD between groups was 4.08"2012: Ertaş et al. Low serum free
triiodothyronine levels are associated with the presence and severity of
coronary artery disease in the euthyroid patients: an observational
study. "Continuous
variables are expressed as mean±standard deviation [...] the FT3 levels remained
as a significant predictor of CAD (OR: 0.266, 95% CI: 0.097-0.731, p=0.01)
[...] FT3
remained as a significant predictor of the severity of CAD (OR: 0.238, 95% CI:
0.083-0.685, p=0.008) (Table 3)."Appendix II:
Some citations from Mark Starr's book Type 2 Hypothyroidism: The
Epidemic"In
1998, I recruited a Ph.D. exercise physiologist to perform basal metabolic rate
testing for my pain patients. The doctor was very conscientious and tried to
make certain the patients were relaxed and proper procedures followed. He
performed basal metabolism tests on 50 consecutive pain patients. All of these
patients had normal thyroid blood tests.
My
50 patients' metabolism averaged 15% below normal. A significant number of their
metabolic rates were in the 30 - 40% below-normal range. Several tests were
above average as well. When a basal metabolism test was previously used to aid
doctors in making the diagnosis of hypothyroidism, a test result of 10% less
than normal or lower was considered strongly indicative of the
illness."
"Only
one patient has developed diabetes while under my care. [...] No other patients
have been diagnosed with diabetes while under my care. In addition, none of the
many diabetic patients under my care have developed any of the common problems
that afflict diabetics such as chronic renal failure, blindness, heart attacks,
gangrene, or peripheral neuropathies. Dr. Eaton's research remains just as valid
as when it was first published in 1954."Appendix
III: Citations from William Kountz' monograph Thyroid Function and its Possible
Role in Vascular Degeneration
"Other
observers as well have found that degenerative changes, which may result in
debilitation of an individual, may cause a rise in the rate of oxygen
consumption. This rise is not believed to be due to increased glandular activity
but rather to an increase in the physiological strain that disease associated
with degeneration imposes upon the organism."