An opinion re. pathogenesis, diagnosis and management Long Covid:

In 2021, I wrote a post entitled “Long Covid: a report from China” [1], in response to “Euthyroid Sick Syndrome (ESS), in Patients with COVID-19”, by Runmei Zou, et al [2].
Now, two years later, “long Covid” still affects approximately 10% of people who contract Covid 19, including a number of celebrities: so it is still a hot subject.
I therefore feel it imperative that I comment on it once more.

Background
Since long Covid was first described, much effort has been put into its investigation; but no firm answers have been forthcoming and the enigma continues.
The condition has 2 aspects:
(1) continuing organ damage, which is variable as to site and severity and
(2) patient complaints, of symptoms including weakness, tiredness, muscle aches, intestinal upset, cognitive loss, ennui and unbearable fatigue, such that productive work becomes extremely difficult, or impossible.

Regarding the organs, the best guess to date is that the “spike protein” of the Covid virus causes inflammation of the lining (the “endothelium”) of the smallest blood vessels and the inflammation excites the blood “platelets” (blood constituents which form blood clots in response to injury), resulting in microscopic clots in the tiniest blood vessels.
However it may be that hyperactive platelets begin to stick together in the large blood vessels, forming micro-clots which then get stuck in the smallest vessels, producing inflammation of the endothelium.
Regardless of the mechanism, microscopic blood clots plug the capillaries in affected organs, reducing the blood flow, causing inflammation and adversely affecting function.

I can add little to the conversation regarding this “endothelialitis”*, excepting that a trial of low-dose aspirin, to prevent formation of micro-clots, might prove valuable.

I do however wish to comment on the symptoms: there may be a solution (below).

*Re. Endothelialitis, go to an excellent article, published by Turner et al. on 4/23/23 [3]
For detail re.aspirin in Covid 19, see an explanation by Zareef et al., in 2021 [4].

The article by Zou et al., re. ESS in “Long Covid”

Zou et al [2] reported finding that 41 (27.52%), out of 149 long-covid cases, had “Euthyroid Sick Syndrome” (ESS) [5].
Of the 41 people affected by ESS, the median age was 58 (IQR: 50–66Yr). (34.15%) were male and 65.85, female.
The sole criterion for diagnosing ESS was “Serum FT3 <2.3 pg/ml with low or normal TSH” (rT3 values unavailable).

 About ESS

“Euthyroid Sick Syndrome” (ESS) is also known as Functional Hypothyroidism, Nonthyroidal Illness, Subclinical Hypothyroidism and Low T3 Syndrome.
Perhaps it should be called “Intracellular T3 Starvation”, but the best (certainly the most descriptive) term is “Intracellular Hypothyroidism” (IH), since the condition is due to elimination of T3 inside the cells [6].

IH follows elevated cortisol, produced in response to stress, because cortisol blocks conversion of T4 to T3 and destroys any pre-existing T3 [6a].
The result is catastrophic, intracellular “T3 starvation”: T3 in the cells falls to zero because T3 is not being made from T4, and pre-existing T3 is changed into T2.

IH may be transient, if there is rapid elimination of the stressful factor.
It may persist, as an ongoing response to a chronic condition, or it may self-perpetuate, if it contributes to and complicates stress, as with stress of psychological origin.

The important laboratory markers for IH are
– Low serum T3, because T3 is made in the cells and exported to the blood, but conversion of T4 to T3 has stopped.
– Increased serum reverse T3, produced from the T4 which normally, would have been converted into T3.
– Reduction of the T3/rT3 ratio, to a value of less than 20: see Cameron Sutherland’s T3/rT3 ratio table, below.
– Normal T4 and TSH, because the thyroid gland is still making T4 and the pituitary gland is not affected by cortisol. An elevated serum cortisol also contributes to the diagnosis, but is of lesser diagnostic value, especially in chronic IH.

C. Sutherland’s table: “ratio of T3 (triiodothyronine) to rT3 (reverse T3)”
by permission from Cameron Sutherland:
T3 (picomoles/L) is in the light blue column.
T3 (nanograms/DL) occupies the yellow column.
Light blue horizontal numbers are reverse T3 values.
Normal T3/rT3 values are located in the pink area.
Subnormal T3/rT3 values are in the white area.

About the T3/rT3 table:
T3 is represented vertically on the left, (picomoles/L in blue, nanograms/DL in yellow).
rT3 is shown in (horizontal) blue numbers on a yellow background.
Normal T3/rT3 ratios are on a pink background.
Low T3/rT3 ratio, diagnostic of IH, are on a white background.

About “normal” rT3
The (currently accepted) normal range for rT3, “5 – 25 ng/DL”, is nonsensical:
(1) With a reverse T3 level of 21, IH will exist if the T3 is less than 6.4 Pm/L, which is in the hyperthyroid range: the accepted normal range for T3, 3.2 – 6.2, was adjusted to 2.8 – 5.8, in 2021).
(2) Therefore a serum rT3 level of >20, without a FT3 level, is sufficient to diagnose IH.
(3) There is no need to consider “normal” for rT3, since it is nonfunctional.
(4) There is however a need for an approximate “desirable” rT3: perhaps, 5 – 13
(an rT3 of <13 ng/DL indicates the absence of IH if the FT3 is 4.0 or more.

Caveat:
The currently accepted normal levels for TSH, T4, T3 and rT3 are all suspect [6b, 6c,]:
– The TSH range should be 2.5 – 4.0 [6d].
– The T4 range, 12–30 pmol/L, is too wide, but does not present any diagnostic difficulty.
– The low limit of the T3 range, originally 3.2 pmol/L, has been revised to 2.8 pmol/L: as in the table, when T3 is 3.2, the T3/rT3 ratio falls below 20 if rT3 exceeds 10 ng/DL.
– The rT3 range, 5-25, is also unreasonable: if T3 is 2.8, IH exists if rT3 exceeds 10. Further, if T3 is 5.8, rT3 must not exceed 18 (see Cameron Sutherland’s table, above).
– If we accept that “normal T3” = 3.2 – 6.2, “acceptable rT3” should be 5 – 13.

Differences between the two Long Covid patient groups, in Dr. Zou’s article
The patients were assigned to two groups according to serum FT3 values: an ESS group, whose FT3 was (arbitrarily) below 2.3 and a non-ESS group, whose FT3 was greater.
The patients with ESS had stronger inflammatory responses (higher CRP, ESR and Procalcitonin), but lower lymphocyte counts, than those without ESS.
They had more fever, fatigue, shortness of breath, cough, expectoration, and anorexia.
The ESS patients had similar TSH, with significantly lower T4 and FT4, as compared with non-IH patients, but TSH and T4 parameters are not significant, when considering IH.

Caveat:
Cortisol and rT3 levels had not been done during hospitalization, so the diagnosis of ESS was not absolute; but a serum FT3 of <2.3 Pg/ml, when FT4 is normal, supports a logical, presumptive diagnosis of hypothyroidism.

 Why is this report important?

(1) The authors proved that over 25% of their long Covid patients had Intracellular Hypothyroidism: it is reasonable to assume that 25% of people with long Covid have IH.
(2) IH is a complication in all severe illness, so IH after Covid infection is not surprising.
(3) By applying a “cutoff” of T3 = <2.3, instead of T3 = <2.8 (? <3.2), to diagnose ESS,
Zou et al. underestimated the prevalence of IH in the group.
If they had used <3.2, the lower limit of normal for T3, or if the T3/rT3 ratio had been available, the percentage of patients diagnosed with IH would have been much higher.*

(4) IH responds well to oral T3, titrated to serum T3 of 5.0 – 6.2 [6]: therefore successful therapy with oral T3 is likely.

*A diagnosis of IH is confirmed when the T3/rT3 ratio is <20: in 7 years of metabolic medicine practice, a T3/rT3 ratio less than 20.0 was often found even when FT3 was as high as 3.9 or 4.0 Pm/L (unpublished data).
Therefore Zou et al. should have included those whose FT3 was <3.2, the lower limit of normal for FT3.

The “workup”, for persons who have “long Covid” symptoms

Following routine history and physical examination, the following tests should be done:
· Complete blood count and major (renal, hepatic, cardiovascular etc.) organ tests,
· DHEA, free testosterone, estradiol, estrone, progesterone,
– HS CRP, ESR, Homocysteine,
– TSH, FT3, FT4, reverse T3,
– Thyroid Antibodies,
– Vitamin D,
– Other tests, as necessary, such as tests for cancer and other causes of chronic fatigue.

Management of IH
IH should be diagnosed, assessed and treated by a healthcare professional trained in metabolic medicine [8, 9].
Since intracellular T3 is zero, the best therapy is oral T3, titrated upwards based on weekly testing.
Since we cannot assess intracellular T3, the nominal “target” of therapy is a serum T3, of >5.0 and <6.3.
Slow-release capsules of T3 work rapidly and very well: quick release tablets are more prone to side-effects.
Treatment is started with a low dose (usually, 5 µg daily, occasionally 1-2 µg daily).
Therapy is monitored with weekly assays of T3 and the dose is titrated upward until serum FT3 is 5.0 – 6.2 [9].

Side effects are explained carefully, to the patient and the closest caregiver: at the first sign of side effects, the dose of T3 is reduced by 5 µg/day.
However no significant adverse effects were encountered, during seven years practice in managing IH.

Therapy with T4 massively increases serum reverse T3. It does not change the intracellular, or serum, T3.

Therapy should also be directed towards correction, or elimination, of any associated disease and of the stressors responsible for increased cortisol secretion.

Caveats:
The above observations and opinions are based on my practice of BIHRT and management of intracellular hypothyroidism, from 2014 to 2020, but I discontinued practice in the early days of the Covid pandemic and had no cases of “Long Covid”.
Therefore the opinions above, while accurate in terms of the management of IH and presumably applicable to the management of Long Covid, do not reflect actual experience with the management of that condition.

IH occurring as an accompaniment to severe, brief acute illness or trauma, tends to settle and disappear with recovery from the underlying condition.
However IH resulting from chronic stress will only subside if the stressor is eliminated.
Further, IH tends to self-perpetuate, due to psychological stress/cortisol release caused by the anxiety, inconfidence, confusion and depression which chronic, deep intracellular hypothyroidism produces.
Even when an illness is expected to be brief, immediate correction of IH will assist in the patient’s recovery; an FT3 test can be done quickly and will justify a T3 prescription, or provide evidence for reducing it.

An FT3 result of <3.2 indicates probable IH, to be diagnosed if rT3 is >10. Therefore instead of awaiting the reverse T3 result, which is usually delayed, oral T3 therapy should be started immediately and titrated to increase the serum FT3 to 5.0.

The triiodothyronine prescription should be combined with support of other hormones, vitamins and minerals, following a full metabolic “workup”.

Diagnosis should be confirmed, and IH therapy supervised, by a physician trained in metabolic medicine [7], defined by Dr. R. Klatz and Dr. R. Goldman, in 1992 [8].
However management of the underlying condition should be at the discretion of the “MRP” (the most responsible physician).

Online advice
A study of online information reveals many different attitudes to ESS (IH).
For example, an article saying that ESS is a self-correcting biochemical anomaly, occurring naturally in ICU cases, which does not require treatment [10] is to my mind, a superficial assessment.
Again, any article which does not mention, or discounts, reverse T3 cannot be applicable to a consideration of IH.
The idea that ESS (IH) will correct itself [10], may appear to be reasonable when intracellular hypothyroidism is results from transient illness.
However, to apply a “hands-off” approach to the management of chronic IH, is to sentence the patient to ongoing symptoms. This at best, would be an un-empathetic approach to a truly debilitating problem: at worst, the patient may progress to myxedema.

REFERENCES

[1] Long Covid: a report from China, by G. A. Harry, in CBHRT.ca,
https://cbhrt.ca/2021/08/17/long-covid-a-report-from-china/

[2] Euthyroid Sick Syndrome in Patients With COVID-19, Runmei Zou^1†, Chenfang Wu^2†, Siye Zhang², Guyi Wang², Quan Zhang³, Bo Yu², Ying Wu², Haiyun Dong², Guobao Wu², Shangjie Wu⁴ and Yanjun Zhong^2*Front. Endocrinol., 07 October 2020, Sec. Thyroid Endocrinology, Volume 11 – 2020 | https://doi.org/10.3389/fendo.2020.566439 https://www.frontiersin.org/articles/10.3389/fendo.2020.566439/full
The original paper was published online, by Front Endocrinol (Lausanne), 2020 Oct 7;11:566439.
DOI: 10.3389/fendo.2020.566439.
I accessed it via https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575767/ DOI: 10.3389/fendo.2020.566439. PMCID: PMC7575767PMID: 33117282.

[3] “Long COVID: pathophysiological factors and abnormalities of coagulation” by Simone Turner, M Asad Khan, David Putrino, Ashley Woodcock, Douglas B Kell and Etheresia Pretorius, in “trends in Endocrinology and metabolism”, 4/19/23, at https://www.sciencedirect.com/science/article/pii/S1043276023000553#bb0040

[4] “Aspirin in COVID-19: Pros and Cons” by Rana Zareef^1†, Marwa Diab^1†, Tala Al Saleh^2†, Adham Makarem², Nour K. Younis³, Fadi Bitar^1,2,4 and Mariam Arabi^1,2,4* , in Front. Pharmacol., 10 March 2022, Sec. Pharmacology of Infectious Diseases, Volume 13 – 2022, https://doi.org/10.3389/fphar.2022.849628 https://www.frontiersin.org/articles/10.3389/fphar.2022.849628/full

 [5] Euthyroid Sick Syndrome, by Serhat Aytug, MD Medscape, Updated: Oct 06, 2022 https://emedicine.medscape.com/article/118651-overview

[6] IH (intracellular hypothyroidism), by G. A. Harry, in cbhrt.ca,
https://cbhrt.ca/2023/04/27/intracellular-hypothyroidism-ih/

[6a] stress causes hypothyroidism, by G. A. Harry, in cbhrt.ca,
https://cbhrt.ca/2022/12/14/stress-causes-hypothyroidism/

[6b]Thyroid tests: should our thyroid hormonal assessment be reviewed?, by G. A. Harry, in cbhrt.ca,
https://cbhrt.ca/2021/11/05/thyroid-tests/

[6c] Think about normal, by G. A. Harry, in cbhrt.ca,
https://cbhrt.ca/2021/10/23/thinking-about-normal/

[6d] The evidence for a narrower thyrotropin reference range is compelling,
by Leonard Wartofsky ¹ , Richard A Dickey, J Clin Endocrinol Metab, 2005 Sep; 90(9):5483-8 PMID: 16148345
DOI: 10.1210/jc.2005-0455 .https://pubmed.ncbi.nlm.nih.gov/16148345/

[7] Specialty spotlight – metabolic medicine, Royal College of physicians, London, UK, https://www.rcplondon.ac.uk/education-practice/advice/specialty-spotlight-metabolic-medicine,

[8] A4 M/MMI, https://www.a4m.com/about-a4m-mmi.html

[9] T3 and intracellular hypothyroidism, by G. A. Harry, in CBHRT.ca,
https://cbhrt.ca/intracellular-hypothyroidism/

[10] Euthyroid Sick Syndrome, Kavitha Ganesan, Catherine Anastasopoulou, Khurram Wadud, In “Stat Pearls”, NIH,
https://www.ncbi.nlm.nih.gov/books/NBK482219/

INTRACELLULAR HYPOTHYROIDISM

Intracellular thyroid 3 deficiency, which I refer to as Intracellular Hypothyroidism (IH), has been called many names (see below), but has never been recognized as a bona fide metabolic abnormality deserving of its own title.
This is perhaps a part of the reason why it has not been taken seriously by mainstream medicine and why its diagnostic panel has not been added to the family doctors’ armamentarium, now 9 years since it was definitively described in 2014.
It is time for doctors, indeed for the entire population, to elevate this miserable, dangerous, vexing, disturbing, upsetting, ubiquitous metabolic abnormality to its rightful place as a syndrome on its own, so that it can be seen as the pervasive, morbid condition which plagues so many of us.
This article therefore is (hopefully) intended to educate our people and their doctors: to help us navigate this life, free of the yoke of intracellular thyroid 3 hormone starvation.

History of IH
Our understanding of the metabolism of thyroid hormones within our cells has been nicely explained by Dr. Kent Holtorf, who in 2014, first described of the effects of intracellular T3 starvation, ascribing it to failure of thyroid hormone transport into cellular tissue [1].
Subsequently, writing with Erika Schwartz as the metabolic process became clearer, he briefly considered giving IH the title “reverse T3 dominance”: rT3 was credited with an active role in blockading access of T3 to thyroid receptors [2].
His final paper on the subject [3] succinctly explains the true situation; to quote him,
”D1 converts T4 to active T3 throughout the body, but not in the pituitary, where T4-T3 conversion is controlled by D2.
D1 but not D2 is suppressed and down-regulated (decreasing T4 to T3 conversion) by cortisol, secreted in response to physiologic and emotional stress.”

Simply put, the situation is clear: under stress, no T3 is produced intracellularly, because D1 is blocked by cortisol.
Also, any pre-existing T3 is destroyed by D3, again with cortisol as the trigger: thus intracellular T3 starvation results.

Definition:
Stress-related, intracellular T3 starvation, previously termed “Reverse T3 dominance” by Kent Holtorf and Erika Schwartz, is called “Functional Hypothyroidism” by the Metabolic Medicine community. It is also known as “Subclinical Hypothyroidism”, “Euthyroid Sick Syndrome” and “Nonthyroidal Illness Syndrome”, by mainstream medicine.
However the most appropriate term is Intracellular Hypothyroidism (IH), because the condition actually is insufficient T3 within the cells [4].

Etiology:
We now know that the aberration is due to two intracellular effects of cortisol: blockade of Deiodinase 1, with failure of conversion of T4 into T3 and activation of Deiodinase 3, which converts T4 to reverse T3 and T3 to T2.
As defined, IH (intracellular T3 deficiency) results from the actions of cortisol, which is released by the adrenal glands in response to stress: Cortisol blocks Deiodinase 1, preventing conversion of T4 to T3 and it activates Deiodinase 3, which converts T4 to rT3 and pre-existing T3 to T2: rT3 and T2 are both metabolically inactive [5].  

Incidence:
Intracellular Hypothyroidism is ubiquitous. Conjecturally, it is the most pervasive metabolic aberration.
It may result from, or may cause, illness, but notwithstanding, it accompanies all life-threatening illnesses.
IH is found in the vast majority of chronic debilitating conditions, in prolonged depression and in morbid obesity, in anorexia nervosa and starvation.
It complicates severe physical injury, major surgery, significant psychoshock and any acute illness severe enough for admission to an intensive care unit.
It is associated with heart failure, cardiomyopathy [6,7], Long Covid [8], PTSD, Chronic Fatigue Syndrome [9], ME, Fibromyalgia, the post-finasteride syndrome, infertility with recurrent abortion, major depression, schizophrenia, chronic true hypothyroidism and a host of other conditions, including neurological and neuromuscular diseases, such as Multiple Sclerosis, Parkinson’s disease, Alzheimer’s disease, Hoffman’s syndrome [10], stiff person syndrome [11].
It is reasonable to conclude that IH accompanies each and every severe disease, but “the message has been lost in translation”: as an example, an extremely thorough, erudite and otherwise admirable report on ALS [12], published in 2021, considers all possible etiologies of ALS: the reported battery of tests included thyroid profiles, but there was no mention made of reverse T3, without which IH cannot be diagnosed.

Duration:
IH may be short-lived, existing only as long as the stressful episode persists, or may be a long-term accompaniment to chronic stress [13].
It tends to self-perpetuation, because the confusion, psychological uncertainty and anxiety which hypothyroidism produces keep the person’s “subconsciously perceived” stress high even after the original stressful situation has gone.
Thus it is often confused with chronic fatigue syndrome (CFS) and it is probably the cause of “Long Covid” symptoms [8].

Diagnosis:
IH can be asymptomatic, especially in confident people who have high self-esteem and tend to endure mild symptoms without complaint [13]: some people are able to hide, or ignore, their low-thyroid symptoms.
However asymptomatic IH is easily diagnosed on the basis of the T3/rT3 ratio.
Caveat: in uncomplicated true hypothyroidism, the TSH is elevated to >2.5 [14] and serum FT4 and FT3 are low, whereas in IH, TSH and FT4 may be normal, but FT3 is at, or below, the low end of the “normal” T3 range and reverse T3 is sufficiently increased to reduce the T3/rT3 ratio to less than 20.0 [15].
The diagnosis of IH is usually missed by doctors, because TSH is traditionally believed to be the only necessary diagnostic parameter for thyroid function and in IH, TSH production is normal, because the pituitary gland is unaffected by the condition.
Therefore a “thyroid profile“, including TSH, free T4 (F T4), free T3 (FT3) and rT3 should be included in every diagnostic test series, regardless of the reason for the investigation.

Comparison with true hypothyroidism:
True hypothyroidism (TH) may coexist with IH, in which case investigation usually suggests a diagnosis of TH, because:
(1) TSH is elevated to > 2.5
(2) FT4 is low, or below the normal range,
(3) FT3 is at, or below, the low end of the normal range,
(4) rT3 production is restricted by the low T4, so it is only minimally elevated and the T/rT3 ratio is borderline.

Thus in combined true and intracellular hypothyroidism, the IH is often masked until T4 is prescribed and a follow-up thyroid profile is done. The situation then becomes obvious, because:
(1) TSH has returned to normal,
(2) FT4 has increased,
(3) FT3 remains low,
(4) rT3 has increased, due to preferential conversion of exogenous T4 to reverse T3 and the T3/rT3 ratio is less than 20.

Caveat:
The “normal” ranges for TSH, FT3 and rT3, as advertised by traditional allopathic medicine are all suspect: see “Think About Normal” [15], at https://cbhrt.ca/2021/10/23/thinking-about-normal/, or via “research gate”.
Also see “THYROID TESTS: SHOULD OUR THYROID HORMONAL ASSESSMENT BE REVIEWED?”,
At https://cbhrt.ca/2021/11/05/thyroid-tests/

Calculation of the T3/rT3 ratio, from the thyroid profile results:
T3 is reported in Picomoles per litre (Pm/L) and rT3 is reported in Nanograms per decilitre (ng/DL)
To obtain the ratio, we first convert the T3 value to ng/DL, by dividing FT3 by 0.0154.
We then divide the T3 (ng/DL) by the rT3 value: this gives us the “T3/rT3 ratio”*.
The accepted normal ratio is >20 and the preferred optimum is >24.
Intracellular hypothyroidism is diagnosed if the ratio is <20.

*Cameron Sutherland’s T3/rT3 ratio table is available online, at CBHRT.ca: /media/driveD/AUser/Documents/A WORK AIDS/Cameron Sutherland’s T3 – rT3 Worksheet: see a truncated version, below.
Brief perusal of this T3/rT3 ratio table will show that if serum T3 is 5.2, a normal T3/r T3 balance will obtain unless the rT3 value is > 17 and that when serum T3 is 6.2, a normal balance obtains until rT3 exceeds 19.

Rating the severity of IH:
It is reasonable to rate the severity of intracellular hypothyroidism thus: 7-10 = Severe, 11-15 = Moderate, 16-20 = Mild.
However the degree of IH varies with the individual’s stress level and it is in the patient’s interest to assume the worst.

Treatment protocol – choice of therapy:
(1) When IH, or combined TH and IH, is diagnosed, triiodothyronine should be prescribed rather than thyroxine [3], because since exogenous thyroxine will be preferentially converted into reverse T3, the intracellular T3 concentration will not increase and the IH will not be resolved [4].
(2) Appropriate therapy for any associated disease, if available, should be prescribed concomitantly.

The choice of triiodothyronine (T3) format is important: a tablet, “Cytomel”, is available, but the T3 is rapidly released and absorbed [16], producing a “Spike” of serum T3 two-and-one half hours post-dose, with resumption of the patient’s symptoms, in the afternoon.
Compounded T3, in a slow-release format, is preferred, because it does not produce a “spike and crash” phenomenon [4] and symptom relief persists throughout the day.

Treatment protocol [4] – Titrating the dose of T3:
The prescription begins with 5 µg of triiodothyronine (T3), taken at, or close to, 4 AM, so as to mimic the diurnal rhythm of thyroid hormone release.
Serum T3 is estimated weekly*, increasing the dose of T3 by 5 µg each week until an FT3 of 5.0-6.2 pmol/L is attained. When a serum T3 level of 5 pmol /L, to 6.2 pmol/L has been reached, the prescription is renewed without change *.
If a T3 test result of >6.2 pmol/L is reported, the dose is reduced.
Serum rT3 is repeated, as part of the thyroid profile, 2 weeks after the maximum dose is attained, so as to confirm normalization of the T3/rT3 ratio.

Follow-up:
So as to avoid recurrence of IH, it is best to maintain serum FT3 between 5.0 and 6.2 pmol/L: a brief perusal of Cameron Sutherland’s T3/rT3 ratio table.
Fluctuating stress may render cortisol production and resulting effects on intracellular T3 concentration variable, therefore the patient’s symptomatology, FT3 and T3/rT3 are reviewed every 3 months for a year and thereafter, yearly.

Discontinuation of therapy:
Occasionally, stress can be completely eliminated, in which case IH may go into remission. When this happens, it may be reasonable to discontinue T3 treatment. However a relapse to intracellular hypothyroidism is likely, if stress recurs.

• Caveat:
  The T3/rT3 ratio shows whether the abnormality of thyroid hormone metabolism needs to be corrected.
  However T3/rT3 is not a “target”, in terms of calculating the dosage of slow-release T3 for the individual patient: the serum T3 level is better.
• The dosage of slow-release T3 is increased until the serum T3 is between 5.0 and 6.2 pmol/L (see below).
  However the patient’s symptoms are more important than blood test results: for “perfect” physical and psychological function, some individuals need a T3 serum level at, or slightly over, the accepted upper limit.
• Intracellular hypothyroidism is of particular importance in pregnancy: for a pregnant woman, IH is no different than true hypothyroidism, excepting that it is not recognized and is therefore not treated, much to the detriment of the fetus, who is liable to all the effects of maternal hypothyroidism, including cognitive deficits, ADD, ADHD, dyslexia, autism and schizophrenia [17].

*The half-life of T4 is 6 or 7 days, so we repeat the thyroid profile 6 weeks after prescribing thyroxine, to ensure testing at a “steady-state” of T4 serum concentration. T3’s half-life is 22 hours [16], so the T3 can be checked at 7 days post-Rx. **The half-life of oral Liothyronine varies with the individual’s thyroid function status and with the method of calculation, so it is variously reported by different investigators.
Perhaps the best estimate to date is that provided by Jacqueline Jonklaas et al [7] in 2015; but in terms of comparison with the half-life of T4, a factor of 1:6 is appropriate.

REFERENCES

[1] Thyroid Hormone Transport into Cellular Tissue, by Kent Holtorf, Holtorf Medical Group (HMG), Journal of Restorative Medicine 3(1):53-68, April 2014, DOI:10.14200/jrm.2014.3.0104

[2] Erika T. Schwartz, MD, Kent Holtorf, MD, Hormones in Wellness and Disease Prevention: Common Practices, Current State of the Evidence, and Questions for the Future. Prim Care Clin Office Pract 35 (2008) 669–705
https://custommedicine.com.au/health-articles/reverse-t3-dominance/

[3] Peripheral Thyroid Hormone Conversion and Its Impact on TSH and Metabolic Activity, Kent Holtorf, MD, Journal of Restorative Medicine 2014; 3: page 30, 2014, DOI 10.14200/jrm.2014.3.0103

[4] Gervais A. Harry, “T3 and intracellular hypothyroidism”, 2022.
Https://cbhrt.ca/intracellular-hypothyroidism/

[5] “Cortisol”, by G. A. Harry, https://cbhrt.ca/cortisol/

[6] Myocardial Induction of Type 3 Deiodinase in Dilated Cardiomyopathy (experimental, Mice), Ari J. Wassner,¹Rebecca H. Jugo,¹David M. Dorfman,²Robert F. Padera,²Michelle A. Maynard,¹Ann M. Zavacki,³Patrick Y. Jay,⁴ and Stephen A. Huang¹ . Thyroid. 2017 May 1; 27(5): 732–737. Published online 2017 May 1. doi: 10.1089/thy.2016.0570PMCID: PMC5421592PMID: 28314380 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421592/

[7] Hypothyroidism-induced reversible dilated cardiomyopathy, by P Rastogi, A Dua, S Attri, and H Sharma, J Postgrad Med. 2018 Jul-Sep; 64(3): 177–179. doi: 10.4103/jpgm.JPGM_154_17
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066629/

[8] Euthyroid Sick Syndrome in Patients With COVID-19, by Runmei Zou,^1,† Chenfang Wu,^2,† Siye Zhang,² Guyi Wang,² Quan Zhang,³ Bo Yu,² Ying Wu,² Haiyun Dong,² Guobao Wu,² Shangjie Wu,⁴ and Yanjun Zhong^2,*

Front Endocrinol (Lausanne). 2020; 11: 566439. Published online 2020 Oct 7. doi: 10.3389/fendo.2020.566439

[9] Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study.
By Begoña Ruiz-Núñez,^1,2,* Rabab Tarasse,¹ Emar F. Vogelaar,³ D. A. Janneke Dijck-Brouwer,¹ and Frits A. J. Muskiet¹
Front Endocrinol (Lausanne). 2018; 9: 97. Published online 2018 Mar 20. doi: 10.3389/fendo.2018.00097 PMCID: PMC5869352 PMID: 29615976

[10] Hoffman’s syndrome – A rare facet of hypothyroid myopathy, by Swayamsidha Mangaraj and Ganeswar Sethy, Neurosci Rural Pract. 2014 Oct-Dec; 5(4): 447–448. doi: 10.4103/0976-3147.140025PMCID: PMC4173264PMID: 25288869 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173264/

[11] “Stiff person syndrome” – https://my.clevelandclinic.org/health/articles/6076-stiff-person-syndrome

[12] Amyotrophic lateral sclerosis (ALS) and the endocrine system: Are there any further ties to be explored? , By Alexios-Fotos A Mentis, Anastasia M Boujea and George P Chrousos, in “Aging Brain”, Volume 1, 2021, 100024

[13] Biography of a Doctor, by G. A. Harry, Https://cbhrt.ca/2023/04/25/biography-of-a-doctor/

[14] The evidence for a narrower thyrotropin reference range is compelling. By Leonard Wartofsky ¹ , Richard A Dickey, J Clin Endocrinol Metab, 2005 Sep; 90(9):5483-8PMID: 16148345 DOI: 10.1210/jc.2005-0455 .https://pubmed.ncbi.nlm.nih.gov/16148345/

[15] https://cbhrt.ca/2021/10/23/thinking-about-normal/  &nbsp;

[16] Jonklaas J, Burman KD, Wang H, Latham KR. Single-dose T3 administration: kinetics and effects on biochemical and physiological parameters. Ther Drug Monit. 2015 Feb;37(1):110-8. doi: 10.1097/FTD.0000000000000113. PMID: 24977379; PMCID: PMC5167556.

 (17) Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study, by
S L Andersen  ¹ , P Laurberg, C S Wu, J Olsen,
PMID: 24605987, DOI: 10.1111/1471-0528.12681

[18] Clinical Endocrin., Volume81, Issue5, Review, November 2014, Pages 633-641: Defending plasma T3 is a biological priority^† Sherine M. Abdalla, Antonio C. Bianco: 05 July 2014 https://doi.org/10.1111/cen.12538

Abstract

This is an autobiographical report of my own medical history of intracellular hypothyroidism, offered at the invitation of “Cureus” publishers and in the interest of furthering my colleagues’ knowledge of the syndrome from which I suffered for 40 years.
My intent herein is to assist others in the prevention or alleviation of this condition.
I offer this history without intent to compromise known and accepted methods of management and without intent to profit in any way from its publication.
I describe a 40 year history of steroidopenia and intracellular hypothyroidism (IH), which began at age 40.

The step-by-step evolution of the syndrome is laid out chronologically and the eventual cure is explained with reference to detail via my website.

A few supporting references are provided.

Introduction 

I had an extraordinarily stable, supportive and appreciative family, which provided me self-confidence and self-reliance, and rendered me extremely steady, stress resistant and subjectively tranquil.
However admittedly, I am subject to mild precognitive apprehension (fear?).

Professional history: a chronology of stress

1961: While studying at the University of the West Indies (“UWI”, https://www.uwi.edu/) in Jamaica, I married.

1964: I earned the MB, BS degree from London (England) University and following internship, worked for 18 months as the sole assistant MD at my father’s 164-bed rural, government hospital (pop. 6000), in Jamaica and was then “transferred” to a 65 bed rural hospital, with a population of 4,000, as solo “medical officer”.

July, 1966: I returned to the UWI to prepare for FRCS certification in general surgery, but subsequently elected to specialise in Urology and chose to study in Canada.

1968: Emigrating to Toronto with my wife and 6-month-old, adopted son in December, I did a six-month, family-practice “locum”, prior to beginning a 5-year urology residency in June of 1969.
Our second son was born in 1970 and our daughter, in 1972.
Resident’s pay was level with the poverty line of 1972: I supplemented my earnings with house-calls and the remaining income shortfall was covered by a bank loan.

1974: Newly certified FRCSC (in Urology), I returned to Montego Bay, Jamaica, as urologist for a population of 600,000.

1975: Professionally, all was well; but socioeconomic conditions were difficult and marital harmony was poor.

1976: Montego Bay was stressful, due to marital separation, socio-economic and political factors: I returned to Canada and began a Urology practice in Toronto, serving the inner city, in competition with 27 other urologists.

1979: I bought a “duplex” in downtown Toronto and renovated it myself.

1980: My legs lost all hair and I developed patellar tendinitis.

1981: The tendinitis continued, with the beginnings of patellar exostoses. I gained weight slowly and had severe constipation for the first time, with intermittent bouts of IBS: colonoscopy was negative.
I sold the “duplex” in a real estate boom, used the profit to purchase two smaller units, was caught in the subsequent real estate crash/interest rate crunch and eventually had to accept a net loss.

1982: Constant, severe hives began: complete laboratory testing was normal (HSCRP was not done).
The patellar exostoses became larger and more painful and the origins of the hamstrings at the ischial tuberosities developed tendinitis, sufficient to render a long motor vehicle journey intolerable.
Radiological investigation yielded a diagnosis of disseminated idiopathic skeletal hyperostosis (DISH) [1].

1983: My urology practice was moderately successful. I divorced from my first wife and remarried, producing a son in 1984 and another in 1986. Heberden’s nodes [2] and flexor tendon nodules [3] developed in both hands.
Hypercholesterolemia was discovered and treated with Baycol (subsequently Pravachol, then Crestor).

1994: Patellar and Ischial pain, plus hyperalgesia of subcutaneous bone (patellae, elbows, knuckles, etc.) continued.
My professional practice was busy, but I developed prostate cancer: I consulted with Dr. Patrick Walsh and had a radical prostatectomy [4] in Baltimore in December. Subsequently, I was unable to work for 3 months.

1995: My urology practice was adversely affected and the Ontario health insurance program refused to reimburse the costs of the prostatectomy.

1996: The cumulative costs of my divorce, a new family with two children, prostatectomy in Baltimore, practice loss following the surgery, Canada’s predatory fee-for-service system and its punitive income tax law resulted in bankruptcy.

1997: Ontario’s premier, Michael Harris, closed all three of my hospitals: I was “fired”, with no recourse.
I accepted a position as chief of Urology at the “North Western Armed Forces Hospital” in Tabuk, Saudi Arabia.

1998: My professional duties in Saudi Arabia were enjoyable and trouble-free, but social conditions were stressful. I did not feel “stressed” subjectively, but the constipation / IBS continued and fibromyalgia aches began.

2000: Returning from Saudi Arabia, I discontinued Urology and joined a family practice clinic.

2001: Weighing 193 pounds, I developed type -ll pre-diabetes, which responded to weight loss of 20 pounds.

2003: My novel, “XCRATH!”, written in Saudi Arabia, was printed via Amazon.com.

2004: The family practice went well (XCRATH! didn’t), but the IBS and fibromyalgia continued.

2006: Early in June, two new symptoms began:
(1) Anxiety and reduced perception of traffic flow during my daily highway commute and
(2) Cardiac dysrhythmia, due to multiple, benign extrasystoles.
At about the same time, I developed an interest in bioidentical hormones: I began to prescribe DHEA for my patients and to experiment by taking it myself [5].
Within a few days of starting on DHEA, both symptoms subsided: I was calm and “in control” on the highway and the dysrhythmia stopped.
After three weeks, there was an improvement in both the fibromyalgic pain and the tendinitis.
I elected to continue taking DHEA.

2008: The exostoses, palmar tendon nodules and Heberden’s nodes regressed slowly, but the IBS continued.

2013: I began a “BIHRT” study course with the American Academy of Anti-Aging Medicine (A4M) and self-diagnosed exceptionally severe Intracellular Hypothyroidism (IH):
My reverse T3 (rT3) was 34 Ng/DL and my T3/rT3 was < 7.0.  
Note (1): Nominally, “normal” rT3 is <25, but clinically, optimal rT3 is <14 [5]
Note (2): T3/rT3 should exceed 20 and optimally, should be more than 24.

For the IH, I experimented briefly with Desiccated Thyroid (DT): it made no subjective difference and caused an increase of my reverse T3 from 34 Ng/DL, to 54 Ng/DL.

2014: While playing doubles squash, the same three front teeth were broken by a squash racquet, resulting in a series of very expensive dental surgeries.

2015: I stopped playing squash due to rupture of the short head of the right biceps while playing. I again tried desiccated thyroid, this time with moderate success, in that my free T3 rose from 3.7, to 4.8.

2016: The A4M certified me in antiaging and metabolic medicine and granted me the “ABAARM” degree; but my IBS exacerbated. Colonoscopies showed multiple diverticula and mild colitis.

2017: IBS symptoms continued. I relocated to a rural area, began practising BIHRT as a specialty and treated my IH with Triiodothyronine (Cytomel) while continuing to take DHEA and progesterone.
In April I developed classical Polymyalgia Rheumatica.
Prednisone “cured” the polymyalgia instantly, but the IBS symptoms (6 stools daily, with urgency) worsened.
HSCRP was 134 (N = < 1.0), indicating very high IL-6 production and a CAT scan showed a diverticular abscess.
Antibiotic therapy, continued through October, was unsuccessful.
Sigmoidectomy was proposed, but delayed due to hospital bed shortage.

2018: Within a week following sigmoidectomy in February, my HS CRP normalized, the IBS symptoms disappeared, the hives went away and the fibromyalgia pain stopped (all this, after 39 years!).

2020: I had Covid in February/March, with classical “Covid toes” and in June a symmetrically identical, extremely itchy neurodermatitis began.
In July, I began to experience moderately severe shortness of breath, with tachycardia.

2021: The neurodermatitis and exertional dyspnea persisted.
I retired in July, at age 82.

2022: In February, my exertional dyspnea improved.
In June, complete cardiorespiratory evaluation, including spirometry, stress test with Persantine, echocardiography and CT of chest with contrast was entirely within normal limits.
By my 83rd birthday on 3 May, I was breathing normally.

Retrospective analysis

Although I was not consciously aware of stress between age 20 and age 75, I was subject to subconsciously perceived stress, resulting from the following list of stressors:

• Medical school, with marriage as a student at age 23,
• Managing a remote, 60 bed, Jamaican hospital (population 4,000, solo, with no local specialists,
• Moving to Canada for a 5-year residency in Urology with children and an unemployed wife,
• Two years in Montego Bay, Jamaica, as the only urologist for 600,000 people,
• Relocating, after marital separation, to a solo Urology practice in Toronto, under adverse conditions.
• Net real estate losses in 1982.
• Prostate cancer in 1994.
• Bankruptcy in 1996.
• Total loss of professional income due to hospital closures in 1997.
• Chief of Urology in Tabuk, Saudi Arabia, from 1997 to 2000.
• Fibromyalgia and diverticulitis, from 1998 to 2017.
• Sigmoid diverticular abscess, 2017.

Unrecognized chronic stress culminated in intracellular hypothyroidism (IH), by 1979.
The IH produced, over time, a cascade of conditions which culminated in diverticulitis and fibromyalgia.
IL-6, from the diverticulitis, caused polymyalgia rheumatica, successfully treated with prednisone.
The prednisone facilitated development of a diverticular abscess, which failed to heal with antibiotics.

Eventual cure
– NeuroHormone support (DHEA, progesterone) starting in 2006,
– Correction of Intracellular Hypothyroidism: minimal success with desiccated thyroid starting in 2014, moderate success with Triiodothyronine (Cytomel) in 2015 and complete control with slow-release, compounded triiodothyronine, since 2017.
– Sigmoidectomy in 2018, for a potentially lethal, pelvic abscess which was the end result of the “cascade”.

Covid 19 in 2020 resulted in minor “long Covid” symptoms *; but cardiorespiratory evaluation proved completely normal and my health is now excellent.

Summary:

Chronic stress caused Intracellular Hypothyroidism, which became overt in 1979, with leg-hair loss, tendinitis with slowly progressive DISH, constipation, diverticulosis and weight gain.
Stress from prostate cancer, urology practice “downturn”, bankruptcy, being “fired” by Ontario’s premier, (Michael Harris) and relocating to Saudi Arabia in 1997, caused subconscious PTSD.
The PTSD exacerbated the IH, which, combined with increased muscle inflammation due to chronically elevated IL-6, presented as fibromyalgia in 1998 [5-7].

By 2001 further weight gain, due to continuing Intracellular Hypothyroidism, resulted in early type II diabetes, which resolved with a reduced diet and weight loss.

In 2006 DHEA eliminated my anxiety, reduced the fibromyalgia slightly and corrected dysrhythmia.

Stress from “semi-retirement” in 2014 up-regulated the IH and with it, constipation/IBS/diverticulitis. Desiccated thyroid improved my “thyroid profile”, but not my symptoms.

Through 2016, chronic diverticulitis led to an early diverticular abscess, damaging the bowel mucosa, which maintained high IL-6 production to heal itself.

In 2017, Massive elevation of IL-6 from an infected diverticulum led to polymyalgia rheumatica (PMR).

Prednisone, prescribed for polymyalgia rheumatica, downregulated glucose management, reinstating my prediabetes, which in turn, facilitated exacerbation of a sigmoid abscess.

In 2018, Sigmoidectomy resulted in complete cure of the IBS, hives and fibromyalgia.
50 µg of slow-release, Compounded triiodothyronine eliminated the intracellular hypothyroidism completely; but occasionally, mild hyperthyroid symptoms ensued. I am now taking 40 µg.

Comments

• The Heberden’s nodes and flexor tendon nodules were incidental, caused by age-related DHEA deficiency. They had nothing to do with IL6, Intracellular Hypothyroidism or Diabetes.
• The prostate cancer may have been facilitated by DHEA deficiency.
• IL-6, a cytokine, heals damaged bowel but produces inflammation elsewhere, especially in muscles.
• Polymyalgia rheumatica (PMR) is produced by IL-6 [8]. I cannot categorically say the same for fibromyalgia, but I suspect that in my case, it was.
• IL-6 interestingly, is elevated by anxiety, which may have played a part in my fibromyalgia and PMR [9].
• Glucocorticoids (for example, prednisone) block IL-6 instantly and completely, eradicating muscle pain, at the cost of compromised glucose management and failure of the bowel to heal.
• “Intracellular Hypothyroidism” is a condition in which intracellular Triiodothyronine production is hobbled, by Deiodinase 1 blockade and Deiodinase 3 promotion. It can coexist with true hypothyroidism [9].  
• “Perceived stress” is subconsciously registered stress, which produces a stress response even though the individual is subjectively stress-free.
  “Subjective stress”, consciously noted and “felt”, can be described by the individual.
  “Objective stress” is stress as observed by others.
• Regardless of its origin, stress results in increased cortisol production: cortisol suppresses DHEA and actively eliminates intracellular production of T3 from T4 [10, 11].

Current status

2023: Since the surgery in February of 2018 I have been well, apart from the long-Covid symptoms, now gone.
Now aged 83 and retired since July 2021, I am very well.
Detailed cardiopulmonary investigation in 2022 was normal, perhaps due to taking DHEA, Progesterone and T3.
Heberden’s nodes and palmar, flexor tendon nodules responded to DHEA supplementation and resolved.
The DISH continues to subside and my spinal flexibility has improved with the aid of exercise and yoga.
My cognition is subjectively normal and my short-term memory is excellent.
I am not as strong as I was at age 60, but I exercise with 15 pound weights and do yoga, twice-weekly. I have no sarcopenia and my BMI is 26.1.
I walk the golf course in summertime and play pickle ball regularly, during winter, usually in two-hour sessions.
My skin quality is commensurate with age 65: I have few wrinkles.
My early cataracts have not progressed. My visual acuity and colour vision have improved, on compounded T3: I do not need eyeglasses.
My cholesterol profile has been normal since I started taking DHEA in 2006 (statins discontinued, 2015).
The Heberden’s nodes have not recurred.
The patellar exostoses are smaller by 50% and I can kneel without pain.
I continue on Triiodothyronine, 40 µg at 4 AM, DHEA, 50 mg at 8 AM,  Progesterone 100 mg at bedtime, with Melatonin, 10 mg and Magnesium Threonate.
I also take Omega 3, DHA, NAC 900mg, MTHF 1mg, Vitamin C 2 g, Vitamin D3 5,000 iu and a multivitamin.

Gervais A. Harry, MB, BS, LMCC, FRCSC, ABAARM [retired].
17^th April, 2023.

References

[1] New developments in our understanding of DISH (diffuse idiopathic skeletal hyperostosis), by
Sarzi-Puttini, Piercarlo; Atzeni, Fabiola,
Current Opinion in Rheumatology: May 2004 – Volume 16 – Issue 3 – p 287-292PMID: 15103260
https://pubmed.ncbi.nlm.nih.gov/15103260/
DOI: 10.1097/00002281-200405000-00021

[2] Generalized osteoarthritis and heberden’s nodes,
by J. H. Kellgren and R. Moore, Br Med J. 1952 Jan 26; 1(4751): 181-187,
PMCID: PMC2022370, PMID: 14896078
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2022370/
DOI: 10.1136/bmj.1.4751.181

[3] Diagnosis and treatment of swellings in the hand, by Saiidy Hasham and Frank D Burke,
Postgrad Med J. 2007 May; 83(979): 296-300. PMCID: PMC2600075 ,
PMID: 17488856
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600075/
DOI: 10.1136/pgmj.2005.043992

[4] Radical prostatectomy with preservation of sexual function: Anatomical and pathological considerations, by Dr Patrick C. Walsh, Herbert Lepor, Joseph C. Eggleston, First published: 1983,
Citations: 783. https://onlinelibrary.wiley.com/doi/abs/10.1002/pros.2990040506
https://doi.org/10.1002/pros.2990040506

[5] Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis,
by Luke Furtado O’Mahony 1 , Arnav Srivastava 1 , Puja Mehta 2 , Coziana Ciurtin 3,
Rheumatology (Oxford), 2021 Jun 18;60(6):2602-2614, doi: 10.1093/rheumatology/keab146, PMID: 33576773, PMCID: PMC8213433,
https://pubmed.ncbi.nlm.nih.gov/33576773/
DOI: 10.1093/rheumatology/keab146

[6] IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients,
by Danelia Mendieta, Dora Luz De la Cruz-Aguilera, Maria Isabel Barrera-Villalpando, Enrique Becerril-Villanueva, Rodrigo Arreola et al. J.Neuroimmunol, 2016 Jan 15;290:22-5, Epub 2015 Nov 26. PMID: 26711564 DOI: 10.1016/j.jneuroim.2015.11.011
https://pubmed.ncbi.nlm.nih.gov/26711564/
DOI: 10.1016/j.jneuroim.2015.11.011.

[7] Fibromyalgia and cytokines,
by Ignasi Rodriguez-Pintóab, NancyAgmon, Levinac Amital, and Howarda Yehuda Shoenfeld, in Immunology Letters, Volume 161, Issue 2, October 2014, Pages 200-203
https://www.sciencedirect.com/science/article/abs/pii/S0165247814000133
https://doi.org/10.1016/j.imlet.2014.01.009

[8] Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis,
by N E Roche 1 , J W Fulbright, A D Wagner, G G Hunder, J J Goronzy, C M Weyand, Arthritis Rheum, 1993 Sep, 36 (9): 1286-94. doi: 10.1002/art.1780360913. 1993 Sep;36(9):1286-94. PMID: 8216422,
https://scholar.google.ca/scholar?hl=en&as_sdt=0%2C5&as_vis=1&q=Correlation+of+interleukin-6+production+and+disease+activity+in+polymyalgia+rheumatica+and+giant+cell+arteritis&btnG=
DOI: 10.1002/art.1780360913

[9] Clinical anxiety, cortisol and interleukin-6: Evidence for specificity in emotion-biology relationships, by Aoife O’Donovan, Brian M.Hughes, George M.Slavich, Lydia Lynch, Marie-Therese Cronine, Cliona O’Farrelly, Kevin M.Malone, in Brain, Behavior, and Immunity, Volume 24, Issue 7, October 2010, Pages 1074-1077 https://doi.org/10.1016/j.bbi.2010.03.003
https://www.sciencedirect.com/science/article/abs/pii/S0889159110000565

[10] “T3 and Intracellular Hypothyroidism”, by G.A. Harry, https://cbhrt.ca/intracellular-hypothyroidism/

[11] “Stress causes Hypothyroidism”, by G. A. Harry, https://cbhrt.ca/2022/12/14/stress-causes-hypothyroidism/

This opinion piece is in response to an interesting report on fetal neurocognitive development, reviewed by Lily Ramsey, LLM, which I received today, Mar 29 2023..
It is entitled “Maternal weight gain in pregnancy and fetal neurodevelopmental disorders”
The report, based on children born in Sweden
from January 2007, to December 2010,
was authored by Dr. Chinta Sidharthan,

Rates of maternal weight gain over the course of pregnancy and offspring risk of neurodevelopmental disorders. Image Credit: Hazal Ak / Shutterstock

Dr. Siddharthan, reporting on a Swedish study says (paraphrased): “Neurodevelopmental disorders (NDD) are prevalent. The main three, ASD, ADHD, and intellectual disability, often coincide. While mutations are associated, biological, environmental and
social factors also contribute.”

Dr. Siddharthan relates 2nd and 3rd trimester gestational weight gain (GWG) rates,
to fetal ADHD and ASD.
A slow GWG in the 2nd trimester increased the risk by 9%, while
a high GWG in the 3rd trimester raised the risk by 28%.

Her conclusion is that poor GWG in the 2nd trimester,
with excessive GWG in the 3rd, are contributing factors to NDD.

She does not mention the First trimester.

This article and its expressed opinion should be evaluated in the light of current knowledge: a few related articles are offered, for comparison, below.

(1) Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis,
by Spyridoula Maraka,^1,,2 Naykky M. Singh Ospina,^1,,2 Derek T. O’Keeffe,¹ Ana E. Espinosa De Ycaza,¹ Michael R. Gionfriddo,^2,,3 Patricia J. Erwin,⁴ Charles C. Coddington, III,⁵ Marius N. Stan,¹ M. Hassan Murad,^2,,6 and Victor M. Montori^1,,2, in “THYROID”. 2016 Apr 1; 26(4): 580–590, doi: 10.1089/thy.2015.0418, PMCID: PMC4827301,
PMID: 26837268

Abstract (paraphrased):
A new nationally representative study published online in the Journal of Affective Disorders found that one in four adults, aged 20-39, with attention deficit hyperactivity disorder (ADHD) had generalized anxiety disorder (GAD).
This question is therefore important, worldwide.

(2) Subclinical Hypothyroidism in Pregnancy May Have Long-Term Effects on Metabolic Parameters, by Sun Y Lee, in J Clin Endocrinol Metab. 2020 Jul; 105(7): e2628–e2629, Published online 2020 Apr 14. doi: 10.1210/clinem/dgaa198, PMCID: PMC7216923, PMID: 32285101

Abstract (paraphrased):
Adequate thyroid hormone is essential for normal fetal Neurocognitive development.
Because the fetal thyroid gland does not mature until 18 to 20 weeks’ gestation, there is a significant fetal need for maternal thyroid hormone production in early pregnancy.
Overt maternal hypothyroidism in pregnancy is known to be associated with adverse outcomes, both in the pregnancy and in the baby’s development, such as miscarriage, prematurity, low birth weight and lower IQ.

(3) Influence of maternal TH during gestation, on fetal brain development.
This excellent paper is a seminal treatise on thyroid hormone function, which Everyone should read.
It was authored by Nora K. Moog,^a Sonja Entringer,^a,b,c Christine Heim,^a,d Pathik D. Wadhwa,^b,c,e Norbert Kathmann,^f and Claudia Buss^a,b,, In Neuroscience. 2017 Feb 7; 342: 68–100. Published online 2015 Oct 3. doi: 10.1016/j.neuroscience.2015.09.070, PMCID: PMC4819012, NIHMSID: NIHMS731226, PMID: 26434624

Abstract (paraphrased):
The importance of maternal thyroid function to the fetus, especially as related to iodine deficiency, was reported over a century ago (Curling, 1850, McCarrison, 1909).
Maternal thyroid dysfunction may impair the child’s cognitive and motor development.
It has long been known that thyroid hormones (TH) are obligatory to brain development and maturation. (Zoeller, 2003, de Escobar et al., 2008, McLeod and McIntyre, 2010).

The developing fetus needs maternal T3, since its thyroid can’t make thyroid hormone until mid-gestation.
Without T3, normal brain development is impossible.

Recent evidence shows that early in gestation, even mild maternal hypothyroidism may adversely affect fetal neurocognitive development, retarding brain growth and causing the “misconnected wiring” which leads to cognitive disorders.
It is therefore important to understand that stress, in the first trimester, may cause maternal hypothyroidism and affect the fetal brain.
However the effect of stress on the thyroid, as it affects the fetal brain, has not been addressed to date.

MY VIEW OF THE EFFECTS OF STRESS, IN THE FIRST TRIMESTER

The thyroid and adrenal glands communicate with the hypothalamus and the pituitary gland, and their hormones regulate and counter-regulate one another: a change in one parameter is reflected in variation of the others.
A stress-related increase in cortisol production, via its down-regulation of Deiodinase 1 and up-regulation of Deiodinase 3, causes Reduction of intracellular and serum T3 levels to a minimum.
Therefore maternal stress can reduce the mother’s serum T3 sufficiently to produce fetal hypothyroidism and prevent normal neurodevelopment.
However this interaction has been overlooked in the literature, due to mainstream medicine’s taboo on testing of T3, reverse T3 and the T3/reverseT3 ratio *.

* Clicking the link, “taboo on testing”, will take you to the Canadian Ministry of health’s “CHOOSING WISELY” campaign page: Thyroid hormones are mentioned in item #11 , under the headline “13 Tests and treatments to Question”.
The entire page is an interesting read, for anyone interested in preventive care: it outlines the Canadian Ministry of health’s “CHOOSING WISELY” campaign to reduce the cost of medical tests, including thyroid investigations (the direct attack on thyroid testing is clearly stated: to view it, click here).

WHAT ALL THIS MEANS, WITH REGARD TO THE ARTICLE IN QUESTION

(1) Reduced, or retarded fetal neurocognitive development, reflected by ASD, ADHD, intellectual disability and possibly schizophrenia and gender dysphoria, can be viewed
as due to maternal hypothyroidism, including stress-related “low T3 syndrome” (intracellular hypothyroidism), a diagnosis which is easily made by testing for T3, reverse T3 and the T3/rT3 ratio.
(2) GWG variations in the 2^nd and 3^rd trimesters may reflect maternal hypothyroidism. However it is difficult to correlate 2nd and 3rd trimester GWG with a fetal deficiency whose origin lies between the 8th and the 20th week of gestation.
The increased GWG probably results from the hypothyroidism and in any case, the damage to the fetus by “T3 starvation” has been done before the 3rd trimester begins.
(3) As previously suggested in my blog post, “Preventive Care, as it should be”, maternal thyroid function should be assessed prior to initiating pregnancy, or at Least coincident with the diagnosis of pregnancy.
The investigation should include not only TSH and thyroid antibodies, but FT3, FT4 and reverse T3. The serum T3 and the T3/rT3 ratio will provide an accurate assessment of the prospective mother’s ability to supply the developing baby with T3 in the first 20 weeks of pregnancy.
(4) If this is done, we just might eliminate fetal neurocognitive maldevelopment and relegate dyslexia, ADD, ADHD, ASD, schizophrenia and gender dysphoria, all of which have been shown to be related to maternal hypothyroidism, to the annals of the past.

 

Today’s news-feed (March 29, 2023) included an “important article report”, entitled
“A higher dose of magnesium each day keeps dementia at bay”.

The report, from the Neuroimaging and Brain Lab at the Australian National University (ANU), states that the brain age of people consuming more than 550mg of magnesium daily is approximately one year younger at age 55, than that of people with a normal magnesium intake of about 350mg per day.

Dietary Magnesium is related to larger brain volumes

The original article, “Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences “, by  Khawlah Alateeq, Erin Walsh and Nicolas Cherbuin,, DOI: 10.1007/s00394-023-03123-x, was published by Research Gate and reported by europepmcc.org,  NIH and the European Journal of Nutrition.
The article involved more than 6,000 cognitively healthy subjects in the UK, aged 40-73.
It concluded that higher dietary Mg intake is related to better brain health in the general population, and particularly in women.
It follows a previous (2020) research gate article, by Zonderman.

My previous notes on Magnesium

Having found this article, I accessed my previous notes regarding magnesium, which reads as follows (abstract):
Magnesium is an essential nutrient for normal body functions: after potassium, Magnesium is the second most common metal in the cells.
It is involved in 300+ biochemical processes, activating many intracellular enzymes.
It is important for protein synthesis, membrane stabilization, antibody activity and immune response.        

Dietary Magnesium

Magnesium is a major constituent in many grains, fruits and nuts (especially, almonds). However, because the fields on which our food is grown have become magnesium-deficient over time, deficiency is very common in humans. Anyone who has constipation and (or) muscle cramps is probably either hypothyroid, or short of magnesium, or both.

In young people, the small intestine absorbs 30–50% of the magnesium intake: the percentage diminishes in old age, chronic Kidney disease and increasing intake.

The blood contains only 0.3% of the total body magnesium: half of the magnesium in the body is stored in bone, with less than 1% in body fluids.
In the brain, the concentration of magnesium is much higher than in the blood.

Magnesium and the Brain

In brain injury and in neurological diseases, the magnesium concentration goes down: prescribed magnesium reduces brain swelling, restores the ability of the blood-brain barrier to keep toxins out and improves the speed and efficiency of healing:
I interpret that to mean that in brain injury and neurological diseases, brain swelling and deterioration are due, at least in part, to low magnesium levels.

Magnesium and (just about) everything else

Magnesium deficiency is associated with constipation, muscle cramps, migraine, asthma, depression, anxiety, diabetes, high blood pressure, atrial fibrillation, insomnia, chronic fatigue, dementia, osteoporosis, chronic pain, fibromyalgia, constipation, brain injury, cerebral palsy, stroke and brain haemorrhage.
Therefore in these conditions, magnesium is recommended for treatment.
In short, magnesium is essential to health: your liability to these conditions will be reduced if you supplement your magnesium intake.

Magnesium can be given by mouth, intravenously or by intramuscular injection.
It is better taken at night, because it promotes sleep: it should be taken with progesterone and melatonin, because progesterone (reliably converted to Allopregnanolone), magnesium and melatonin work together to the generation of new brain cells, maintainance of existing brain cells and repairing of oxidative and inflammatory damage to their axons and dendrites.

The commonest magnesium “salts” recommended are the citrate, chloride, sulphate, gluconate, acetate and lactate.
The recommended daily allowance is 320-420mg/day.
Magnesium Bisglycinate and Threonate are theoretically better, because they cross the blood-brain barrier more reliably.
However magnesium citrate, available in capsules, is least expensive and works well.
A popular magnesium preparation, “calm magnesium”, is a very expensive powder.

Magnesium and chronic kidney disease

I had also filed an article, Published: 25 January 2022 in Clinical and Experimental Nephrology volume 26, pages 379–384 (2022), by Yusuke Sakaguchi , entitled
“The emerging role of magnesium in CKD”.
Dr. Sakaguchi concluded that magnesium is essential to bone health, preservation of kidney function and prevention of arteriosclerosis: he highly recommended it, in full dosage, as part of the treatment for chronic kidney disease.

The bottom line

Magnesium is an active player in approximately 300 metabolic processes in the body.
Most of us are at least slightly deficient in magnesium.
Magnesium is a constituent of nuts, vegetables and protein sources; nevertheless, supplementing dietary magnesium is necessary for most of us.
There is no need for concern regarding “overdosage”, because unused magnesium in the diet is swiftly removed by the kidneys and/or the bowel.
If you do take more than you need, the resulting loose stool gives a quick reminder to reduce your dosage.
The article by Alateeq, Walsh and Cherbuin provides us with an additional reason to supplement our magnesium intake and I am happy to let you know about it.

Women with rheumatoid arthritis more likely to achieve remission if they take sex hormones, finds research, by University of South Australia, in “Rheumatology” (2022). DOI: 10.1093/rheumatology/keac357

This paper appeared in my newsfeed today: I have paraphrased it for brevity.

Abstract:
Rheumatoid arthritis (RA)affects < 2% of the world’s population and is primarily genetic.
It mainly causes joint disease but can also affect the whole body, including organs.
At age less than 50 years of age, RA is 4x more prevalent in women than men.
It is more aggressive in women and the prognosis is worse.
It is twice as common in women over 60 years.
The peak age of onset of rheumatoid arthritis among females is 45-55 years, corresponding with a drop in estrogen. Furthermore, at the onset of menopause there is an increase in pro-inflammatory proteins.
Early menopause, or menopause under 45 years, increases the risk of developing rheumatoid arthritis and the incidence spikes sharply, post-menopause.
Conversely, younger women with rheumatoid arthritis who become pregnant experience a 50% decline in inflammatory activity.

In a study of 4474 women with rheumatoid arthritis, led by the University of South Australia, patients were treated with Tocilizumab and other immuno-suppressive medications:
– Pre-menopausal women had fewer symptoms than peri- or post-menopausal women.
– RA patients using HRT or oral contraceptives (OCs) had a better chance of remission.
– Post-menopausal women, comprised 63% of the participants (only 8% of them were on HRT). They were less likely to achieve remission, compared to pre-menopausal women .
– Post-menopausal women aged <45 years) made up 5% of the participants:
25% were pre-menopausal, 9% were peri-menopausal and 63% were post-menopausal.
– Remission rates were higher in those taking HRT or OCs while treating RA.
– RA remission was twice as high in peri-menopausal women.
– Women entering menopause without HRT or OCs were less likely to achieve remission.”

This is very interesting, in that it suggests that HRT should be used to treat RA.
However the study appears to have been undertaken without consideration of a prior (May, 2014) report and it seems that the authors did not investigate and/or treat, for Proteus Mirabilis.

Therefore, Vide Infra:

(1) Rheumatoid arthritis is caused by a Proteus urinary tract infection,
by Alan Ebringer  ¹ , Taha Rashid
PMID: 23992372, DOI: 10.1111/apm.12154
2014 May;122(5):363-8. doi: 10.1111/apm.12154. Epub 2013 Aug 29.

Abstract:
Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis.
Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries.
The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection.
The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted on by peptidyl arginine deiminase, thus explaining the early appearance of anti-citrullinated protein antibodies in patients with RA.
Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages.

(2) March 2006: the original article was published by a Ebringer and Rashid. titled “Rheumatoid arthritis is an autoimmune disease triggered by Proteus
urinary tract infection” , by ALAN EBRINGER & TAHA RASHID, in a report from the School of Biomedical and Health Sciences, Kings College London, London, UK
Abstract:
Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age.
Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus
urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of
cytopathic auto-antibodies.
Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.

(3) PubMed Central, 2016 Apr 1 Proteus mirabilis and Urinary Tract Infections, by Jessica N. Schaffer and Melanie M. Pearson , in (original article Microbiol Spectr. 2015 Oct; 3(5): 10.1128/microbiolspec.UTI-0017-2013, doi: 10.1128/microbiolspec.UTI-0017-2013 PMCID: PMC4638163 NIHMSID: NIHMS724705 PMID: 26542036

Proteus mirabilis is well-known, as the species that swarms across surfaces, overtaking any other species present in the process.
If you want to be a real expert on Proteus mirabilis, read this seminal article; but be warned – it is “the last word” on Proteus, written for microbiologists only!

n^*

Erythritol and Heart Disease

Who uses the artificial sweetener, erythritol?

Here is a minimally altered report by F. Perry Wilson, MD, MSCE, Feb. 28, 2023.

This is not my usual blog, in which my comments are my own words:
The first section (A) is my paraphrase of Dr. Wilson’s opening segment.
The 2nd section (B) is an extensive, direct quote from the body of Dr. Wilson’s report.
The 3rd section (C) is my “take” on overeating, obesity and the disease cascade which results from overconsumption of foodstuffs.

The reasons why I am doing it this way are that:
– The “body” of Dr. Wilson’s report is already succinct: my paraphrasing of the entire paper would detract from his message, while gaining little in terms of brevity.
– His diagrams and their explanation however, are instructive and important.
– Our society’s approach to the problem of foodstuff overconsumption is counterproductive: in “THE BOTTOM LINE” (C), I propose a solution.

(A)

ARTIFICIAL SWEETENER, ERYTHRITOL

The artificial sweetener, ERYTHRITOL, a sugar substitute derived from corn, is also found in many fruits, including peaches, pears and watermelons: our bodies make some too. It is used in many food products, including chocolate, chewing gum, beverages, baked goods and other items.
A recent article warns us of the dangers of erythritol, noting a survey in the USA, which showed the following consumption of erythritol among the population surveyed (Fig 1).

Population group	Grams /day, mean	Grams / day, 90th %	Grams /day, 95th %
Children, 1-12 years	5.9	13.2	15.8
Boys, 13-19 y.o.	7.6	19.3	15.8
Girls, 13-19 y.o.	7.3	15.6	15.8
Males, 19-65 y.o.	5.5	12.8	18.9

“Sugar Substitute Linked to Heart Disease”, is by F. Perry Wilson, MD, MSCE, 2/20/23.
I have paraphrased it and removed two statistical diagrams, to make this note shorter and more understandable, for my lay readers.

(B)

Dr. Wilson begins
He reminds us of our modern predilection for high-calorie, high salt, high sweetness foods, in which sucrose (cane sugar) is replaced with sugar substitutes: a line of small molecules and polypeptide artificial sweeteners and so-called “natural” sugar alternatives, which together constitute a $10 billion–dollar industry,

He says: “Is This Thing You Eat Everyday Secretly Killing You?”, targeting Erythritol, a sugar alcohol equalling sucrose in sweetness, which is found in corn and is therefore “natural”, allowing manufacturers to claim “no artificial sweeteners”.

Erythritol is rapidly absorbed from the small intestine and excreted mainly in the urine.
It is not metabolized either by our tissues or by bacteria, so it doesn’t contribute to tooth decay, doesn’t raise blood sugar, doesn’t supply energy and doesn’t cause obesity. Overall, it sounds like an ideal substitute for sugar.
However there is a hidden problem: according to an article in Nature Medicine,
Erythritol may contribute to heart attacks.

Dr. Wilson goes on to say (here, I quote directly from his report, including his relevant diagrams, with only minimal adjustment of syntax and punctuation):

“The researchers started with a metabolomic analysis of just over 1,000 people being assessed for heart disease.
Modern metabolomic studies look at the levels of hundreds, sometimes thousands, of metabolites circulating in the blood to see which might be associated with a given disease.
In this case, focusing on sugar and sugar-substitute metabolites, erythritol topped the pack.
Those who were observed to develop a major adverse cardiovascular event, had significantly higher erythritol levels at baseline than those who did not.

There are two problems with this: First, because metabolomic studies check so many metabolites, a few “strong hits” are guaranteed just by chance alone.
Therefore results of investigations need to be validated by replicating the tests.
The authors did this, showing in an independent American dataset that those in the highest quartile of erythritol levels were much more likely to have a major heart event eventually.

Figure 2: red line shows the 3-Year survival of people with the highest erythritol blood level.

Of course, just because erythritol levels are higher in people who go on to have heart attacks doesn’t mean that erythritol causes the heart attacks.
People who consume sugar substitutes may be different in important ways compared with those who don’t; think about factors like diabetes, obesity and even socioeconomic status.
The authors adjusted for many of these, but as we’ve said many times before, perfect adjustment is impossible.

The authors clearly wanted to ask – If erythritol has a causal link to cardiovascular disease, what‘s the mechanism?
They hypothesized that erythritol in the blood might stimulate platelets to clump together and clot, more easily.
Sure enough, that’s just what they found.
In a test tube, as the concentration of erythritol increased toward 45 micromolar, platelets began to get stickier.”

In an experimental model of time-to-carotid artery occlusion, mice given erythritol had faster clotting in arteries (Fig 3, copied from Dr. Wilson’s report).

Figure 3: “Vehicle” is the liquid in which the artificial sweetener, erythritol, was dissolved.
Mouse carotid arteries were completely blocked by clot less than 10 minutes after the solution was injected

Dr. Wilson continues:
“Okay. If there’s one thing I’ve learned from reading studies of artificial sweeteners, it’s to check the concentrations. It’s one thing to say that a given sweetener causes cancer in rats who are fed 100 times the typical daily dose. It’s quite another to say that this occurs when the dose is at physiologic levels.
So, 45 micromolar — that’s the concentration where all this platelet action is seen – can we put that in context?
Well, in the American validation cohort, the highest quartile of erythritol levels comprised people with levels ranging from 6 to 46 micromolar. So, right off the bat, it’s clear that 45 micromolar is on the high side. 
Of course, maybe you don’t need erythritol levels to be 45 micromolar all the time; maybe just spiking for a while can increase clotting. To assess this, the researchers measured erythritol blood levels in eight healthy controls after consuming 30 g erythritol (Fig 4).”

Figure 4, from Dr. Wilson’s report: Bood levels of erythritol get incredibly high and stay above 45 from about 30 minutes to 2 days after ingestion of Erythritol, 30 g.
30 g of erythritol raises the blood erythritol level to >45 µmol, in all 8 people, within half an hour.
The erythritol level does not go below 45 µmol until one day after ingestion and does not return towards minimum levels for between 3 and 7 days.(Wikipedia says that 80% is excreted in the urine within 24 hours, but that does not disprove Dr. Wilson’s report).
So if the above diagram is right, at 30 g daily, your blood level would go like this (+/-):

DOSE	30	30	30	30	30	30	30
Level	50	75	87.5	93.8	96.9	98.4	99.5

Dr. Wilson continues:
“If we want to put this together, we can probably say that you might not want to eat or drink 30 g of erythritol every day. The authors argue that 30 g is exactly what we’re taking in per day, citing an FDA filing, but I checked that: 30 g is actually the 90th percentile of intake in the United States, with the mean reported at 13 g.

Even 13 g seems too high. This food diary study from Europe estimates daily intake at about 5 or 6 g. And that’s among people who reported using all sugar-free products in their daily consumption.”

Figure 5: consumption of erythritol in Europe (from Dr. Wilson’s report).

Dr. Wilson continues:
“So, no, I’m not terribly worried right now about my monkfruit sweetener, my sugar-free gum or my toothpaste.
While the harms from sugar substitutes are still mostly theoretical, the harms of sugar are all too real.
Erythritol may well be the lesser of two evils here.
It would be great to have all the sweetness of sugar and none of the harms.
Of course, I’m reminded of a truism when it comes to the science of diet: It’s rare that you can have your sugar-free cake and eat it too.”

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson, and his new book, How Medicine Works and When It Doesn’t, is available now.

(C)

THE BOTTOM LINE (Dr. Harry)

The message from this article is clear: too many of us attempt to sidestep the triple threat of obesity, hypertension and diabetes, while avoiding the self-control necessary to stop overeating.
Clearly the conclusion that sugar is the cause of obesity, while perhaps correct, has led us to avoid sugar while indulging our desire for more food than we need.
It’s tempting to offer platitudinous advice, such as “Too much of a good thing is good for nothing”, “Don’t jump over a precipice to avoid a tiger”, “Practice moderation in all things” or “Maintenance is cheaper than repair” ………… I could go on, but there is a practical way.

Don’t ask “How can we fix this?” – ask, “Why is it this way?”

We can do better than to concentrate on “How can we fix this?”.
Instead, we should figure out “Why do so many of us have such an urge to eat?” and
“Is there some way of reducing the urge?”, because the question leads to the answer.

The answer is in our metabolism: the “raison d’être” of our increased appetite, reduced basal metabolic rate and lassitude is our uncompensated high-stress modern life, which leads to hypercortisolemia, resulting in intracellular hypothyroidism
(intracellular “T3 starvation”), with lassitude, reduced BMR and weight gain.

THE HORMONES:

Ghrelin, often called “the hunger hormone”, stimulates the appetite. It is released by the empty stomach and is said to be lower in obesity.
It also reduces thermogenesis by our brown-fat cells, thereby reducing energy consumption and encouraging storage-fat growth.
Ghrelin secretion increases in parallel with cortisol following psychological stress (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682420/).

Cortisol: stress triggers increased cortisol production and cortisol triggers
– blockade of Triiodothyronine (T3) production,
– destruction of existing T3,
– higher Ghrelin production, with increased appetite, reduced fat-burning and reduced basal metabolic rate,
– lassitude, with reduced energy expenditure and weight gain.
The result is the “couch potato” syndrome.

STRESS REDUCTION

Stress reduction, in our now-worldwide civilization, is extremely difficult (if not impossible) to achieve, so we have no way of directly reducing cortisol production.
We can however supply our cells with Triiodothyronine (T3), which will return our metabolic rate to normal and cancel the psycho-cognitive effects of “T3 starvation”.
In this way the perceived stress can be lowered, resulting (hopefully) in a reduction of Cortisol, reduction of Ghrelin, reduced appetite and weight loss.

The recurring theme: “intracellular T3 starvation”.

We are thus back to an argument which I have made before: evaluation of “thyroid profile” should be routine in the assessment of all symptoms and syndromes, so that “T3 starvation” (intracellular hypothyroidism) can be diagnosed and treated.
Doing so would eliminate a major factor in the development of our diseases, including overeating, obesity, hypertension, psycho-cognitive deterioration and reduced myocardial efficiency.

So, rather than trying to avoid obesity by assuaging our hunger/overeating-disease problem with nonfattening, poisonous sweetners, which don’t prevent obesity anyway, why not investigate the reasons for hunger, correct our hormonal aberrations and enjoy our sugar-sweetened snacks?

So we don’t need to avoid sugar

Instead, let’s change our ways and do as follows:

• Assess cortisol production, BMI, BMR, T3 and rT3 metabolism.
• Normalize thyroid hormone metabolism by treating with triiodothyronine, thus reducing Ghrelin secretion, improving the basal metabolic rate and resolving the lassitude problem: this will slowly improve the BMI.
• Stop using artificial sweeteners: if you want sweet foods, sweeten with sucrose.
• Assess hormone balance and correct such problems as may be discovered.
• Particularly, correct DHEA deficiency and increase exercise level, so as to convert fat stores to muscle tissue and correct progesterone deficiency, so as to improve sleep and reduce the tendency to anxiety and depression.
  

REFERENCES

Sweetener Review: Erythritol | Is it Really “Natural” and The Perfect Sweetener?
https://www.whatsugar.com/post/is-erythritol-natural-or-artificial

Yet Another Worry — This Time It Is Erythritol McGill University. Office for Science and Society: Separating Sense from Nonsense
https://www.mcgill.ca/oss/article/health-and-nutrition/yet-another-worry-time-it-erytritol

Erythritol: Is This ‘Healthy’ Sweetener the Real Deal? By Dr. Josh Axe, DC, DNM, CN
March 1, 2023 https://draxe.com/nutrition/erythritol/

Well, hello again!

Those few of you who have chosen to follow this blog will, quite likely, have thought of this eventuality….. And here it is!

I have just finished rereading my novel, XCRATH!, about spaceflight to a new planet which has 3% Xenon in its atmosphere, which I completed in 2004.

At first, in trying to “be Canadian, buy Canadian”, I self-published via Trafford publishing, in Vancouver.
When I got the first copy, it turned out to be visually substandard, with a very dull cover, clumsy looking graphic, and not-so-great paper.
I was quite upset, but eventually I got a beautiful version, with my son Nigel Harry’s graphic (above), published to my satisfaction via “CreateSpace”, a subsidiary of Amazon.com, in 2005.

Incidentally, Amazon closed “CreateSpace” in 2018: the book however is still available from “Kindle Direct Publishing” (KDP) and it looks just like the photograph above.

I have not read it since the time of publishing with CreateSpace and had forgotten much of the detail, so rereading it now proved to be interesting and a real pleasure.

Unsurprisingly, I am delighted with it.
Not only is it well-written: it is well composed, with all the plot “angles” covered, all surprising twists explained and no non-sequiturs.

As often happens (as professional editors will tell you) in spite of 7 “rounds” of editing back in 2002 – 2005, in this reading I found 8 correctable errors in 253 pages – a missing comma, a transposed “a”, an absent apostrophe, and the like.
However nothing truly embarrassing turned up: the errors, such as they are, do not render reading difficult, or detract from the thoroughly enjoyable story.
I will of course re-edit it and expunge those errors from future printings, but the current version is close to perfect and I doubt that any reader will notice those small errors.

I am particularly pleased with it because all my scientific predictions have turned out to be correct.
We’re starting to talk about fusion/ion drives, faster than light travel and gravity waves on the one hand and on the other, our world is now consumed with guilt and apprehension regarding climate change, pollution, pandemics, loss of life among the whales, war, zero population growth, genetic damage, micro-plastics, etc. etc.

So now I can’t resist the urge to invite those of you who have not seen the book, to have a look at it.

But be warned!
Writing the way I do, I seem to lecture and pontificate at times: the language is archaic and heavy in spots, but it fits the characters and situations and it’s all in fun.
The English is quite good, but the writing style and vocabulary are a little bit ancient.
Of course that isn’t surprising, since I wrote it at age 60: most of my vocabulary and syntax came from pre-1950s works by Dickens, Poe, Tennyson, Irving, Herman Melville, Conan Doyle, Orwell, Aldous Huxley and their ilk.

XCRATH! is interesting, in that the extra-terrestrial, alien society which the humans find on their new planet has achieved the goals to which we on earth now aspire: anti-sexist inclusivity (reminiscent, in a way, of Sawyer’s Neanderthals), eco-conservation, true democracy, antiprejudice, female supremacy and egalitarianism.

The ideas and “happenings” in the novel are quite distinct from those of my many gurus, AC Clarke and C J Cherryh, Asimov and Heinlein, Niven and Card, Frank Herbert and that lot, but the philosophy expresses many of their ideas.
I’m sure that Toronto’s Margaret Atwood and Robert J Sawyer, for both of whom I have great respect, would approve my take on sociology (I am closer to Sawyer than to Atwood), but of course “XCRATH” is a “poor boy”, compared with that section of the competition!

Note that you will get a much prettier book from Amazon.com (now “KDP”, for “Kindle Direct Publishing), than you will from Amazon.ca, which carries the Trafford version.

Of course I’d like to send you, all and each, a copy for free, but since I don’t charge for the website, I can’t afford it (!).

I do hope that some of you will have a look at this book.
By the way, Chapter 9 (“WARP”) begins with explanations of faster than light travel, warp speed and other technicalities: if you are not mathematically inclined and you find it difficult, skip to page 43, in which the human voyagers discover their new planet.

Happy reading!

Gervais.

On March 2nd, I got the current issue of the Green Medicine Newsletter, a monthly health blog, by Dr. Jonathan Wright, who is one of my Gurus.
The subject this time is Macular Degeneration, which causes blindness in 9% of the population over 70 years of age. The information provided is not new, but I’m sure you will find it interesting, if you haven’t heard it all before.

WHO NEEDS THIS INFORMATION?

This is important to people who have been diagnosed with macular degeneration; but also to those who have indigestion problems of one sort or another, because they are more likely to develop it.
The bottom line is that macular degeneration should be preventable and that it is inexpensively, and often, treatable.

THE CAUSE OF MACULAR DEGENERATION

Dr. Wright suggests that a lack of certain key nutrients causes macular degeneration and that deficiency of these nutrients may be due to either a poor diet, or a failure of the stomach and intestines to digest and absorb one or more of them.

In his post, he explains:

• Many people with macular degeneration are not absorbing nutrients necessary to the eyes, either due to low stomach acid, or insufficient pancreatic juice, or both.
• Some people habitually neutralize their stomach acid with antacid, like Rolaids, Tums, and Maalox, not realizing that “acid indigestion” is a misnomer: the symptoms are actually due to a lack of stomach acid, not an oversupply.
  Hydrochloric acid (HCl), the superstrong acid secreted by the stomach, is essential:
  it splits your food molecules up into absorbable bits.
  HCl is necessary for digestion: taking antacids for “acid indigestion” can reduce stomach acid to zero and prevent absorption of minerals and other essential nutrients, from your food!
• Some people take medications, like Zantac, Tagamet and Pepcid, which prevent HCl production by the stomach.
  These folks not only have low stomach acid: they will also lack sufficient pancreatic digestive enzyme, because the pancreas secretes its “juice” in response to HCl.
• Stomach acid can be augmented with HCl capsules, with meals.
  Apple cider vinegar (ACV), taken in the morning, works well for some people in terms of stopping the symptoms when there is only slight reduction of stomach acid. However ACV is very, very weak compared with HCl.
  It may not return the digestion of food to normal, so a capsule of HCl is a better idea.
• A stool test for undigested protein should be done: it will tell whether you are under-producing pancreatic enzymes, in which case capsules with HCl, plus pancreatic enzymes, will help.
• Capsules containing HCl and pepsin, the main pancreatic protein digesting enzyme, or Betaine hydrochloride and pepsin, are available.
  However, rather than treating yourself “empirically” on the basis of this information, you should discuss the subject with an “open-minded” family doctor, or with a pharmacist.

WHICH NUTRIENTS ARE “KEY”?

According to Dr. Wright, the key nutrients and their approximate daily doses are:
Selenium , 300 µg,
Zinc Picolinate or Citrate, 60 – 90 Mg,
Taurine, 1 G,
Vitamin E, 400 – 800 units,
N-Acetyl Cysteine (NAC),

– I would add 10mg Melatonin, 1-200mg CoQ10, 10mg Lutein, 2 mg Copper, 2G Vit C, 2000 iu Vit D and 150 mg magnesium.

– Adding these nutrients to the diet may not be necessary if the diet and the eyes are normal, since appropriate treatment with HCl results in normal digestion and absorption.

– If “Achlorhydria” (nonproduction of HCl) has resulted in even mild anemia, an iron preparation should be taken with the HCl capsule.

CAVEATS:

• Low stomach acid can cause anemia: if the hemoglobin is low, the stomach function should be checked.
• Legend has it that thyroid hormone makes macular degeneration worse.
  In support of this idea, doctors give an eye injection which blocks the action of thyroid hormone inside the eye and it often improves vision.
  However a logical question exists: if thyroid hormone causes macular degeneration, why don’t we all have the disease?
  My suggestion therefore (as with all major medical conditions) is that a “Thyroid profile” test series, including thyroid antibodies, TSH, FT4, FT 3 and reverse T3 should be done and if intracellular hypothyroidism is diagnosed, it should be treated with slow-release triiodothyronine (T3), as usual.
• This post contains information which may be of some help to the reader who has macular degeneration, perhaps as a baseline for discussion with a doctor.
  It is not an instruction or a prescription for macular degeneration and should not be interpreted as such.
• Some doctors “play by the book”, with no room for ideas they are not familiar with.