Friday, July 13, 2012

Are you free, T3?

Measuring thyroid hormone level is a very simple matter in clinical practice. For total T4 you can do it in-house if you don't care too much about accuracy. A commercial lab is better. Very occasionally you meet a patient with very clear cut markers of thyrotoxicosis which has a T4, as measured by a commercial lab, which is persistently within the upper end of the lab reference range for normality.

For these (usually cats) we check the free T4 level. Free T4 is not cheap, despite the name, and takes some time to come through from a referral lab. We use this test because almost all of the total T4 in plasma is bound to albumin and assorted other plasma proteins. We need the "unbound" or active concentration thyroxine because this is what does what it does. Of course no one really wants to measure free T4 anyway, what we want is the actual active hormone, T3. Preferably free T3. However, for many cases, free T4 is good enough.

Measuring T3 or (gasp) even free T3 is another ball game and is something I only request occasionally. Usually when trying to get to the bottom of apparently hypothyroid dogs when all lab results come back "borderline low". Unfortunately free T3 is not available in the UK and sample gets couriered to the USA. I think the courier must swim the Atlantic judging by the time taken.

But ultimately even the free T3 is only a surrogate for the level of T3 which is actually bound to its receptor within the nucleus of each cell, including those of the brain.

Measuring receptor occupancy this is neither easy, clinically appropriate nor commercially available. But fortunately there is a surrogate.

You can get an idea of whether the brain thinks there is enough T3 sitting on its receptors by whether it is asking for more. It asks for more using (eventually, after several steps) TSH, thyroid stimulating hormone. This is released from the pituitary as a signal to the thyroid to increase production.

So the rule of thumb with a suspected hypothyroid patient is to ask whether the TSH level is elevated, ie is the brain unhappy with the current thyroid level. When you don't have the time or finances available for that courier to swim the Atlantic, this is what we use. It's a surrogate, but useful.

As so often, this is just basic clinical chemistry. It defines how I view hypothyroidism.



So let's put some folks on a diet, get them down to 10-15% below their start weight and look at their thyroid status. Keep them as weight stable as you can and look at total T3 levels on three different diets.

Not surprisingly the level of thyroid hormone falls with weight loss. The run-in diet provides weight stability before weight loss and the T3 is 137ng/dl.

The same folks after weight loss, and on 310g/d of carbs, have a T3 of 121ng/dl.

On 205g/d of carbs the T3 is about the same at 123ng/dl. But with carbs restricted to 50g/d of it drops a whopping 29ng/dl to 108ng/dl, twice the drop of the more moderate carb diet phases.

There you have it. Eat LC and thyroid deficiency, here you come.

OK, so the next question is: What does the brain think about all of this? Remember T3 is not free T3 and certainly not nuclear bound T3, so we have to look at the surrogate. What is the message from the brain to the thyroid gland concerning the adequacy (or not) of current thyroid levels? Which way does the TSH, our crude surrogate for effective neuronal nuclear bound T3, shift?

The run-in TSH is 1.15microIU/ml, this is on obese weight stability. It goes up (the Badness direction) to 1.27microIU/ml on high carb, 1.22microIU/ml on moderate carb and it drops (the Happy direction) a gnat's whisker to 1.11microIU/ml on LC.

Summary: Despite the limited fall in T3 on higher carb diets, the brain is not happy with thyroid status. TSH goes up. Gimme gimme gimme, more more more.

However, even with the greater fall in total T3 under LC eating, the brain is happy with whatever level of free T3 it is "seeing", as judged by TSH level. Should the brain be happy?

There are hints. In particular the TEE was reduced least in the LC phase of the study. There was a reduction in TEE of course. But less than for either of the other two phases imposing weight stability at reduced BMI. Despite the largest drop in total T3. It seems like a reasonable idea that both free T3 and receptor bound T3 might actually be higher under LC eating. As so many times, we will never know.

Another way of looking at the change would be to consider whether as much free T3 is needed on a LC diet. Sam Knox provided this rather nice link in the comments to The lost 300 post. It's certainly worth thinking about. Of course, I quite like the idea. But then I would!

So will low carbohydrate eating lead to thyroid deficiency? Who knows, in the long term. This was a very short study. But in this paper the brain seems quite happy with 108ng/dl of total T3 as judged by a TSH of 1.11microIU/ml.

This does not look like hypothyroidism to me.

But then I'm just this clinician see...

Peter


And here's an aside on LC eating and 24h urinary cortisol. I'll just stick the key quotes from the discussion:


"As in previous studies, discrepancy between cortisol regeneration measured during dynamic testing and the more conventional index of 24-h urinary endogenous cortisol/cortisone metabolite ratios (Table 2) reflects the confounding effects of 5 alpha- and 5 beta-reductase activities on ratios of steroids excreted in urine."

Translation: Relying on 24h urinary cortisol may mislead you. That might help with LC bashing, but you're still misled.


"Low-carbohydrate intake appears to be the key factor responsible for alterations in glucocorticoid metabolism"

Translation: LC eating is what is KEY to IMPROVING glucocorticoid metabolism.


"...extraadrenal regeneration of cortisol is responsive to the macronutrient content of the diet. In these obese men, a low-carbohydrate diet reversed the increase in metabolic clearance of cortisol (3), increase in 5 alpha- and 5 beta-reductase (4), and decrease in hepatic 11 beta-HSD1 (5, 6) previously described in obesity.

Translation: LC eating reverses the nasty effects of obesity.


"The increase in 11 beta-HSD1 activity, and hence intrahepatic cortisol concentrations, caused by a ketogenic low carbohydrate diet has implications for the efficacy of different dietary strategies in reversing the metabolic consequences of obesity."

Translation: LC eating wins hands down for correcting the metabolic consequences of obesity.



24h urinary cortisol? Pah.

39 comments:

smgj said...

As a hypothyroid person I'm not too fond of the TSH test. You can add to it's inability to measure what's happening at the cellular level that it's influenced directly by iodine from food and may normally in humans vary by quite a lot during the day and are naturally low in infectious illnesses...

I'd propose using basal temperature measurements as an added safety for validating the TSH results.

Stipetic said...

Good morning, Peter. William of Occam would be proud.

However, you are making way too much sense. Join the crowd and be more obtuse. Obfuscate. Stop being a bloody clinician.

Back to my high fat frappe.

Manythings said...

Thank you for this. I stopped doing science at "o" level but I believe I have a good BS detector and pick technical things up pretty quickly if they are explained clearly and logically, as they are here.

Wout Mertens said...

Hi Peter,

I was reading that first paper too and I think it doesn't entirely test LC.
These are the macronutrient ratios C/F/P by energy:
Low fat was 60/20/20, low glycemic was 40/40/20 and low carb was 10/60/30; run-in diet was 45/30/25.

Notice how the LC diet is suddenly high protein. So does this test LC or HP? No way to know.

They were also feeding them isocalorically which may have been less than 2000kcal and thus the LC would qualify as VLC for me (<50g).

Furthermore both other diets provide way more carbs than the body can use straight-up in a day and thus cause conversion to fats and possible metabolic derangement in already metabolically challenged individuals.

It would have been nice to see "adequate" carbs tested, ie. more than 50g but less than 150g (still low carb by many people's standards but not forcing your body to create a lot of glucose itself).

A nice thing about this study is that it hints that the slow carb thing is not so useful in practice (and it makes you fart a lot).

O Numnos said...

During my first foray into v.low carb eating I experienced all the classic thyroid related issues of dry skin, brittle nails, low heart rate and cold intolerance. It was also low fat and hence low calorie, certainly less than maintenance.

My second foray into v.low carb (not so extreme in calorie restriction) showed similar but milder symptoms - mostly the dry skin/brittle nails thing again, which completely cleared up when I upped the fat to around maintenance calories.

A previous poster (I forget who) queried whether it was mostly a calories issue.

A low calorie high carb diet might be interesting....I'm not going to try it though ;-)

Javeux said...

Wasn't reverse T3 measured at all? I thought lowering calories could eventually lead to euthyroid sick syndrome, which wouldn't majorly affect TSH or T4, but would see a drop in T3 as rT3 rises. Seeing a comparison of the T3:rT3 ratio of each diet would've interested me.

Do you ever treat animals with synthetic T3? There seems to be a lot of controversy around this with disgruntled patients not happy with T4-only and endos telling them T3 is unnecessary. Are their hands tied by the research, and should further research be carried out on the subject of T3?

john said...

Peter,

One problem with TSH measurements could be that pituitary cells seem to be more "resistant" to changes in calorie intake or other factors? While things look okay with normal/low TSH, receptor-bound t3 elsewhere may be low.

It seems like the measurement for rt3 is a decent marker for overall receptor-bound t3. There are human hypocaloric studies where t3 decreased but rt3 did not (I think others may show increased rt3 though). Anyway, metabolic rate usually stays higher despite decreased t3 [compared to higher carb].

I often have my friend, who is a doctor, test my achilles reflex, which I believe is one "classic" test for hypo (I obviously do not need a doctor to take my reflexes, but I do need someone who does that a lot in order to have other data points [people] for comparison). I eat high fat, and my relfex is quick and strong.

There is an Italian group that did some short term (3 weeks or so) studies* in high fat (20% carb) mice using pretty good diets (just a smidgen of soya oil), and they [sometimes] found increased t3, increased calorie intake, same weight.

*http://www.ncbi.nlm.nih.gov/pubmed/10535383

Retinoic acid induces expression of Mct8**, and there are studies of vitamin A lowering TSH. Mine seems a bit high at 1.5.

**http://www.ncbi.nlm.nih.gov/pubmed/20573951

tess said...

thank you, thank you, THANK YOU, Peter! very interesting and enlightening stuff, indeed! fills in a lot of intellectual holes in my understanding!

having been hypothyroid almost all my 57 years, i understand this problem quite well from the patient's point of view. since going paleo, my hair and skin have never been dry and fragile, though -- i wonder if people who have these problems mightn't have a problem with their diets in the form of too little saturated fats and complete proteins?

Nancy said...

I have high reverse T3 and low free T3 on low carb.

WilliamS said...

My own endocrinologist, after years of exclusively treating hypothyroidism, has concluded that he has absolutely no idea what a particular patient's TSH, total T4, or freeT4 should be, apart from obviously pathological extremes.

He's very smart. He knows what he doesn't know. He thinks.

Different people clearly do better at quite different TSH and T4 levels, which is consistent with the very wide "normal" lab ranges. But there's no way to know which person should be at TSH 0.5 and which one at TSH 2.5.

Unless you ask them how they feel, that is. Radical!

Harder with the dogs and cats, I know—though our own hypothyroid greyhound tells us very clearly when her dose is suboptimal: spooky behavior, fur loss, and skin hyperpigmentation tell us, no matter what the labs say.

As for total T3, free T3, and reverse T3, my endo stopped even testing these years ago. He found them useless. They never added anything to asking patients how they feel (and monitoring TSH and T4 to avoid gross overdosing or underdosing). Interestingly, this is true even when values fall well outside "normal" ranges, which is why he feels no need to measure them at all.

I am very skeptical of any grand conclusions drawn simply because, say, a dietary change "lowered T3." How can anyone know that is a bad thing? Ron Rosedale believes lowered T3 on low carb diets is actually a sign of slower aging. That sounds pretty good.

karl said...

I dug into this a couple of years ago - I think there is MUCH that isn't well understood. Here are my notes and a drawing for what they are worth.

@ WilliamS
There is no agreement on just how to treat hypothyroidism - the research to figure out if T4+T3 treatment is worth it has not been done - yet the body produces 20% as T3 and there are tissues that can not on their own convert T4=>T3 so my take is combined T4+T3 is the conservative treatment - most likely to mimic nature. (The problem with using T3 is is has a shorter half life.)

What really blows my mind, is that Hypothyroidism is one of the most common treated diseases and using only TSH to tweak the dosages has failed many. YET - because there is no likely patentable medicine, thyroid treatment research goes unfunded.

karl said...
This comment has been removed by the author.
karl said...

Forgot the links to my notes:


http://wiki.xtronics.com/index.php/About_Hypothyroidism

http://wiki.xtronics.com/index.php/Interventions_for_Preventative_Heart_Health#Thyroid_hormone
http://wiki.xtronics.com/index.php/Tests_for_Preventative_Heart_Health#Thyroid_Tests

mfairchild said...

smgj: would you explain how the TSH test is influenced by iodine? Does it push it up or down?

ItsTheWooo said...

The thyroid changes in this study were entirely expected and explained by functional inhibition of thyroid gland activity in response to energy deficiency.


As the fat tissue is atrophied, and continued to be atrophied, dropping leptin, insulin, and a lower SNS conspire to conserve energy.

The lower TSH correlating with lower carbohydrate intake matches leptin levels. Leptin insufficiency prevents the synthesis of hypothalamic TRH which will decrease TSH. All patients were euthyroid so none will exhibit that pathological rising TSH which is a sign of the thyroid failing to work. The reason the TSH was progressively lower with carbohydrate is because this mirrors body fat atrophy and adaptive thyroid inhibition.


The same is true of free t3/t3; as leptin declines less t4 is converted to t3, related to lower sympathetic tone. The lower sympathetic tone will also suppress vital signs and conserve energy. REE was found higher in the lower carb groups but most likely this was not mediated by the thyroid or the sympathetic nervous system, which are ALWAYS lower in an attempt to inhibit further fat loss. The higher energy output in the lower carb group probably relates to defaulting energy this way due to a deficient ability to store nutrition secondary to low insulin.

As the low carb groups waste energy, their fat tissue atrophies and leptin / insulin drop accordingly, which exerts a central negative feedback control on the thyroid gland. TSH production declines, and conversion of t4->t3 slows.


This is why low leptin/insulin correlate entirely with the lower TSH and lower T3. It's not an issu eof carbs, it's an issue of body fat atrophy.

Because of this feedback between leptin/insulin/SNS/body fat/thyroid...
The ironic thing is high thyroid activity in a fat person suggests failure to lose weight and body fat growth. A slowing of thyroid is an assuring sign that you are succeeding/maintaining.


This can only be circumvented with sympathetic drugs (phen/fen, cardiac deaths anyone) or leptin injections, or submitting yourself to become fat again (eating to raise insulin to store fat to raise leptin to get your thyroid wasting energy maximally).

If anyone in the CICO camp can find me a diet where you are able to lose as much body fat, keep it off, but maintain a rocket thyroid gland please let me know. My research and self experience leads me to see that thyroid follows energy balance in the fat tissue, signified by insulin/leptin/sns.

As stated, the slowing of thyroid in the low carb group(s) is like the superior drop in leptin - it is a sign their body fat is superior atrophied and their body is having a really hard time growing fat tissue.

It's too bad they didn't do dexa scans. Given the extent of differences in endocrine parameters I would have bet a week's pay that the VLC group was a lot lower in body fat.

ItsTheWooo said...

Example of leptin/insulin control of thyroid:

When I was fat my TSH was WNL but slightly elevated ~2.

As I lost weight my TSH continued to drop. It was below 1 at my thinnest. In pathological thyroid function a TSH that is low suggests hyperthyroidism, but I actually had every sign of hypothyroidism. This suggests my brain was purposely NOT making TSH.

When I took leptin, my TSH continued to increase, and my T3 increased. Subjectively my energy was much higher and in spite of the fact I continued to emaciate body fat I felt warmer.

tess said...

but Wooo, Peter's info explains why i feel adequately energetic on VLC, not full of hypo symptoms like i SHOULD feel according to CW. i DO get those symptoms even at LC levels.

ItsTheWooo said...

@tess thyroid status is not black and white; it's not like you either are or are not hypothyroid; thyroid activity is a gradient where one crosses over to under or over active thyroid. Some people naturally have slightly higher or lower thyroid activity.

For example, I have "adequate" energy, I do not feel cold that often, and all of this remains true as long as I keep insulin and leptin high enough to maintain my weight, or slowly gain body fat.

The moment I start restricting calories and losing any body fat worth mentioning, eventually I will feel cold and lethargic. Low carb will make it worse because low carb causes more fat tissue atrophy at the same calorie intake; there is less insulin stimulation of fat tissue to make leptin and bolster thyroid (and also keep me fatter).

OTOH If I was taking leptin, I would feel warmer and much more energetic, with symptomatic higher T3 (and my body fat would thin as well).

In all of these cases I am "euthyroid" as I do not have thyroid illness. However, my thyroid can shift from high normal to low normal to based on endocrine status mediated by my fat tissue.

Regarding your case, tess, you have pathological hypothyroidism, primary thyroid disease. You are not at all like dieters who are 30 years old and healthy and euthyroid. Our thyroid fluctuates functionally in response to energy changes.

In your case, the reason VLC improves your thyroid could be any number of issues.

- A VLC has less fiber to inhibit absorption of levothyroxine, your medication is therefore more effective.
- The digestive environment of a vLC results in superior absorption of levothyroxine. It is known levothyroxine is absorbed best on an empty stomach; the VLC diet is more similar to fasting than a LC diet.
-You may have an autoimmunity to some dietary element like wheat which inhibits your thyroid (common in pathologial hypothyroidism) which you are opting out of when you go VLC



However, as a person without hypothyroidism, with a normal thyroid that is functionally inhibited or not by my fat tissue status, I can say that VLC produces more lower thyroid symptoms than LC does, and high carb produces the least. Of course this mirrors perfectly my level of fatness and fat tissue energy balance and predicted SNS/leptin/insulin levels.

WilliamS said...

karl said:

"There is no agreement on just how to treat hypothyroidism - the research to figure out if T4+T3 treatment is worth it has not been done - yet the body produces 20% as T3 and there are tissues that can not on their own convert T4=>T3 so my take is combined T4+T3 is the conservative treatment - most likely to mimic nature. (The problem with using T3 is is has a shorter half life.)"

You are right.

For years my endo has been asking the big shots at Harvard to do these studies—or at least send over a resident or two to observe the results in his practice. They won't.

The T3 studies that have been done, and are held up as refutation of combined T4/T3 therapy, used grossly too much T3. In this scenario, patients who've been on T4 only therapy initially feel like a million bucks since they're starved of T3, but eventually feel like crap due to T3 overdose and the resulting depletion of long term T4 reserves.

We hypothyroids do need T3 in addition to T4, but we don't need a massive overdose. Try giving 10x too much insulin to a diabetic in a study and see how "evidence based medicine" evaluates insulin therapy. The dead bodies will be a bit of a problem.

I can tell you that after years of experimentation, my endo has found that almost every hypothyroid person needs both T3 and T4 supplementation, but with T3 does only 1.2% or so of T4 does. In contrast, Armour and other pig thyroid extracts contain roughly 20% T3. Great in the short run for patients starved of T3 by conventional docs, but terrible in the long run.

The conventional docs are wrong to say we poor suffering hypothyroids need only T4. The holistic docs are wrong to say we need only "natural" (pig) thyroid extract, which has *too much* T3. We are not pigs (most of us, anyway). And unlike the pigs, we get the pig hormones like Armour via our digestive systems and livers, which radically change the ratios of the constituent hormones. Grinding up pig thyroids and putting them in your mouth is "natural" in only a bizarro kind of way. The pigs don't actually do that.

You are also correct that T3, the active hormone, has a short half life, unlike T4, the long term storage form of thyroid hormone. Early on, my endo realized that T3 (or thyroid extract, which he also uses to supply T3, along with T2, etc.), should be delivered in a time-release form. He once met a pharmacist at a party who explained how easy it would be to prepare time-release T3 or pig thyroid extract, providing exactly the desired (low) dose of T3 over many hours. The rest is history: thousands of happy patients, many refugees from the Harvard big shots, but apparently none migrating in the opposite direction. I know I won't. It works. Their way does keep you alive, but for much of the time you're not sure what the point is. I know. I did it for years.

The studies to validate this could be done, should be done. But as you say, T3 is un-patentable, like low carb diets. We need a NuSci for hypothyroidism. It's almost as big an epidemic as obesity.

For anyone interested, the latest on all this will be here:

http://www.amazon.com/Functional-Approach-Hypothyroidism-Traditional-Alternative/dp/1578263875/ref=sr_1_3?ie=UTF8&qid=1342225763&sr=8-3&keywords=kenneth+blanchard+hypothyroidism

If you can't wait, his earlier book:

http://www.amazon.com/What-Your-Doctor-About-Hypothyroidism/dp/0446690619/ref=sr_1_1?ie=UTF8&qid=1342225763&sr=8-1&keywords=kenneth+blanchard+hypothyroidism

His comments on a couple of the T3 studies often trotted out to defend T4-only therapy:

http://jcem.endojournals.org/content/89/3/1486.1.full

ItsTheWooo said...

@WilliamS
Your situation reminds me of my own. You know T3 will helps hypothyroid patients, just like I know leptin will help weight reduced obese patients.

Ultimately there is no money to be made in any of these treatments, because you can't patent hormones... at least not for long. I'm not surprised no one cares about hte overwhelming research showing leptin replacement + diet will control obesity, and I"m also not surprised a tiny dusting of T3 makes life a ton better for hypothyroid patients.

Also, re diabetes: the morons in charge already warn diabetics not to control their blood sugar TOO well and to keep their a1c in the range of vessel and nerve damage. This is based from studies with aggressive use of OHAs and insulin leading to excessive deaths in general.

The people Stephan Guyenet works for are waiting for the magic obesity drug that works by some novel mechanism to cauterize the reward pathways in the brain and produce anorexia. So far they've not had luck with this, it tends to make people want to kill themselves even when they succeed. Who would have thought: suppressing reward pathways leads to misery. Duh. Drug induced depression.

It's also quite unfortunate that a chronically activated reward value of food is a symptom of obesity and not a cause, and eating less of glucose food w/o fixing anything else is a grossly sub optimal way of attempting to control it.

Richard said...

Woo

I don't think it's quite that bad, but then I've never been obese or even close. I had 10 extra lbs for a long time, and didn't worry much about that.

I agree that the idea of food reward causing obesity is quite unsupportable, and the reward idea is, as you say, an effect, not a cause.

The problem here is that we may be talking about several different situations: Normal people who have some extra weight, thin people who want to stay that way, fat people who can be helped and easily recover, and fat people who can lose weight and still have serious problems with their metabolism.

The way I see it the answer for all of this is low carb, possibly with varying degrees of very low carb to start with. Regardless of the patient or complaint.

What has to be considered is that the results may be slightly different and the people may have various reactions over-all. But if someone complains enough about the results of low carb, they can try the alternate approach. Which would be what???

Second, as discussed elsewhere, "normal" thyroid means very little. Years ago (about 25), when i weighed 145 as opposed to 155 now, after being at 165 for many years, I was told by my doctor that based on my thyroid levels I should be fat and sleepy. But clearly i wasn't. So there was no need to do anything.

The question is whether you want to treat the patient or the numbers.

Going into a lengthy analysis of how the system works chemically and biologically is necessary at some level, but there is always a good chance you have it wrong. Not because you haven't thought about it carefully, but because just like any other scientific proposition, it is just the best information we currently have.

What does matter is how people feel on low carb and if their health generally or frequently or sometimes improves.

I am uncertain from your post, as with most of your posts, exactly what your bottom line is in terms of low carb. It seems like you are saying your thyroid is dropping, in an effort to preserve the fat and save energy, Perhaps. Or it could be you simply do not need all that thyroid hormone if you are not metabolizing that much carbohydrate.

How do you feel?

My view remains that as an omnivore a few carbs is okay and may even be good. But carbs in excess makes the body believe that an adequate supply of real food (protein and fat) is not available. So the body starts to store the excess carbs as fat for use later. The body is waiting and hoping for better times and proper food. Sad to say, in the current Age of Carbs, that day may never come.

After some period of time of excessive carb consumption the metabolism is hopelessly damaged. Or is it? At that point low carb may help, but the question is whether the damaged metabolic parts can recover, and if so, how long will it take? Weeks or months, or years?

The idea that the fat is trying to save itself which results in lower thyroid is related to the idea of the set point. We might as well talk about food reward.

karl said...

@mfairchild

Evolutionarily, the original thyroid hormone was probably iodine. What is added to the iodine makes it more potent.

Way high iodine can cause a form of hypothyroidism, but what I think you are talking about is that one needs less thyroid hormone if there is more iodine available - thus I would expect that iodine would push TSH down as the iodine acts like very weak T3. (At one time they treated hypothyroidism with iodine - that was all they had. )

Two more links
http://iodineonmymind.com/facts


http://www.anaesthetist.com/icu/organs/endocr/thyroid/thyfx.htm

Javeux said...

WilliamS,

Is the "alternative" part of Blanchard's approach referring to CAM junk? From what I've read, there seems to be a lot of sense in the idea of T4+T3, but having proponents associate themselves with CTM and other unscientific treatments seems like a great way to lose credibility.

By the way, there's an ongoing petition for T4+T3 research for anyone in the UK http://epetitions.direct.gov.uk/petitions/19000

WilliamS said...

ItsTheWooo said...

"Your situation reminds me of my own. You know T3 will helps hypothyroid patients, just like I know leptin will help weight reduced obese patients.

Ultimately there is no money to be made in any of these treatments, because you can't patent hormones"

Yes, and in addition the unbelievable resistance to change in the medical establishment is another big problem. After all, T4 is unpatentable, too, like insulin.

Some of it I think is justifiable fear of reprisals for venturing outside the standard of care. The system is highly authoritarian, despite all the propaganda about "evidence based medicine." Some is just a failure to think, plus careerist resistance to admitting error, institutionalized rigidities, etc.

It is so easy to dismiss highly promising, virtually risk-free ideas such as trials of low-dose T3 or leptin supplementation for suffering patients—no supporting randomized controlled studies! Of course the emperors saying this know perfectly well how much of what doctors do routinely lacks RCT support as well.

There are other kinds of evidence. Like watching patients get better before your eyes. That does require being willing to open them. This will take a long time.

WilliamS said...

Javeux said...

"Is the 'alternative' part of Blanchard's approach referring to CAM junk? From what I've read, there seems to be a lot of sense in the idea of T4+T3, but having proponents associate themselves with CTM and other unscientific treatments seems like a great way to lose credibility."

I haven't read the new manuscript, but I imagine "alternative" here refers to his use of T3 and pig thyroid extract—which, outside of psychiatry at least, is well outside the mainstream standard of care and is the province of "alternative" practitioners.

The "traditional" part I imagine refers to his use of T4, which mainstream docs use exclusively for hypothyroidism but many "alternative" practitioners shun. (They seem to think it's unnatural, but really it is a kind of bioidentical hormone replacement. So is T3.)

I see plenty of "junk" and "unscientific treatments" in both conventional and alternative medicine. Lots of glass houses in both worlds I'm afraid.

O Numnos said...

This paper http://www.ncbi.nlm.nih.gov/pubmed/7326852 looked at long-term Thyroid hormone status in obese patients on a (very) hyporcaloric diet some of whom recieved supplemental T3 and others a placebo.

The extract tells us nothing about the diet - one assumes it's low fat at the level of calories unless protein and/or carbs are very low.

I assume they were looking at weight loss as a proxy for metabolic rate correlated to hormone status.

No difference in weight loss between groups, no sig change for placebo group in T4/rT3 or free T3.

Mind you this was severe long term calorie restriction.

smgj said...

@Karl - High iodine may actually rise TSH - in order to get the iodine into the thyriod. Dr. Brownstein talks about this.

And it's nearly useless to discuss the effect of iodine on thyriod without adding selenium into the equation. Iodine without enough selenium may severly harm.

As for the fact that LCHF seems to lower thyroid pathways, it may well be that fat-adapted humans need less thyriod hormons. But I don't think blood tests ever will tell us the truth about that.

@WilliamS - the t3 in dessicated are protein-bound so it will NOT act identical to syntetic t3 in the body. But how the difference will manifest itself - except for a much longer half-life - I don't know.

George Henderson said...

In terms of hot and cold as symptoms of t3 levels, what about serotonin?
Will supplementing 5-HTP when "euthyroid sick" alter symptoms?
t3 enhances serotonin; what if low serotonin is sometimes mistaken for, or the only troublesome symptom of, euthyroid low T3?
This experiment, if successful, might suggest simpler adjustments than gaining weight or taking T4/T3.
Intakes of EPA, DHA and AA might also need to be higher than in some strict low-PUFA diet plans, due to LDL-R/thyroid crosstalk phenomenon.
As indeed they are in Inuit diet.

smgj said...

GeorgeH - That are very interesting thoughts about omega3s and thyroid. I'll certainly look for more onformation on the subject.

When it coms to hot/cold one also have to realise that iron stores, copper and zinc have an impact on basal temperature.

ItsTheWooo said...

@Richard
I am sorry to be the bearer of bad news but body fat is actively regulated by the CNS. This does not mean we can't force weight lower or higher, it only means we will have to FORCE it that way, i.e. under/over eat on purpose many days; and if we fail to do that our weight will naturally edge to the baseline.

Progressive weight gain or loss can occur but only in some kind of endocrine pathology; e.g. hyperinsulinemia & hypoglycemia from a tumor or a FUBAR metabo -> fatafataftaf forever.


WIth that said, the body fights weight loss. Tricking your fat tissue to deflating -> lower leptin -> suppresion of hypothalamic TRH/TSH, more rT3, less free T3, lower SNS (gimped fat oxidation), diabetilicious liver spewing sugar like crazy, glucose intolerance/IR, and a myriad other ways to make you chub up until the leptin hits the sweet spot (i.e. your fat tissue grows and makes lots of it to soak your brain in it).

Really, these findings aren't controversial. They are SUPER common.

The golden rule: The better , more effective, more powerful the diet... the more severe the lack of leptin, thyroid, and counter regulation to the fat growth suppression.

Therefore, VLC = me suppression of leptin & thyroid, cuz VLC = inhibited fat growth.

WilliamS said...

smgj said...

"the t3 in dessicated are protein-bound so it will NOT act identical to syntetic t3 in the body. But how the difference will manifest itself - except for a much longer half-life - I don't know."

My endo uses both T3 and compounded desiccated thyroid extract. They both work very well, at the right doses and delivered in time release form. He has had to learn through experience how to set and adjust the doses and forms of administration for each—impossible to derive this info from the chemistry (and he is also a PhD organic chemist).

He has found that time release is very beneficial in both cases. An exception is topical administration, as I am doing at the moment, where unlike in the gut it seems that the absorption process itself provides the needed slow release.

George Henderson said...

A few weeks ago our dog (kelpie 2YO) became depressed then spooky, lost hair, and had discouloured patches on skin.
She also lost tolerance to fleas and they drove her crazy. We treated her, vet diagnosed flea allergy as cause of hair loss, prescribed antibiotics (she also had mastitis) and steroids.
These helped, I also gave her Vit D and fish oil as it's midwinter.

Since reading this, thyroid involvement seems likely.
I've added kelp to her food and she loves it (which surprised me as she hates greens). I'll keep you updated.

Could low vit D and low serotonin in midwinter trigger low thyroid, which would then cause Th2 immune problems, resolved by corticosteroids?

This suggests that even the mastistis could be linked to the vthyroid:
http://browncnc.wordpress.com/2011/01/26/thyroidendocrine-crosstalk-part-3-a-the-thyroid-gland-has-crosstalk-with-every-tissue-in-your-body/
(Admittedly it's from an ayurvedic chiropracter, but it seems credible).

There are crucial relationships between the thyroid gland and the reproductive/endocrine systems in males and females.

In females, thyroid imbalances lead to pituitary-gonadal dysfunctions which include alterations in FSH and LH hormone coordination and release, ovarian FSH receptor site sensitivity, and peripheral progesterone receptor sensitivity. These imbalances lead to miscarriages, ovarian cysts, infertility, migraines, weight gain, mood disorders, depression, and abnormal menstrual cycles. Sometimes the endocrine symptoms are so pronounced that the thyroid culprit is overlooked. Conversely, the use of synthetic hormones such as birth control pills or hormone replacement therapy (HRT), in addition to insulin surges and stress responses, lead to abnormal spikes of hormones such as estrogen, cortisol, and testosterone, which disrupts healthy thyroid function.

Estrogen and thyroid:
http://physrev.physiology.org/content/82/4/923.full

http://www.wisegeek.com/what-causes-mastitis.htm
Diabetes and thyroid problems can also cause mastitis.

Yup.
This was a very timely post Peter.
A little more iodine in the Kelpy's diet from now on.
Thanks very much.

George Henderson said...

Kelp for the Kelpie...

Olga said...

Hi Peter:
Thanks for this post about iodine. I am curious about the link to the paper suggesting that high carb increases T3 production and therefore iodine requirements. It has also been suggested that going low carb may cause iodine deficiency in some people, since bread is a source of iodine due to the use of calcium propionate as a dough conditioner. Here is a post from Richard at Free the Animal about this: http://freetheanimal.com/2010/01/the-hidden-benefit-of-the-sad-iodine.html Any thoughts?

Olga said...

One more point. Is it possible that there is so much repair going on in the body when switching to low carb that the iodine present in the body is rapidly consumed by various systems resulting in depletion? Where as,the body may be getting a just adequate amount of iodine while it limps along on the SAD from bread containing ca propionate (most breads in North America).

Amber Wilcox-O'Hearn said...

Thank you for this.

I completely agree with your comments on the cortisol paper. We just did a post on ketogenic diets and cortisol on ketotic.org. the first part was about the myth that gluconeogenesis requires an excess of it, but the second part is going to address, among other things, why urinary cortisol is not a particularly useful measurement here, and how a ketogenic diet seems to improve what really matters.

Amber Wilcox-O'Hearn said...

Link for that post is Ketogenic Diets, Cortisol, and Stress: Part I — Gluconeogenesis

Olga said...

Has anyone noticed that the groups of people who seem to be able to live healthily on a high carb diet (ie Kitavans Tokelauans, Okinawans, to name a few) all live near the ocean? Could the high consumption of fish and increased mineral concentration of the soil be part of the puzzle? Does anyone know of any groups of people who are land locked who enjoy the level of health of the Kitavans on a high carb diet? Also, accroding to Dr Brownstein http://www.vitamincfoundation.org/iodine.htm the great lakes region has some of the lowest soil iodine levels in the world.

George Henderson said...

After a week of kelp the kelpie is quite different. Wags tail, is affectionate again, looks good (no longer prematurely aged posture and emo behaviour). Despite ongoing rain and darkness.
Brilliant.