Thursday, February 25, 2010

Arteriosclerosis in 1957

I was born in 1956, so I was an infant at the time these photographs were being taken. Each one records a personal tragedy. We should learn from them.

All illustrations are taken from Henry Moon's classic 1957 paper.

This is a normal coronary artery. It has been stained to emphasise elastic tissue. Note the continuous folded band of elastin with nothing visible between the elastic layer and the artery lumen (there is actually a single layer of epithelial cells here).

The thicker layer outside the thin black elastic layer is media and is made of muscle. The more granular layer outside the muscle layer is the adventitia. The slide comes from a 5 months gestation human foetus who died, without being born, in a tragic accident. Accidental death autopsies are where all of the pictures in this post come from. Non are cardiac patients.

Next is this picture of the coronary artery of an infant who was 4 days old. Note that most of the intima (dark red wavy layer) is normal and that all of the media is normal. But look at the lower right, there is an abnormal area of the elastic layer. It is shredded and there is fuzziness over the surface. This is the earliest stage of arteriosclerosis noted in this series.

If we next go on to look (slide below) at the coronary arteries from an infant of four months of age we can see a small section of normal intima, with intact elastic layer, on the upper left of the section of artery with normal muscle in the media outside it. Over the rest of the artery the elastic layer is grossly disrupted or absent, the intima is grossly thickened and the muscular media is still relatively normal, though it is a bit thickened at the lower area of the section:

And then we have this superb section actually through a branch of the coronary artery of a child of three years of age. There are some areas of elastic tissue intact but much of it is damaged and the intima has generally thickened wherever the elastic tissue is disrupted. The effect is most marked by the mouth of the branch. The smooth muscle layer (media) is still quite normal but somewhat thickened at the mouth of the branch too.

These last two high magnification images in one picture are stained to show the material of which the thickened intima is composed. In the lower image the changes extend in to the muscular media too.

Do you think it might be cholesterol?

You know, LDL-C, the stick-and-die stuff? Oddly enough if you do frozen sections and stain them with sudan red there are very occasional macrophages with a little lipid in their cytoplasm scattered thinly through this gunk.

But no, the wall to wall stuff stained with Prussian Blue is mucopolysaccharide, I think nowadays it's called glycosaminoglycans or GAG.

To me it's really weird how a cardiologist can think that LDL causes this, and that statins might stop it.

But then the world is a weird place!


It's Friday and we're heading south for the weekend so the blog will be quiet for a few days.


x said...

1956 was a good year!

Drs. Cynthia and David said...

Hey I was born in 1956 too! My first job after college (before grad school) was as a lab tech for a cardiologist, analyzing cadaver samples of normal and atherosclerotic arteries. The normal ones were smooth and pink, and the diseased ones crunchy from calcification and yellow. We found lots of glycolipids in the diseased samples. Imagine if instead of testing for cholesterol, they had tested for glycolipids and explored to role of sugar in atherosclerosis. Maybe Yudkin would have won out over Keys and sugar would have been recognized as the killer all these years instead of fat!

Beth said...

So, for the non-doctor here -- are you saying that that these babies already had arteriosclerosis and were, thus, sick, or that having some degree of arteriosclerosis is normal?

It seems strange to me to think that a 4 day old baby would have the beginnings of heart disease.

I'm with you on the weirdness (and tragedy) of the LDL idea, but I am curious what really is happening.


donny said...

"A Serotonin-Dependent Mechanism Explains
the Leptin Regulation of BoneMass,
Appetite, and Energy Expenditure"
Leptin inhibition of bone mass accrual requires the
integrity of specific hypothalamic neurons but not
expression of its receptor on these neurons. The
same is true for its regulation of appetite and energy
expenditure. This suggests that leptin acts elsewhere
in the brain to achieve these three functions.We show
here that brainstem-derived serotonin (BDS) favors
bone mass accrual following its binding to Htr2c
receptors on ventromedial hypothalamic neurons
and appetite via Htr1a and 2b receptors on arcuate
neurons. Leptin inhibits these functions and increases
energy expenditure because it reduces serotonin
synthesis and firing of serotonergic neurons. Accordingly,
while abrogating BDS synthesis corrects the
bone, appetite and energy expenditure phenotypes
caused by leptin deficiency, inactivation of the leptin
receptor in serotonergic neurons recapitulates them
fully. This study modifies the map of leptin signaling
in the brain and identifies a molecular basis for the
common regulation of bone and energy metabolisms.
This study made me wonder about the wisdom of trying to maximize brain serotonin levels with a high carb diet.

I hadn't known that leptin shows up in animals with skeletons. And in animals without skeletons, serotonin increases appetite. In the Carbohydrate Addicts Diet book by the Hellers, serotonin is described as a satiation hormone, once you've eaten enough carb, it shuts off appetite. Just like dopamine tells you when you've had enough cocaine, I guess.

So, is serotonin involved in arterial bone-ification?

Serotonin Mechanisms in Heart Valve Disease I
Serotonin-Induced Up-Regulation of Transforming Growth Factor-β1 via G-Protein Signal Transduction in Aortic Valve Interstitial Cells

5-HT and TGF-β1 Increase the Synthesis of Both Collagen and Glycosaminoglycans
Both 5-HT and TGF-β1 (Figure 4) increased collagen synthesis by SAVICs, as measured by 3H-proline incorporation. The addition of TGF-β1 to SAVIC cultures resulted in significantly increased collagen synthesis at concentrations of 0.01 ng/ml to 10 ng/ml of TGF-β1 (Figure 4A) with results comparable to those seen with 5-HT. Total protein synthesis was assessed using a [3H]leucine incorporation assay. TGF-β1 has no effect on total protein synthesis at a concentration of 1 ng/ml or lower, but total protein synthesis was inhibited (P < 0.05) at 10 ng/ml of TGF-β1 (Figure 4B) . A stimulatory effect of 5-HT on collagen synthesis was observed at doses ranging from 1 μmol/L to 100 μmol/L of 5-HT (Figure 4C) . However, collagen synthesis stimulated by 5-HT was significantly reduced by an anti-TGF-β antibody (Figure 4D) , thus indicating the specificity of 5-HT stimulation of TGF-β1.

donny said...


I left this next one in a comment I left on an earlier blog you did involving fructose and endotoxins;
Elevated dietary fructose intake, altered intestinal motility and barrier function may be involved in the development of non-alcoholic fatty liver disease (NAFLD). As intestinal motility and permeability are also regulated through the bioavailability of serotonin (5-HT) we assessed markers of hepatic injury in serotonin reuptake transporter knockout [SERT(-/-)] and wild-type mice chronically exposed to different monosaccharide solutions (30% glucose or fructose solution) or water for 8 weeks. The significant increase in hepatic triglyceride, tumor necrosis factor- (TNF) and 4-hydroxynonenal (4-HNE) adduct as well as portal endotoxin levels found in fructose fed mice was associated with a significant decrease of SERT and the tight junction occludin in the duodenum. Similar effects were not found in mice fed glucose. In contrast, in SERT(-/-) mice fed glucose portal endotoxin levels, concentration of occludin and indices of hepatic damage were similar to those found in wild-type and SERT(-/-) mice fed fructose. In fructose fed mice treated with a 5-HT3 receptor antagonist hepatic steatosis and the loss of SERT in the duodenum were significantly attenuated. Our data suggest that a loss of intestinal SERT is a critical factor in fructose-induced impairment of intestinal barrier function and subsequently the development of steatosis.

So, serotonin protects against leaky gut. In severe leaky-gut, could gut-derived serotonin end up somewhere it doesn't belong, in excess?

donny said...

Maybe a little backwards there, I'm kind of wandering around in the dark.

If "5-HT and TGF-β1 Increase the Synthesis of Both Collagen and Glycosaminoglycans" and if gut-integrity is dependent on actions of serotonin...

Is arterial integrity all that different from gut integrity? Hyperglycemia and hypoglycemia are both bad, cycling back and forth may not be ideal. Weird swings in serotonin might have similar issues, periods of over- and under-healing? (Maybe not just similar. Does hypoglycemia have consequences in poor healing? Stan the Heretic posted on HeartScan Blog about lp(a) and hypoglycemia.

According to Pauling, vitamin c goes up in animals when they're sick. According to Bernstein, insulin resistance and glucose go up with infection. Does increased glucose=increased substrate for vitamin c production? Is this wasteful? Could it get a wounded, glycogen-depleted ice age ancestor in trouble?

donny said...

Lipoprotein(a) [Lp(a)] is a unique lipoprotein complex in the blood. At high levels (> 30 mg/dl), Lp(a) is considered an independent risk factor for cardiovascular diseases. Serum Lp(a) levels are largely genetically determined, remain relatively constant within a given individual, and do not appear to be altered by factors known to influence other lipoproteins (e.g. lipid-lowering drugs, dietary modification and change in body mass). Since regular exercise is associated with favourable changes in lipoproteins in the blood, recent attention has focused on whether serum Lp(a) levels are also influenced by physical activity. Population and cross-sectional studies consistently show a lack of association between serum Lp(a) levels and regular moderate physical activity. Moreover, exercise intervention studies extending from 12 weeks to 4 years indicate that serum Lp(a) levels do not change in response to moderate exercise training, despite improvements in fitness level and other lipoprotein levels in the blood. However, recent studies suggest the possibility that serum Lp(a) levels may increase in response to intense load-bearing exercise training, such as distance running or weight lifting, over several months to years. Cross-sectional studies have reported abnormally high serum Lp(a) levels in experienced distance runners and body builders who train for 2 to 3 hours each day.

The type of exercise that increased lp(a) there looks like the type that comes with serious glycogen depletion.

I looked at the weight training because I knew that steroids decrease lp(a), I thought maybe increasing testosterone etc. through exercise would be good. Maybe with something more like slow-burn, it would be.

One thing about a high protein diet (not low carb, just high protein); it might or might not work against hyperglycemia, depending on what it's replacing, but it knocks hypoglycemia right on its ass. (I'm thinking fish eaters vs vegetarians here.) They've done studies on niacin, for avoiding ketosis in cattle (by preventing hypoglycemia.) Niacin is one of the anti-lp(a) treatments Dr Davis advocates.

Sorry for so many posts, I got carried away.

.^ said...

Off topic again ... (I seldom have the expertise to comment on your expert posts)

I noticed an interesting thing the other day. It's high summer here in NZ and the cicadas are everywhere. My cat likes to catch them in mid-air and bat them against the wall until they're completely knackered and can't fly, then she eats them up (crunch, crunch). Seems to be none the worse for it. So a cat can at times be an insectivore.

Stephan Guyenet said...

Hi Peter,

Very interesting. I think you might enjoy my upcoming post on copper deficiency and heart disease. Those lesions are typical of copper-deficient animals.

Owen said...

Hi Peter, I am posting for the first time, but have been an avid reader for over a year. I'd like your opinion on this but I think the answer to Beth's question is hypothyroidism.

I am getting all this from reading Broda Barnes, but his argument that hypothyroidism leads to excessive deposits of mucopolysacchrides seems to float. He claims to have very good success preventing cardiac events in likely patients by putting on Armour. From what I've read the only thing he didn't want people eating is polyunsaturated fat... I assume b/c he thought it caused cancer.

You haven't commented much on hypothyroidism on Hyperlipid, but I'm curious how you think it adds up as a general health threat compared to something dietary like eating carbs. Are the people having problems with carbs also hypothyroid? Is low-carb just bypassing a slow metabolism?

You did mention the heart disease - thyroid connection in the Framingham post on 3/10/09, so I'm guessing you support this idea in some sense.

Just FYI my own experience was that my eczema wasn't clearing up on a gluten-free, almost no-carb diet so I tried Barnes' theory and ordered some generic Armour from Thailand and have been doing much better since- my skin, but also mood, energy and I haven't been very cold at all this winter.

I'm still gluten-free and get almost all my fat from dairy and meat with nuts showing up here and there for flavor. But it's been much more enjoyable since I've added back a good amount of carbs like sugar in my Yorkshire gold, orange juice to mix with cream for breakfast, lots of potatoes and a gluten-free bread that is just rice flour, tapioca, milk and butter.

After reading your recent posts on corn oil/fish oil and liver damage I am pretty convinced that sugar intake with a minimum of PUFA won't cause metabolic syndrome and now I am really starting to feel that heart disease isn't likely either with adequate T3 and T4.

Now if this is the case, the real question is why are so many people, including infant, hypothyroid? I know Ray Peat blames PUFA for this as well...

Elizabeth said...

Hi Peter;

when you eat your dark chocolate and coffee doesn't the fibre kill you off? I range between the 99 and 90% and not only does it strip the insides of my cheeks but it completely ahh.... blocks me up so to speak. The fibre is 15 grams per hundred grams - that's alot. When I do have it I have about 30 grams in a day. You??

Thanks, Elizabeth, hassling you nutritionally as usual.

Owen said...

Oh, I was thinking about this just now and realized I should also mention that while reading Barnes is what really convinced me to try thyroid supplementation, it was Emma posting about it on her Plant Poisons and Rotten Stuff blog that first got me going on the thought. I was in a similar situation to her where lots of foods other than gluten were causing me grief- I might end up with a rash or runny nose from eating salami, an apple or a boiled potato. I was suspecting some sort of salicylate/amine/glutamate problem which really can limit your diet!

So when she started posting about a food allergy - thyroid connection last year I jumped on that idea and now I believe it's definitely true. The best explanation I've heard for why this is the case may have nothing to do with mucopolyssachrides and could simply have to do with body temperature: that digestive enzymes don't work well when you are constantly running a temp in the sub-97 F range, as I was.

But I also think it's significant to mention because though I mentioned Ray Peat's idea on PUFA being anti-thyroid, in my own case I am going to guess it was autoimmune, possibly Hashimoto's and very possibly caused by gluten.

Helen said...

Peter - This is very interesting (and alarming) - but, as another reader requested, could you translate? What do you think caused the arterial thickening?

donny said...

What do low thyroid, fatty liver, insulin resistance have in common? Insufficient energy for the liver to do its work properly?

Glutamine is taken to feed the gut in treatment of leaky gut. Fructose-->leaky gut. Does fructose deplete atp in the gut in a way similar to the fructose induced atp depletion in the liver? Fructose starves the gut, glutamine feeds it? apoB and Hdl and all that are produced in the gut as well as in the liver. I saw a study where glutamine fed to rats caused the apoB produced in the liver to be released in a different manner; larger and fluffier. Glutamine has obvious connections to the Krebs cycle and energy in general which I can make no claim to understand.

Glutamine, in another study, caused fat cells to become insulin resistant. When is a cell insulin resistant? How about when it's not hungry? When it's been fed glutamine?

Homeostasis isn't about how much calcium or cholesterol or sodium goes into the system, it's about what's done with it once it gets in. It's all about the work.

"Bad" gut bacteria-- if they thrive in a high sucrose (fructose) environment, do they compete for some of the metabolites (like glutamine) that might help the gut and the liver to handle the fructose load? I think you could put "alcohol" just about everywhere I put fructose. I wonder if you could put "glycine" or "taurine" where I put glutamine?

Pasi said...


Do you have a reference for that glutamine, liver and type of ApoB?

Fructose (and ethanol) will increase gut permeability and one way they could do it is lowering the ATP needed for proper function of the tight junctions. Gut function needs lot of ATP and fatty acids, BCAA, glutamine provides fuel source for the Krebs cycle.

"Adenine nucleotide levels indicate viability of intestine, and ATP levels in enterocytes appears to be important for the maintenance of intestinal barrier function. The importance of ATP for maintaining normal permeability characteristics in epithelial monolayers has been extensively documented. Profound ATP depletion led to loss of both the “gate” and “fence” functions
of tight junctions."

Glutamine decreases the amount of glucose carbon directed to Krebs cycle. That is connected to increased UCP-2 expression which is also related to insulin resistance.

Peter said...

Chainey, you want to see the effect of a live insect on a pet rat! Anyone who considers them herbivores has not fed them insects!

Hi Stephan, yes, copper appears to be important for the correct formation of elastin (and collagen too???). Could the fall in heart disease since the 1940s be from the gradual deterioration of copper piping? In copper piped houses it seems unlikley that any of us would be copper deficient nowadays, especially as the copper corrodes..... oooh, was just looking up a non related ref and fell on this

and all the follow on papers... Now will the arrival of plastic piping reverse the fall in cvd we have enjoyed despite dietary advice? When did we start with copper pipes???? The pig paper actually reminds me of the ascorbate knock out mice who do aortic failure without typical arteriosclerosis. Hmmmmmm

Hi Owen,

I have no doubt that thyroid deficiency accentuates CVD but I doubt any of the infants providing the specimens in the paper were thyroid deficient, especially at 4 days of age. I would need more than Ray Peat's opinion on this as he has blotted his copybook by mis-citation too many times for me to believe anything he says... More's the pity if he's correct, but if he was the refs he cites would actually say what he claims. That would be nice!

Thyroid deficiency in adults with a damaged thyroid giving inadequate response to injury, now that's more believable but does not make thyroid disease primary problem...

Hi Elizabeth,

I've just had an off blog conversation about fibre and what do I really think. I think eating whole foods, even low carb, makes fibre unavoidable, so worrying about "some" is pointless and I tend to listen when Stephan discusses these things. Looking at resistant starches there is some benefit at 5g/d, cf zero g/d and absolutely no benefit at 10g/d, ie a U curve. I'm suspicious fibre behaves the same way. Some is possibly helpful, loads is neutral or deleterious. But it can't be too bad as WHEL and PPT were neutral despite huge increases in fibre intake. If you have IBD this may not apply...

Helen, from Moon and Rinehart's 1952 paper:

"The remarkable frequency with which fibrosis of the intima, increased mucoid ground substance and fragmentation of the internal elastic membrane occurs even in young individuals logically raises the question as to whether or not these changes may be regarded as "normal" or nonpathologic. Although we do not intend to discuss this question at present it should be pointed out that processes which predispose to or cause eventual dysfunction of an organ should by definition be regarded as pathologic."

The blend from normal to pathologic is gradual and there are arguments available both ways at this stage. Obviously this level of arteriosclerosis is quite different from the unstable plaque full of cholesterol crystals and omega 6 PUFA. I hope there is a series of posts coming here.

Donny, to much to read there to comment at the moment. But gut ATP and tight junctions is interesting...


Peter said...

Just out of interest

"The installation of lead piping was generally discontinued in the early 1950’s and new use of it actually made illegal from 1969. The use of lead solder in the joints of other pipework was made illegal in 1987."

"During the early 1930s, with the advent of thin wall or light gauge copper tube, other jointing methods developed; i.e. capillary and compression fittings; the cost of copper water services pipeworks became competitive with other materials and a new era was opened to the plumbing and heating engineer."

Give 10-15 years for the copper to start to leach in to the water....

Now folks are worried by epidemiology (yawn, Zzzz) linking Alzheimers to copper. Like it used to be aluminium or saturated fat...

Anyway, I'll stick with my lamb's liver for the copper and risk dementia. Living in a plastic piped house nowadays!


donny said...

Glutamine promotes triglyceride absorption in a dose-dependent manner

Dietary proteins may play a role in lipid absorption. Whether amino acids are specifically involved is unknown. We hypothesized that enterally administered L-glutamine (L-Gln) given with a lipid meal increases triglyceride (TG) absorption in rats. Mesenteric lymph fistulae and gastroduodenal feeding tubes were placed in adult male Sprague-Dawley rats. The animals received an enteral bolus of Intralipid (5 ml) followed by enteral infusion of increasing concentrations of L-Gln in saline (0, 85, 170, or 340 mM) or equimolar concentrations of the inactive isomer D-Gln or an essential amino acid mixture without Gln. Lymph was collected continuously for 6 h and analyzed for TG content. Animals infused with 85 mM L-Gln had a 64% increase in total TG output vs. controls (P < 0.05) despite no difference in lymph flow rate. Total TG output for animals infused with 340 mM L-Gln declined by 43% vs. controls (P < 0.05). The effect of Gln in promoting lymphatic fat transport is specific to L-Gln and not shared by D-Gln or an equivalent amino acid mixture. L-Gln is capable of either promoting or impairing lymphatic TG transport in a dose-dependent manner.

Apolipoprotein B (apo B) is essential for chylomicron (CM) formation and thus TG output (6). AA are needed to form apolipoproteins, and as such, the enhancement of observed TG output may be an effect of high AA concentrations. Furthermore, supplemental Gln has been shown to increase total protein synthesis in jejunal enterocytes (10). However, it seems unlikely that the effect of Gln on intestinal lipid absorption is mediated through increased apo B secretion for the following three reasons. First, the equimolar AA did not have a significant effect on TG output. Second, TG flux is not believed to stimulate intestinal apo B synthesis. Instead, enterocytes transport absorbed dietary lipid by increasing the size of CM particles and not by increasing their number (9). Third, perhaps the effect of Gln is achieved by supplying more energy to the process of CM packaging, since energy is required for this process and Gln has been demonstrated (22) to be the preferred energy source by the enterocytes.
That's all from this;

The highest level of glutamine they tried actually had the opposite effect. The lower levels of glutamine may have improved the energy status of the enterocytes, and their ability to handle lipids; the higher level may have satisfied enterocyte "hunger" a little too well; so the enterocytes selfishly ignored the fat.

Okay, that brought me to a weird place. Corn oil has been shown to cause luxusconsumption in a number of rodent studies, compared to saturated fats.

This study's good enough for the basic idea;

"Effect of High Fat Diets on Energy Balance and Thermogenesis in Brown Adipose Tissue of Lean and Genetically Obese ob/ob Mice"

Maybe that's not such a good idea; feed a little glutamine, a cell has enough energy to handle lipids properly. Too much, and it's too content to do its job. If you assume the cell is basically selfish, and that the processing of dietary fat to the benefit of the rest of the body is incidental as far as it's concerned, then a thermogenic effect of corn oil-- easier access to the energy in the corn oil vs saturated fat-- might have the same effect as excess glutamine.

Owen said...

Well I should clarify that the bulk of my post on thyroid was regarding Broda Barnes' experience treating his patients. I only mentioned Peat's theory about PUFA as a possible explanation for why hypothyroidism might be so common (if you believe it is...) Mary Shoman's claim is that it's because of the fluoride in drinking water competing with iodine for uptake. IMO due to how common Hashimoto's and Ord's thyroiditis are I think the autoimmune aspect points to something like gluten, if only as an aggrivating factor.

But back to Barnes, he noted that where parents were hypothyroid, children also were (with the implicit idea that before antibiotics a lot of these people would have died young of infection before they had children of their own, much less before that made it to middle-age and developed CVD.)

From his book "Hypothyroidism: The Unsuspected Illness":

"My youngest patient was a three-week-old infant who from birth had been unable to breathe through his nose because of a continuous upper repiratory infection. He was low in thyroid function as were both his parents. His resistance became normal within a few weeks on thyroid treatment."

So it's one possible explantion. I guess my main reason for posting is to ask what else could be the reason for mucopolyssachride deposits in foetus in gestation or new born?

blogblog said...

re: Chainey
Cats love eating insects. One of my cats was always catching and eating house flies. We had a grasshopper plague in my town in the 1970s and this cat ate nothing but grasshoppers for an entire week.

Peter said...

Hi Owen,

I have to add the proviso that while i have not read Dr Broda Barnes I have heard from people I respect that he talks sense.

I would accept that if an environmental factor is affecting both mother and father then it would not be too surprising that it might affect their child. How many of us are subclinically hypothyroid is an interesting question.

The changes in the images are present in essentially all of the infants who have been through the birth process, the numbers involved are listed in the paper. Thyroid insufficiency may be common but I cannot see it being ubiquitous.

It would be interesting to see what effect caesarian section has on the incidence of the changes but back in the 1950's this was not the normal birth process for human beings.

It is quite obvious that CVD is essentially an elastosis and if hypothyroidism, like copper deficiency, produces an elastosis it fits well with my ideas. I'll try to get some pictures up soon which make the process a little clearer but I've other things to do today...


L said...

I am a latecomer to this discussion but I do have an observation that may be relevant in the debate of the role of gluten in autoimmunity. For several years I have followed a Weston Price-type diet - compared to the standard western diet, moderately high fat, moderately low carb, but including grains, albeit in the case of wheat almost exclusively sour-fermented. I also have autoimmune thyroid disease. Over the past months I have eliminated grains, which has also necessarily reduced carbs and increased fat. I titrate my thyroid dose based on symptoms and since eliminating the grains have now restabilised my dose at less than half my previous level.

Now this is highly unscientific sample size of one, and there could be confounding factors at work. However, this order of magnitude makes me at least highly suspicious that grains were playing a substantial role in my condition - both in its origins and symptoms.

Peter, I love your site; I've been browsing through the entire backlog of posts. Thank you!

Peter said...

Hi Lucy,

I'm even later here... I think it is difficult to separate gluten from autoimmunity. Some things will step in to replace it, alcohol, fructose and soy saponins all seem able to damage gut barrier function. But gluten is the big one...

It's interesting that your thyroid is improving. Mostly when it's cooked it stays cooked! Alex comments occasionally and describes his thyroid as "toast". Quite appropriate!