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A member of my Discord server asked a very good question that I haven’t really addressed, here is part of the answer. Feel free to join my Discord server to view the original question, it’s free, but you should be able to get the gist.

I think the speculation that there is a sweet spot is correct as at either extreme of temperature ATP production becomes unstable.

I do remember seeing posts of people claiming they were hypothyroid right around the time Paul Jaminet introduced the Perfect Health Diet. I also remember some of the more extreme people saying the chilliness people where experiencing was a sign that they were doing things right. LOL.

I’m not sure who originated the idea that ketosis was causal in thyroid dysfunction/low T3 except that, very consistently, lower T3 is associated ketosis type diets and starvation and further I’m not quite sure where the idea even comes from as far as being “harmful” as the effect ON SERUM is expected. Not very many of them provided evidence for this, so I’m not sure if it was based on signs and symptoms or symptoms alone. But the effect is physiological not pathological; at least initially.

Regardless, across species there is an inverse correlation between T3 and longevity and like with temperature there probably is a sweet spot for T3 as well but serum measurements are highly variable. What is important is local tissue levels which we don’t have commercial tests for; but we can do this in the lab with PCR, which I have done when I was researching the effects that viruses have on cellular thyroid hormone metabolism.

I’ve mentioned in the past that when cells are provided with the correct energy substrates that hormones are background. There is normal circadian oscillation for catabolic and anabolic processes but in a situation where appropriate energy substrates are used hormones remain in the background.

Lifecycle oscillations of thyroid hormone are also orchestrated by physiological processes such as in utero and during birth, stress, cold, the death of a family member or a bad breakup. In healthy adults, there also is an postive association between T3 and waist size that nobody seems to want to address. Indeed, T3 administration above physiological amounts causes diabetes to develop.

As well, during illness thyroid hormone levels decrease, adjuvant therapy with thyroid hormone during these situations tends to exacerbate the illness pointing in the direction that fluctuation in thyroid hormones is an adaptive process.

Thyroid hormones are catabolic, sometimes they appear anabolic but this is only because during catabolism, anabolic parameters also increase.

Increased T3 is a symptom of hypoxia both at the cellular, tissue, and organism level and the level of hypoxia in vivo is largely an effect of 2 things 1) the predominant metabolic substrates being provided to your cells and 2) the external availability of oxygen.

When does thyroid hormone increase? Under carbohydrate load and under anaerobic/hypoxic conditions. Given that thyroid hormone is catabolic this makes sense, as the increased local thyroid hormone concentration is secondary symptom of anaerobic/carbohydrate metabolism.

But why?

Excess carbohydrates in a normoxic environment is maladaptive, as I’ve pointed out in the past in my energy and structure blog posts, carbohydrates are a primitive fuel source this is why high-level organisms utilize fatty acids for their basal metabolism unless the situation is such that they are in a hypoxic environment. Even in naked mole rats although serum levels of thyroid hormones are low, ultrastructurally (cellular and tissue level) there is increased secretion of the hormones.

One of the functions of thyroid hormones is to orchestrate “form”, what this means is that through very carefully controlled fluctuations in cellular respiration you can change the phenotype of a cell, you can also kill cells with thyroid hormones which is part of their function as well in organisms that go through metamorphosis. For example, in tadpoles as the frog develops thyroid hormones increase to supraphysiological levels at the posterior-proximal junction of the tadpole tail, ROS and autophagy increases and the tail essentially cauterizes off.

Thyroid hormones are a necessary to “keep form”, thyroid hormones activate during carbohydrate/hypoxic situations in order to keep the cells utilizing carbohydrates from degenerating into more primitive cell types, for example, cancer. When this mechanism fails, for any number of reasons, whether it be fueling the basal metabolism with primitive energy substrates, external hypoxia, internal hypoxia from antimetabolic compounds, at the end of the day thyroid hormones help to maintain “form”, structure, and function. In a very real sense not only is thyroid hormone catabolic, it is protective and can be better classified as a stress hormone. It is an organizer.

One of the things that happens during Paleo style diets with all the PUFA, nuts, antinutrients, excess protein, etc., is that all of these things have an inhibiting effect on respiration. While serum levels of thyroid hormones fall, it is only because ultrastructural levels of thyroid hormone increase, that is, more is being used than can be produced, hence the nuclear blast of unsavory symptoms.

So your last point:

“This was the main reason I always steered clear of ketogenic diets. What do you make of that? Could it be simply the cumulative inhibitory effect of PUFA, since these people were probably not discriminating againsts those fat sources? Could it be the compounding of these diets + exercise that causes this? Excessive protein elevating cortisol and that in turn suppressing thyroid function?”

You hit the nail on the head exactly. Lower serum = higher ultrastructural levels = emergency = maintaining form because of the hypoxia induced from Paleo style diets is more important than thermoregulation. Your physiology is redirecting ATP and H+ pools to maintain form to survive verses cozy metabolically generated warmth.

Saturated fat does not do this. I steer clear of ketosis. Ketones are a symptom of hypoxia. We are indeed omnivores, glucose is essential for optimal health, people who say well, we have gluconeogenesis and ketones aren’t thinking about things in the broader context. It’s like, we have those pathways as evidence that yes, some glucose is required and probably optimal, we do not have the high output gluconeogenic pathways that true carnivores have. And when are those pathways active? Hmmm.

I hope that that answers at least part of your question. Ask any follow up questions and I’ll be sure to address them. This is a good topic.

Aside: One of the interesting things to look at is that RPF folks can sometimes initially loose weight, that is a function of elevated thyroid hormones trying to rescue the metabolism, but if they continue and ignore all shitty symptoms all of the sudden they blow the fuck up whether it is weight gain or worsening problems such as panic attacks, helplessness, social avoidance, etc. These of course are all symptoms of hypoxia … unless they start taking thyroid hormone. I prefer the advice “… let us avoid the problem to begin with …” the situation with the folks on the RPF is first physiological then pathological. Yikes.

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The Bitter Citizen Discord Server

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This post stems from a question on Discord about why I’ve moved away from drinking milk (and if you haven’t joined my Discord server, please do, there are a lot of smart people on there with lots of different experiences).

This is going to be a bit all over.

Most of the benefits of milk are from the milkfat and some of the more exotic lipids contained in the milkfat.

The galactose is beneficial in certain contexts because over the long term if your cells have a diabetic like phenotype or a hypoxic phenotype (dare I say they are basically the same thing), galactose will shift the cell state to increase OXPHOS increasing ATP and oxygen consumption, glucose doesn’t seem to be able to shift the cell metabolic phenotype in a positive direction except to maintain whatever state the mitochondria are in and potentially worsen it if cells are in an already diabetic like phenotype and glucose isn’t being directed properly. Fructose definitely can in the right contexts.

Glucose is not a good metabolic substrate to rely on predominately if you are an organism that relies on palmitic acid driven OXPHOS and like to breathe oxygen; and I would distinguish between a basal and peripheral metabolism here. From my experiences you can have quite a bit of potatoes and still have room to breathe.

It’s important to note that acute exposure to galactose will not cause this shift, cells have to be exposed chronically (environmentally) for the shift to occur permanently. Once the steady state is restored cells will happily burn palmitic acid and a nice physiological insulin resistant state can be restored.

When I think about milk and in particular the galactose and ketones increasing at altitude it’s not hard to imagine that milk is the input which produces the desired metabolic output i.e. moving from a hypoxic to normoxic environment. Not too much different than fructose driven glycolysis in low oxygen environments.

When I think about ketones and their ability to “prevent” or “reduce” the consequences of hypoxia I think given how high they are in human babies that mitochondria are still developing oxidative capacity and the internal “atmospheric conditions” are being buffered if not facilitated by lactate.

Tissue unsaturation does increase as one climbs in altitude and this may account for the higher rates of skin cancer and so do ketones.

All energy substrates have “innate”, yikes, pros and cons that will make your life adaptive or miserable as internal and external environmental factors change. One prediction would be that as oxygen becomes less available there is more reliance on glucose as a suitable energy substrate along with raises in ketones and lactate. And in some cases fructose. When exogenous glucose is not available fat serves the ketone lunch.

This is why ketosis is not appropriate in my opinion except as an intervention. Ketosis is a side effect, the benefits come from SFAs.

And while the intervention can resolve symptoms, it does not as far as I can tell “cure” things, it just keeps life going but you still slowly fall apart.

To cure things, you have to provide stimulus that can rebuild structure. And so, this builds on my energy and structure post.

So why don’t we want to drink milk all the time if it has the benefits of restoring OXPHOS? Restoring is the key word here. Well when I drank milk all the time I found that my diet was quite limited and I’m a guy who likes variety and thinks monotherapy diets are interventions not cures and tend to think they predispose people to orthorexia and a host of other psychological problems.

Eventually you get tired of milk and want a bit of substance. I tend to pay attention to what I’m hungry for, I tend to trust that, maybe a bit too much for some people, maybe not enough, I’m cautious and there is some logic behind how I judge whether or not a craving is a real need verses something more psychological. That doesn’t mean you shouldn’t eat something for psychological reasons and there is definitely some interplay in which a psychological craving might have overall benefit. But let’s not get too spooky here.

When you get to the point where your like, I’d like to chew on something, it’s probably a good sign that you need to chew on something besides the meat in your meat and milk diet.

For those of you who understand my cryptologic you’ll know that I’m not a fan of fruits and vegetables, but I am a fan at the same time because I like a little NERF ball. That is Nuclear factor (erythroid-derived 2)-like 2 or NRF2.

I think, though this is working through some higher level signaling (not everyone can conceptualize the implications of metabolic substrates and NRF2 is a good place to have that dialog), that this is one of the ways antioxidants work, it’s not because they are functionally benefiting the system, it’s because they are assaulting the system and whittling out adaptation by increasing our own mammalian antioxidant system (this explains the dose bell curve of antioxidants as well), since exercise, antioxidants, and other stressors (psychological stress) hit NRF2 it is a good common ground and the proverbial point in which “cures” as differentiated from “interventions” happen or can happen.

Once OXPHOS is stable, how do you approach making it antifragile? You begin by coming off your monotherapy diet and stress testing it. Not much different than a baby. You start by gently exposing it to the environment. If you protect your baby too much it will be maladapted and if you stress it too much it will be maladapted. You want that sweet spot or zone of proximal development a psychological concept which originated with Lev Vygotsky which I think applies to physiology or is a good way to conceptualize physiology.

And that is the beginning to a long process. I started off with herbs and spices and a bit of starch. Even herbs and spices were a bit uncomfortable at first much like the first time you pick up a weight or attempt a long walk or a short jog. But it starts there. And for now, that’s were we’ll end.

Best wishes,

Ed

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