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Growing crops for biofuel cannot produce more carbon than it consumes over long time scales, because the only source of carbon available to the system is the carbon in the atmosphere. If they are saying biofuels aren't carbon neutral over long time scales, where is this extra unlimited supply of carbon coming from?

High intensity deliberate practice that you can only do for short amounts of time per session

How is that different from flow work?

I'm not sure if you've read Mihály Csíkszentmihályi or not, but he argued that flow states are more likely when a task is more complex/challenging, and the person has a high level of appropriate skill that makes it possible (with substantial effort) to complete the task.

For me this often occurs while programming, sailing, or doing math- especially if I need to solve a new problem with those skills that will be especially challenging.

Once I'm in 'flow' it is a distinct mental experience - I am totally into it and lose any sense of time passing, or of needing to motivate myself until I am interrupted either by my own body, or by something external.

Cal Newport in Deep Work (his own word for flow work) defines "Deep Work" as anything that requires skills that would take at least a year to develop if a person was already generally educated, smart, and motivated.

I stopped using pomodoros for flow-work, because it would break my flow state. I've found roughly 2 hour chunks work better for flow, without any particular warning to stop me if I feel like going longer. If I am in flow, I want it to keep going as long as possible, until I am fatigued, or the problem is solved.

But I would have thought that if there was widespread 'central hypothyroidism', someone would have twigged by now, since that form does show up if you do a full panel of hormone tests

Which tests? I am not aware of any simple blood test that measures the endpoint of thyroid activity on metabolic rate (except, arguably, cholesterol levels), rather than just the state of the T4->TRH->TSH->T4 feedback loop.

mostly T4 with a bit of extra T3', but no-one has particularly clear ideas on what works and what doesn't or why

The challenge with T3 is it has a very short half-life, one would need to take very small doses impracticably often to achieve stable levels. Taking mostly T4 with a bit of T3 helps compensate for the reduction in T3 production due to feedback without the problems caused by trying to obtain nearly all T3 directly from a supplement.

Thanks for the reference to Ray Peat, I hadn't heard of him before. Can you link to the best expression of his thoughts?

His own essays at are the only accurate source, but can be challenging to read. Most of the summaries you will find online don't do him justice.

he was basically making his patients hyperthyroid

Why is this a reason not to reject it? He is essentially arguing that the major cause of cardiovascular disease is population-wide high rates of hypothyroidism. It would be a circular argument to dismiss that because his treatment leads to a greater than average metabolic rate. One would also need evidence of a disadvantage that outweighs the advantages. His patients seemed to be doing well, or at least he doesn't report them exhibiting any classic signs of hyperthyroidism. He was primarily adjusting dose based on body temperature to the upper end of the normal non-hyperthyroid range.

to help them lose weight

I have seen studies on thyroid supplementation as a weight loss strategy, and it causes loss of lean tissue (muscle, etc.) more than fat.

You wouldn't need to invoke the idea of 'hormone resistance' because TSH and T4 tests normally used to diagnose hypothyroidism don't measure the active hormone - T3. T4 is just a prohormone with very little direct activity on metabolic rate.

In primates, metabolism is regulated primarily in the liver by T4->T3 conversion, so if this is inhibited for any reason it will suppress metabolism without showing up on those tests. Low calorie intake, and poor nutrition are known to cause this (e.g. Euthyroid sick syndrome). In cases of poor liver conversion, supplementing T4 can actually make symptoms worse, as it will further suppress metabolism by lowering the small amount of T3 production from the thyroid (via the TSH feedback loop).

I assume you have heard of Ray Peat? I personally had good luck applying his ideas to increase my energy levels, and my pulse, body temperature, and cold tolerance raised as well - without supplementing thyroid. His general idea is pretty simple- just look at what conditions and nutrients maximize T4->T3 conversion, and provide them (low stress, high nutrient diet).

Broda Barnes work is very interesting. It blows my mind that he published a paper in The Lancet showing that desiccated thyroid lowered cholesterol levels and seemed to prevent cardiovascular disease in his patients, and that it remains virtually un-discussed and uncited (

You're right, we do understand the pathophysiology of many diseases, and those are the ones that have been mostly eradicated. The major chronic diseases that remain are very poorly understood such as type II diabetes, cancer, cardiovascular disease, and alzheimer's.

I spend a lot of time reading about 'alternative' ideas about these diseases, and many seem promising, but aren't taken seriously by the mainstream. It's definitely possible that they're ignored for a good reason, but I haven't been able to find the reasons yet. This is the biggest problem I've found with trying to be 'critical of everything.' In very few instances do I find myself quickly understanding and agreeing with the mainstream view. Instead, the more I read the more my opinion seems to diverge from the mainstream view. I have made an effort to discuss these issues personally with specialized experts, so they could help point out factors I may be missing, or not understanding correctly. I am a PhD candidate in the life sciences, so I have the opportunity to meet with research professors at my university in person to help clarify my understanding.

Here are two example theories, regarding cancer and cardiovascular disease in particular.

1) The idea that cancer isn't initiated by genetic mutations, but that mutations are a downstream phenomena that results after damage to the mitochondria occurs.

This stems from the initial observation by Warburg, that lack of control over glycolysis is part of the cancer cell phenotype. This phenotype can be triggered by a large number of factors which inhibit mitochondrial respiration including hypoxia. Later it was found that the mitochondria in cancer cells undergo a phenotypic change, where the cristae structure is lost. Nuclear transfer experiments have shown that a 'mutated' cancer nucleus placed into a healthy cell cytoplasm does not exhibit a heritable cancer phenotype. Conversely, a healthy nucleus placed into a cancerous cell cytoplasm does exhibit a heritable cancer phenotype.

Here is a review article covering the evidence for this hypothesis:

Cancer as a metabolic disease: implications for novel therapeutics

More evidence for this hypothesis includes the observation that active thyroid hormone levels (T3) are inversely correlated with cancer mortality rates in the general population. T3 is a key regulator of mitochondrial respiration:

Thyroid hormones and mortality risk in euthyroid individuals: The Kangbuk Samsung Health Study.

2) The finding that treatment for hypothyroidism drops cholesterol levels significantly, and virtually abolishes cardiovascular disease without the side effects seen from statins. The late Broda O. Barnes was an experimental endocrinologist and a clinical doctor, and he extensively documented this phenomena in his books and publications.

The idea here is that the central mechanism of cardiovascular disese is a low metabolism which inhibits cholesterol clearance from the blood via reduced steroid hormone synthesis, and reduced bile synthesis. The pathophysiology of cardiovascular disease begins with a long residence time of cholesterol particles in the blood, resulting in their oxidation. This can be reversed by any strategy that restores a normal (higher) metabolic rate: a carefully designed diet and/or thyroid hormone supplementation.

Here is a good introduction to this idea:

The Central Role of Thyroid Hormone in Governing LDL Receptor Activity and the Risk of Heart Disease

I am not insisting that these ideas are correct, or are some sort of 'well proven answer' to these diseases. I'm just pointing out that they seem promising, but are relatively ignored. If they prove accurate, much of the mainstream research on these phenomena would seem to be barking up the wrong tree.

You might notice that both of these examples are essentially the same theory. This is an appealing concept to me: most age-related chronic diseases may be centered around a common process of age related impaired mitochondrial function and/or improper hormonal regulation of mitochondrial function. Insufficient chemical energy (ATP) to fuel normal biological function would have widespread consequences, and could present as a diverse array of seemingly disconnected symptoms. I'll admit, this sounds somewhat like a modern molecular version of vitalism. However, unlike vitalism it makes specific testable predictions, and involves a very specific mechanism. It's also consistent with the 'free radical' and 'tissue peroxidizability index' theories of aging, which involve (among other things) progressive oxidative damage of unsaturated fats (such as cardiolipin) in the mitochondrial inner membrane.

I have been attempting to do this with biology and medicine, seriously for about 5 years now. Not by actually repeating experiments, but in trying to understand the original evidence, and see if I agree that it was interpreted correctly. Of course this is nearly impossible as biology is too broad and complex for one person to understand all of the details.

It's a confusing mess, but I think I am still learning a lot. Even if I come to agree with most of the mainstream ideas, I'd like to think I'd then understand them more deeply, in a way that is more functionally useful.

For much of medicine, there really isn't any biological basis or evidence to review. Much of modern medicine involves covering up symptoms with drugs proven to do this, without understanding the underlying cause of the symptom.

Excellent post, thanks for putting so much work into a clear explanation. I will re-investigate Ling's work more carefully, and also see if I can find the mistakes in his thermodynamics calculations you mention. I have been biased towards his work and not looking critically enough, because it seems to explain some surprising observations about drug activity I've found in my own research- but that's no excuse.

I am interested in the possibility that Ling could be entirely wrong about membrane physiology, but this gel phase shift phenomena could still be important in the cell. If Ling and Pollack are wrong about long distance effects from protein surfaces, that might not destroy their arguments as the cytosol is very dense, and the distance between proteins is very short. Albert Szent-Györgyi also did some work on this idea that is very different from Ling's.

One of my committee members works on physics simulations of protein hydration shells, and I am going to meet with him and see what he thinks about this. The simulations I have seen don't show significant water structuring, as the water molecules have too much thermal energy.

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