Hormones Are Never In Charge

All they do is communicate biochemistry from one tissue to another. Their abnormalities are never the root cause of anything.

Hormones matter, but they are never in charge. Their abnormalities are never the root cause of anything.

All hormones do is communicate the biochemistry of one tissue to the biochemistry of another tissue.

I am not strictly against the use of exogenous hormones, just like I am not strictly against the use of NSAIDs for debilitating pain, but I believe it is rare that anyone who prescribes hormones first dives as deeply as they should into fixing a person’s biochemistry.

None of what I write below is meant to detract from my empathy for those who are suffering, are in emergencies, or have serious goals and either genuinely have no time or at least perceive they have no time to solve the puzzles I raise. Nevertheless, I will now tell it like it is.

Three Reasons For Hormones to Be Messed Up

There really are only three reasons for hormones to be messed up:

• You don’t have the raw materials to make the hormone. For example, you can’t make thyroid hormone if you have no iodine.
  

• Your situation dictates that you should not make hormones the way the textbook says you should, or the way you think you should, in which case they are not really messed up. For example, if you are too low in body fat, your brain does not trust your energy stores to carry forth a pregnancy, so it will restrain your fertility. If you are too high in body fat, your brain will deduct the stress of carrying the extra body fat from its calculation of your energy abundance and will restrain your fertility. You want a baby, so you see this as as problem, and your doctor uses a reality distortion filter known as medical diagnosis to view the issue so diagnoses it as infertility, but your brain is actually correct in its judgment.
  

• You have not solved the small number of highly unique idiosyncratic bottlenecks in your energy metabolism. Your brain correctly deducts the unusable portion of energy from its calculation of your energy abundance. For example, you have an impairment in short-chain fatty acid oxidation. You ate 700 Calories as fat, but your brain correctly recognized that 300 of those Calories were useless. So, neither your caloric intake on paper nor your actual body fat reflect what is really available to invest in fertility or in long-term improvements to your health. Your brain understands this and has adjusted your hormones accordingly.
  

The problem with stepping in with exogenous hormones is:

• In the first case, this was lazily skipping over fixing nutrient deficiencies that are important to fix on their own regardless of the hormonal impacts.

• In the second and third cases, you are arguing with your brain when your brain is right. This is like arguing with your spouse that in fact you are not out of money and you will prove it by buying all the nice things you can find on your credit card.

Exceptions to the Rule

I can think of some exceptions to the above “three reasons” rule, but they do not invalidate the principle.

You could have a tumor pressing against your pituitary, or you could have a tumor secreting massive amounts of adrenaline. In these cases the problem is still biochemical, it’s just the biochemistry that led to the tumor.

I will delay incorporating menopause into this framework, because honestly I need to think more about it.

Finally cognitive processes act as direct inputs. For example, a belief can stimulate the release of cortisol. Even cognitive processes, however, are intimately intertwined with the biochemistry of neural cells. It is very difficult to tease out, for example, whether one needs to work on mindset versus brain biochemistry. But if one seeks to optimize both, this should lead to success.

Now, let’s get back to the rule, and consider an example.

Leptin, Insulin, and Thyroid Hormone As an Example

Let’s take the relationship between insulin, leptin, and thyroid hormone as an example.

As covered in Lesson 23 of my Energy Metabolism course, insulin release is not a direct response to carbohydrate ingestion, but is rather primarily a response to ATP opening up potassium channels and secondarily to overflow of materials into the citric acid cycle. Under normal circumstances, ATP production will be greatest in the pancreatic beta-cell when carbohydrate intake exceeds what is needed to restore glycogen content in the liver and therefore abundant carbohydrate reaches the pancreas. Overfilling the citric acid cycle will occur to the greatest extent when most of the remainder of the energy from the meal is protein. Nevertheless adding additional fat on top of the carbohydrate and protein (not replacing them with fat) will provide even more ATP and conserve glucose and protein for filling up the citric acid cycle, and thus lead to yet more insulin release.

As covered in my zinc podcast, each six insulin molecules is connected by a zinc ion. Upon their release, the zinc traverses to the pancreatic alpha cell and shuts off glucagon release, and traverses into target cells such as muscle to increase insulin signaling. This makes zinc essential to insulin sensitivity.

However, many amino acids, through mostly unknown mechanisms, stimulate glucagon release, and this is thought to allow protein to enhance insulin secretion to stimulate amino acid uptake into muscle without causing low blood sugar.

The conventional hypothalamic-pituitary-thyroid axis says that the hypothalamus makes thyrotropin-releasing hormone (TRH), which acts on the pituitary to stimulate the release of thryoid-stimulating hormone (TSH), which acts on the thyroid to produce thyroid hormone.

However, insulin also acts on the thyroid alongside TSH to increase thyroid hormone production.

Leptin also stimulates the production of thyroid hormone, probably through its actions in the hypothalamus. While leptin is made by body fat primarily in proportion to the amount of fat stored, its release is also stimulated by insulin.

The actions of leptin and insulin on the hypothalamus are largely mediated by their enhancement of ATP-dependent potassium channels. Their actions are opposed by transcription factors that are elicited by internal stress, signaled by inflammation, and external stress, signaled by cortisol.

The model that emerges is as follows:

• Leptin is primarily a signal of long-term energy stores.

• Insulin is primarily a signal of short-term energy stores.

• Cortisol signals external stress, which is a demand on energy stores.

• Inflammation signals internal stress, which is a demand on energy stores.

• The hypothalamus makes a simple calculation of energy abundance that looks something like, in very simplified form, (ATP * (leptin + insulin)) - (inflammation + cortisol) = energy abundance.

• The energy abundance term dictates what is available for fertility and long-term investments in health.

Target cells then decide how to respond to these signals. The liver as the metabolic hub of the body will largely dictate whether thyroid hormone should be activated or inactivated. Cells that cannot afford to comply with the signals of thyroid hormone, insulin, and leptin, will make their own entirely appropriate decisions to not comply, leading to “resistance” to these hormones in the standard hormone-centric view of medicine and endocrinology.

Being underweight and underfed detracts from the energy supply half of the equation, while being overweight and overfed creates internal stress that adds to the energy demand side of the equation.

Now, we could point out the need for specific nutrients. For example, we obviously need zinc if insulin is literally made as a granule of six insulin molecules per zinc ion. We obviously need iodine if there are three or four iodine atoms per molecule of thyroid hormone. That selenium reduces anti-thyroid antibodies shows that it too is important.

But these specific examples just betray the complexity behind them. That selenium reduces anti-thyroid antibodies suggests that Hashimoto’s results from local stress within the thyroid gland rather than the systemic stress signaled by cortisol and inflammation that would antagonize thyroid production at the level of the hypothalamus. But this “stress” is the oxidative stress involved in using copious amounts of hydrogen peroxide in the synthesis of thyroid hormone. This means that the entire antioxidant network — vitamin E, vitamin C, glutathione (from protein), iron, copper, zinc, manganese, riboflavin, niacin, and the thiamin, calcium, and magnesium that are necessary for the pentose phosphate pathway — is important.

The centrality of ATP and citric acid cycle overflow means all the nutrients involved in ATP production and the citric acid cycle are important, and that includes every single B vitamin, all the electrolytes (sodium, potassium, calcium, magnesium, phosphate, bicarbonate), iron, copper, molybdenum, and sulfur.

As such, literally any nutrient deficiency could compromise these hormones!

And what about the 1,451 inborn errors of metabolism creating impairments in these pathways? In “How I Found My Health “Super Unlock” After 20 Years of Research and 20,000 Genes Tested” I estimated that each person is carrying one to six mutations that are nutritionally actionable in ways that go completely outside of maintaining normal nutritional status and create specific impairments in energy metabolism when unoptimized.

How to Approach Hormones

Putting aside the importance of managing mindset, spiritual orientation, and social connections, and putting aside the topic of menopause I am saving for another day and the issue of tumors that may require surgery or other medical treatments, I offer the following as a sensible approach to hormone problems.

One should certainly start with the low-hanging fruit of optimizing body composition. Experiment with different approaches based on shifting macros, counting calories, fad diets, or whatever seems to work to lead to the most effortless normalization of body composition. If obesity proves intractable, I think that calls for a more sophisticated approach. I will specifically address this next week.

There is nothing wrong with using trial and error for supplements that are shown to lead to some specific effect in animals or humans, such as vitamins A and D, MK-4, iron, or boron to raise testosterone, or using MK-7 or inositol in polycystic ovarian syndrome.

There is also nothing wrong with using isolated nutritional tests, such as plasma selenium or serum iodine, to see whether specific nutrients relating to specific thyroid conditions need correction.

However, when such low-hanging fruit does not do the trick, I believe one should start by running comprehensive nutritional screening and using the Cheat Sheet to correct any deficiencies that are found.

If this does not normalize the hormones, I believe the next step is to run comprehensive screening for energy metabolism impairments to optimize around the specific bottlenecks.

The goals should be as follows:

• to supply the body with the raw materials needed to make the correct hormones,

• to supply the body with the raw materials to make the signals that regulate those hormones

• to give the brain the right reasons to believe that energy is abundant. These include maintaining healthy body composition and removing any bottlenecks in energy metabolism by optimizing any actionable genetic impairments in the metabolic pathways.

Disclaimer: I am not a medical doctor and this is not medical advice. I have a PhD in Nutritional Sciences. Do not make any decisions about hormone treatments on the basis of this article and discuss any changes to your hormone regimen with the prescribing doctor.

Join the Quarterly Question Contest

Have a question for me? Enter the Quarterly Question Contest for a chance to win by popular vote a well researched and presented answer! Learn more here.

Join the Masterpass

Masterpass members get access to premium content (preview the premium posts here), all my ebook guides for free (see the collection of ebook guides here), quarterly question contests (see here), all my courses for free (see the collection here), and exclusive access to massive discounts (see the specific discounts available by clicking here). Upgrade your subscription to include Masterpass membership with this button:

Learn more about the Masterpass here.

Please Show this Post Some Love

Take a Look at the Store

• At no extra cost to you, please consider buying products from one of my popular affiliates using these links: Paleovalley, Magic Spoon breakfast cereal, LMNT, Seeking Health, Ancestral Supplements, MASA chips. Find more affiliates here.

• For $2.99, you can purchase The Vitamins and Minerals 101 Cliff Notes, a bullet point summary of all the most important things I’ve learned in over 15 years of studying nutrition science.

• For $10, you can purchase The Food and Supplement Guide for the Coronavirus, my protocol for prevention and for what to do if you get sick.

• For $10, you can purchase Healing From COVID Vaccine Side Effects for yourself or a loved one if dealing with this issue. It also contains an extensive well-referenced scientific review, so you can also use this just to learn more about my research into the COVID vaccines.

• For $29.99, you can purchase a copy of my ebook, Testing Nutritional Status: The Ultimate Cheat Sheet, my complete system for managing your nutritional status using dietary analysis, a survey of just under 200 signs and symptoms, and a comprehensive guide to proper interpretation of labwork.

• Get on the waitlist for my new Biochemical Optimization Program at bioopthealth.com.