Part 5: All thyroid meds are bioidentical, but individual response varies widely

This post concludes my response to a misleading video (10).

THYROID HORMONE PHARMACEUTICALS

A suspicion many people have is that thyroid hormone pharmaceuticals are very different from the thyroid hormones our bodies produce.

Let’s look into the claim that they are “bioidentical” in structure and function.

Synthetic thyroid hormone has a counter-clockwise rotated molecule (it is a “levorotary” isomer). Early research has proven that D-thyroxine (dextrothyroxine, once marketed as Choloxin, a clockwise rotated molecule) has different properties and effects than L-thyroxine (levothyroxine). Most importantly, the D-isomer has about 7% the potency as the L-isomer, which means that the structure is important to its function. The L-isomer was preferred because of adverse cardiovascular effects of the D-isomer. Differences have also been found between synthetic T3 L-triiodothyronine (liothyronine) and its D-isomer. (3)

Is naturally secreted thyroid hormone an L-Isomer? yes.

In 1972, a chemical study of thyroid hormones was done using naturally derived thyroxine crystals. (3b) They found that at the ether oxygen, the rotation of thyroxine was 120 degrees  and triiodothyronine was 125 degrees counter-clockwise, and at the joint between the aromatic rings of the molecule, thyroxine is rotated 23 degrees.

Therefore, the article calls both of our natural hormones “levo”-rotatory molecules.

They say that in theory, a wide variability is possible in the structure of the molecule, but they did not find much variability in their data set, and therefore this is the configuration that our bodies probably favor.

Four years later, chemists published a thorough analysis of multiple combinations of thyroid hormone structures, testing them for their relative biological potency to understand which structural features were necessary for hormonal activity. The ideal structure and function of the levo-isomers of both T4 and T3 hormones were confirmed as the ones that exert the maximal effect. They have understood the preferred hormone structures that bind to our hormone transporters and hormone receptors. (3c)

Science has learned a lot from these early studies. More recently, many brands of levothyroxine were analyzed and were found to contain 99% pure L-isomers. (3d)

As for function, molecular chemistry has continued to learn about the activity of both synthetic isomers and our naturally-secreted and naturally-converted hormones, because the differences do matter. (4) Studies of the genomic and nongenomic activity of thyroid hormones in various organs and tissues are still being published. (4b) 

Therefore, we now know a lot about the structure and the function of thyroid hormones and have found little to no difference between the L-isomer synthetics and naturally secreted thyroid hormones.

Animal-derived desiccated thyroid pharmaceuticals, licensed by Health Canada and the FDA, are also potent, containing a ratio of 4:1 to 4.2:1 T4 and T3 hormone. No publications that I know of have ever claimed any difference between these molecules and human thyroid hormone molecules.

Both synthetic and animal-derived thyroid hormone pharmaceuticals have faced pharmaceutical challenges, but they can be (and now are) carefully regulated for standardized T4 and T3 content in a pill before ingestion. (27-27c, 29)

The measurable end result of all thyroid hormone pharmaceuticals is that they yield T3 and T4 molecules in our bloodstream.

These molecules, when measured by “immunoassay” lab tests, appear to be the same as those that a human thyroid gland secretes. (28, 28b) 

RESPONSE TO THYROID PHARMACEUTICALS

Given that the structure and function of thyroid hormone pharmaceuticals is likely very close to 100% bioidentical to natural thyroid hormone…

What’s different between naturally-secreted hormones and pharmaceuticals?

Our individual response:

A) The pathway to absorption (through the GI tract vs. directly secreted from a gland).

B) The amounts and ratios of T4 and T3 that you end up with in your bloodstream, which is not exactly the same as the amount and ratio that you take in, and varies from person to person.

C) Your individual body’s response to the amount and ratio of T4 and T3 you have in bloodstream.

As for absorption, synthetic thyroid hormone is almost the same as natural, but it is bound to sodium (salt). Our bodies easily unbind it from the salt, but sometimes we have difficulty absorbing it through the GI tract (specifically, the small intestine). We absorb 60-80% of what we ingest from a pill or capsule. (4b) Levothyroxine (L-T4) is notorious for binding to other things like calcium, and therefore product monographs advise that you to take it separately from all interfering substances.

Absorption issues are relatively easy to overcome: we just take more thyroid hormone until T4 or T3 levels show up in our bloodstream. This is why some people need higher doses than others to get equal levels of hormone in blood.

Conversion and metabolism is another issue altogether, and this is where individual patients’ biology makes more of a difference than the biochemical source of the hormone (synthetic or animal).

T4 hormone must be converted to T3 hormone for almost all of its essential biological activity in every organ and tissue of the human body. Under normal circumstances, about half of T4 becomes inactive Reverse T3 (RT3)  instead of T3. The T3 hormone is also susceptible to conversion to T2.

Does an individual’s thyroid hormone conversion rate matter to health?

Yes, absolutely.

Both the amount and the ratio of T3 and T4 in your bloodstream have measurable effects on health, again, according to many studies too numerous to cite here. It’s because all of our organs require just enough, and not too much, T3 hormone, to function properly. Most of our organs depend on the amount of T3 available in bloodstream plus their local ability to convert T4 into T3 beyond bloodstream.

The rate of conversion to the inactive (RT3) versus active (T3) hormone depends on many factors, but none of them are about the pharmaceutical origin. The three major variables are a) the individual’s health status, b) excess thyroid hormone, and c) genetics.

Added to hormone conversion are individual differences in response — there are  transporters that carry hormones into cells, and differences in the sensitivity of hormone receptors from person to person. These issues are discussed in different blog posts. 

AGAINST PHARMACEUTICAL PREJUDICE

The video I’m responding to didn’t favor one thyroid hormone medication over another. However, this topic naturally flows from what I’ve just covered.

Prejudice against ALL thyroid hormone pharmaceuticals is just as naive and unscientific as sweeping prejudice against ANY one of them in favor of another.

As you can see, response to thyroid hormone pharmaceuticals during hypothyroid therapy is extremely individualized and complex.

AFTER the point of ingestion and absorption (and our body’s response to any fillers or inactive ingredients), thyroid hormones are like a machine with many cogs and levers.

Individualized differences from patient to patient are more likely to account for 99% of the different responses we have to various thyroid hormone medications and ratios.

Therefore, we ought to leave behind the often irrational and discriminatory debates over animal vs. synthetic vegetable-derived sources of thyroid hormone being better or worse than each other, or better or worse than the thyroid hormones we produce naturally.

ALL pharmaceutical thyroid therapies yield virtually bioidentical thyroid hormones in bloodstream.

ALL are potentially equally safe and effective, but all are not equal to the individual patient’s body.

ALL must be supervised with care toward safety and effectiveness, with due attention to symptoms, Free T3 and Free T4 levels, not just TSH, because individual patient response, especially in Free T3 levels, varies widely. Science proves that Free T3 levels cannot be predicted in therapy by measuring TSH or T4. (26-26f)

Prejudice for or against one pharmaceutical or another, or against certain ratios or combinations, will inevitably result in harmful discrimination against some thyroid patients.

Pharmaceutical prejudice will mean that only some thyroid patients will get the thyroid treatment that yields the most effective thyroid hormone levels and ratios in bloodstream and throughout the body, while others are left to suffer on the therapy that a doctor or medical system may prefer but which does NOT work well for the patient.

CONCLUSION

Discriminating between animal vs. synthetic source or T3 vs. T4 hormone in medication is medically and morally worse than discriminating between a patient who is a vegetarian and one who is not.

Instead, we should choose the therapy that works best for the individual patient when dosed to safety and effectiveness.

Choosing a therapy modality and optimizing dosage to measurements of thyroid hormone action is a more valid field of controversy than the pharmaceutical source.

Let’s stop prejudice against any, or all, thyroid hormone pharmaceuticals.

Let’s keep learning and discerning.

REFERENCES

See the reference list for all 5 posts in this series: “REFERENCES for “Thyroid science naivety and quackery” posts