Thyroid Absorption (and Sudden Changes in Levels)

Updated January 11, 2025

Thyroid Program

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This information is for educational purposes only, to facilitate quality conversations between patients and their personal physician(s). Several essential considerations are required to safely administer any protocol for an individual. This information is NOT intended to diagnose, treat or encourage self-treatment of any medical condition.

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Absorption of thyroid medication(s) is a challenge for some.  Low absorption is usually manifest as low levels of hormone despite high rates of intake, such as 4 grains of desiccated thyroid or more.

The classic recommendations are to take thyroid medicine in the morning at least one hour before food or any supplements containing calcium or iron.  Despite these precautions, some people’s levels just don’t raise despite higher doses. We usually will switch brands when this happens.  Very occasionally a person will have a strong negative reaction to a particular brand, which makes the decision easier. Oftentimes it is highly individual (idiosyncratic) and cannot be predicted or explained. This is why it is optimal to monitor levels and symptoms, especially if there are additional healing modalities occurring that might change utilization and requirements. Sometimes levels change rapidly, which can occur in either direction. Clearly higher levels are generally more concerning than lower levels, so going slowly is always a preferred option unless individual circumstance requires a faster approach.

These articles give us guidance about the factors affecting thyroid absorption. Stomach acid and the pandemic of upper gut symptoms can affect absorption.  Also, since thyroid hormone is more soluble in fat than water, there is a possibility that absorption can be enhanced by taking thyroid with a fatty (non-calcium, non-iron) food such as avocado or some nut butters.

Levothyroxine Therapy in Gastric Malabsorptive Disorders.2021

Effects of grapefruit juice on the absorption of levothyroxine.pdf

Can Grapefruit Juice Affect My Thyroid Medicine-The New York Times.pdf

Low Absorption vs. High Utilization?

Since the Iodine within the thyroid medication (___% of T4 by weight and ___% of T3 by weight) has numerous functions, it might be that the thyroid medication is serving in part as a delivery system for Iodine to the cells, and there may be certain points where requirements change suddenly.  For example, a series of stressors and/or toxins, or a woman’s cycle, can change enough of the biochemistry to affect a change in iodine requirement.  There is research supporting this idea (here).

The Tyrosine component of T4 and T3 (___% of T4 and ___% of T3) can also be utilized, and is used to make dopamine, adrenaline and melanin as well as thyroid hormone. If there is a tyrosine deficit, perhaps one of these molecules is more important than thyroid hormone to the body.

The conversions between the forms of thyroid including T2 and T1 (also called iodo-thyronines) are influenced by the totality of the hormonal environment, binding protein levels, and numerous factors.

We have seen numerous cases where levels fluctuate in a zig-zag pattern. This is often brought on by a change in food, drink and stress level, all which occur during vacations, which is often when we see a stable pattern become unstable.

 

to compound thyroxine, what oil can it be mixed with, is there a usp standard  1/2025

ChatGPT said:
When compounding thyroxine (levothyroxine), the choice of oil depends on the desired formulation and its intended use (e.g., oral, topical). Common oils used for compounding may include:
  1. MCT oil (Medium-Chain Triglycerides) – Often used for oral solutions or suspensions due to its stability and ease of absorption.
  2. Olive oil – Sometimes used for oral preparations, as it is well-tolerated and has a long shelf life.
  3. Sesame oil – Can also be used in oral or topical formulations due to its stability and hypoallergenic properties.

There is no specific USP standard for mixing thyroxine with a particular oil, as the formulation can vary based on compounding pharmacy practices and patient needs. However, it is essential to ensure that the selected oil does not interfere with the stability or bioavailability of thyroxine.

If you are compounding thyroxine, it is important to follow general compounding guidelines and ensure that the oil used is pharmaceutically acceptable, along with following the correct proportions for stability and dosage accuracy. It is also recommended to consult with a pharmacist for the most appropriate formulation based on your specific requirements.

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is there any data on the effect of various oils on the bioavailability
ChatGPT said:
There is some data on the effect of oils and fats on the bioavailability of orally administered medications, including thyroxine (levothyroxine). However, specific studies on the interaction between different oils and thyroxine are limited. The bioavailability of thyroid medications like thyroxine can be influenced by factors such as the presence of food, fat, and oil, due to changes in gastric emptying and absorption.

Effects of Oils on Bioavailability

Here is a general overview of how different oils may affect the bioavailability of oral drugs:

  1. Medium-Chain Triglycerides (MCT Oil):

    • Effect on bioavailability: MCT oil is known to be rapidly absorbed and metabolized in the liver. It may enhance the solubility and absorption of lipophilic (fat-soluble) compounds, which could potentially improve the bioavailability of drugs. However, specific studies on thyroxine and MCT oil are lacking.
    • Potential benefit: MCT oil could improve the bioavailability of fat-soluble compounds in general, although it may have minimal impact on hydrophilic drugs like thyroxine.

  2. Olive Oil:

    • Effect on bioavailability: Olive oil contains monounsaturated fats, which can enhance the absorption of fat-soluble drugs. In some cases, olive oil may slightly enhance the absorption of thyroid hormones due to its ability to stimulate bile secretion, which helps with the digestion of fats.
    • Research: While there is limited data on olive oil specifically affecting thyroxine, there are studies suggesting that olive oil can enhance the bioavailability of other lipophilic drugs.

  3. Sesame Oil:

    • Effect on bioavailability: Sesame oil is rich in polyunsaturated fats and has been shown to improve the solubility of some fat-soluble drugs. It may have a mild effect on the bioavailability of lipophilic compounds, but its direct impact on thyroxine absorption is unclear.
    • Research: Research on sesame oil’s effect on thyroid hormone bioavailability is not well-documented, but in other contexts, it may improve absorption of fat-soluble substances.

  4. Coconut Oil:

    • Effect on bioavailability: Similar to MCT oil, coconut oil contains medium-chain fatty acids, which can be absorbed more efficiently and may enhance the absorption of lipophilic drugs. However, as with MCT oil, the effect on thyroxine specifically is not well-studied.
    • Potential benefit: Coconut oil may increase the absorption of certain medications, but its impact on thyroxine absorption is unclear.

  5. Fish Oil:

    • Effect on bioavailability: Fish oil contains omega-3 fatty acids, which can influence the absorption of fat-soluble medications. Some studies suggest that fish oil may improve the bioavailability of certain drugs, though this effect is more likely with lipophilic drugs.

Key Considerations for Thyroxine:

  • Stability: Thyroxine is sensitive to light, heat, and air, and its bioavailability could be influenced by the oil’s ability to protect it from degradation.
  • Absorption Timing: Thyroxine is best absorbed when taken on an empty stomach, typically 30 to 60 minutes before breakfast, as food, especially fats, can delay absorption.
  • Drug Interactions: Oils, particularly those high in fat, may alter gastric emptying time and influence thyroid hormone absorption. Therefore, if oils are used in compounding, timing and dosing should be carefully considered.

In summary, while oils may influence the absorption of lipophilic medications, there is limited direct evidence on their effect on thyroxine specifically. It is important to ensure that the formulation of thyroxine, whether in oil or another medium, does not interfere with its optimal absorption.

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doesnt saying fats impede absorption suggest that it shouldnt be mixed with oil
ChatGPT said:
Yes, you are correct that the general recommendation for levothyroxine (thyroxine) is to avoid taking it with food, especially fatty foods or oils, because fats can delay its absorption. This is why thyroid hormone medications are usually taken on an empty stomach, at least 30-60 minutes before breakfast, to ensure optimal absorption.

Why Fats Can Impede Absorption:

  • Gastric Emptying: Fatty foods or oils can slow down gastric emptying, meaning they delay the movement of food and medications from the stomach to the small intestine where absorption occurs. This can reduce the effectiveness of medications like levothyroxine, which relies on timely absorption for proper dosing.
  • Bile Secretion: While fats can help the absorption of lipophilic (fat-soluble) compounds, thyroxine is not a fat-soluble compound. Thus, oils and fats may not necessarily enhance its absorption and could potentially reduce its efficacy by slowing down the digestive process.

Compounding Considerations:

If thyroxine is being mixed with an oil for a compounded formulation (e.g., for a suspension or topical application), it would be important to consider the impact on bioavailability:

  • Oral Dosing: For oral doses, mixing thyroxine with oil may not be advisable, as the oil could potentially interfere with its absorption, making the medication less effective.
  • Topical Dosing: In some cases, topical formulations might use oils as carriers for drugs, but for thyroxine, this is typically not a common or recommended route due to the concerns about absorption and the effectiveness of the hormone.

Best Practice:

Given that food, especially fats, can delay or impair the absorption of levothyroxine, mixing it with oils for oral administration would not typically be recommended. It is best to take thyroxine with water on an empty stomach, far away from meals and fatty substances, to ensure the medication is absorbed properly.

If the formulation involves using an oil for another reason (e.g., as a stabilizer or in a topical form), this should be done with caution, keeping in mind the potential impact on absorption and effectiveness.

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what is the solubility of levothyroxine in oils and other solvents? table

The solubility of levothyroxine (LT4) in various solvents and oils is not widely documented, as it is typically formulated in solid forms (tablets, capsules) or aqueous solutions for oral or intravenous administration. However, based on its chemical properties and general knowledge of solubility behavior, I can provide some estimated solubility information for levothyroxine in common oils and solvents:
Solvent/Oil Solubility Notes
Water Very low (practically insoluble) Levothyroxine is very poorly soluble in water.
Ethanol (95%) Slightly soluble Levothyroxine has limited solubility in ethanol.
Isopropyl alcohol Very slightly soluble Solubility is minimal in isopropyl alcohol.
Acetone Very low Levothyroxine is poorly soluble in acetone.
DMSO (Dimethyl sulfoxide) Soluble Levothyroxine is soluble in DMSO, which is a strong solvent for many compounds.
Olive oil Very low Levothyroxine has low solubility in olive oil.
MCT oil (Medium-chain triglycerides) Very low Levothyroxine is poorly soluble in MCT oil.
Coconut oil Very low Levothyroxine shows very low solubility in coconut oil.
Sesame oil Very low Levothyroxine has low solubility in sesame oil.

Key Points:

  • Levothyroxine solubility: It is known to have poor solubility in water and oils. This is why it is typically provided in tablet form or as aqueous solutions in pharmaceuticals, which can help with its absorption and bioavailability.
  • Oil-based formulations: Although levothyroxine may not dissolve well in oils, oils are sometimes used in formulations to create suspensions or emulsions, but the solubility remains limited.
  • DMSO: As a strong polar aprotic solvent, DMSO can dissolve a wide range of compounds, including levothyroxine.

For specific compounding or formulation purposes, solubility in oils and other solvents would need to be tested experimentally for the exact product and conditions being used. 

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