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Q&A. Dosing T3 in light of circadian rhythm

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[Post updated Aug 5, 2020 with additional sample images.]

Question

In response to my post The Significance of the TSH-T3 Circadian Rhythm, Julien wrote:

“Thank you for such an informative article.

If I interpreted this correctly, for the hypothyroid patients on combined T3+T4 therapy, it would seem that taking the T4 dose early in the day and taking most of the daily T3 dose in the evening would help the body match the normal circadian rhythm of these hormones.”

Answer

Good question, Julien. Thyroid therapy is never going to totally mimic the natural circadian rhythm, but we can certainly try and see if it boosts our health.

This is going to be a long answer. My two recent posts on the circadian rhythm focused on the “healthy thyroid” and people who are not yet in need of interfering with natural rhythms by using thyroid medication.

That’s why I’ve made my reply a new post–so I can talk about the differences in thyroid therapy.

Timing a levothyroxine (LT4) dose is more about absorption than circadian rhythms

If you take synthetic T3 and T4 separately, rather than desiccated thyroid (NDT) in which they are combined at a fixed ratio, don’t worry about the timing of your Levothyroxine (LT4) dose. There is no need for a daily peak in FT4 levels. There’s only a tiny FT4 rise within 4 hours after a dose, and it’s hardly a blip on any circadian rhythm map.

With T4 dosing, it’s almost all about maintaining a steady absorption rate from day to day by NOT taking calcium, magnesium or iron or even coffee too close to it (the list of interferences is huge: check a recently-updated product monograph like Eltroxin, page 17). Many people even take T4 at bedtime and find improved absorption.

Create a T3 24-hour rhythm.

In Russell’s 2008 research article, they found that ““FT3 levels peak approximately 90 min after TSH levels at around 0404 h and remain above the median level from 2200–1000 h.” — so being above the median (average) daily value usually occurred between 10pm and 10am.

The MAIN key is to try to make your T3 dosing “rhythmic” on a daily basis. It ought to be

  1. Distributed enough (not just one dose a day in a big pulse) and
  2. Lopsided enough (with some down-time vs. a peak dosing window, and some tapering off). If you dose without enough of a daily break from T3 dosing, the body can get confused about the lack of rhythmicity and not know when to sleep.
  3. Respectful of night-time or “pre-waking” hours. This dosing window is an extremely powerful and helpful place to dose T3, but managing it in the context of sleep disorders and conventional schedules can be a challenge.

Working with these principles, use safe and cautious experimentation and measuring to place the T3 dosing rhythm where it fits your body’s other rhythms the best.

NOT circadian: One T3 / NDT dose per day, or LT4 monotherapy

Before I give dosing examples in further images below, I want you to see what happens if you are a hypothyroid patient who is NOT dosing with the above FT3 circadian rhythm in mind.

  1. If you were to take only ONE T3 dose per day, 10 mcg, on top of a daily dose of LT4 taken at the same time of day.
  2. If you take NO T3 doses and are just on standard LT4 monotherapy.

In this graph, the 0.00h is when a daily dose is taken and 24.00 is just before the next daily dose is taken, regardless of the time of day.

As you can see, on standard LT4 monotherapy (blue-green dots on the line) the FT3 levels are relatively flatlined. The little rise and fall is mostly due to T4-T3 conversion rate changing, and because FT4 levels rise a little by 4 hours post-dose.

If you are taking LT3 + LT4 (or desiccated thyroid NDT) and if you only take one dose per day, there are two ways it does not match circadian rhythm:

  1. There will be a higher peak FT3 that may confuse your pituitary gland and over-suppress TSH levels (making your doctor think you are overdosed when you are not), and
  2. Even if you were to take the single LT3 dose before going to bed, the peak FT3 is short-lived and then falls to baseline. It may not sustain itself long enough to work in synergy with other hormone peaks during the night.

A fabulous resource

Paul Robinson’s “Circadian T3 Method” (CT3M) — a book and some of his blog posts at paulrobinsonthryoid.com — discusses many of these rhythmic factors, dose timing and dose strength, and how to measure your vital signs.

A lot of the decision-making wisdom he offers about dose timing is based on the principle of supporting the natural circadian rhythm of cortisol and other hormones with the T3 dose you are taking.

His book on CT3M and its principles can be adapted to a person taking only a little T3 with mostly T4, even though it is written for those like me on 100% T3 monotherapy.

People who use Paul Robinson’s protocol tend to

Building doses gradually on each other produces a “cycle” whose peaks are weighted on half to 3/4 of a 24-hour period.

Samples of dosing for FT3 rhythms

This section shows you images of example dosing to rhythms for

T3 mono: Unique elements

If you are taking fast-release LT3 alone, you may need to take one or two smaller booster doses or, a microdose through the mid-day to ensure distribution (not letting your T3 levels plummet too far) while creating the overall lopsided effect of a sine wave curve. Without much if any FT4 in circulation as a foundation, there is little to no baseline T4-T3 conversion as a cushion to fall on.

Option 1 : Daytime peak

The peaks will shift accordingly depending on the strength and timing of your doses.

Option 2: Pre-midnight peak

As you can see, the model is not perfect in the image below, where the 8AM purple line does not align on both sides of the image as it should.

Nevertheless, even this misalignment at 8am visually represents the subjective experience of some patients: A strong FT3 at night seems to endure longer into the next day without symptoms of hypothyroidism. This may be because of T3’s synergy with other hormones near their peaks.

Option 3: post-midnight peak

Another way to do it is to time-shift the rhythm quite a bit to approximate the daily FT3 peak and valley of Russell’s group of 29 people with healthy thyroids. You’d dose to build up levels at 6-9PM and then, around midnight, dose to create your highest peak during the night, and then allow FT3 levels to taper off by 9-10AM. It’s not a perfect approximation.

Desiccated thyroid (NDT): Unique features

If you are taking desiccated thyroid (NDT), some patients have reported having a more gentle slow-release effect. This may be due to its being bound to thyroglobulin rather than sodium in the tablet.

Therefore, depending on how your body absorbs it, instead of having a peak FT3 level 2.5 or 3 hours later, it may gradually rise to a lower peak 4-8 hours post-dose depending on absorption. Note that the estimates below are based on anecdotal evidence of the gentler effect of the T3 from NDT, since we do not have any published studies on desiccated thyroid dose pharmacokinetics.

Option 1: two doses

On two doses, it’s challenging to build to a single peak per day without layering like this. Evenly spaced doses will create a two-peak day. The model above puts the lowest point of the day at 4pm when Russell’s model places it from 10am to 3pm.

Option 2: Three doses, midnight peak

Three doses offers a little more flexibility. You could have two smaller doses and one large one, or one small and two large.

Make your own plan. You could try drawing your own graph on a piece of paper. Get out a pencil and a ruler. Put the timeline on the bottom. Create either dose-response curves (from the 10 mcg LT3 Saravanan image above) or approximate angles that peak. Consider your lifestyle factors, your sleep challenges, and how much of Russell’s 2008 circadian rhythm graph you want to try to imitate.

Perfect mimicry of “the healthy norm” is not required. A little time-shifting is ok.

In Russell’s 2008 study of circadian rhythms, mild time-shifting was normal. Some people had TSH peak 2.5 hrs before the FT3, with: “20 of 24 subjects showing peak correlation [between TSH and FT3] at between -0.5 and -2.5 h, suggesting that FT3 lags behind TSH by these amounts.”

Dosing thyroid hormone is never going to mimic nature 100%. It is not like having a healthy thyroid that secretes directly into your bloodstream every minute of every day, at a flexible rate, on top of a flexible T4-T3 conversion rate across all your cells.

A pattern that works for many patients taking T3 is often a little time-shifted forward or backward from the natural FT3 circadian rhythm peak, simply because nobody enjoys waking up just to take a pill so that it will peak in bloodstream 2.5 to 5 hours after taking it.

It’s not necessarily a major problem to have a daily T3 rhythm that is time-shifted away from what you see in “healthy-thyroid” people who sleep approximately 10pm-6am, eat three meals, and work during the day.

Why is it not too damaging? Because even in health, the TSH peak can time-shift if you’re a shift worker, a project-based worker, or in a northern or southern region with different day lengths over the year. When we travel overseas to a new time zone, our bodies can adapt, though we do pay a price.

Nevertheless, consider a night-time T3 dose and/or a pre-rising dose.

If you want your FT3 to peak at the time other hormones need it or expect it to arrive, you may choose to be the servant of your body’s needs, despite the inconvenience of aiming for nighttime above-average FT3 levels.

You can force your body to wait 3-6 more hours for your T3 peak to arrive, or you can force T3 to peak a little earlier than it would in perfect thyroid health, but your other hormones might not be very happy with you.

A multitude of our hormones adapt to daylight and sleep schedules, not just TSH and FT3. Shifting your T3 dosing schedule to conflict with your sleep and circadian rhythm may disrupt your melatonin rhythm, cortisol rhythm, and other rhythms.

Our circadian rhythms are synchronized through our central “CLOCK” gene in the hypothalamus (Hastings et al, 2018), which communicates with other organs and glands to orchestrate their function. Each organ has its own clock. Just imagine how many 24 hour sine waves our bodies naturally manage! This is a growing field of medicine, and more science articles have been written on it since 2015.

In Jansen’s 2015 study of longevity, which I reviewed in my Circadian Rhythm Part 2 article, the people who had a parent living over age 90 had the most “prompt” and timely response of FT3 when the TSH rose during the night.

Nowadays, you can purchase devices that create a silent vibrating alarm on your wrist, and you can put a glass of water and pill on your night table as you go to bed.

Try to estimate roughly how many hours since rising, or after bedtime, your TSH would have risen if you were not dosing thyroid hormone.

As for the health risks of breaking up your sleep schedule just to take a pill, risk is more about how many hours per day you get, not about whether you break up your sleep into shifts.

“Both short and long sleep durations are significantly associated with increased risk of coronary heart disease.

Compared with 7h sleep duration per day, the risk of coronary heart disease increases 11% for an hour decrease and increases 7% for an hour increase.”

(Wang et al, 2018)

Time for a disclaimer — There’s no promise that a night-time or pre-waking dose will work miracles for you. It won’t immediately make your dosing optimal. It certainly can’t cure an underdose or overdose. Of course, it may create challenges for people who have sleep disorders. But it might actually help you sleep, since the nighttime T3 is natural. It might boost your health in unexpected ways by supporting other hormones’ 24-hour rhythms. Your body might want you to at least give it a try.

Evening and night responses to T3 dosing vary

Response to evening and nighttime T3 dosing varies among patients who dose various T4-T3 combos, or desiccated thyroid, or people on T3-only.

It’s extremely individualized because we each have unique metabolic handicaps.

Take daytime doses as needed to cover “gaps” in your schedule.

You’ll learn when you need even a small dose if you start to feel drowsy or lose the ability to think clearly during the day, become cold, or get a slow heart rate.

Know your T3 tool

Having a T3 prescription is a major biochemical tool, a blessing in disguise that can help us tweak many metabolic pathways.

Therefore, a fundamental piece of education is to understand the T3 dose-driven rhythm as a tool (see our FT3 Peaks and Valleys article, and T3 withdrawal article). I’ve offered some tips for optimizing flexible-ratio T3-T4 combination therapy, and research-based guides for optimizing T4 monotherapy are coming soon.

One of the T3 pharmaceutical’s strongest assets (which some doctors think is a weakness!) is its fast-acting nature, which goes hand in hand with its short half-life. It does not take long for your body to tell you if you’ve moved in the wrong direction, and if you make a mistake, you can just backtrack.

The FT3 peaks created by dosing will always be much higher than natural ones, even if you only take a small dose of 5 mcg.

Our T3-T2 metabolism and T3 clearance rates can be different as well (far more loss to two inactive types of T2 during the peaks).

Keeping a record of vital signs we can measure (heart rate, blood pressure, body temperature, symptoms) can help us tweak the dose strength and timing to see what works best for us as an individual, but sometimes even measurable biomarkers like our heart rate can be difficult to read.

The potency of the T3 tool

The T3 pharmaceutical is a potent metabolic tool, so be cautious.

Even without a change in your total T3 dose per day, Paul Robinson and patient experience attest that simply moving a dose by 15-30 minutes in relation to waking, sleeping or eating can shift what happens all over our bodies for the next 5 hours, or 5 days. Moving or changing the size of the first dose of the day (the overnight, pre-waking dose) can sometimes have the same impact as raising the total T3 dose per day, it’s that powerful.

If your T3 dosage tweak did not cause an immediate negative response, it’s wise to wait about 5 days for your whole body to adjust to any minor change. Some tissues exchange thyroid hormone with blood more slowly than others.

Splitting pills and spreading out doses is a valid strategy. Taking “too much” at once can backfire with hypothyroid-like symptoms as too much T3 gets quickly metabolized to T2 and other derivatives like Triac.

If you have overdosed a little and it’s causing thyrotoxic symptoms, keep Milk Thistle supplements on hand for safety because the silychristin it contains can mildly block MCT8 transporters from taking up too much T3 into cells (Jörg et al, 2016).

If you’ve been wise enough to keep your experiments small, a mildly thyrotoxic phase will only last 3-6 hours post dose, and rest assured that Deiodinase type 3 is our body’s “blocking” defense system for managing temporary T3 peaks.

On the other hand, sometimes too small a dose is not enough to respond to the physiological need at that time of day.

Why is it so tricky and individualized?

Each person has a different ideal T3 dosing rhythm not only because of genetic variation, but because of the variety of our disabilities. Our non-thyroidal circadian rhythms can become time-shifted and de-synchronized during thyroid disease and therapy.

“Optimal” therapy truly is individualized, even in 100% thyroid health and physical health. It takes time to learn what your body needs. Each of us has different physiological strengths and weaknesses.

Too many people become discouraged when they meet biochemical targets recommended by others and still aren’t feeling well (such as targets recommended by the Stop the Thyroid Madness group). Your thyroid disability is unique. Therapy is adaptive, not a rigid prescription that is the same for everyone.

Have hope, and move forward.

We don’t have to know it all, we just need to know our T3 tools and how to use them cautiously, know some basic circadian rhythm principles, and gradually get to know our individual bodies enough. It is our role to micromanage dosing schedules within the daily dosage our doctors prescribe.

My own T3 story

People who dose even a little T3 can learn a lot about how T3 dosing works from people who depend ONLY on T3.

I’ve learned a lot about T3 dosing through my own experience since 2016. I’m a rare thyroid patient, an oddball, on T3 monotherapy, and I’ve described it like being in a wheelchair. Of course, I’m not a representative of all T3 monotherapy patients. There’s a lot of diversity even among those who dose T3.

My T3 caution, my plea for sanity

I am seeing too many tragic failures of T3 monotherapy lately. Do not simply jump to T3 mono because you’re struggling to become optimal on your current T4-inclusive therapy.

I’ve seen some people confess to trying T3 monotherapy because they have become afraid of T4 hormone or Reverse T3 hormone, because of people spreading the myth that Reverse T3 “blocks” T3. Those are not valid reasons. This is not based on science.

There are even some people who recommend keeping RT3 to the lowest two digits in the RT3 reference range or below. That’s ridiculous and metabolically backwards, like wagging the tail of a dog to make him feel happy. Reducing RT3 is not a valid therapy target. Untreated hypothyroidism has an extremely low RT3; is the lowness of RT3 helping them? No, it’s a side effect of their low T4 state. I could go on…

This ill-informed RT3 fearmongering and RT3 targeting is truly harming people, and it makes me angry to see it!

T3 hormone is not a cure-all. It’s not like a supplement, not at all like dosing a vitamin. It shifts your entire body to a more limited and volatile thyroid hormone fuel source. Not very many people truly need T3 mono, and some people truly can’t adapt to it.

T3 mono is a last-resort and compassionate therapy for people

Considering the option of T3 mono ought to involve careful planning and a very gradual transition, not a sudden switch. Once you’re there, it is still like balancing on the edge of a knife, and it takes a lot of work to manage safely.

Patient support groups

Thyroid Patients Canada now has a set of moderators for its own private patients-only support group. Our principles are “share wisely, seek evidence, and reason carefully.”

For Canadian thyroid patients only, see a very large, active and diverse group on Facebook called Canadian Thyroid Support Group.

Paul Robinson has a private Facebook group for questions about his latest book, The Thyroid Patients Manual. Another group on Facebook that is based on his T3-only protocols is called T3 Support.

For those not on Facebook, HealthUnlocked, mainly UK-based, is a good Thyroid-focused public message board.

Links to blog posts on thyroid circadian rhythm

[Part 1. Circadian rhythms of TSH, Free T4 and Free T3 in thyroid health, a descriptive overview of how the rhythm works, with tips on the timing of thyroid lab tests outside of thyroid therapy]
[Part 2: The significance of the TSH-FT3 circadian rhythm. How the TSH and FT3 response combine to create a healthy, individualized FT3-FT4 ratio that can sustain a person in subclinical hypothyroidism and in extreme old age.]

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