Circadian (15): rT3 and Leptin

I hope the previous two articles have opened your eyes to a new paradigm of understanding test results. Most people want to look at results as isolated islands, when in fact the body is a whole world of interconnected lands. That is why PTH has only been viewed in the context of parathyroid or renal issues, and ASCA is only used to differentiate Crohn’s disease from its cousin, ulcerative colitis. It takes a bit more than the widespread dogmatic reading of medical sciences to link up the physiology of our disparate organs. Don’t be surprised if your doctor needs a bit more time to do this.

When I first started my clinic, a pathology provider grew quite concerned with how "random" my requests were. Of course, they couldn't see why I was requesting ASCA, PTH, rT3, and leptin together, amongst others. I advised the representative during the visit that I am convinced of the science behind these and pointed out that I initially learnt about many of them from their own handbook. I offered to have an in-person conversation with their pathologists (medical doctors with a specialty in pathology testing) to help them understand what I see. The meeting did not happen, and I have since been left to continue to practise as I see fit, at least until the next eyebrows are raised.

What I am trying to tell you is that if you can’t get your doctors to do PTH or ASCA, you might want to give up on rT3 and leptin. The tests are downright conventional, yes, but trust me, your doctor is not. If the first time they hear about a test is when you say you heard of it online, they will immediately throw it into the "alternative" basket and permanently turn away from it. The huge online world has also done its bit to fuel this dichotomy—for example, I have heard of multiple vigorous supplement pitches as a direct result of testing rT3. The irony is that most online supplement health influencers have done the very things they claim have failed conventional medicine: blanket treatment and reliance on pills.

Reverse T3, or rT3, is a direct descendant of the thyroid hormone T4 that puts a brake on the impact of the hormone. Anyone on thyroid hormone replacement medication, such as thyroxine, will consequently have higher than average rT3, as the body is trying to slow down the avalanche of thyroid hormone that suddenly enters the system. At night, you want to have more rT3 than usual; otherwise, you have so much energy you can’t sleep. That makes it a good circadian marker, unless, of course, you are sick or on thyroid replacement.

To look at the thyroid clock, you have to consider both the rT3 and its active counterpart, free T3, normally reported by Australian labs in pmol/L. The tests have to be done fasting first thing in the morning to anchor them down to a specific light-clock and gut-clock. When these are standardised, a free T3 / reverse T3 ratio of 0.02 or larger means that your body clock is synchronised at multiple different levels with the thyroid hormone. But be careful not to jump straight to the conclusion of a dysfunctional thyroid with a ratio smaller than 0.02, as most T4 conversion happens in the liver, gut, kidneys, muscles, and fats. A low ratio simply means something in the body is adrift from the thyroid clock—which makes it a very good general circadian test, although not very helpful in pointing out where it went wrong.

Our last marker, leptin, is even less known than rT3. Leptin is what our fat cells use to signal to the brain how much energy storage it has. If I may, as an oversimplification, when the brain sees leptin, it stops making hunger hormones and focuses instead on satiety. This is important, as we want to be able to maintain our sleep cycles without being interrupted by hunger pangs.

Upon waking up, leptin will naturally decline to allow for energy refill via food consumption. The problem happens when your brain starts to ignore this important messaging from the fat cells, a phenomenon called "leptin resistance." We start to have more frequent meals and late-night snacks to keep the leptin message loud to the half-deaf brain. Not seeing all of the energy, the brain signals for the body to keep more savings rather than spending its currency, resulting in an increase in waist size. Now we have more fat cells to tell the brain, in the language of leptin, to stop this whole cycle, but the brain is becoming more and more resistant to the loud yelling. It’s a downward spiral that can only end in disaster.

So, if it is obvious to you that you have the extra waist size, you don’t need to test your leptin—your adipose clock is already desynchronised. But leptin is handy if you are comfortable with your waistline but are not completely sure you have the fat clock right due to impulsive hunger, nighttime appetite, non-restorative sleep, and relentless fatigue. It is even better if you are a bloke, as the strict reference range, in my opinion, is wrongly discriminative against women who may be healthier when carrying higher adiposity.

Perhaps one day I will write in-depth articles on subjects like thyroid and leptin as I have on circadian. But for now, we have covered fundamental circadian biology, and I am very happy for you if you have managed to follow me this far. We will conclude this series next week by answering the most practical question you may have: what do I do to fix my body clock?