Free Thyroxine (fT4) – Optimal Health, Metabolism and Longevity

What thyroid hormones are needed for

A properly functioning thyroid is important for many functions in the body, including:

• Metabolism
• Energy
• Heart rate
• Healthy cholesterol levels
• Mental  and brain health
• Bone health
• Fertility
• And many other functions (R).

The most common thyroid blood tests done at your GP, and why they aren’t enough

If you have gone to the doctor and your thyroid hormones tested out of range (ie in the ‘red’/ danger zone), you will likely get a prescription to add more hormones (or block their production if you had too many).

A sluggish thyroid usually gets ‘treated’ by a prescription of T4, the precursor hormone. Chances are you know several friends or family members on it, as it is being given out quite frequently. Now one would think, why are they giving out T4, when the active form really is T3? We will discuss elsewhere in more detail soon, but in a nutshell, for many people T4 medication will in fact help normalise thyroid hormone function, as the body will use it to turn it into T3, the active form.

However, there are some where T4 (synthetic thyroxine) does not help improve symptoms, and a combination with T3, the active form, shows better symptom improvement.

Within Functional Medicine we obviously take this even one step further and ask the question of why.  ‘Why is the body not producing enough thyroid hormones (or too much) in the first place? What are underlying triggers, such as inflammation from an imbalanced gut microbiome, hidden food intolerances, too much or too little of nutrients needed to make thyroid hormones (such as iodine, selenium, protein), heavy metal toxicity and more  that block the conversion?’

Why simply testing TSH and free T4 is not enough

We used to think that TSH, the thyroid stimulating hormone sent from the brain to the thyroid, is an adequate representation of what is happening with our actual thyroid hormones. That is because when everything works smoothly, TSH levels are tightly regulated by how much thyroid hormones we have floating around the body, via feedback mechanisms. Ie, if enough thyroid hormones are present, the brain down regulates its stimulating action (lowered TSH), and if not enough thyroid hormones are present, it would ramp up the stimulation (increased TSH). We used to also think that each body has a set point from birth that decides if we are more prone to be on the low or high end of thyroid levels – for life.

Hence why most often only TSH levels get tested.

However, more recent research indicates that TSH is in fact not enough to represent what is happening with our thyroid hormones, and only adding free T4 to the test panel, which has become more common practise, is still inadequate.

Research suggests that free T3 levels likely can not reliably be predicted by TSH and free T4 levels, and direct measurement of free T3 to be vital to properly assess thyroid health (R).

There is mounting evidence of metabolic and clinical consequences that could be attributed to low serum T₃ concentrations in patients treated with levothyroxine (the most commonly prescribed synthetic T4 replacement) despite normal TSH concentrations — including increased bodyweight, slower basal metabolic rate, elevated serum cholesterol concentrations, and statin utilisation (R).

In these cases, simply testing for TSH and free T4 won’t show us the full picture. These tests could be coming back perfectly fine, when in fact free T3 is low.

Why free T4 in normal ranges does not necessarily mean it is optimal

While we might intuitively think that a higher level of T4 might be better, there is in fact a bell sized curve. Research indicates that while low T4 levels aren’t good, high levels aren’t great neither!

Higher T4 levels, in particular as we get older, have been linked to increased mortality, accelerated aging, decreased lifespan, free radical production and heart issues (R, R).

A study found that free T4 levels in the top quartile of the normal range was linked to a higher incidence of atrial fibrillation, coronary heart disease, heart failure and mortality (R, R).

On the contrary, higher T3 is linked to better health outcomes as we get older. One of the possible reasons suggested could be that as we age, the enzymes needed to convert free T4 into free T3 slow down, and with it T4 increases, while T3 reduces. This might also explain why younger individuals often do better with T4 hormone replacement therapy, while older individuals might struggle to reap the same benefits (R).

In summary: For optimal health, metabolism and longevity, we want free T4 to be in the middle of the normal range, while free T3 is best when at the top end of the normal range.