“I’ve had my blood tests done, everything’s fine, but I still feel unwell.” We explain why and how to sort it out

The expert highlights three values that ‘are almost never tested for in a blood test and which explain the majority of the cases we are discussing’. The first is haemoglobin. “The result for this parameter may fall within the limits considered normal, yet iron stores may still be depleted or empty. The thing is, as haemoglobin is the last indicator to drop, the figure shown alongside it in the blood test may not reflect what is actually happening in the body.”

"To know for certain, we also need to know the ferritin and transferrin levels – two biomarkers that are not always included in a standard blood test,’ she points out. “Ferritin not only measures iron stores, but also inflammation, which is why it is important to measure both levels at the same time. One tells us about iron stores and the other is the transporter. And depending on whether we look at them together or separately, they can provide us with different information.”

The second factor to be assessed in cases such as these, where the cause of the symptoms is unclear, is vitamin D and also vitamin B12. “The results of these two indicators can provide us with a great deal of information, as they are often the underlying cause of tiredness, fatigue or listlessness… The good news is that these are two levels that are easy to correct,” explains the specialist in Gastroenterology and Advanced Digestive Endoscopy. The feeling of tiredness and exhaustion is a very common symptom, particularly amongst middle-aged women. According to a recent survey carried out by the Spanish Society of General Practitioners (Semergen), seven out of ten adults admit to feeling tired ‘quite frequently’.

And the third factor – which is the one Dr Esteban comes across most often in her practice ‘and which almost nobody studies’ – is the hormonal one. "The thyroid, cortisol and sex hormones explain why the same symptoms are experienced very differently at different stages of life. Sometimes the doctor tells you that simply checking for normal TSH levels (the hormone that regulates how the thyroid gland functions) is more than enough, but that is not the case. We must look beyond that. It is also important to measure free T4 (which assesses how the thyroid is functioning and helps diagnose problems such as hypothyroidism or hyperthyroidism) and thyroid antibodies (proteins that the immune system mistakenly produces to attack the thyroid gland) to gain a comprehensive understanding of the patient’s thyroid function.”

Regardless of the results, the specialist points out that it is not a question of requesting these three biomarkers for every patient who comes to the clinic, “but if a person has been experiencing tiredness, fatigue or inflammation for months or years, these values should be taken very seriously because they provide a great deal of information. The idea is not to test for everything, but to know where to look. Hormonal markers, for example, are an area where testing without a clear criteria can lead to even more confusion.”

According to specialists, the cause of all these symptoms is usually low-grade chronic inflammation triggered by factors such as stress, a diet high in ultra-processed foods, or changes in the gut microbiota. ‘It involves a subtle and persistent activation of the immune system across various organs, which persists over time without any obvious infectious cause and leads to persistent inflammation.’ Unlike acute inflammation (such as a blow or a wound), low-grade inflammation does not present with obvious signs such as localised heat or redness of the skin, but acts as a silent internal wear and tear. It does not cause pain, fever or elevated blood test results. “It is like a fire that burns for several years, causing a slight elevation in several markers at the same time,” explains the specialist.

For Dr Esteban, the ‘fundamental mistake’ when dealing with a case of this nature is that people look for the inflammation causing that fatigue and listlessness as if it were located in a specific place. As if there were a blood test that would tell us ‘is there inflammation or not?’. But it doesn’t work like that. “Low-grade inflammation isn’t confined to a specific location. It leaves its mark on many people, and the mark it leaves on each person is different. That’s why a normal test result doesn’t mean there’s nothing wrong. What does matter is how the results are interpreted, and that discussion must be had with a professional who knows the patient well.”