Chronic fatigue 2/2: Tired all the time? What to test, and what to do

In part one, we looked at how multiple things can cause fatigue. So, searching for one supplement that will “give you your energy back” rarely works. The answer depends on what’s actually driving your symptoms.

What does your fatigue actually feel like?

No blood test measures fatigue directly. Start by distinguishing between sleepiness, weakness, reduced stamina, and difficulty thinking clearly. Also pay attention to when it appears: on waking, after meals, during exercise, after an infection, after starting a new medication, with heavier periods, or after increasing your training load.

For one to two weeks, track your sleep, meals, caffeine, activity, medications, and symptoms. The pattern over time can reveal things that a single test result cannot.

For people with ADHD or autism, it is also worth considering executive, sensory, and social overload, masking, and associated sleep issues. This kind of load can be exhausting even when there is no specific biological abnormality.

Could biomarkers help explain fatigue?

Biomarkers do not measure fatigue itself. They can help identify mechanisms that may be causing or contributing to it. Their value comes from interpreting them alongside your symptoms.

• Iron allows haemoglobin to carry oxygen, but it is also needed for myoglobin and for enzymes involved in energy metabolism, including in the mitochondria. This is why low iron stores can affect stamina and recovery before anaemia appears. Ferritin estimates iron stores; transferrin and transferrin saturation reflect how much iron is available; and a full blood count shows whether red blood cells are affected. CRP adds useful context because inflammation can raise ferritin and mask an iron deficiency. If a deficiency is confirmed, its underlying cause should also be investigated.

• Thyroid hormones regulate many metabolic processes as well as body temperature and heart, muscle, and brain function. Low thyroid activity can therefore be associated with fatigue, feeling cold, constipation, or slowed thinking. TSH reflects the signal from the pituitary gland, while free T4 measures the main hormone produced by the thyroid. Depending on the context, free T3 can add further information, and anti-TPO antibodies can help identify autoimmune thyroiditis. Because the symptoms are non-specific, results need to be interpreted together.

• Glucose fuels the brain and muscles, while insulin helps tissues use it. When tissues become less sensitive to insulin, the pancreas may initially produce more insulin to keep blood glucose normal. This compensation can happen before fasting glucose or HbA1c rise, so fasting insulin and HOMA-IR can provide additional information. Fatigue after meals may be a reason to explore this pathway, but it does not by itself indicate insulin resistance.

• During an inflammatory response, certain cytokines can affect sleep, motivation, and how difficult effort feels, part of the reason people feel drained during an infection. hs-CRP does not measure these cytokines or identify the cause of fatigue; it can indicate a low-grade systemic inflammatory response. If it remains elevated, the cause should be investigated, and it can also help with the interpretation of ferritin. A normal value does not rule out localised inflammation or post-infectious fatigue. Conversely, a high value in the 24–72 hours after intense exercise may simply reflect a normal acute response to training rather than chronic inflammation.

• Cortisol plays a role in alertness, blood pressure, and glucose mobilisation. It normally rises around waking and then falls throughout the day. The Cortisol Awakening Response (CAR) measures this morning rise using several saliva samples in the 20–30 minutes after waking. A flatter response, or cortisol that remains elevated in the evening, can be considered alongside sleep, stress, and daily schedule.

• Among micronutrients, vitamin B12 and folate are essential for red blood cell production, and B12 also supports neurological function. Deficiencies can therefore cause fatigue and cognitive symptoms, with or without anaemia. A marked vitamin D deficiency can contribute to muscle weakness and pain. Magnesium is involved in many enzymatic reactions, ATP utilisation, and neuromuscular function.

• The kidneys maintain electrolyte balance, remove waste products, and produce the erythropoietin needed for red blood cell production. The liver plays a role in glucose storage and nutrient metabolism. Creatinine, estimated GFR, electrolytes, transaminases, and GGT can help identify impaired function that may reduce energy or stamina.

Significant exposure to certain heavy metals can also contribute to fatigue. This is most relevant in the context of occupational exposure or specific household sources, such as renovating an older property or eating large amounts of predatory fish.

A normal standard blood panel does not mean your fatigue is not real. The Lucis approach broadens the analysis to include additional markers and functional targets, helping to look for imbalances that first-line tests may not reveal. These functional targets are used as optimisation benchmarks, not diagnostic thresholds.

ASSET

Visual: seven fatigue profiles side by side, what you observe and what it points to (sleep and medications, iron, thyroid, glucose regulation, post-exertional malaise, timeline of a recent change, heavy metals). An English version of the newsletter infographic.

What you can do while you investigate the cause

1. Protect your sleep

Keep your wake-up time relatively consistent, including at weekends, and get natural light in the morning. Both help stabilise your sleep-wake rhythm.

Caffeine blocks adenosine receptors. Because adenosine builds up over the day and contributes to sleep pressure, caffeine can interfere with sleep even after its stimulating effects have worn off. Try stopping caffeine eight to nine hours before bed, or earlier if you are sensitive to it.

Alcohol may make it easier to fall asleep, but it disrupts sleep architecture. It initially increases deep sleep while suppressing REM sleep, then as it is metabolised later in the night, it can lead to more frequent waking and less restorative sleep. It can also worsen sleep-disordered breathing.

If you snore heavily, someone has noticed pauses in your breathing, you wake feeling as though you are choking, or you struggle to stay awake during the day, sleep hygiene alone is not enough: sleep apnea should be investigated. It is common and significantly underdiagnosed.

2. Make sure you are eating enough

A “healthy” diet can still be insufficient if your activity increases without your portions increasing too. In active people, poor recovery, reduced performance, repeated injuries, or changes to the menstrual cycle can be signs of low energy availability.

As a practical rule, include a source of protein, carbohydrates appropriate to your activity level, vegetables, and fats at each meal. On training days, do not automatically cut carbohydrates; increase them around your session if your energy or recovery starts to decline.

Adjust your hydration according to thirst, heat, and losses from exercise.

3. Correct deficiencies without overlooking the cause

Pair plant-based iron sources such as legumes, tofu, and whole grains with vitamin C. Keep dairy products, tea, and coffee one to two hours away from iron-rich meals or iron supplements, as they can reduce absorption.

People following a vegan diet need a reliable source of vitamin B12. Certain digestive conditions and medications can also interfere with absorption.

When a deficiency is significant, food alone may not be enough. Supplementation should be tailored and then reassessed. Iron should not be taken without first checking your iron status.

4. Review your medications and supplements

Some antihistamines, anti-anxiety medications, painkillers, antidepressants, muscle relaxants, and cardiovascular medications can cause drowsiness or low energy, particularly after a dose increase.

Track your medications and supplements, including dose and timing, and look for any relationship with when the fatigue began. Do not stop a prescribed treatment on your own. Speak to your prescriber about the timing, dose, or possible alternatives.

5. Match your activity to your current situation

If you are sedentary, break up long periods of sitting, walk regularly, and introduce strength training gradually.

If you train frequently and your sleep, performance, or recovery are getting worse, temporarily reduce your training load and make sure your energy intake is keeping up with your expenditure.

A significant and prolonged worsening of symptoms after light activity, sometimes not until the following day, is different from normal training fatigue. Particularly after an infection, this warrants medical advice before increasing activity.

6. Set a time to end your day

Set a time to close your email, turn off notifications, and write down tomorrow’s tasks so you are not still organising them in your head once you are in bed.

During the hour before bedtime, dim the lights and, where possible, replace screens with something calmer. Bright light and stimulating content often delay sleep.

For neurodivergent people, building in daily time with less noise, fewer interactions, and fewer decisions can be just as important as physical rest.

Track meaningful changes

Rather than relying only on a fatigue score out of 10, track when the fatigue appears, how you feel on waking, your concentration, post-meal fatigue, and recovery between workouts.

If your fatigue persists, gets worse, or starts limiting your daily life, keep investigating. A blood test cannot detect sleep apnoea, intermittent arrhythmias, medication side effects, depression, or post-exertional malaise.

The goal is not to achieve perfect results, but to connect your symptoms, your context, and measurable data so you can act on the factors that are actually present.

Discover Lucis and explore the factors that may be contributing to your fatigue.

Listen to the episode

Listen to our latest podcast episode, where Anaïs Gautron and Davis d’Hont explore the most common causes of chronic fatigue.

Scientific references

1. Al-Naseem A, Sallam A, Choudhury S, Thachil J. Iron deficiency without anaemia: a diagnosis that matters. Clinical Medicine. 2021;21(2):107–113. doi:10.7861/clinmed.2020-0582.

2. Bateman L, Bested AC, Bonilla HF, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: Essentials of diagnosis and management. Mayo Clinic Proceedings. 2021;96(11):2861–2878. doi:10.1016/j.mayocp.2021.07.004.

3. de Baaij JHF, Hoenderop JGJ, Bindels RJM. Magnesium in man: Implications for health and disease. Physiological Reviews. 2015;95(1):1–46. doi:10.1152/physrev.00012.2014.

4. Ebrahim IO, Shapiro CM, Williams AJ, Fenwick PB. Alcohol and sleep I: Effects on normal sleep. Alcoholism: Clinical and Experimental Research. 2013;37(4):539–549. doi:10.1111/acer.12006.

5. Gardiner C, Weakley J, Burke LM, et al. The effect of caffeine on subsequent sleep: A systematic review and meta-analysis. Sleep Medicine Reviews. 2023;69:101764. doi:10.1016/j.smrv.2023.101764.

6. Green R, Allen LH, Bjørke-Monsen AL, et al. Vitamin B12 deficiency. Nature Reviews Disease Primers. 2017;3:17040. doi:10.1038/nrdp.2017.40.

7. Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: A systematic review of randomised controlled trials. BMJ Open. 2018;8. doi:10.1136/bmjopen-2017-019240.

8. Karshikoff B, Sundelin T, Lasselin J. Role of inflammation in human fatigue: Relevance of multidimensional assessments and potential neuronal mechanisms. Frontiers in Immunology. 2017;8:21. doi:10.3389/fimmu.2017.00021.

9. Latimer KM, Gunther A, Kopec M. Fatigue in adults: Evaluation and management. American Family Physician. 2023;108(1):58–69.

10. Mountjoy M, Ackerman KE, Bailey DM, et al. 2023 International Olympic Committee’s consensus statement on Relative Energy Deficiency in Sport (REDs). British Journal of Sports Medicine. 2023;57:1073–1097. doi:10.1136/bjsports-2023-106994.

11. National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. NG206. 2021.

12. Stalder T, Oster H, Abelson JL, Huthsteiner K, Klucken T, Clow A. The cortisol awakening response: Regulation and functional significance. Endocrine Reviews. 2025;46(1):43–59. doi:10.1210/endrev/bnae024.

13. Zajac L, Johnson SA, Hauptman M. Doc, can you test me for “toxic metals”? Challenges of testing for toxicants in patients with environmental concerns. Current Problems in Pediatric and Adolescent Health Care. 2020;50(2):100762. doi:10.1016/j.cppeds.2020.100762.

This content is for informational purposes only and does not constitute medical advice, a diagnosis, or a prescription. Lucis functional targets are not diagnostic thresholds. Persistent, unusual, or disabling fatigue should be discussed with a healthcare professional. Seek prompt medical attention for chest pain, difficulty breathing, fainting, confusion, neurological symptoms, significant bleeding, or a rapid deterioration in your general condition.