• Dr Laura Stix

The top 5 causes of persistent fatigue

There is always a reason for why you are chronically tired and have no energy -- sometimes it just takes some sleuthing!

Chronic persistent fatigue

Last updated: Nov 30, 2020

We all know what it feels like to be tired and dragging our butts. But sometimes that fatigue lingers on, day after day, and it may not be clear why it's happening.

Additional symptoms that commonly occur alongside persistent fatigue can include:

  • brain fog or a "heavy head"

  • not feeling rested even after many hours of sleep

  • inability to concentrate

  • poor memory

  • muscle fatigue or weakness

And we all know that diet, exercise and sleep are very important, so it can be frustrating when it feels like you're doing everything right but still not making headway on boosting energy levels. You see the medical doctor and they run blood work and tell you everything is "normal" but you still feel like garbage.

There's a reason for everything, so it's just a matter of knowing how to sleuth through your health profile and run the right lab tests to ultimately figure it out.

It's also important that lab work is interpreted correctly, understanding there is an optimal range; it's not ok to just be "normal".

For example, I commonly see blood work for Vitamin D where people are in the low end of the range but still "normal" (the range is 75-250). Optimal levels are around 150-200 and the older an individual becomes, the less natural vitamin D they produce in the sun. Supplementing and supplementing at the appropriate level (most are far too low) requires professional guidance and supervision. Testing and proper test interpretation is essential -- especially when vitamin D plays such an important role in the body including immune function, mental health, calcium absorption and bone health.

Here are the top 5 (of about 13 or so) key underlying issues that cause persistent fatigue. Often it's a combination of more than one:

1) Thyroid Problems - These are incredibly common (particularly hypothyroidism) and are under-diagnosed.

It makes for very difficult weight loss even when someone has "subclinical" hypothyroidism (meaning that lab values are still within the range, but are not optimal). Conventionally, only TSH is typically run to assess thyroid function, however in order to get a complete understanding of how the thyroid is functioning and what may be impacting it, a full thyroid panel must be run including TSH, free T3, free T4, reverse T3, TPO and TG antibodies.

Added to this problem are common nutrient deficiencies that the thyroid needs to function well or heavy metals or toxins that can negatively impact the thyroid.

2) Anemia - This could be due to low iron, B12, folate, genetic conditions, or a result of chronic disease and inflammation.

The "normal" reference range is massive for ferritin (the storage form of iron) and is far too low for B12 (in Canada you're considered "normal" if above 110, while Japan you are deficient if below 500).

Checking markers for inflammation can sometimes be important with this because ferritin does not only tell us about iron stores - it is also an indirect marker for inflammation. This is why an iron panel should be run alongside ferritin, as well as other markers for inflammation, in order to accurately interpret ferritin results.

3) Cortisol Imbalance (or what is termed "HPA Axis Dysfunction") - So, so common and various stressors on the body and mind can impact this. This means not only psychological stress, but ANY stressor on the body, like toxins from the environment, inflammation, lack of sleep, etc.

Being stressed all the time puts strain on the body where, over time, the brain begins to dial down the signaling to the adrenal gland which means less cortisol is made, and thereby less energy.

A single morning blood draw does not capture the rhythm of cortisol release, nor is it a reliable measure for more subtle cortisol issues -- urine and saliva are best, taking usually 4 or 5 samples across the day to check for the rise and fall of cortisol. I like running the DUTCH test for this (and other hormones) -- you can check out their website and sample reports here.

4) Nutrient Deficiencies - Even fresh, organic foods are depleted in the levels of nutrients they once held decades prior. I discuss this in my magnesium article you can check out here if you like.

The millions of reactions that take place in our body require specific vitamins and/or minerals to do the job, so if something is missing, a whole chain of reactions gets mucked up like a jammed conveyer belt. I discuss how challenging magnesium is to test and unfortunately many nutrients are not very straightforward. The reason is because what we find in the blood is not a reflection of what is actually in the tissue.

Some lab tests are useful (like testing red blood cell zinc, or serum vitamin A or Vitamin D) but many are not. A hair mineral analysis can be a useful tool that captures both the minerals, as well as a variety of heavy metals in the body (no vitamins though). Here is the test I prefer from Doctor's Data. No test is perfect and this test assumes we are excreting well and it's showing up in the hair (and that there isn't environmental contamination).

The most common significant vitamin and mineral deficiencies are magnesium, zinc, vitamin E, B vitamins, and vitamin D (technically it's a hormone, not a vitamin). This doesn't include things like L-carnitine, choline, creatine, antioxidants, or other nutrients we source from food but are still very important.

5) Blood Sugar Dysregulation - Many people are overweight and most commonly this is due to ongoing insulin production (this is why diabetics who are given insulin will gain weight, and indirectly worsen the problem).

Every time we eat something, ANYTHING, even a walnut, some insulin is produced. All insulin wants to do is push glucose (sugar) into cells and store it for energy (or as fat). When increased insulin is present we cannot burn fat.

You can imagine then that if someone has a meal, a snack, a meal, a snack, etc there is a constant yo-yo-ing of blood sugar and insulin (and some inflammation). When blood sugar goes up, so does insulin. When blood sugar drops down, we can feel weak, lethargic, fuzzy headed, trembly, cravings -- it's not good.

Because carbohydrates play such a large role in our everyday lives (sandwiches, pizzas, buns, muffins, pasta, potatoes, grains, crackers, cookies, etc) most people are not metabolically flexible. This means that their body relies on carbs for energy and does not use fat stores well. You know you are metabolically flexible if you can go several hours without food (and function well, sometimes better, doing so).

I use to have what's called "Reactive Hypoglycemia" from my "healthy" high carb diet. Even though I wasn't overweight, if I didn't have some sort of a carb snack/fruit handy I would get shaky and lightheaded, sometimes even cold sweats!

One simple starting point for this is to implement 16 hrs of fasting every day and to never snack between meals. I can now go 24 hours without any food and not have any issues.

When testing for blood sugar issues (and insulin resistance) I like to see HbA1C (your average blood sugar over the last 2-3 months) as well as sometimes a fasting glucose & fasting insulin to calculate the HOMA-IR (an estimate of insulin resistance).


It's frustrating to feel fatigue day after day when you feel like you're doing everything right. Fortunately, with some solid health detective work, the answers can typically be found and corrected for - the key is to know what to look for. These were the 5 main causes of persistent fatigue (from a list of about 13) so watch for additional posts on the other, less common, contributing factors to fatigue.