Tired All The Time? Understanding Adrenal Fatigue And Mitochondrial Dysfunction May Be The Key To Reclaiming Your Energy

Feeling perpetually tired seems to be a condition of living in the modern world. We all have a lot on our plates these days, and for many, there’s an extra helping of fatigue. A lack of quality sleep may be to blame for some people, but for others, the cause of their always-tired, run-down feeling is not so obvious. Two of the more insidious causes of perpetual exhaustion are adrenal fatigue and mitochondrial dysfunction. Read on to learn if either (or both) of these may be the reason you are tired all the time… and what you can do to reclaim your energy!


Tired All the Time?  Understanding adrenal fatigue and mitochondrial dysfunction may be the key to reclaiming your energy

Stressed Out and Tired? It May Be Adrenal Fatigue…

If your fatigue is coupled with prolonged chronic stress, irritability, and a dependence on caffeine or other stimulants, then adrenal fatigue may be the root of the problem. Other symptoms can include brain fog, cravings for salty and sweet foods, and feeling tired upon waking (even after a good night’s sleep), but getting a “second wind” in the evening.

To understand adrenal fatigue, it’s important to understand the body’s stress response system, the hypothalamic-pituitary-adrenal (HPA) axis. When the body is under stress, the HPA axis triggers the adrenal glands (two small glands that sit atop the kidneys) to release adrenaline and cortisol to help us deal with the stressor—this is also known as the “fight or flight” response.1 This system works beautifully in instances of acute stress, such as running from danger; however, the chronic stress that is more common in our modern world—financial stress, emotional stress, work stress, pandemic stress, etc.—leads to a constant activation of the HPA axis. This, in turn, leads to elevated cortisol levels. But eventually, when the adrenals have become so overworked that they can no longer keep up with the body’s demand for cortisol, the result is abnormally low cortisol levels (this can take years to develop). Chronically elevated cortisol comes with its own side effects—high blood sugar, weight gain, sex hormone imbalances, poor immunity, depression and anxiety, and increased oxidative damage and inflammation—but it is low levels of cortisol that characterize adrenal fatigue. This is when symptoms such as chronic fatigue, mood disorders, low blood sugar, sleep disturbances, and other symptoms manifest.2

…Or Is It Mitochondrial Dysfunction?

Commonly called the “powerhouses” of our cells, mitochondria are found in almost all cells in the human body—and are especially concentrated in cells with high-energy needs, like those in the heart, liver, muscles, and brain—and their main function is to create the energy that powers our bodies. To produce the large amounts of energy our bodies need to function, mitochondria must be in optimal health, if they are not, mitochondrial dysfunction occurs. This can result from nutrient deficiencies, environmental toxins, stress, and inflammation and oxidative damage, especially the oxidative damage that is created within the mitochondria as a byproduct of producing all of that energy. Mitochondrial dysfunction is also related to aging as well as chronic disease, and can be a contributing factor to metabolic diseases like type-2 diabetes and obesity, heart disease, cancer, and neurodegenerative diseases.3 4 5 Mitochondrial dysfunction also appears to alter the body’s stress response (the HPA axis) and may even contribute to adrenal dysfunction.6 And it is directly related to severe fatigue.

Build a Strong Foundation: Support Your Body’s Natural Ability to Make Energy

While adrenal fatigue and mitochondrial dysfunction are unique issues, each with its own symptoms, fatigue is a defining characteristic of both. Before we look at individual adrenal and mitochondrial nutrients, it is important to consider a few foundational supplements. These are nutrients that are required for our bodies to produce energy—suboptimal levels of any of them will interfere with normal energy production. Consider them the first step to reclaim your energy.

B complex.

The family of B vitamins—including thiamine, riboflavin, niacin, pyridoxine, B12, biotin, pantothenic acid, folate, and choline—are all involved in turning food into energy and are necessary for the biochemical reactions that create energy in the mitochondria. Without optimal levels of all of the B vitamins, your body cannot effectively make energy—an inadequate amount of any one of them will negatively affect energy production.A deficiency in any of the B vitamins also has a harmful effect on the mitochondria by interrupting normal energy production, leading to an accumulation of toxic byproducts in the mitochondria and increasing oxidative stress.8

Vitamin C.

One of the first signs of a vitamin C deficiency is fatigue, or “lassitude,” and irritability.9 Vitamin C is essential for the synthesis of carnitine, which transports fat into the mitochondria to be burned for energy and studies have found that supplemental vitamin C reduces fatigue.10 11


This mineral is involved in hundreds of biochemical processes in the human body, and energy production is one of them. Magnesium is needed to convert carbohydrates and fats into energy and also plays a crucial role in the actual structure of the form of energy that our mitochondria create, called ATP (adenosine triphosphate). ATP binds to magnesium to create a functional form of energy that our bodies can use. Magnesium is also required by certain enzymes that work within the mitochondria to maintain their health and normal function and deficiencies have been directly connected to dysregulation of the HPA axis and anxiety.12 13

Restore Balance to the HPA Axis and Optimize Mitochondrial Health

Restoring adrenal function and optimal mitochondrial health takes time. In addition to the following supplements, it is also critical to incorporate lifestyle practices that reduce stress and to clean up your diet (i.e., replace the sugar, caffeine, and refined grains/carbs with plenty of fresh vegetables, quality protein, and healthy fats). Note: Many of the supplements that support the body’s stress response (HPA axis) also supports energy production and mitochondrial health. You may have to try different combinations to see what works best for you.

For Adrenal Fatigue, Try This:

  • Pantothenic Acid. Vitamin B5, or pantothenic acid, plays a key role in helping the body produce stress-related hormones, like cortisol, in the adrenal glands. When chronically stressed, B5 deficiency can result, leading to impaired adrenal function and an inability to respond to stress in a healthy way. Try: 300-500 mg/daily, in addition to a B complex.14
  • Vitamin C. One of the highest concentrations of vitamin C in the body is found in the adrenal glands, where it helps make adrenal hormones and modulates levels of cortisol.15 Try: At least 1,000 mg three times daily. (Too much vitamin C will loosen your stools; if that happens, reduce the amount.)16
  • Phosphatidylserine (PS). This is a special type of fat that makes up the structure of healthy cell membranes, particularly in the brain. Research has found that PS has the ability to modulate the HPA axis, blunting the cortisol response to stress, which is helpful for those whose HPA axis may be chronically overstimulated and have high cortisol levels. Try: 300-600 mg/daily.17
  • Rhodiola. This adaptogenic herb helps increase the body’s resistance to stress and fatigue. It has a unique mode of action, impacting both the HPA axis and energy production—normalizing the release of stress hormones like cortisol, while also boosting energy production in the mitochondria. Supplementation has been shown to significantly reduce stress symptoms and fatigue. Try 500 mg/daily.18

For Mitochondrial Dysfunction, Try That:

  • CoQ10. This vitamin-like substance is fundamental for powering energy production in the mitochondria and has been used to treat genetic defects in mitochondrial energy production that cause extreme fatigue. CoQ10 also acts as a powerful “intramitochondrial” antioxidant, protecting mitochondria from the oxidative damage created by energy production. Statin drugs block an enzyme that the body needs to make CoQ10 (fatigue is a common side effect of these drugs), making supplementation for those on statin medications a must. Try: 100-300 mg/daily.19 20 
  • Alpha Lipoic Acid (ALA). This nutrient has been coined a “mitochondrial nutrient” by researchers, as it has been shown to improve mitochondrial function. ALA also increases antioxidant levels in the body and inhibits increases in oxidative damage due to aging. When taken with other mitochondrial nutrients like L-carnitine and CoQ10, ALA seems to work even better at decreasing oxidative mitochondrial damage and improving mitochondrial function. Try: 200-600 mg/daily.21 22 23
  • L-Carnitine. L-carnitine is directly involved in transporting fatty acids into the mitochondria to be used to make energy, and a deficiency is associated with reduced mitochondrial function. Carnitine has also been used as an anti-aging supplement because of its ability to enhance energy production in the mitochondria that naturally declines with age. One trial including 70 centenarians who were supplemented with carnitine found that supplementation of 2 grams/day for six months lead to significant improvements in physical and mental fatigue and fatigue severity, as well as an increased capacity for physical and cognitive activity. Try: 2,000 mg/daily; to get the most benefits, take these three mitochondrial nutrients (CoQ10, ALA, and carnitine) together.24 25 26


Adrenal fatigue and mitochondrial dysfunction are complex health issues to tackle. While these supplements provide a critical start, consider making an appointment with your local Natural Grocers’ Nutritional Health Coach (NHC) for one-on-one guidance.



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