What Are The Most Important Supplements For Chronic Fatigue Syndrome?

To overcome chronic fatigue syndrome you need specific nutrients that target your mitochondrial function.

But what vitamins and minerals (and at what doses) are necessary? And which are just marketing hype?

Supplements get a bad rap. But they come by it honestly. All too often I see a new supplement ‘’guaranteed to increase your energy’’. But when you look at the ingredients list, you’ll typically see ‘’proprietary blend’’. The term proprietary blend is how manufacturers get around listing the actual amounts of vitamins and minerals in their supplements.

Proprietary blends are clever ways to make inferior supplements look legitimate. They are often accompanied by marketing campaigns that promise the world. But they hardly ever work the way they claim.

In the post, I do away with all the hype. Here, you’ll focus on exactly which supplements are needed in structuring a successful treatment plan to overcome chronic fatigue syndrome. The information presented here is based on scientific research, not marketing hype. You can rest assured that all of the supplements I list have been clinically tested for their efficacy in improving energy production and alleviating chronic fatigue syndrome.

Remember, not all supplements are created equal. Inexpensive brands found at drugstores often won’t be able to be well absorbed by your body. Similarly, very high priced products may have an expensive marketing campaign to support and not offer a superior product. Purchase supplements with price points in the middle of the range. These brands are available online or in-store at health and wellness businesses.

Supplements needed for chronic fatigue syndrome

If you’ve read any of my previous posts, you’re well aware that the root cause of chronic fatigue syndrome is mitochondrial dysfunction. Therefore, the supplements you take should be aimed at improving mitochondrial function. Below, I list the best researched-based supplements for chronic fatigue syndrome.

1. D-Ribose

D-ribose is a simple sugar that was originally discovered in the 1940s. D-ribose is incredibly important in your body’s energy production pathways — it’s an actual structural component of ATP.

It wasn’t until the 1990s that researchers found D-ribose to help patients who suffered a lack of blood flow to their heart (ischemia). D-ribose was shown to improve recovery following cardiac surgery and improved function of the heart in cases of congestive heart failure. And it did all this through improving mitochondrial function. (1)

In those with chronic fatigue syndrome, the linings of the capillaries (small blood vessels) become thickened. This prevents adequate amounts of oxygen from to supply the tissues. It’s like your cells are never quite able to fully catch their breath. (2)

The lack of oxygen forces your cells to produce energy via anaerobic metabolism (anaerobic = without oxygen). This is a terribly inefficient way for your cells to create energy. And its hypothesized that this is precisely what’s going on in chronic fatigue syndrome.

If your cells are never able to produce enough ATP, lactic acid builds up. Have you ever felt so tired that it hurt? That’s the build-up of lactic acid in your cells. D-ribose helps your cells to clear out the lactic acid and rebuild their ATP stores. Over time, this will help to increase your energy levels. (3)


Those with chronic fatigue syndrome will need far more d-ribose than can be achieved in a healthy diet. I recommend you start with 3–5 grams of d-ribose each day. (4) If you don’t notice a change in your energy levels within a few days, increase your dose. D-ribose is extremely safe to take in high doses. Some trials have done doses of 10–15 grams per day without any negative effects reported. (5)

Ensure you take d-ribose every day. Otherwise, your energy pools will quickly become drained without it.

For those of you with blood sugar abnormalities, you may find that d-ribose has a negative effect. This occurs because d-ribose is a simple sugar. And simple sugars can cause fluctuations in your blood sugar. A simple trial of this supplement will determine whether or not d-ribose is right for you.

2. Coenzyme Q10

I’m confident you’re familiar with coQ10 (coenzyme Q10). It’s been touted as a miracle supplement in the prevention of heart disease. (6) The way in which it exerts these magic effects on your heart’s health is through the mitochondria. CoQ10 is an essential ingredient in the Krebs or, citric acid cycle — the cycle used by your mitochondria to create energy from oxygen and food. (7)

Your body naturally produces coQ10 all on its own. Though it requires a decent amount of the amino acid tyrosine, a bunch more vitamins, and even some minerals — it’s a lot of work to make coQ10.

As you age (especially after age 30), your body produces less and less coQ10. This is when supplementation becomes essential. If you have chronic fatigue syndrome (regardless of your age) you should be supplementing coQ10. (8)

CoQ10 targets a specific site of your cells energy production cycle (Krebs or citric acid cycle) called complex 1. It is in this area where the largest amount of free radicals are produced. Supplementation has been shown to decrease free radical damage and improve cell health.

When your cells and body start lacking coQ10, your mitochondrial function starts to fail. They become less efficient at making ATP or energy; and more efficient at producing cell-damaging free radicals. If you’re fighting chronic fatigue syndrome, you need to do everything you can to optimize your mitochondrial function. (9)


Oil-based or liposomal versions of coQ10 are the most absorbable by your body. Ensure that your coQ10 supplement comes in the form of ubiquinol as this is the most usable form for your body. (10)

Take 600–3000mg of CoQ10 each day. It has been shown to be completely safe even at the upper range of dosing.

Unfortunately, this is a supplement I recommend taking for life. The benefits of having healthy levels of coQ10 justify the price tag of lifelong supplementation.

3. Acetyl L-carnitine

As you age, your body’s ability to produce L-carnitine decreases. Much like coenzyme Q10, supplementation after the age of thirty is recommended. Also similar to coQ10, L-carnitine assists with mitochondrial function (albeit in an altogether different way than coQ10). (11)

L-carnitine acts as a bus driver for your fatty acids. Its transports them into your mitochondria where the fatty acids can be used to produce ATP or, energy. If you’re low in L-carnitine, your body will struggle to transport fatty acids into the mitochondria. This will results in impaired energy production — a fancy term for fatigue. (12)

Remember, when your body uses glucose for fuel, one molecule of glucose results in 36 molecules of ATP produced. But 1 molecule of fatty acids results in 128 molecules of ATP production. If you want to overcome fatigue, you need to make mighty mitochondria. L-carnitine is essential in getting your body to start using fatty acids for fuel. (14, 13)

But that’s not all L-carnitine can do. It also has an important role in removing lactic acid from your cells. Those with chronic fatigue syndrome often have a buildup of lactic acid in their cells. One studied showed that supplementation of L-carnitine significantly lowered lactic acid levels compared to controls.

Vegetarians are at increased risk for L-carnitine deficiencies. The highest concentrations of L-carnitine are found in animal proteins. For those with chronic fatigue syndrome, the amount of L-carnitine obtained from food sources will be inefficient. supplementation is absolutely essential.


For conditions like chronic fatigue syndrome and myalgic encephalitis, I recommend taking one gram of L-carnitine daily. (15)

4. Vitamin B3 and Vitamin B12

All of the B vitamins are important in mitochondrial health. All of them. Taking a methylated supplement of B-complex vitamins will form a solid foundation. But you will need additional support via vitamin B3 and vitamin B12. (16)

Vitamin B3:

Vitamin B3 is typically known as niacin. If you’ve ever taken too much of this vitamin you’ll have experienced redness, or, flushing of your skin with an accompanying itch. This is known as a niacin flush. Fortunately, there are new forms of niacin (which I’ll describe below) that make for happy skin and mitochondria. (17)

The most important function of vitamin B3 (as far as energy production is concerned) is being a precursor to nicotinamide adenine dinucleotide (NAD or NADH). Without NAD/NADH, your mitochondria would be far less efficient at producing ATP. Nad/NADH helps to balance the electrons created when your body synthesizes ATP.


New forms of vitamin B3 known as nicotinamide riboside seem to be the most efficient at improving mitochondrial and ATP production. If you’re unable to find nicotinamide riboside, opt for niacinamide — but ensure it’s a slow release formula. This will prevent any of the uncomfortable skin reactions.

Take 500–1500mg daily.

Vitamin B12:

Vitamin B12 is known as cobalamin. This is the form many supplements come in. But for those with chronic fatigue syndrome, you’ll want to take your vitamin B12 in its methylated form — methylcobalamin. (18)

Vegetarians and vegans are at increased risk for vitamin B12 deficiencies. If you ascribe to either a vegetarian or a vegan diet, ensure you are supplementing B12 daily.

Those with CFS, tend to have decreased stomach acid, IBS, SIBO, and other gut-related pathologies. This will significantly interrupt the absorption of vitamin B12. Chronic fatigue patients, opt to get your vitamin B12 via monthly or bi-weekly injections. This vitamin is incredibly safe at high doses. There is no need to worry about overdosing. If you’re unable to obtain B12 injections, sublingual forms of methylcobalamin or hydroxycobalamin are the next best supplemental form. Avoid capsules or tablets as they are poorly absorbed.


Bi-weekly or monthly B12 injections or 5000mcg sublingual on a daily basis.

5. Magnesium

Anywhere from 40–70% of the developed world’s population is thought to be deficient in magnesium. (19) Keep in mind, this number comes from running something called serum magnesium levels. Serum magnesium is the magnesium levels found in your blood. And recent research suggests this is not an accurate measurement for your body’s magnesium stores. This is because the majority of magnesium is stored in your cells (99%!), not your blood! (20) Even if your lab test from your family doctors shows your magnesium levels to be normal, keep in mind that these are serum levels, not cellular levels. You could still be deficient in magnesium. Estimates put magnesium deficiency to be closer to 80% for all of the developed world.

Magnesium is one of the few supplements I recommend nearly all of my patients take indefinitely. Especially if they are active or treating conditions like chronic fatigue. The levels of magnesium found in the soil today are not adequate to supply the demand your body requires. This is why supplementation is essential. I’ve not found it possible to get enough magnesium through food sources — both for myself and with my patients.

When it comes to chronic fatigue, magnesium is absolutely essential in the product of ATP. Magnesium works in the opposite way of calcium. In a simplified example, calcium helps your muscles contract. Magnesium is needed to help your muscles relax. If any of you have ever experienced tension in your muscles (I’m sure everyone has) you can certainly agree that it’s far harder to relax a muscle than it is to contract one! Part of the reason could be due to all the calcium you’re getting through diet and supplements and the minimal amount of magnesium.


200mg twice a day. If you have sleep issues, I recommend one dose before bed.

Opt for magnesium glycinate or bisglycinate. These forms of magnesium do not pull water into your large intestine. Too much water in your large intestine results in urgent and loose bowel movements — something anyone who has taken too much (or the wrong type) of magnesium has experienced.

6. Iron

Iron is one supplement I encourage you to take only after having your levels first tested. Ensure you check both serum iron and ferritin levels. Ferritin is the long-term storage form of iron. If your iron levels are within normal ranges, I do not recommend iron supplementation. One of the main symptoms of too much iron is fatigue — a common symptom in a condition known as hemochromatosis. Other terrible effects of excessive iron include Alzheimer’s and Parkinson’s disease.

But if your iron levels are low, adding an iron supplement can have a dramatic increase in your energy levels. Heme iron is synthesized by your mitochondria. If your mitochondria don’t have enough heme, they start to degrade. (21) Remember, in conditions where fatigue is the main concern, you want to do everything you can to ensure your mitochondria are thriving. Iron is also required for your body to transport oxygen to its tissues.

Can you guess what the main symptom of low oxygen levels in your tissues is?

Yep, fatigue. Get your iron levels tested. And supplement iron if your levels are low. But not if they’re in normal ranges.


I don’t have a recommended dose for iron supplementation. It is entirely dependent on your levels. With that said, I would encourage you all to consume a serving of liver every week. Liver is full of iron and other fat-soluble vitamins. Your mitochondria will love it! (even if your palate doesn’t)

Ok, there you have it! These supplements should form the foundation of your chronic fatigue treatment plan. A whole food, ketogenic diet is also essential in the treatment of CFS. You cannot supplement yourself out of fatigue. Lifestyle changes (like your diet) need to be incorporated for treatment to be effective.

Now, I want to hear from you!

What supplements have you found to increase your energy? Share your experiences in the comments section below!

Originally published at Fatigue to Flourish.